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106 BY TONS AND MADS

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DRUGS ACTING ON CARDIOVASCULAR SYSTEM
Part 1: Introduction to Cardiovascular System Chapter 42
Cardiovascular System
- responsible for delivering O2 & nutrients to all cells of
the body and removing waste products for excretion.
consists of a pump (heart) andinterconnected series of
vessels that continually move blood
● Heart - hollow, muscular organ divided into 4 chambers
(upper L&R Atrium “porch/entryway” & lower L&R
Ventricle).
● Auricle - an appendage attached to each atrium w/c
collects blood that is then pumped into the ventricles
○ R Auricle larger than L Auricle
● Ventricles - pump blood out of the heart
● Arteries – carry oxygenated blood away from heart.
● Veins - return blood loaded w/ CO2 and toxins
(unoxygenated) back to the heart .
● Arteries & veins linked by microscopic Capillaries, Automaticity: P(Pale) Cells can generate action potentials
where exchange of O2, CO2 & metabolites occurs without being excited to do so by external stimuli. During
● AV valves (Cardiac Valves) (Tricuspid and Bicuspid)- diastole these cells undergo sponta-neous depolarization
thin tissues anchored to annulus (fibrous ring) gives because they decrease flow of K out and leak Na into the cell,
structure and helps to keep organ open and divided into causing an action potential.
distinct chambers.
○ close tightly when ventricles contract, Cardiac Action Potential
preventing blood from flowing backward into the 2 types: Myocyte and Pacemaker potential
atria. Typical Phases Myocyte potential : "
● Septum - separates right half of heart from left half ○ 0 (Rapid depolarization) “Upstroke” - point of stimulation
● Pulmonary & Aortic Valves (Semilunar Valves) - ○ 1 (early rapid repolarization) - Na are equal inside &
separate aorta and pulmonary artery from the heart and outside
anchored onto two fibrous rings (annuli) These keep ○ 2 (plateu) - less permeable to Na
blood flowing in one direction. ○ 3 (Final rapid repolarization) - K rapidly moves out
○ open w/ the pressure of ventricular contraction ○ 4 (resting membrane potential) “Diastolic Depolarization -
& close tightly during diastole. Na-K Pump returns the membrane to its previous state
● Circulatory system - 60,000 miles of interconnecting SA generates impulse 90-100x/min, AV 40-50x/min complex
blood vessels. ventricular muscle cells 110-20x/min
Cardiac Cycle - 2 step process: Systole & Diastole

Conductivity - property of cardiac cells wherein specialized


cells of heart can conduct an impulse rapidly through the system
so that the muscle cells of the heart are stimulated at
approximately the same time.
● SA node sets the pace for the HR because it depolarizes
faster than any cell in the heart.
● Other cells in the heart are capable of generating an impulse
○ Systole - contraction of the ventricles. if anything happens to the SA node
○ Diastole - relaxation of the cardiac muscle; ● Sinus rhythm - When the SA node sets pace for HR
Myocardium - form two intertwining networks atrial and ● AV Node -specialized for slow conduction.
ventricular syncytia; enable atria and ventricles to contract ● Purkinje Cells - specialized for rapid conduction.
Frank–Starlings law of the heart - “the increased filling ● Absolute refractory period - minimal amount of time that
pressure of the right heart results in increased cardiac output” must elapse between 2 stimuli applied at one site in heart
for each of these stimuli to cause an action potential;
Cardiac Conduction impossible to stimulate that area of membrane; reflects
● SA Node - acts as pacemaker of the heart ocated near responsiveness of heart cells to stimuli.
the top of the right atrium
● Atrial Bundles - conduct impulse thru atrial muscle. Autonomic Influences - generate AP & could function w/o
● AV node - slows impulse & allows delay needed for connection to the rest of the body.
ventricular filling then sends the impulse from the atria ● PSNS (10thCN Vagus)
into the ventricles by way of the bundle of His ○ Slow HR & decrease speed of conduction thru AV
● Bundle of His - enters septum & divides into 3 node allowing heart to rest & conserve strength
branches. ○ With dominant influence in the SA node, keeping the
● Bundle Branches (3) - conduct impulses thru resting HR at 70-80 beats/min.
ventricles. ● SNS
● Purkinje Fibers - deliver impulse to the ventricular ○ Stimulates heart to beat faster, speed conduction thru
walls. AV node, causes heart muscles to contract harder.
-Network of specialized tissues that stimulate contraction ○ Important during exercise or stress (when body
without any innervation. These continuous, rhythmic needs more O2)
contractions are controlled by heart itself; brain does not
stimulate the heart to beat.This safety feature allows the heart Myocardial Contraction - end result of electrical stimulation
to beat as long as it has enough nutrients and oxygen to ● Sarcomere - Basic (functioning) unit of cardiac muscle
survive, regardless of the status of the rest of the body. w/c is made up of 2 contractile proteins:
-Modified Cardiac myocytes ○ Actin - thin filament
○ Myosin - thick filament w/ small projections
● Z Bands - outer edges of sarcomere (anchor of
proteins)
● Troponin - keep protein apart when at rest.
● Actomyosin Bridges - formed by actin & myosin,
generate active force in muscle. Continue to form as
long as there is calcium.

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106 BY TONS AND MADS

- Each vertical square represents 0.1mV of electrical


charge
- Each horizontal square equals 0.04 s of time
- Approximate values for normal intervals:
- PQ (PR) interval - 0.16 s - Reflects the normal
delay of conduction at the AV node
- QT interval - 0.3 s - Reflects the critical timing of
repolarization ofventricles
Myocardial Contraction - QRS interval - 0.08 s
Cellstimulated -> Ca enters cells (slowly @ phase 2or3) -> - P wave - 0.08 s
Reacts w/ troponin & inactivates it -> actin & myosin react w/ - ST interval - 0.1 s - Reflects important
each other forming actomyosin bridges information about repolarization of ventricles
● Bridges formed break quickly, & myosin slides along to
form new bridges. Arrhythmia or Dysrhythmia
● As long as calcium is present the actomyosin bridges - disruption in cardiac rate/rhythm
continue to form. - interfere with the work ofheart, disrupt the cardiac
● As cell reaches repolarized state, Ca is removed from output
cell by sodium–calcium pump, and calcium released SINUS ARRHYTHMIAS
from storage sites returns to the storage sites. ● Sinus Tachycardia- faster than normal HR>100bpm (adult),
● The degree of shortening (the strength of contraction) is w/ normal-appearing ECG pattern. If too fast = decreased
determined by the amount of calcium present cardiac filling time & decreased CO. Can be cause by exercise,
● The further apart the actin and myo-sin proteins are fear, or stress.
before cell is stimulated, more bridges will be formed
and the stronger the contraction will be.(Starling’s law)
Electrocardiography - recording patterns of electrical impulses
as they move thru the heart; diagnostic tool
● ECG - is a measure of electrical activity of the heart.
Normal ECG consists of:

● Sinus Bradycardia - slower than normal HR <60bpm, with


normal-appearing ECG pattern. Allows increased time for
ventricular & increased CO. Often seen in athletes. Rate
might be too slow to adequately perfuse all of the tissues.

● P wave (atrial wave) - denoting atrial contraction;


formed as impulses originating in the SA node.
● QRS spike (prominent peak as ventricles contract) - a
brief hesitation before the AV node is activated;
represents depolarization of bundle of his (Q) & SUPRAVENTRICULAR ARRHYTHMIAS Originate above the
ventricles (RS) ventricles, not in SA node; abnormally shaped P wave. Normal
● T wave (large slow wave) – caused by ventricular QRS complexes (ventricles still conducting impulses normally)
recovery; represents repolarization ○ Premature Atrial Contractions- Ectopic Focus (shift in
heart’s pacemaker from SA node to other site) in atria that is
generating impulse out of normal rhythm.
○ Paroxysmal Atrial Tachycardia - rapid HR originating in
atria, sporadically occurring.
○ Atrial Flutter - sawtooth-shaped Pwaves reflecting a single
ectopic focus generating a regular, fast atrial depolarization.
2:1 or 3:1 ratio of Pwaves to QRS complexes
○ Atrial Fibrillation - irregular Pwaves representing many
ectopic foci firing in an uncoordinated manner thru atria.
unpredictable num-ber of impulses are transmitted to the
ventricles

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106 BY TONS AND MADS
c.
Veins are thin-walled, very elastic, low-pressure
vessels hold large quantities of blood gpoing
back to the heart. “capacitance system”;.
3. Coronary Circulation

● Coronary Arteries branch of base of aorta “sinuses of


Valsalva”.
Atrioventricular Block or Heart Block - slowing or lack of ○ Receive blood during diastole (at rest).
conduction @AV node. May be due to: structural damage, ○ circulation pattern is “End Artery Circulation”.
hypoxia, or heart muscle injury. ○ Left coronary feeds septum and anterior areas
○ 1st Degree Heart Block - All from SA node arrive in including conduction system
ventricles but after longer-than-normal period, ○ Left Coronary supplies most of right side of the
characterized by lengthening of P-R interval beyond normal heat including SA node
(0.16-0.20 sec). Each P wave is followed by QRS complex. ● Pulse Pressure - SP minus DP
○ 2nd Degree Heart Block - Some impulses are lost & do ○ The pressure that fills coronary arteries.
not get thru, resulting in slow rate of ventricular ○ The difference b/n systolic (ejection) pressure &
contraction. QRS may follow 1, 2, 3, or 4 P waves. diastolic (resting) pressure.
○ 3rd Degree Heart Block or Complete Heart Block - No ○ Monitored to evaluate filling pressure of
impulses from SA node get thru the ventricles, much slower coronary arteries.
ventricular automaticity takes over.
■ total dissociation of P waves from QRS complexes & Main Forces that Determine Oxygen Consumption
T waves. Because P wave can come at any time P-R ● Heart Rate - more pumping, more O2 requirement.
interval is not constant. ● Preload - volume of blood in ventricles at end of
■ QRS complexes appear at very slow rate & may not diastole; “stetch”
be sufficient to meet body’s needs. ○ Amount of blood brought back to heart to be
pumped throughout the body.
Ventricular Arrhythmias - abnormal heartbeats that originate ○ more blood return, harder heart will work.
below AV node (ventricles) originate from ectopic foci that do ○ Blood volume is determinant of preload.
not use the normal conduction path-ways. QRS complexes ● Afterload - resistance LV must overcome to circulate
appear wide & prolonged, & T waves are inverted reflecting blood; “squeeze”
slower conduction across cardiac tissue. ○ Resistance against w/c the heart has to beat.
○ Premature Ventricular Contractions (PVCs) - Can ○ higher resistance, the harder heart will have to
arise from single ectopic focus in ventricles, w/ all of them contract to force open valves & pump blood.
having the same shape OR Arise from many ectopic foci, ○ BP is the measure of afterload.
w/c produces different shapes. Runs or burst of PVCs ● Stretch on Ventricles
reflects extensive damage or hypoxia in myocardium. ○ If ventricular muscle is stretch before it is
○ Ventricular Fibrillation - bizarre, irregular, distorted stimulated to contract, more actomyosin bridges
wave. Fatal because it reflects lack of any stimulation of will be formed.
ventricles resulting in NO blood being pumped to the body ○ If stimulated harder than usual (happens w/
or brain. Thus, there is total loss of CO. sympathetic stimulation, more bridges will be
formed. More bridges, more energy required.
SYSTEMIC ARTERIAL PRESSURE - Greatest during systole &
lowest during diastole
● Hypotension - A low BP from loss of blood volume or
from failure of the heart muscle to pump effectively.
○ If severe, can progress to shock & \ death as
cells are cut off from their O2 supply.
● Hypertension - Constant, excessive high blood
pressure that can damage fragile inner lining of blood
vessels & cause disruption of blood flow to tissues.
○ Puts tremendous strain on ❤ muscle, increasing
myocardial O2 consumption & puts ❤ muscle at
risk.
○ Can be caused by:
■ 1.) Neurostimulation of blood vessels
that cause constriction (raising BP);
■ 2.) Increased volume in the system,
■ 3.) Unknown cause (in most cases).
Circulation Drugs given are aimed to changing one or more of normal
1. Pulmonary Circulation (Heart-Lung) -right side of reflexes that control vascular resistance of force of cardiac
heart sends blood to the lungs where CO2 & some muscle contraction.
waste products are removed from blood & O2 is picked ● Vasomotor Tone - degree of constriction (from nerve
up by the RBC. fibers of SNS) experienced by a blood vessel relative to
a. RA is Low Pressure where all of the its maximally dilated state; an essential determinant of
deoxygenated blood from the body flows. As BP. These impulses work to:
blood flows into atrium, pressure increases. ■ Dilate vessels if more blood is needed in an area.
When pressure becomes greater than RV, blood ■ Constrict vessels if increased pressure is needed
flows into the RV; “rapid- filling phase” in the system.
2. Systemic Circulation - flow of blood between the ■ Maintain muscle tone so that vessels remain
heart and all parts of body, except lungs; left side of patent & responsive.
heart sends O2 blood out to all of the cells in the body. ● Impulses coordination is regulated thru
a. The entire arterial system contains muscles who Medulla in “Cardiovascular Center”.
offer resist-ance to the blood sent by LV, ● If increase pressure is needed, cardio center
generating pressure. “resistance system”. increases sympathetic flow. If pressure rises
b. Blood from the tiny arterioles flows into the too high, sympathetic flow is decreased.
capillary system. Oxygen, fluid, and nutrients ● Renin - Angiotensin - Aldosterone System
pass through arterial end of capillaries and enter increases BP when activated when blood flow to the
tinterstitial area between tissue cells. Fluid at kidneys is decreased and juxtaglomerular cellsrelease
venous end (contains CO2 and other waste enzyme renin. Renin transported to liver, converts
products) is drawn back into the vessel. angiotensinogen (produced in tliver) to angiotensin I.
“capillary fluid shift”, carefully regulated by a Angiotensin I travels to lungs, converted by
balance between hydrostatic forces and oncotic angiotensin-converting enzyme (ACE) to angiotensin II.
pressure Angiotensin II travels through body and reacts with
angiotensin II receptor sites on blood vessels to cause

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106 BY TONS AND MADS
severe vasoconstriction. -> increases BP and increase ○ Atrial Natriuretic Peptide (ANPs) in heart.
blood flow to kidneys ↑total peripheral resistance and ○ Brain Natriuretic Peptides (BNPs) in the brain.
↑BP -> decrease release of renin. ○ Other Natriuretic Peptides: - CNPs & DNPs
○ Angiotensin II -> Angiotensin III-> causes ○ Act to inhibit reninangiotensin-aldosterone system & cause
release of aldosterone from adrenal cortex -> diuretic, natriuretic, & BP lowering effect.
retention of Na and water -> release of (ADH)-> ○ ANP & BNP release in response to high ventricular filling.
↑Blood Volume -> ↑BP -> decrease release of
renin. Venous Pressure (VP)
- Pressure veins that may sometimes rise above normal if
heart is not pumping effectively or unable to pump out
all blood that is trying to return to it. Inability to pump
out all blood results in backup or congestion of blood
(venous congestion).
● Heart Failure (HF) - Failure of heart muscle to do its
job (pump effectively) blood backs up and the system
becomes congested
○ Rise in VP from blood backup increases the HP on
venous end of
capillaries.
○ Higher HP than OP
will cause fluid to be
lost into the tissues
which account for
edema Tin HF.
○ Pulmonary Edema -
left side of the heart
● fails.
○ Peripheral,
Abdominal, & Liver
edema occur when
the right side of the
heart fails.
Other Factors that Contribute Fluid Loss in Tissues
● Protein Loss
○ Can lead to fall in Osmotic Pressure & inability
to pull fluid back into the vascular system.
○ Noted in Renal Failure, when protein is lost in
the urine.
○ Seen in Liver Failure, when liver is no longer
able to produce plasma proteins.
● Fluid Retention
○ stimulated by Aldosterone & ADH, can increase
HP; fluid is pushed out under higher pressure &
the balancing pressure to pull it back into the
Natriuretic Peptides vessel is not sufficient.
○ Formed in atria of the heart & in the brain.
Part 2:Drugs Affecting Blood Pressure (Chapter 43) PPT
Drugs Affecting Blood ○ Blood volume drops dramatically due to severe
Pressure blood or fluid loss.
3 Elements that Determine ○ There’s extreme stress & the body’s levels of
Pressure of CV System: norepinephrine are depleted, leaving the body
1. Heart Rate - # of unable to respond to stimuli to raise BP.
times each minute that
heart beats White Coat Hypertension - BP readings at health care
2. Stroke Volume - provider's office are higher than they are in other settings
amount of blood that
pumped out of the DRUG THERAPY ACROSS THE LIFESPAN
ventricle with each Children
heartbeat ● hypertension may start as a childhood disease; More likely
3. Total Peripheral to have secondary hypertension caused by renal disease or
Resistance - congenital prob (coarctation of aorta). Tx should be done
resistance of muscular very cautiously because long-term effects of
arteries to the blood antihypertensive agents are not known.
being pumped ● Lifestyle changes should be instituted 1st before drug
therapy: wt loss & increase activity.
BARORECEPTORS (Pressure receptors) ● If drug therapy is needed, mild diuretic or calcium-channel
-specialized cells located in the carotid sinus & in aortic arch, & blockers should be considered 1st.
carotid arteries that serve as BP sensors, mediating thru ANS. ● If drug therapy is used, a mild diuretic may be tried first, -
-Sensory input is received by Medulla in Cardiovascular monitor blood glucose & electrolyte regularly.
(Vasomotor) center. ● Beta-blockers have been used with success in some children.
-If ↓pressure, medulla (thru ANS) directly stimulates ↑cardiac ● Careful follow-up is needed to monitor BP changes.
rate and output and vasoconstriction = ↑total peripheral ● Safety & efficacy of ACE inhibitors & ARBs have not been
resistance and ↑BP. established in children.
● Calcium channel blockers used to treat hypertension in
HYPERTENSION - “Silent Killer” - BP above normal limits or a children and maybe a fi first consideration if needed.
sustained period Adults
● Essential Hypertension - no known cause ● Instruct about adverse effects & safety precautions in hot
○ Total Peripheral Resistance is elevated; Organs weather or with conditions that cause fluid depletion.
are effectively perfused; No symptoms Evaluate interacting effects if taking any other drugs.
● Secondary Hypertension - From known cause ● Stress the importance of other measures that lower BP: wt
● If untreated may risk for: CAD & cardiac death, stroke, loss, smoking cessation, & increase activity.
RF, & vision loss. Left ventricle thickens bec muscle must ● ACE inhibitors, ARBs, & Renin should NOT be used in
constantly work hard to expel blood at greater force pregnancy.
HBP - a sign of overworked heart and blood vessels; can lead to ● Calcium-channel blockers & vasodilators should NOT be used
atherpscclerosis and CHF if untreated; The underlying danger is in pregnancy unless benefit clearly outweighs potential risk
prolonged force on the vessels, the muscles in the arterial to fetus.
system eventually thicken, leading to a loss of responsiveness in ● Advise childbearing women to use barrier contraceptives
system. Thickening of heart muscle and increased pressure to while taking meds.
generate every time it contracts increase workload of heart and ● Drugs do enter breastmilk & can cause serious adverse
risk of coronary artery disease (CAD) effects. Caution should be used or use other feeding
method.
HYPOTENSION - BP becomes too low, can progress to shock Older Adults
● Can occur in following situations: ● Frequently prescribed with one of antihypertensive drugs &
○ Heart muscle is damage & unable to pump are susceptible to toxic effects. If renal or hepatic dysfunction
effectively. is present, reduce dose & monitor very closely.

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106 BY TONS AND MADS
● Coordinate total drug regimen w/ careful attention to ● Enalaprilat (generic)
interactions among drugs & alternative therapies. ○ 1.25mg q6h IV over 5 mins
● Use special precautions in situations that lead to fall in BP: ○ Short term tx of acute HPN when oral therapy is
fluid loss (diarrhea, vomiting, lack of fluid intake, excessive not feasible.
heat w/ decreased sweating that comes w/ age). ● Fosinopril (generic)
● Dizziness, fall, & syncope can occur if BP fall too far. Always ○ 20-40mg/d PO
take BP before administration if in institutional setting. ○ Tx of HPN; adjunct therapy for HF; for adult
use.
STEPPED CARE MANAGEMENT OF HYPERTENSION ● Lisinopril (Prinivil)
● Step 1: Lifestyle Modification are Instituted ○ 20-40mg/d PO for HPN; 5-20mg/d PO for HF;
○ Weight Reduction 5-10mg/d PO after MI;.
○ Smoking cessation ○ Tx of HPN, HF; tx of stable pts w/in 24h after
○ Moderation of alcohol intake acute MI to increase survival; for adult use.
○ Reduction of salt in diet ● Moexipril (Univasc)
○ Increase in physical activity ○ 7.5-30mg/d PO, base on response;
● Step 2: Inadequate Response ○ Tx of HPN in adults.
○ Continue lifestyle modifications in step 1. If not ● Perindopril (Aceon) 4mg/d;
sufficient to lower BP to an acceptable level, ○ Tx of HPN, may be used alone or as
drug therapy is added: combination drug to control BP; for adult use.
■ Diuretic (decreases serum Na+ levels & ● Quinapril (Accupril)
blood volume) ○ 20-80mg/d PO, based on response for HPN;
■ ACE inhibitor (blocks conversion of 10-20mg/d PO BID for HF;.
angiotensin I to angiotensin II) ○ Tx of HPN, adjunctive tx to HF; for adult use.
■ Calcium-channel blocker (relaxes muscle ● Ramipril (Altace)
contraction) or other autonomic blockers ○ 2.5-20mg/d PO for HPN, 5mg PO BID for HF;
■ Angiotensin II receptor blocker (blocks ○ Tx of HPN, adjunctive tx to HF; for adult use.
effects of angiotensin in blood vessels ● Trandolapril (Mavik)
● Step 3: Inadequate Response ○ 1-2mg PO QID for HPN; 4mg/d PO, titrate
○ Consider change in drug dose or class, or slowly to that level for HF; Tx of HPN, HF, &
addition of another drug for combined effect. after MI; for adult use.
(Note: Fixed combination drugs should only be
used when the patient has been stabilized on RENIN INHIBITOR
each drug separately) ● Aliskerin(Tekuna) 150-300mg/d PO based on response.
● Step 4: Inadequate Response ○ Used alone or as part of combination therapy in
○ All of the above measures are continued. tx ofadult HPN.
○ A 2nd or 3rd agent or diuretic is added if not
already prescribed. ANGIOTENSIN II RECEPTOR BLOCKERS All “Used alone or
as part of combination therapy for tx of HPN in adults”
● Azilsartan (Edarbi) 80mg/d PO
● Candesartan 16-32mg/d PO
● Eprosartan (Teveten) 400-800mg/d PO.
● Irbesartan (Avapro) 150-300mg/d PO,
○ slowing progression of diabetic nephropathy in
patients w/ HPN & type 2 Diabetes.
● Losartan (Cozaar) 25-100mg/d PO,
○ slowing progression of diabetic nephropathy w/
elevated serum creatinine & proteinuria in
patients w/ HPN & type 2 Diabetes.
● Olmesartan(Benicar) 20-40mg/d PO
● Telmisartan (Micardis) 40-80mg/d PO
● Valsartan (Diovan) 80-320mg/d PO based on response, Tx of
HF in pts intolerant to ACE inhibitors.
CALCIUM-CHANNEL BLOCKERS reduce dose in pts w/
hepatic impairment & patients
● Amlodipine (Norvasc) 5-10mg/d PO,Used alone or as part of
combination w/ other agents for tx of HPN & angina in
adults.
● Clevidipine (Cleviprex) Initially 1-2mg/h by IV infusion,
titrate quickly by doubling dose q 30sec, usual maintenance
dose 4-6mg/h. Reduction of BP when oral therapy is not
possible or desirable.
● Diltiazem (Cardizem) 60-120mg PO BID Extended release
preparation used to tx HPN in adults, other preparations are
used for angina.
● Felodipine (Plendil) 10-15mg/d PO, do not exceed 10mg/d in
ANTIHYPERTENSIVE AGENTS geriatric patients or in patients w/ hepatic impairments.
● Altering the body’s regulatory mechanisms is best tx Used alone or as part of combination w/ other agents for tx
currently available for HPN considering unknown cause. of HPN in adults.
● Tx does not cure HPN but aimed at maintaining BP w/in ● Isradipine (generic) 2.5-10mg PO BID, 5-10mg/d PO -
normal limits to px damage. controlled release. Used alone or in combination w/ thiazide
● Not all patients respond in same way due to varied factors diuretics for tx of HPN in adults.
that contribute to each person’s HPN. patient’s response to ● Nicardipine (Cardene) 20-40mg PO TID; 0.5-2.2mg/h IV
a given antihypertensive agent is very individual, so the drug based on response, switch to oral form as soon as feasible;;
of choice for one patient may have little to no effect on 30-60mg PO BID- sustained release. Used alone or in
another patient. combination w/ other agents for tx of HPN & angina, IV
● Several different types of drugs may need to be used in form for short-term use when oral route is not feasible; for
combination. adults’ use.
● Nifedipine (Procardia XL) 30-60mg/d PO Extended release
ACE INHIBITORS - reduce dose in geriatric patients & pts w/ preparations only for the tx of HPN in adults, other
renal impairment. preparations are used for angina.
● Benazepril (Lotensin) 20-40 mg/d PO, ● Nisoldipine (Sulfar) 20-40mg/d PO;. Extended release tabs
○ Approved only for tx of HPN in adults. used as mono-therapy for tx of HPN in adults, other
● Captopril (Capoten) PROTOTYPE preparations are used for angina
○ 25mg PO BID-TID for HPN; 50-100mg PO TID ● Verapamil (Calan SR) 120-240mg/d PO, reduce dose in the
for HF: 50mg PO TID for Ventricular morning; extended release capsules; 100-300mg/d at
Dysfunction, 25mg PO TID for Diabetic bedtime. Extended release formulations for tx of essential
Nephropathy; HPN, other preparations are used for angina & treating
○ Tx of HPN; adjunct therapy for HF; Tx of left various arrhythmias in adults.
ventricular dysfunction after MI, diabetic
nephropathy; for adult use. VASODILATORS
● Enalapril (Vaster) ● Hydralazine (generic)
○ 10-40mg/d PO; 2.5mg PO BID for HF or left ○ Adult: 20-40mg IM/IV repeated as necessary.
ventricular dysfunction. ○ Pediatric: 1.7-3.5mg/kg/24h IV/IM in 4-6 divided
○ Tx of HPN; HF; left ventricular dysfunction in doses.
adults. ○ Tx of severe HPN.
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106 BY TONS AND MADS
● Minoxidil(generic) ● Alert surgeon & mark the patient’s chart prominently if the
○ Adult: 10-40mg/d PO in divided doses. patient is to undergo surgery to alert medical personnel that
○ Pediatric (<12y.o): 0.25-1mg/kg/d PO as single the blockage of compensatory angiotensin II could result in
dose hypotension after surgery that need to be reversed w/ volume
○ Tx of severe HPN unresponsive to other therapy. expansion.
● Nitroprusside (Nitropress) ● Give parenteral form of enalapril only if oral form not feasible;
○ Adult & Pediatric: 3mcg/kg/min, do not exceed transfer to oral form ASAP to avoid an increased risk for
10mcg/kg/ min. adverse effects.
○ Tx of hypertensive crisis, also used to maintain ● Consult w/ prescriber to reduce dose in pts w/ RF to account
controlled hypotension during surgery. for their decreased production of renin & lower-than-normal
OTHER ANTIHYPERTENSIVE AGENTS: DIURETIC AGENTS levels of angiotensin II.
- Tx pf mild HPN, often 1st agents used, often used w/ other ● Monitor pt carefully in any situation that might lead to drop in
agents. fluid volume (e.g: excessive sweating, vomiting, diarrhea,
dehydration) to detect & treat excessive hypotension that may
Drugs Affecting Renin-Angiotensin-Aldosterone System occur.
3 Drugs that Alter RAS ● Provide comfort measures to help pt tolerate drug effects.
1. Ace Inhibitors - block conversion of angiotensin I to mall, frequent meals; access to bathroom activities; bowel
angiotensin II. program as needed; environmental controls; safety
2. ARBs Angiotensin II Receptor Blockers- block precautions; & appropriate skin care as needed.
angiotensin receptor site on blood vessels. ● Provide thorough pt teaching,
3. Renin Inhibitor - blocks the reflex at the beginning by ● Offer support & encouragement to help the patient deal w/ the
inhibiting renin. diagnosis & the drug regimen.
Evaluation
ANGIOTENSIN-CONVERTING ENZYME (ACE) ● Monitor for adverse (hypotension, cardiac arrythmias,
INHIBITORS renal dysfunction, skin reactions, cough, pancytopenia,
Therapeutic Actions HF).
- Act in lungs to px ACE from converting angiotensin I to ● Offer support & encouragement to help the patient deal
II = ↓BP, ↓aldosterone production, & ↑serum K levels, w/ the dx & the drug regimen.
along w/ Na+ & fluid loss.
Indications ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs)
- Tx of HPN (alone or combination w/ other drugs), HF, Therapeutic Actions
diabetic nephropathy (DN), & left ventricular dysfunction -Selectively blocks binding of angiotensin II to specific tissue
(LVD) after MI. receptors found in vascular smooth muscle & adrenal
- Used in conjunction w/ digoxin & diuretics for HF & LVD glands; blocks vasoconstriction & release of aldosterone
tx. Therapeutic effect is related to decreased cardiac Indications
workload & blood volume. - Alone or as part of combination therapy for tx of HPN; tx
- For diabetic nephropathy; decreased stimulation of of HF in patients who are intolerant to ACE inhibitors;
angiotensin receptors in renal artery will slow damage slow progression of renal dse in patients w/
Pharmacokinetics hypertension & type 2 diabetes.
-All PO. Enalaprilat parenteral use if PO not feasible or rapid Pharmacokinetics: All PO. Well absorbed & undergo metabolism
onset is desirable. in the liver by cytochrome P450 system. Excreted in feces &
-Metabolized in liver, excreted in urine & feces. Not used urine. Cross placenta, not known whether enter breastmilk
during pregnancy. Detected in breastmilk, known cross Contraindications & Cautions
placenta (associated w/ serious fetal abnormalities). - Allergy; Pregnancy (serious fetal abnormalities & death);
Lactation (serious adverse effects in neonate).
Contraindications & Cautions - If pregnancy occurs, D/C immediately; Use of barrier
- Allergy to ACE; pregnancy (serious adverse effects to fetus); contraceptives is advised.
lactation (decrease milk production, neonatal effects). - Caution in presence of hepatic or renal dysfunction & w/
- Caution: HF (change in hemodynamics detrimental); hypovolemia (blocking of potentially life-saving
Salt/Volume depletion exacerbated by drug effects). For compensatory mechanism).
childbearing: use barrier method of FP. - Candesartan, eprosartan, irbesartan, olmesartan, and
Adverse Effects telmisartan not be used during 2nd/3rd trimester
- Mostly related to vasodilation: Tachycardia, chest pain, because of association with serious fetal abnormalities
angina, HF, cardiac arrythmias, GI irritation, ulcers, and death
constipation, liver injury, renal insufficiency, RF, - Azilsartan, losartan, and valsartan not be used at any
proteinurua, rash, aopeia, dermatits, photosensitivity time during pregnancy.
- Quinapril, ramipril, and trandolapril not associated with Adverse Effects
as many adverse effects - Associated w/ BP drop: hypotension, Headache,
- Benazepril, enalapril, and fosinopril cause unrelenting dizziness, syncope, & weakness.
cough. - G.I complains: diarrhea, abdominal pain, & nausea.
- Captopril - sometimes-fatal pancytopenia, cough, and - Dry mouth, & tooth pain; symptoms of URTIs & cough;
unpleasant GI distress. rash, dry skin, & alopecia.
- Moexipril - unpleasant GI and skin effects, cough, - associated w/ development of various CAs, renal
cardiac arrhythmias; fatal MI and pancytopenia damage. Monitor renal fx when using this.
- Perindopril and lisinopril - sometimes-fatal pancytopenia, Drug-drug Interactions
serious-to-fatal airway obstruction - Risk of ↓serum levels & ↓effectiveness increases if taken
Drug-drug Interactions in combination w/ phenobarbital, indomethacin, or
- ↑hypersensitivity reactions if taken w/ allopurinol. rifamycin. monitor & make dose adjustment.
- Risk of ↓antihypertensive effects if taken w/ NSAIDs - ↓effects if combined w/ ketoconazole, fluconazole, or
- Not combined w/ ACE inhibitors, ARBs or Renin inhibitor. diltiazem. Monitor & adjust dose as needed.
Drug-Food Interactions - Should not be used w/ ACE or Renin inhibitors because
- Taken on empty stomach (1h before or 2h after meal). of potential serious adverse effects.
- Absorption decreases if taken with food. Nursing Considerations
Assessment: History and Examination
(ACE) INHIBITORS Nursing Considerations ● Assess for: Drug allergies; Impaired kidney or liver
Assessment: History and Examination function, Pregnancy & lactation; Hypovolemia (w/c could
● Assess: allergies, Impaired kidney function, Pregnancy potentiate the BP lowering effects)
or lactation, Salt/volume depletion & HF ● Assess baseline status before beginning therapy (to
● Assess baseline status before therapy: temp & weight, determine any potential adverse effects)
skin color, lesions, pulse, BP, baseline ECG, & perfusion, Diagnosis
respirations & adventitious sounds; bowel sounds & ● Ineffective tissue perfusion (total body) related to changes
abdominal exam, renal function test, CBC w/ differential in cardiac output
count, & serum electrolyte. ● Impaired Skin Integrity related to dermatological effects
Diagnosis ● Acute Pain related to GI distress and cough
● Ineffective tissue perfusion (total body) related to changes ● Deficient Knowledge regarding drug therapy
in cardiac output. Implementation
● Impaired skin integrity related to dermatological effects. - Encourage pt to implement lifestyle changes to increase the
● Acute pain related to GI distress & cough. effectiveness of antihypertensive therapy.
● Deficient knowledge regarding drug therapy. - Administer w/o regard to meals, give w/ food to decrease GI
distress if needed.
Implementation with Rationale - Alert surgeon and mark pt’s chart prominently if pt is to
● Encourage pt to implement lifestyle changes, wt loss, smoking undergo surgery (blockage of compensatory angiotensin II
cessation, decreased alcohol & salt diet, & increased exercise, could result in hypotension after surgery)
to increase effectiveness of therapy. - Ensure that female pt is not pregnant before beginning
● Administer on an empty stomach 1h before or 2h after meals therapy, & suggest use of barrier contraceptives while taking
to ensure proper absorption this drugs,

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106 BY TONS AND MADS
- Find an alternative method of feeding the baby. - Allergy to drug; any condition that could be exacerbated
- Monitor pt carefully in any situation that might lead to a drop by sudden fall BP (cerebral insufficiency).
in fluid volume (e.g., excessive sweating) - Use w/ caution in pts w/ peripheral vascular disease,
- Provide comfort measures. small, frequent meals; access to CAD, HF, or tachycardia.
bathroom facilities; bowel program as needed; environmental - Diazoxide used w/ extreme caution in patients w/
controls; safety precautions; appropriate skin care as needed. functional hypoglycemia because this drug increases
- Provide thorough patient teaching blood glucose levels by blocking insulin release.
- Offer support and encouragement to help the patient deal with - Pregnancy (unless benefit outweighs risk), Breastfeeding
the diagnosis and the drug regimen. (adverse effects on the baby).
Evaluation Adverse Effects
- Monitor for adverse effects (hypotension, cardiac - Related to BP Changes: Dizziness, anxiety, & headache;
arrhythmias, renal dysfunction, skin reactions, cough, reflex tachycardia, HF, chest pain, edema; skin rash &
pancytopenia, heart failure). lesions (abnormal hair growth w/ minoxidil); GI upset,
- Monitor the effectiveness of comfort measures and nausea, & vomiting.
compliance with the treatment regimen. - Cyanide toxicity (dyspnea, headache, vomiting,
dizziness, ataxia, loss of consciousness, imperceptible
RENIN INHIBITOR - Aliskiren (Tekturna) pulse, absent reflexes, dilated pupils, pink color, distant
- Directly inhibits renin, inhibiting conversion of heart sounds, & shallow breathing) may occur w/
angiotensinogen to angiotensin 1 leads to ↓BP, nitroprusside, w/c is metabolized to cyanide & also
↓aldosterone release, & ↓sodium reabsorption. suppresses iodine uptake & can cause hypothyroidism.
Indications: Tx of HPN Drug-drug Interactions: Each of these drugs works differently ,
Pharmacokinetics should be checked for drug–drug interactions before use.
- Slowly absorbed from GI tract, w/ peak levels in 3 hrs.
It’s metabolize in the liver, w/ a half life of 24 hrs. Nursing Considerations
- Excreted in urine. Cross placenta & enters breastmilk. ● Assess for conditions, w/c could be cautions/CIs to use
Contraindications & Cautions of the drug: any known allergies to these drugs;
- Pregnancy (serious adverse effects on fetus). impaired kidney or liver function; pregnancy or lactation;
- Lactation (enters breastmilk) CV dysfunction.
- Hyperkalemia (blocks RAS & aldosterone will not be ● Assess baseline status before beginning therapy to
stimulated to be released resulting to hyperkalemia). determine any potential adverse effects
Adverse Effects Diagnosis: same
- Diarrhea, stomach pain, heartburn, cough, rash, Implementation
dizziness, headache & back pain. ● Encourage pt to implement lifestyle changes
Drug-drug Interactions ● Monitor BP closely during administration. Monitor blood
- If combined w/ furosemide, loss of diuretic effect. glucose and serum electrolytes
- Should not be combined w/ ACE inhibitors or ARBs ● Monitor pt carefully in any situation that might lead to
Nursing Considerations drop in fluid volume (e.g., excessive sweating, vomiting,
● Monitor closely. Generally tolerated but cases of diarrhea, dehydration)
angioedema w/ respiratory involvement have been ● Provide comfort measures to help the patient tolerate
reported. Advise pt to report any difficulty of breathing, drug effects; safety precautions if CNS effects occur;
swelling of face, lips, & tongue. —environmental controls; appropriate skin care as
needed; & analgesics as needed.
CALCIUM-CHANNEL BLOCKERS (CCBs) ● Provide thorough patient teaching
- ↓BP, ↓cardiac workload, ↓myocardial O2 consumption. ● Offer support and encouragement
effective in treatment of angina; available in
immediate-release and sustained-release Other Antihypertensive Agents
Therapeutic Actions Diuretic Agents
-Inhibit movement of Ca+ ions across membranes of -Drugs that increase excretion of Na+ & H2O from kidney.
myocardial & arterial muscle cells, altering action potential & -Often 1st agents tried in mild HPN; affect blood Na+ levels
blocking muscle cell contraction. & blood volume.
-This effect depresses myocardial contractility, slows cardiac -Antihypertensive & Lipid-Lowering Treatment to Prevent
impulse formation in conductive tissues, & relaxes & dilates Heart Attack Trial (ALLHAT), reported in 2002 that pts taking
arteries, causing fall in BP & decrease in venous return. less expensive, less toxic diuretics did better BP control than
Indications: Tx of HPN. Mainly use for tx of angina. pts using other antihypertensive agents.
Pharmacokinetics -Use of thiazide diuretic is currently considered the 1st drug
- PO & well absorbed, metabolized in liver, & excreted in used in the steppedcare management of hypertension.
urine. -Although these drugs increase urination & can disturb
- Cross placenta & enter breast milk. Nicardipine is also electrolyte & acid–base balances, they are usually tolerated
available in IV form for short-term use when oral well by most patients.
administration is not feasible. ● Thiazide and thiazide-like diuretics
Contraindications & Cautions ● Potassium-sparing diuretics
- Allergy; Heart Block or Sick Sinus Syndrome, (could be
exacerbated by conduction-slowing effect)s; w/ renal or Sympathetic Nervous System Blockers
hepatic dysfunction. -Drugs that block effects or compensatory effects of SNS.
- Pregnancy (unless benefit outweighs potential risk). 1. Beta-blockers
- Breastfeeding (adverse effects on the baby). -Block vasoconstriction, decrease HR, decrease cardiac muscle
Adverse Effects contraction, & tend to increase blood flow to kidneys, decrease
-relate to effects on CO & on smooth muscle. in the release of renin.
-CNS: dizziness, light-headedness, headache, & fatigue. -Not recommended for all people due to adverse effects.
-GI: nausea & hepatic injury related to direct toxic effects on -Often used as monotherapy in step 2 tx \sed to treat HPN
hepatic cells. -acebutolol, atenolol, betaxolol, bisoprolol, carteolol,
-CV: hypotension, bradycardia, peripheral edema, & heart metoprolol, nadolol, nebivolol, penbutolol, pindolol,
block. propranolol, and timolol.
-Skin flushing & rash 2. Alpha-Adrenergic Blockers
Drug-drug Interactions: vary with each; increase in serum levels -Inhibit alpha1 receptors, decreasing sympathetic tone in the
& toxicity if cyclosporine if taken with diltiazem. vasculature causing vasodilation, thus lowering BP.
Drug-Food Interactions -block alpha2-receptors, preventing feedback control of
- CCBs interact w/ grapefruit juic, concentrations of CCBs norepinephrine release, resulting to increase in tachycardia
increase, sometimes to toxic levels. reflex that occurs when BP decreases.
- Avoid use of grapefruit juice if taking CCB. If w/ toxic -Used to diagnose & manage episodes of pheochromocytoma,
effects, ask W/N patient is drinking grapefruit juice. but they have limited usefulness in essential hypertension
because of the associated adverse effects.
VASODILATORS -phenoxybenzamine and phentolamine
- Act directly on vascular smooth muscle to cause muscle 3. Alpha-&-Beta Blockers
relaxation, leading to vasodilation & drop in BP. -Useful in conjunction w/ other agents (more powerful), blocking
- do not block treflex tachycardia that occurs when blood all of receptors in sympathetic system.
BP drops. -Patients often complain of fatigue, loss of libido, inability to
Indications sleep, GI & genitourinary disturbances
- tx of severe hypertension that has not responded to -Used to tx HPN
other therapy or hypertensive emergencies -carvedilol (Coreg), guana-benz (Wytensin), and labetalol
Pharmacokinetics 4. Alpha2-Agonists
-Nitroprusside IV; hydralazine PO, IV, & IM; Minoxidil PO -Stimulate alpha2-receptors in CNS & inhibit cardiovascular
-rapidly absorbed, widely distributed & are metaboized liver centers, leading to a decrease in sympathetic outflow from the
& primarily excreted in the urine. CNS & resultant drop in BP.
-Cross the placenta and enter breast milk. -Associated w/ many adverse CNS & GI effects, as well as
Contraindications & Cautions cardiac dysrhythmias.

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-clonidine (Catapres), guanfacine (Tenex), and methyldopa acute renal disease, which might interfere with excretion
(generic). of drug; urinary retention because stimulation of
5. Alpha1-Blockers alpha-receptors can exacerbate this; and thyrotoxicosis,
-Used to treat HPN, blocks postsynaptic alpha1-receptor sites. w/c could further increase BP.
-Decreases vascular tone & promotes vasodilation, leading to a ● Use w/ caution in pregnancy & lactation because of
fall in BP. potential for adverse effects on the fetus or neonate; w/
-do not block presynaptic alpha2-receptor, reflex tachycardia visual problems, w/c could be exacerbated by
that accompanies a fall in blood pressure does not occur. vasoconstriction; & w/ renal/hepatic impairment, which
-doxazosin (Cardura), prazosin (Minipress), and terazosin could alter the metabolism and excretion of the drug.
(Hytrin). Adverse Effects
● Most common adverse effects associated with this drug
Antihypotensive Agents are related to the stimulation of alpha-receptors and
● Droxidopa (Northera) 100 mg PO t.i.d.; max 600 mg/d include piloerection, chills, and rash; hypertension and
Treatment of neurogenic hypotension cause by bradycardia; dizziness, vision changes, vertigo, and
autonomic failure. headache; and problems with urination.
● first-choice for treating shock usually sympathomimetic Drug-drug Interactions
SYMPATHETIC ADRENERGIC AGONISTS OR ● risk of increased effects and toxicity of cardiac
VASSOPRESSOR glycosides, beta-blockers, alpha-adrenergic agents, and
● React w/ sympathetic adrenergic receptors to cause effects corticos- teroids if they are taken with midodrine. Pts
of sympathetic stress response: ↑BP, ↑blood volume, & receiving any of these combinations should be
↑strength of cardiac muscle contraction. monitored carefully for the need for dose adjustment.
● These actions ↑BP & may restore balance to CV system
while underlying cause of shock (e.g., volume depletion, BLOOD LOWERING AGENTS (DROXIDOPA)
blood loss) is treated. Therapeutic Actions
Indications: Hypotension or shock ● An amino acid analog that is metabolized to
Contraindications & Cautions: Used w/ caution w/ any disease norepinephrine by dopadecarboxylase.
that limits blood flow, with tachycardia, or with hypertension. ● Widely distributed throughout the body, & it is thought
Adverse Effects that its actions on BP are related to the norepinephrine
● effects of stimulation of sympathetic system; ↓GI activity effects causing vasoconstriction.
w/ nausea & constipation; ↑RR & changes in BP; Indications
headache; & changes in peripheral blood flow with ● Treatment of neurogenic hypotension cause by
numbness, tingling, & gangrene in extreme cases. autonomic failure.
● used with caution with any disease that limits blood Pharmacokinetics
flow, with tachycardia, or with hypertension. ● Absorbed thru GIT & reaches peak levels in 1-4 hrs. Has
a half-life of 2.5 hours. Widely distributed & metabolized
Alpha-Specific Adrenergic Agents by the normal catecholamine pathways w/ excretion
-Midodrine (ProAmatine) is an alpha-specific adrenergic agent thru the urine.
used to treat orthostatic hypotension Contraindications: No contraindications.
-In 2010, FDA proposed withdrawal of this drug from market. It ● Use w/ caution: Any history of CV issues because the
was a fast-tracked drug that never went through the required stimulatory effects of nonephinephrine can cause
testing, and since the required testing of efficacy and safety exacerbation of these disorders; w/ renal impairment
was never done, FDA felt that the drug should no longer be because this can affect the excretion of the drug.
marketed. It is only drug available for orthostatic hypotension, Nursing mothers should select a different method of
and at this time, negotiations are still ongoing, and the status feeding the baby because of the potential adverse
of the drug’s availability is not known. effects on the baby.
-10 mg PO t.i.d. Adverse Effects
-Midodrine activates alpha-receptors in arteries and veins to ● Most adverse effects are related to sympathetic effects
produce an increase in vascular tone and an increase in blood of the drugs w/c include: supine hypertension,
pressure. indicated for the symptomatic treatment of headache, dizziness, nausea, & arrhythmias.
orthostatic hypotension who have not had a response to any Drug-drug Interactions
other therapy. ● Risk of increased effects if combined w/ any
-rapidly absorbed from GIT, reaching peak levels 1 to 2 hrs. dopadecarboxylase inhibitors.
metabolized in liver and excreted in urine. half-life of 3-4 hrs. Nursing Considerations
pregnancy)for cases in which the benefit to the mother clearly ● Assess for allergy to midodrine; impaired kidney or liver
outweighs the potential risk to the fetus. caution should be function; pregnancy or lactation; CV dysfunction; visual
used during lactation. problems; urinary retention; & pheochromocytoma
● Assess baseline status before beginning therapy
BP LOWERING AGENTS (MIDODRINE - generic) Implementation
● Activates alpha-receptors in arteries & veins to produce ● Monitor BP to monitor effectiveness & changes.
an increase in vascular tone & an increase in BP. ● Do not administer the drug to patients who are bedridden,
Indications but only to patients who are up and mobile,
● For symptomatic tx of orthostatic hypotension in ● Monitor HR regularly when beginning therapy; if bradycardia
patients whose lives are impaired by the disorder and persists, it may indicate a need to discontinue the drug.
who have not had a response to any other therapy. ● Monitor patient w/ known visual problems carefully;
Pharmacokinetics discontinued if visual fields change.
● Rapidly absorbed from GI tract, reaching peak levels ● Encourage pt to void before taking
w/in 1 to 2 hours. ● Provide comfort measures, small, frequent meals; access to
● Metabolized in liver & excreted in urine with a half-life of bathroom facilities; safety precautions if CNS effects occur;
3 to 4 hours. environmental controls; appropriate skin care as needed; and
Contraindications & Cautions analgesics as needed.
● Supine hypertension, CAD, or pheochromocytoma ● Provide thorough patient teaching,
because of risk of precipitating hypertensive emergency; ● Offer support & encouragement
Part 3: Cardiotonic Agents PPT
Cardiotonic Agents ○ Hypertension - Leads to enlarged cardiac muscle bec heart
-increase contractility of heart muscle for pts experiencing HF must work harder than normal to pump against high pressure
in arteries. Puts constant, increased demands for O2 on system
Heart Failure (HF) “dropsy” or “decompensation” bec heart is pumping so forcibly.
● A syndrome that involves dysfunction cardiac muscle, of ○ Valvular Heart Disease - Leads to overload of ventricles bec
w/c sarcomere is the basic unit. valves do not close tightly, allowing blood to leak backward into
● heart fails to pump blood around body effectively. any ventricles, leads to muscle stretching & increased demand for
failure of muscle to pump blood out of either side of the O2 & energy as heart muscle must constantly contract harder;
heart can result in a backup of blood then blood vessels seen less often owing to cardiac surgery and effective
become congested; eventually, cells deprived of O2 and treatment for rheumatic fever
nutrients, and waste products build up End result is heart muscle cannot pump blood effectively
● Disorders that Lead to HF: throughout vascular system. If left ventricle pumps inefficiently,
○ Coronary Artery Disease (CAD) - Leading cause of HF blood backs up into lungs, causing pulmonary vessel congestion
(95%). Results in insufficient supply of blood to meet O2 and fluid leakage into alveoli and lung tissue. In severe cases,
demands of myocardium. Muscles become hypoxic & can no pulmonary edema. If right side of heart, blood backs up leading
longer function efficiently. When evolves to MI, muscle cells die to right side of heart to Liver congestion and edema of legs and
or damaged, leading to inefficient pumping effort. feet. One-sided failure, if left untreated, leads to failure of both
○ Cardiomyopathy - disease of heart muscle that leads to sides
cardiomegaly & eventually complete muscle failure & death;
occur as result of viral infection, alcoholism, anabolic steroid Compensatory Mechanisms in HF
abuse, or collagen disorder. It causes muscle alterations and -↓CO stimulates baroreceptors in aortic arch & carotid arteries,
ineffective contraction and pumping causing sympathetic stimulation (↑HR, ↑BP, & ↑RR & depth,

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106 BY TONS AND MADS
positive inotropic effect (↑force of contraction) on heart & venous return, peripheral resistance, & cardiac workload. Also
↑blood volume (through aldosterone and RAS). suppress body’s response to stress hormones, leading to
-If mechanisms work effectively, may not have S&S of HF. Over increased fluid loss & further decrease in cardiac workload.
time, these effects ↑workload of heart, heart muscle Nesiritide (Natrecor) only drug currently available
overstretches,chambers dilate. Hypertrophy (cardiomegaly), ● In 2005, (FDA) approved BiDil only for use in African American
leads to inefficient pumping & eventually to ↑HF. pts with severe to moderate HF. The drug, BiDil, a
fixed-combination drug containing isosorbide dinitrate and
hydralazine. This combination of drugs had a significant impact
in decreasing deaths and hospitalizations related to HF in
African American patients. BiDil contains 20mg isosorbide
dinitrate and 37.5mg hydralazine rapidly absorbed and peak
levels 1 hour.metabolized in the liver; should not be taken with
any of the phosphodiesterase inhibitors because of the risk of
serious hypotension. Adverse effects: headache, dizziness, and
orthostatic hypotension.
CHILDREN
Digoxin used widely in children with heart defects and related
cardiac problems. The margin of safety is very small, dosage
carefully calculated and double-checked; monitored closely for
any sign of digitalis toxicity and serum digoxin levels monitored.
PDE inhibitorsnot recommended in children.
ADULTS
Instructed to what adverse reactions to report, take own pulse
and keep track of rate and regularity on a calendar, weigh
themselves in the same clothing and at the same time of the day
to monitor for fluid retention. Advised against switching between
brands of digoxin (different bioavailabilities), should not be used
in pregnancy unless benefi outweighs risk. Caution needed
during lactation.
OLDER ADULTS
Older adults frequently are prescribed; more susceptible to toxic
effects. If renal dysfunction present, dosage reduced and
Cellular Changes monitored of digoxin toxicity..
-Myocardial cells are changed w/ prolonged HF-> lack ability
to produce energy needed for effective contractions. CARDIOTONIC AGENTS (inotropic)
Movement of Ca ions into & out no longer effective, leading -affect intracellular calcium levels in heart muscle, leading to
to further deterioration bec muscle contracts ineffectively & is ↑contractility = ↑CO = ↑renal blood flow and ↑urine production
unable to deliver blood to the cardiac muscle. = ↓renin release and ↑urine output = ↓decreased blood
volume = ↓heart workload and relief of HF
SIGNS & SYMPTOMS OF HF -Two types: Cardiac glycosides and newer PDE inhibitors.
● Right Sided HF
- Usually occurs as result of COPD or lung diseases that 1. CARDIAC GLYCOSIDES (DIGOXIN) originally
elevate pulmonary pressure. Commonly occurs with derived from foxglove (digitalis plant)
aging. Venous return to heart is decreased because of Digoxin increases intracellular Ca+ & allows more Ca+ to enter
↑pressure in right side; causes congestion and backup of myocardial cells during depolarization causing:
blood. a. ↑force of myocardial contraction (+inotropic effect).
- Jugular venous pressure (JVP) rises (distended neck b. ↑CO & renal perfusion (diuretic effect, ↑urine output &
veins), liver enlarges and congested with blood (pain ↓blood volume, ↓renin release and activation of RAAS).
and tenderness->liver dysfunction and jaundice) c. Slowed heart rate, owing to slowing of the rate of cellular
- Dependent areas develop edema. (Pitting edema in legs) repolarization (-chronotropic effect).
increase in cardiovascular volume increases blood flow d. ↓conduction velocity through atrioventricular node.
to kidney (increased urine output/nocturia) Indications: treatment of HF, atrial flutter, atrial fibrillation, and
○ Elevated jugular venous pressure Reflecting paroxysmal atrial tachycardia
increase central venous pressure Pharmacokinetics
○ Splenomegaly, Hepatomegaly Enlargement is due - PO & parenteral form; rapid onset of action & absorption
to blood congestion (30-120mins PO, 5 -30 mins IV).
○ decreased renal perfusion when Upright - Widely distributed throughout body; primarily excreted
○ increased renal perfusion when supine -> unchanged in urine. mulate, causing toxicity.
nocturia Contraindications & Cautions
○ pitting edema Reflecting fluid pooling in tissues, -Allergy, ventricular tachycardia or fibrillation,; heart block or
weakness/fatigue sick sinus syndrome; idiopathic hypertrophic subaortic
● Left Sided HF stenosis (IHSS); acute MI (could cause more muscle
-engorgement of pulmonary veins (difficulty breathing, damage); renal insufficiency; & electrolyte abnormalities
tachypnea, dyspnea and orthopnea). Orthopnea occurs in -caution: renal impairment; pregnancy; lactation. Closely
supine position when the pattern of blood flow changes. monitor pediatric & geriatric
Orthopnea is usually relieved when the patient sits up, thereby Adverse Effects
reducing the blood flow through lungs. degree of HF is often -Headache, weakness, drowsiness, & vision changes (yellow
calculated by number of pillows required to get relief halo around objects is often reported).
-coughing and hemoptysis (coughing up of blood). Rales -GIT upset & anorexia. Arrhythmias (glycosides affect action
signaling the presence of fluid in the lung tissue. potential & conduction system)
-develop pulmonary edema (spaces in lungs fill up with fluid, -Digoxin toxicity - anorexia, nausea, vomiting, malaise,
there is no place for gas exchange to occur) depression, irregular heart rhythms, heart block, atrial
○ Anxiety, Tachypnea, Dyspnea, Orthopnea, arrhythmias, and ventricular tachycardia. Antidote: digoxin
Hemoptysis, Rales immune Fab
○ Cardiomegaly, S3, increased heart rate Drug-drug Interactions
○ GI upset, Nausea, Abdominal pain -↑therapeutic effects & ↑toxic effects if with verapamil,
○ Decreased peripheral pulses, hypoxia amiodarone, quinidine, quinine, erythromycin, tetracycline,
○ Pulmonary vein engorgement w/c leads to DOB or cyclosporine; decrease the dose. If one of these drugs
○ Pulmonary Edema in severe cases occurs as body has been part w/ digoxin & discontinued, dose increased.
stimulates sympathetic stress reaction -↑Risk of cardiac arrhythmias if taken with potassium-losing
diuretics. If used, potassium levels should be checked
Treatments for HF -↓effective if combined w/ thyroid hormones,
● Vasodilators (ACE inhibitors & Nitrates) - ↓cardiac metoclopramide, or penicillamine; ↑digoxin dose needed.
workload, relax vascular smooth muscle to ↓afterload, & allow -↓Absorption of oral digoxin if taken with cholestyramine,
pooling in veins, thereby ↓preload of heart & helping to charcoal, colestipol, antacids, bleomycin, cyclophosphamide,
improve function. Diuretics ↓blood volume, w/c ↓venous return or methotrexate; should not be taken at the same time (2 to
& ↓BP, resulting in ↓afterload, preload, & cardiac workload 4 hours apart)
● Beta-adrenergic Antagonists - Stimulate beta receptors in Drug-Food Interactions: Avoid administering oral drug with food
SNS, ↑Ca+ flow into myocardial cells & causing ↑contraction, a or antacids to avoid delays in absorption.
positive inotropic effect. Other sympathetic stimulation effects Nursing Considerations
can cause ↑HF bec heart’s workload is increased by most ● Assess for contraindications or cautions. Perform physical
sympathetic activity. assessment before beginning therapy.
● Human B-type Natriuretic Peptides - Normally produced ● Obtain pt’s weight to determine fluid status. Assess cardiac
by myocardial cells as a compensatory response to increased status,
cardiac workload & ↑stimulation by stress hormones. Bind to
endothelial cells, leading to dilation & resulting in decreased
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106 BY TONS AND MADS
● Inspect skin and mucous membranes, nail beds and ● Obtain patient’s weight, noting any recent increases or
capillary refill. Monitor affect, orientation, and reflexes to decreases, to determine patient’s fluid status. Inspect skin
evaluate CNS effects of the drug. & mucous membranes for color, and check nail beds and
● Assess RR and auscultate lungs for evidence of adventitious capillary refill for evidence of perfusion.
breath sounds ● Examine abdomen for distention; auscultate bowel sounds
● Examine abdomen for distention; auscultate bowel sounds to evaluate GI motility. Assess voiding patterns & urinary
● Assess voiding patterns and urinary output output to provide a gross indication of renal function.
● Obtain baseline ECG ● Obtain baseline ECG to identify rate & rhythm & evaluate
● Monitor results of lab tests, serum electrolyte levels and for possible changes. Monitor results of lab tests, including
renal function tests serum electrolyte levels, CBC, & renal & hepatic function
Diagnosis tests, to determine the need for possible dose adjustment.
● Risk for Imbalanced Fluid Volume Diagnosis:
● Decreased CO (ineffective cardiac muscle function) ● ↓CO related to arrhythmias or hypotension
● Ineffective Tissue Perfusion related to change in CO ● Risk for Injury related to CNS or cardiovascular effects
● Impaired Gas Exchange related to change in CO ● Ineffective Tissue Perfusion
● Deficient Knowledge related to prescribed drug therapy ● Deficient Knowledge
Implementation Implementation
● Consult w/ prescriber about need for loading dose to achieve ● Protect drug from light to prevent drug degradation.
desired results ASAP. ● Ensure patent IV access site available
● Monitor apical pulse for 1 full min before administering drug. ● Monitor pulse & BP frequently during administration to
Hold dose if pulse is >60bpm (adult) or >90bpm (infant); avoid toxicity.
retakepulse in 1 hour. If pulse remains low, withhold the ● Monitor I O & record daily weight
drug, and notify prescriber (digoxin toxicity) ● Monitor platelet counts before & regularly during therapy
● Monitor the pulse for any change in quality or rhythm ate; inspect skin for bruising or petechiae; consult w/
● Check dose & preparation (very small margin of safety) prescriber about the need to decrease the dose at the first
● Check pediatric dose w/ extreme care sign of thrombocyopenia.
● Follow dilution instructions carefully for IV use; Administer ● Monitor IV injection sites & provide comfort measures
IV very slowly over at least 5 mins to avoid cardiac ● Provide life support equipment on standby in case severe
arrhythmias & adverse effects. Avoid IM administration, reaction to drug or development of ventricular arrhythmias
● weighed at same time each day, in the same clothes, Assess occurs.
dependent areas for edema; note amount & degree ● Provide comfort measures small, frequent meals, access to
● Avoid administering oral drug w/ food or antacids Maintain bathroom facilities, safety precautions
emergency equipment on standby: potassium salts, ● Offer support & encouragement
lidocaine, phenytoin, atropine, & a cardiac monitor ● Provide thorough patient teaching
● Obtain digoxin level (0.5 to 2 ng/mL)
● Provide comfort measures to help patient tolerate effects. 3. HYPERPOLARIZATION- ACTIVATED CYCLIC
● Offer support & encouragement NUCLEOTIDE -GATED CHANNEL (HCN) BLOCKERS
● Provide thorough patient teaching. - New class of drug; IVRABADINE, does not affect muscle
Evaluation contraction but affect pace maker to reduce HR
● Monitor response: improvement S&S, resolution of atrial - Slows SA node, in the depolarizing phase = allows more
arrhyth-mias, serum digoxin level 0.5-2 ng/mL). time for ventricular filling & improves CO.
● Monitor adverse effects - Systemic effects seen in beta-blockers are not seen in
● Monitor effectiveness of comfort measures & compliance this drug. No effects on ventricular repolarization or on
w/ regimen. ventricular contractility.
● Evaluate effectiveness of the teaching plan - effects channels in retina, w/c may alter tretinal
St. John’s wort and psyllium ↓effectiveness of digoxin; response to bright light
combination voided. ↑digoxin toxicity has been reported with Indications
ginseng, hawthorn, and licorice. - To reduce risk of hospitalization for worsening HF in pts
w/ stable, symptomatic, chronic HF w/ left ventricular
2. PHOSPHODIESTERASE INHIBITORS (Milrinone) ejection fraction of 35% or less, who are in sinus rhythm
Blocks enzyme PDE=↑myocardial cell cAMP = ↑Ca levels in cell w/ a rate of >70 & who are on maximally tolerated dose
= stronger contraction & prolonged response to sympathetic of beta-blockers or who have contraindication to use of
stimulation -> relaxes vascular smooth muscle-> vasodilation beta blockers.
-> ↑O2 Consumption and arrythmias Pharmacokinetics
Indications - absorbed thru GIT, reaching peak levels in 1 hr.
- Short-term treatment of HF in patients who have not Metabolized in liver & intestines & excreted in feces &
responded to digitalis, diuretics, or vasodilators. Associated bile w/ a half life of 2 hrs & effective duration of 6 hrs.
with development of potentially fatal ventricular Contraindications & Cautions
arrhythmias, use is limited to severe situation - Allergy; active, decompensated HF; hyppotension; sick
Pharmacokinetics sinus syndrome of AV block; resting HR under 60bpm;
- Inamrinone & milrinone available only IV use. widely patient completely dependent on pacemaker,; severe
distributed metabolized in liver, excreted in urine. hepatic impairment,
Contraindications & Cautions - Use w/ caution: w/ atrial fibrillation or moderate heart
- Allergy to inamrinone & milrinone or to bisulfites. block; pregnancy. Not recommended for breastfeeding.
- Severe aortic or pulmonic valvular disease, acute MI, ; Adverse Effects
fluid volume deficit; and ventricular arrhythmias, - Bradycardia, hypertension, atrial fibrillation, & luminous
- caution in elderly, pregnancy (benefit outweighs risk), phenomena (sudden changes in parts of visual field,
and breastfeeding. colored bright lights, image decomposition, multiple
Adverse Effects images).
- Arrhythmias (can progress to fatal ventricular fibrillation) Drug-drug Interactions
hypotension, chest pain, nausea, vomiting, abdominal - Altered plasma concentrations occur w/ strong CYP3A4
pain, thrombocytopenia, vasculitis, pericarditis, pleuritis, inhibitors or inducers; should be avoided. Severe
ascitis, burning at injection site. bradycardia can occur if combined w/ other negatively
Drug-drug Interactions chronotropic drugs.
- Precipitates form when given in soln w/ furosemide. Use Nursing Considerations
alternate lines if both are being given in IV. ● Ensure appropriate use of drug
Nursing Considerations ● Monitor HR & BP regularly
● Assess for contraindications or cautions. Perform physical ● Monitor I & O & record daily weight
assessment to establish baseline status before beginning ● Provide safety measures if visual disturbances occur,
therapy, determine effectiveness of therapy, & evaluate for including limiting driving & operation of hazardous
any potential adverse effects. machinery to ensure patient safety.
● Assess cardiac status closely, including pulse & BP, to ● Provide comfort measures
identify changes or the presence of adverse effects; ● Offer support & encouragement
auscultate heart sounds, noting any evidence of abnormal ● Provide thorough patient teaching
sounds.
Part 4: Antiarrhythmic Agents PPT
ARRHYTHMIAS (dysrhythmias)
- disruptions in impulse formation and in the conduction 5 Phases of Action Potential of Cardiac Muscle Cell
of impulses through the myocardium 1. Phase 0 point of stimulation (depolarization) - Na+
- Involve changes to automaticity or conductivity of the gates open & Na+ rushes into cell; (no charge
heart cells. Changes can result from: electrolyte difference b/n inside & outside of membrane) .
imbalances, decreased O2 delivery, structural damage or 2. Phase 1 Na+ ion concentration equalizes in and out
acidosis or waste product accumulation 3. Phase 2 Plateau Stage repolarization. less permeable to
- may result from drugs that alter the action potential or Na+, Ca+ slowly enters the cell,& potassium begins to
cardiac conduction.
10
106 BY TONS AND MADS
leave the cell. Cell membrane is trying to return to its metabolism & are excreted in urine. Crosses placenta &
resting state, a process called found in breast milk.
4. Phase 3 rapid repolarization a sodium gates are closed Contraindications & Cautions
and potassium flows out of the cell. - Allergy, bradycardia or heart block unless an artificial
5. Phase 4 rest; the sodium– potassium pump returns the pacemaker is in place, because changes in conduction
membrane to its resting membrane potential, and could lead to complete heart block; heart failure (HF),
spontaneous depolarization begins again. hypotension, or shock, which could be exacerbated by
effects on the action potential; electrolyte disturbances,
Hemodynamics which could alter the effectiveness of these drugs.
-study of the forces that move blood throughout CV system - Use w/ caution in patients w/ renal or hepatic
-If these hemodynamic alterations are severe, serious dysfunction, w/c could interfere w/ biotransformation &
complications can occur. Lack of sufficient blood flow to the excretion of these drugs.
brain cause syncope or precipitate stroke; lack of sufficient - Used in pregnancy only if benefits outweighs risks. Not
blood flow to myocardium can exacerbate atherosclerosis and used in breastfeeding.
cause angina or myocardial infarc-tion (MI). Adverse Effects
Types of Arrhythmias CNS effects: dizziness, drowsiness, fatigue, twitching, mouth
Various factors can change cardiac rate and rhythm, resulting in numbness, slurred speech, vision changes, &
an arrhythmia. Arrhythmias can be caused by changes in rate tremors that can progress to convulsions. GI symptoms:
(tachy/bradya); by stimulation from an ectopic focus (PACs or changes in taste, nausea, & vomiting.
PVCs, atrial flut-ter, atrial fibrillation (AF), or ventricular Cardiovascular effects: proarrhythmic effects leading to
fibrillation; or by alterations in conduction through muscle, such development of arrhythmias (including heart blocks),
as heart blocks and bundle-branch blocks. hypotension, vasodilation, & potential cardiac arrest. Respiratory
● Tachycardia depression progressing to respi arrest.
● Bradycardia Other effects: rash, hypersensitivity reactions, loss of hair, &
● Premature Atrial/Ventricular Contractions (PACs) potential bone marrow depression.
or(PVCs) Drug-drug Interactions
● Atrial flutter Increase risk for arrhythmia if combined w/ other drugs known
● Atrial fibrillation to cause arrhythmias (digoxin &beta-blockers) Combined digoxin
● Arrhythmias & quinidine will increase digoxin toxicity. If combined w/
cimetidine, serum levels & toxicity levels increased. Combining
ANTIARRHYTHMIC AGENTS this drug w/ anticoagulant increases bleeding effects.
- affect action potential of cardiac cells by altering their Drug-Food Interactions
automaticity, conductivity, or both; Avoid foods that alkalinize urine (citrus juices, vegetables,
- can produce new arrhythmias “proarrhythmic”. antacids, milk products) if taking quinidine & avoid combining w/
- used in emergency situations when hemodynamics are grapefruit juice for it will increase quinidine level & toxicity.
severe and could potentially be fatal.
- the risk of death for some patients was two to three Class II Antiarrhythmics
times greater than that for untreated patients. Competitively block beta-receptor sites in heart & kidneys
- may block some reflex arrhythmias that help to keep the resulting to decrease HR, cardiac excitability, & CO that stabilizes
cardiovascular system in balance, or precipitate new, excitable cardiac tissue & decrease BP w/c decrease heart’s
deadly arrhythmias. workload & further stabilize hypoxic cardiac tissue.
- important to document the arrhythmia being treated and Indications For treatment of supraventricular tachycardias &
rationale for treatment and monitor a patient regularly PVCs.
CHILDREN Pharmacokinetics
Antiarrhythmic agents are not used as often in children unless, Acebutolol is PO drug. Esmolol is administered IV. Propranolol is
after cardiac surgery or because of congenital heart problems, administered PO or IV. Absorbed from GIT, have an immediate
need to be monitored very closely to deal. Digoxin is approved effect when given IV & undergo hepatic metabolism & excreted
for use in children to treat arrhythmias and has an established in urine.
recommended dose. If other antiarrhythmics are used, the dose Contraindications & Cautions
should be carefully calculated and double-checked. Adenosine, Presence of sinus bradycardia (rate less than 45 beats/min) & AV
propranolol, procainamide, and digoxin have been successfully block (could be exacerbated); Cardiogenic
used to treat supraventricular arrhythmias, with propranolol and shock, HF, asthma, or respiratory depression, which could
digoxin being the drugs of choice for long-term management. worsen due to blockage of beta receptors; &
Verapamil should be avoided in children. Many arrhythmias in pregnancy & lactation because of the potential for adverse
children are now treated by ablation techniques.. If lidocaine is effects on the fetus or neonate.
used for ventricular arrhythmias related to cardiac surgery or Caution should be used in patients with diabetes & thyroid
digoxin toxicity, serum levels should be monitored regularly dysfunction, which could be altered by the
blockade of beta-receptors, and in patients with renal and
ADULTS hepatic dysfunction, which could alter the
Adults receive these drugs most often as emergency measures. metabolism and excretion of these drugs.
Frequent monitoring and medical follow-up is very important Adverse Effects
They should not be used in pregnancy unless the benefit CNS effects: dizziness, insomnia, dreams, & fatigue.
outweighs risk. Class I, III, and IV agents should not be used Cardiovascular: hypotension, bradycardia, AV block,
during lactation; arrhythmias, & alterations in peripheral perfusion. Respi:
bronchospasm & dyspnea.
OLDER ADULTS GI problems: nausea, vomiting, anorexia, constipation, &
Older adults frequently are prescribed one of these drugs. Older diarrhea. Other effects: loss of libido, decreased
adults are more likely to develop adverse effects associated with exercise tolerance, & alterations in blood glucose levels.
the use of these drugs, including arrhythmias, hypotension, and Drug-drug Interactions
congestive heart failure. They are also more likely to have renal Risk of adverse effects increases if these drugs are taken with
and/or hepatic impairment related to underlying medical verapamil; if this combination is used, dose adjustment will be
conditions, which could interfere with the metabolism and needed. There is a possibility of increased hypoglycemia if these
excretion of these drugs. drugs are combined with insulin; patients should be monitored
The dose for older adults should be started at a lower level than closely.
that recommended for other adults. The patient should be Drug-Food Interactions
monitored very closely and the dose adjusted based on patient Food has been found to increase the bioavailability of
response. If other drugs are added to or removed from the drug propranolol, although this effect has not been found
regimen, appropriate dose adjust-ments may need to be made. with other beta- adrenergic blocking agents.
Class I Antiarrhythmics Class III Antiarrhythmics
- Stabilize cell membrane by binding to Na channels, Block potassium (K) channels & slow outward movement of K
depressing phase 0 of the action potential and changing during phase 3 of action potential, prolonging it. These drugs
the duration of the action potential. are proarrhythmic & have the potential of inducing arrhythmias.
● Class Ia prolong the duration of the action potential; Indications Although amiodarone has been associated with such
● Class Ib shorten the duration of the action potential; serious and even fatal toxic reactions, it’s the drug of choice for
● Class Ic extreme slowing of conduction, but have little treating ventricular fibrillation or pulseless ventricular
effect on the duration of the action potential. tachycardia in cardiac arrest situations.
Indications Pharmacokinetics
- Treatment of potentially life-threatening ventricular Amiodarone- available oral or IV form. Dofetilide & sotalol are
arrhythmias and should not be used to treat other PO form only. Ibutilide is given IV. Well absorbed after oral
arrhythmias because of the risk of a proarrhythmic administration & are immediately available after IV
effect. administration & widely distributed. They are metabolized in the
Pharmacokinetics liver and excreted in urine.
- Widely distributed after injection or after rapid Contraindications & Cautions
absorption thru GIT. Undergo extensive hepatic No C/Is if used w/ treat life-threatening arrhythmias for which
no other drug has been effective. Do not use Ibutilide &

11
106 BY TONS AND MADS
dofetilide in the presence of AV block (could be exacerbated by Assess for contraindications or cautions.
the drug). Because sotalol is known to be proarrhythmic, Perform physical assessment to establish baseline before
patients should be monitored very closely at the initiation of beginning therapy & during therapy to determine effectiveness
therapy and periodically during therapy. of therapy & evaluate any potential adverse effects.
Caution should be used with all of these drugs in the presence of Assess neurological status, including level of alertness, speech
shock, hypotension, or respiratory depression; with a prolonged & vision, & reflexes, to identify possible CNS effects.
QTc interval, which could worsen due to the depressive effects Assess cardiac status closely: pulse, BP, HR, & rhythm, to
on action potentials; and with renal or hepatic disease, which identify changes requiring a change in dosage or presence of
could alter the biotransformation and excretion of these drugs. adverse effects; auscultate heart sounds, noting any
Adverse Effects evidenceof abnormal sounds, for early detection of heart
Nausea, vomiting, & GI distress; weakness & dizziness; & failure; and anticipate cardiac monitoring to evaluate heart rate
hypotension, HF, & arrhythmia are common. Amiodarone has & rhythm & aid in identifying arrhythmia.
been associated w/ potentially fatal liver toxicity, ocular Monitor RR & depth, auscultate lungs, for evidence of
abnormalities, & development of very serious cardiac adventitious sounds to identify respi depression & detect
arrhythmias. changes associated with heart failure.
Drug-drug Interactions Inspect abdomen for evidence of distention; auscultate bowel
Causes serious toxic effects if combined w/ digoxin or quinidine. sounds to evaluate GI motility.
Increases risk of proarrhythmias if combined w/ antihistamines, Evaluate skin for color, lesions, and temperature to detect
phenothiazines, or tricyclic antidepressants. Increased risk of adverse reactions and to assess cardiac output.
serious adverse effects if dofetilide is combined w/ ketoconazole, Obtain a baseline ECG to evaluate heart rate and rhythm;
cimetidine, or verapamil. Drug-Food Effectiveness loss if Sotalol monitor the results of laboratory tests, including complete
is combined w/ nonsteroidal anti-inflammatory drugs, aspirin, or blood count, to identify possible bone marrow suppression,
antacids. Absorption of sotalol is decreased by the presence of and renal and liver function tests, to determine the need for
food. possible changes in dose and identify toxic effects.
Decreased Cardiac
Class IV Antiarrhythmics Output related to
Block movement of Ca* ions across cell membrane, depressing cardiac effects
the generation of action potentials & Disturbed Sensory
delaying phases 1 & 2 of repolarization, which slows Perception (Visual,
automaticity and conduction Auditory,
Indications Both diltiazem & verapamil are used as Kinesthetic,
antihypertensives. Gustatory, Tactile)
Pharmacokinetics related to CNS
Diltiazem is administered IV. Verapamil is given IV if used as effects
antiarrhythmic. Risk for Injury related
These drugs are well absorbed after IV administration; are to adverse drug
highly protein bound, metabolized in the liver, & effects
excreted in the urine. Crosses placenta & enters breast milk. Deficient Knowledge
Contraindications regarding drug
& Cautions therapy
Known allergy to any calcium channel blocker; Sick sinus
syndrome or heart block (unless an artificial Implementation
pacemaker is in place) because the block could be exacerbated Titrate dose to smallest amount needed to achieve control of the
by these drugs. arrhythmia to decrease the
Pregnancy or lactation because of the potential for adverse risk of severe adverse effects.
effects on the fetus or neonate; HF or Continually monitor cardiac rhythm when initiating or changing
hypotension because of the hypotensive effects of these drugs. dose to detect potentially
Caution should be used in cases of idiopathic hypertrophic serious adverse effects & to evaluate drug effectiveness.
subaortic stenosis (IHSS), which could be Ensure that emergency life support equipment is readily
exacerbated, or impaired renal or liver function, w/c could affect available to treat severe adverse
the metabolism or excretion of these drugs. reactions that might occur.
Adverse Effects CNS effects include dizziness, weakness, fatigue, Administer parenteral forms as ordered only if the oral form is
depression, and headache. GI upset, nausea, and not feasible; expect to switch to
vomiting can occur. Hypotension, HF, shock, arrhythmias, and the oral form as soon as possible to decrease the potential for
edema have also been reported. severe adverse effects.
Drug-drug Interactions Consult with the prescriber to reduce the dose in patients with
Verapamil has been associated w/: increased risk of cardiac renal or hepatic dysfunction;
depression w/ beta- blockers; additive AV reduced dose may be needed to ensure therapeutic effects
slowing with digoxin; increased serum levels & toxicity of without increased risk of toxic
digoxin, carbamazepine, prazosin, and quinidine; effects.
increased respiratory depression w/ atracurium, gallamine, Establish safety precautions, including side rails, lighting, and
pancuronium, tubocurarine, & vecuronium; & noise control, if CNS effects
decreased effects if combined with calcium products or rifampin. occur to ensure patient safety.
There’s risk of severe cardiac effects if these drugs are given IV Arrange for periodic monitoring of cardiac rhythm when the
w/in 48 hours of IV beta-adrenergic drugs. patient is receiving long-term therapy to evaluate effects on
The combination should be avoided. Diltiazem can increase the cardiac status.
serum levels and toxicity of cyclosporine if Provide comfort measures
the drugs are taken concurrently. Offer support and encouragement regimen.
Provide thorough patient teaching
Nursing Considerations
Part 5: Antianginal Agents
CORONARY ARTERY DISEASE - Caused by spasm of BVs & not just by vessel narrowing.
- Caused by plaque buildup in the wall of arteries that W/ angina at rest, often at same time each day, &
supply blood to the heart (called coronary arteries). usually w/ an associated ECG pattern change.
- Narrowing of vessels caused by Atherosclerosis (fat A heart attack; a myocardial necrosis (ischemia) that results
build up). from occluded coronary vessel/artery.
- Person w/ atherosclerosis has a classic supply-&- Excruciating pain, nausea & severe
demand problem of O2. sympathetic stress reaction may be
- Heart muscle becomes hypoxic manifested as pain, or noted.
angina pectoris, which literally means “suffocation of the If heart muscle has a chance to heal
chest.” w/n 6 -10 wks, scar tissue will form in
the necrotic area & muscle will
ANGINA compensate for the injury.
- Pain as body’s response to a lack of oxygen in the heart If the area of damaged muscle is very
muscle. Pain is felt wherever substance P reacts w/ pain large, muscle may not be able to
receptor. compensate for the loss, & HF &
STABLE/CHRONIC ANGINA even cardiogenic shock may occur.
- No damage to heart muscle, basic reflexes surrounding Acute Myocardial Infarction
pain restore blood flow when activity is stop. Antianginal Agents & Nitrates
- Can go on for a long time w/ no resultant MI. Antianginal Agents
UNSTABLE/PREINFARCTION ANGINA Used to help restore appropriate
- Heart may experience episodes of ischemia even when supply-&-demand ratio in O2 delivery to
patient is at rest. myocardium when rest is not enough.
PRINZMETAL ANGINA Improve blood delivery to heart in one
of 2 ways: (1) by dilating blood vessels&
(2) by decreasing the work of the heart.

12
106 BY TONS AND MADS
O2 demand is influence by: HR, Inspect skin for color, intactness, & any signs of redness,
Preload, Afterload, & Stretch of Ventricle irritation, or
Nitrates breakdown, especially if the patient is using the transdermal or
Act directly on smooth muscle to cause topical form
relaxation & to depress muscle tone. of the drug, to prevent possible skin reaction & ensure adequate
surface for
Nitrates application and absorption of transdermal or topical drug.
Nitrates relax & dilate veins, arteries, & capillaries, allowing Check patient’s oral or buccal mucosa (including the area under
increased blood flow thru vessels & lowers the
systemic BP bec of drop in resistance. Because CAD causes a tongue) if sublingual or buccal forms are ordered to reduce the
stiffening & lack of responsiveness in the risk of
coronary arteries, nitrates have very little effect on increasing irritation & ensure adequate surface for absorption.
blood flow thru arteries but increase blood flow Assess the patient’s complaint of pain, including onset, duration,
thru healthy coronary arteries. intensity,
Indications For prevention & treatment of attacks of angina location, and measures used to relieve it. Investigate activity
pectoris. level prior to
Pharmacokinetics and after the onset of pain to aid in identifying possible
Nitroglycerin is available as sublingual tab, a translingual spray, contributing factors
an IV solution (for bolus injection or infusion), to the pain & its progression.
a transdermal patch, a topical ointment or paste, or a Assess the patient’s neurological status, including level of
transmucosal agent. It can be carried with the patient, alertness, affect,
who then can use it when the need arises. Slow-release forms and reflexes, to evaluate for CNS effects.
also are available for use in preventing anginal Monitor respirations & auscultate lungs to evaluate changes in
attacks. CO.
Amyl nitrate is supplied as capsule that is broken & waved under Assess cardiopulmonary status closely, including pulse rate,
patient’s nose for inhalation. The administration is somewhat blood
awkward for the patient to use by himself or herself. It usually pressure, heart rate, & rhythm, to determine effects of therapy
requires another person to & identify
administer it properly. Isosorbide dinitrate and isosorbide any adverse effects.
mononitrate are available in oral form. Obtain an ECG as ordered to evaluate heart rate and rhythm,
Nitrates are very rapidly absorbed, metabolized in liver, & which could
excreted in urine. Crosses placenta & enter breast indicate changes in cardiac perfusion. • Monitor laboratory test
milk. Nitroglycerin is available in many forms, & absorption, results,
onset of action, & duration vary with the form including liver & renal function test, CBC, hgb level, for dosage
used. adjustment.
Amyl nitrate, upon inhalation, has an onset of action of about 30 functiontestscompletebloodcountandhemoglobinleveltodetermine
seconds. Isosorbide dinitrate & isosorbide Decreased CO
mononitrate, when given orally, have an onset of action in 14 to related to
45 minutes, or up to 4 hours if the vasodilation &
sustained- release (SR) form is used. The drug may have a hypotensive
duration of action of 4 to 6 hours, or 6 to 8 hours effects
if the SR form is used. Risk for Injury
Nitrates related to CNS or
Contraindications cardiovascular
& Cautions effects
Allergy to nitrates; severe anemia (bec the decrease in cardiac Ineffective Tissue
CO could be detrimental in a patient who Perfusion (Total
already has a decreased ability to deliver O2 bec of a low RBC Body) related to
count); head trauma or cerebral hemorrhage hypotension or
(bec the relaxation of cerebral vessels could cause intracranial change in
bleeding); & pregnancy or lactation because cardiac output
of potential adverse effects on the neonate & ineffective blood Deficient
flow to the fetus. Knowledge
Caution should be used in patients w/ hepatic or renal disease, regarding drug
w/c could alter the metabolism & excretion therapy
of these drugs. Caution also is required for patients w/ Implementation with Rationale Evaluation
hypotension, hypovolemia, & conditions that limit CO Give sublingual preparations under the tongue or in buccal
(e.g., tamponade, low ventricular filling pressure, low pulmonary pouch, & encourage patient not to
capillary wedge pressure) because these swallow, to ensure that therapeutic effectiveness is achieved.
conditions could be exacerbated, resulting in serious adverse Ask patient if tablet “fizzles” or burns, w/c indicates potency.
effects. Always check expiration date on
Adverse Effects the bottle & protect medication from heat & light bec these
CNS effects: headache, dizziness, & weakness. drugs are volatile & lose their
Gastrointestinal symptoms: nausea, vomiting, & incontinence. potency.
Cardiovascular problems: hypotension, w/c can be severe & Instruct patient that a sublingual dose may be repeated in 5
must be monitored; reflex tachycardia that mins if relief is not felt, for a total
occurs when BP falls; syncope; & angina, w/c could be of three doses; if pain persists, the patient should go to an
exacerbated by hypotension & changes in CO. emergency room to ensure proper
Skin-related effects: flushing, pallor, & increased perspiration. medical support if an MI should occur.
With the transdermal preparation, there is a Give sustained-release forms w/ water, & caution patient not to
risk of contact dermatitis and local hypersensitivity reactions. chew or crush them because
Drug-drug these preparations need to reach the GI tract intact.
Interactions Rotate the sites of topical forms to decrease the risk of skin
There’s risk of hypertension & decreased antianginal effects if abrasion & breakdown; monitor for
these drugs are given w/ ergot derivatives. signs of skin breakdown to arrange for appropriate skin care as
Risk of decreased therapeutic effects of heparin if these drugs needed.
are given together w/ heparin; if this Make sure that translingual spray is used under the tongue and
combination is used, patient should be monitored & appropriate not inhaled to ensure that the
dose adjustments made. therapeutic effects can be achieved.
Patients should not combine nitrates w/ sildenafil, tadalafil, or Break an amyl nitrate capsule & wave it under the nose of the
vardenafil, drugs used to treat erectile angina patient to provide rapid
dysfunction, because serious hypotension & cardiovascular relief using the inhalation form of the drug; this may be
events could occur. repeated with another capsule in 3 to 5
Drug-Food minutes if needed.
Interactions None is mentioned Keep a record of the number of sprays used if a translingual
Nitrates spray form is used, to prevent
Nursing Considerations Nursing running out of medica- tion and episodes of untreated angina.
Diagnosis Have emergency life support equipment readily available in case
Planning of severe reaction to the drug
Assess for contraindications or cautions. or myocardial infarction.
Perform a physical assessment to establish baseline status Implementation with Rationale - cont’d Evaluation - cont’d
before Taper the dose gradually (over 4 to 6 weeks) after long- term
beginning therapy & during therapy to determine effectiveness therapy because abrupt
& to withdrawal could cause a severe reaction, including MI.
evaluate for any potential adverse effects. Provide comfort measures to help the patient tolerate drug
effects. These include small,

13
106 BY TONS AND MADS
frequent meals to alleviate GI upset; access to bathroom combination is used, the patient should be monitored closely
facilities if GI upset is severe or and a dose
the patient experiences incontinence; environmental controls adjustment made.
such as temperature, An initial hypertensive episode followed by bradycardia occurs if
controlled lighting, and noise reduction to decrease stresses that these drugs are given with
could aggravate epinephrine, and a possibility of peripheral ischemia exists if
cardiac workload; safety precautions such as lying or sitting beta-blockers are taken in combination
down after taking the drug with ergot alkaloids.
and assistance with ambulation to reduce the risk of injury; There also is a potential for a change in blood glucose lev- els if
reorientation; and these drugs are given with insulin or
appropriate skin care as needed. antidiabetic agents, and the patient will not have the usual signs
Offer support and encouragement to help the patient deal with and symptoms of hypoglycemia or
the diagnosis and the hyperglycemia to alert him or her to poten- tial problems. If this
drug regimen. combination is used, the patient
Provide thorough patient teaching, including the name of the should monitor blood glucose frequently throughout the day and
drug; dosage prescribed; should be alert to new warnings
proper technique for admin- istration (oral, sublingual, about glucose imbalance.
transbuccal, transdermal, Drug-Food
inhalation spray, or topical); need for removal of trans- dermal Interactions
or topical drug before Food has been found to increase the bioavailability of
application of the next dose; the importance of having an propranolol, but this effect has not been found
adequate supply of drug (e.g., with other beta-adrenergic blocking agents.
teaching the patient to count the number of sprays used for a NOTE: See or refer to your previous module (Chapter 31) for the
translingual spray so as nursing considerations associated with beta-blockers.
not to run short); measures to prevent anginal attacks, and Calcium Channel Blockers
actions to take when an Therapeutic
attack occurs; use of medication during an attack (such as the Actions
number of tablets and Inhibit movement of Ca+ ions across membranes of myocardial
time span that the patient can take sublingual tablets); & arterial muscle cells, altering the action
measures to avoid adverse potential & blocking muscle cell contraction. A loss of smooth
effects, warning signs of problems and signs and symptoms to muscle tone, vasodilation, & decreased
report immediately; and peripheral resistance occur. Subsequently, preload & afterload
the need for periodic monitoring and evaluation to enhance are decreased, w/c in turn decreases cardiac
patient knowledge about workload and oxygen consumption.
drug therapy and to promote compliance. Indications
Treatment of Prinzmetal angina, chronic angina,
Beta-Adrenergic Blockers effort-associated angina, & hypertension. In Prinzmetal
Beta-blockers competitively block beta-adrenergic receptors in angina: relieve coronary artery vasospasm, increasing blood flow
the heart & juxtaglomerular apparatus, to the muscle cells. Also block the
decreasing the influence of sympathetic nervous system on proliferation of cells in the endothelial layer of blood vessel,
these tissues. The result is a decrease in slowing progress of the atherosclerosis.
the excitability of the heart, a decrease in CO, a decrease in Verapamil -used to treat cardiac tachyarrhythmias bec it slows
cardiac O2 consumption, & a lowering of conduction more than the other calcium
BP. channel blockers do. Drug of choice depends on patient’s dx &
Indications ability to tolerate adverse drug effects.
Indicated for long-term management of angina pectoris caused Pharmacokinetics Well absorbed after oral administration,
by atherosclerosis. Sometimes used metabolized in the liver, & excreted in urine. Have an onset of
in com- bination with nitrates to increase exercise tolerance. action
Treatment of Prinzmetal angina bec they could cause vasospasm of 20 mins & a duration of action of 2 to 4 hrs. Cross the
due to blocking of beta-receptor placenta & enter breast milk.
sites. Contraindications
Propranolol & metoprolol can also be used to prevent & Cautions
reinfarction in stable patients 1 to 4 weeks after Allergy to drug; pregnancy or lactation bec of potential for
an MI. adverse effects on fetus or neonate.
This effect is thought to be caused by suppression of myocardial Caution used with heart block or sick sinus syndrome, w/c could
O2 demand for a prolonged period. be exacerbated by the conduction-slowing
Pharmacokinetics Absorbed from GIT after oral administration & effects of these drugs; with renal or hepatic dysfunction, w/c
undergo hepatic metabolism. Reach peak levels in 60 could alter metabolism & excretion of these
to 90 minutes & have varying duration of effects, ranging from 6 drugs; & w/ heart failure, w/c could be exacerbated by the
to 19 hours. decrease in CO that could occur.
Contraindications Adverse Effects
& Cautions CNS effects: dizziness, light-headedness, headache, & fatigue.
Contraindicated in patients w/ bradycardia, heart block, & GI effects: nausea & hepatic injury related to
cardiogenic shock because blocking of the direct toxic effects on hepatic cells. Cardiovascular effects:
sympathetic response could exacerbate these diseases. hypotension, bradycardia, peripheral edema, &
Contraindicated w/ pregnancy & lactation heart block. Skin effects: flushing & rash.
because of the potential for adverse effects on the fetus or Drug-drug
neonate. Interactions
Caution should be used in patients w/ diabetes, peripheral Potentially serious: increased serum levels & toxicity of
vascular disease, asthma, COPD, or cyclosporine if taken w/ diltiazem & increased risk of
thyrotoxicosis bec the blockade of sympathetic response blocks heart block & digoxin toxicity if combined w/ verapamil (bec
normal reflexes that are necessary verapamil increases digoxin serum levels). Both
for maintaining homeostasis in patients w/ these diseases. Many verapamil & digoxin depress myocardial conduction. Very close
patients with these complicating monitoring if used in combination & do
disorders receive beta-b, and these patients need to be appropriate dose adjustments if needed. Verapamil has also
monitored carefully to avoid serious adverse been associated w/ serious respiratory
effects. depression when given with general anesthetics or as an adjunct
Beta-Adrenergic Blockers to anesthesia.
Adverse Drug-Food
Effects Interactions
CNS effects: dizziness, fatigue, emotional depression, & sleep None is mentioned
disturbances. GI problems: gastric Calcium Channel Blockers
pain, nausea, vomiting, colitis, & diarrhea. Cardiovascular effects Nursing Considerations Nursing Diagnosis Planning
can include heart failure, reduced Assess for contraindications or cautions.
cardiac output, and arrhythmias. Respiratory effects can include Perform a physical assessment to establish baseline
bronchospasm, dyspnea, and cough. status before beginning therapy and during therapy to
Decreased exercise tolerance and malaise are also common determine the effectiveness and evaluate for any
complaints. potential adverse effects.
Drug-drug Inspect skin for color and integrity to identify possible
Interactions adverse skin reactions.
A paradoxical hypertension occurs when clonidine is given with Assess the patient’s complaint of pain, including
beta-blockers, & an increased onset, duration, intensity, and location and measures
rebound hypertension w/ clonidine withdrawal may also occur; it used to relieve the pain. Investigate activity level prior
is best to avoid this combination. to and after the onset of pain to aid in identifying
A decreased antihypertensive effect occurs when beta- blockers possible con- tributing factors to the pain and its
are given w/ nonsteroidal antiinflammatory drugs; if this progression.

14
106 BY TONS AND MADS
Assess cardiopulmonary status closely, including Monitor for adverse effects
pulse rate, blood pressure, heart rate, and rhythm, to (hypotension, cardiac
determine the effects of therapy and identify any arrhythmias, GI upset, skin
adverse effects. reactions, headache).
Obtain an ECG as ordered to evaluate heart rate and Monitor the effectiveness of
rhythm. • Monitor respirations and auscultate lungs to comfort measures and
evaluate changes in cardiac output. compliance with the
Monitor laboratory test results, including liver and regimen.
renal function tests, to determine the need for Evaluate the effectiveness
possible dose adjustment. of the teaching plan (patient
Decreased Cardiac Output can name drug, dosage,
related to hypotension and proper administration,
vasodilation adverse effects to watch
Risk for Injury related to for, specific measures to
CNS or cardiovascular avoid them, and the
effects importance of continued
Ineffective Tissue follow-up).
Perfusion (Total Body) Very effective in treating angina & has
related to the added benefits of decreasing blood
hypotension or change in glucose levels when used in diabetic
cardiac output patients & decreasing the incidence of
Deficient Knowledge ventricular fibrillation, atrial fibrillation,
regarding drug therapy and bradycardia in chronic angina
The patient will receive patients.
the best therapeutic PIPERAZINE ACETAMIDE AGENT
effect from the drug PIPERAZINE ACETAMIDE AGENT
therapy. Therapeutic
Actions
Calcium Channel Blockers Mechanism of action not understood.
Implementation with Rationale Evaluation Does prolong the QT interval, it does not decrease HR or BP, but
Monitor the patient’s blood pressure, cardiac rhythm, and it does decrease myocardial workload,
cardiac output closely while bringing the supply & demand for oxygen back into balance.
the drug is being titrated or dose is being changed to ensure Indications Ranolazine is approved as a first-line treatment for
early detection of angina or for use in combination with nitrates, betablockers, or
potentially serious adverse effects. amlodipine.
Monitor blood pressure very carefully if the patient is also taking Pharmacokinetics Rapidly absorbed, reaching peak levels in 2 to
nitrates because there is 5 hours.
an increased risk of hypotensive episodes. Metabolized in the liver with a half-life of 7 hours and is excreted
If a patient is on long-term therapy, periodically monitor blood in urine and feces.
pressure and cardiac Contraindications
rhythm while the patient is using these drugs because of the & Cautions
potential for adverse Ranolazine is contraindicated for use with any known sensitivity
cardiovascular effects. to the drug; with preexisting prolonged QT
Provide comfort measures to help the patient tolerate drug interval or in combination with drugs that would prolong QT
effects. These include small, intervals; and with hepatic impairment and
frequent meals to alleviate GI upset; environmental controls, lactation.
such as limiting light, Caution should be used with pregnancy or renal impairment.
maintaining temperature, and avoiding excessive noise and Patients must be cautioned not to cut, crush,
interruptions, which could or chew the tablets, which need to be swallowed whole. Safety
aggravate stress and increase myocardial demand; and taking precautions may be needed if dizziness is an
safety precautions, such issue.
as providing periodic rests and assisting with ambulation if Patients must be cautioned not to cut, crush, or chew the
dizziness occurs, to prevent tablets, which need to be swallowed whole.
injury. Safety precautions may be needed if dizziness is an issue.
Offer support and encouragement to help the patient deal with Adverse Effects Dizziness, headache, nausea, and constipation
the diagnosis and the are the most commonly experienced adverse effects.
drug regimen. Drug-drug
Provide thorough patient teaching, including the name of the Interactions
drug and dosage Drug–drug interactions can occur with ketoconazole, diltiazem,
prescribed; measures to avoid adverse effects and prevent verapamil, macrolide antibiotics, and HIV
anginal attacks; actions to protease inhibitors; these combinations should be avoided
take when an attack occurs; warning signs of problems, and because ranolazine levels may become extremely
signs and symptoms to high. Digoxin levels may become high if the two drugs are
report immediately; and the need for periodic monitoring and combined; if this combination is needed, the
evaluation to enhance digoxin dose will need to be decreased. Tricyclic antidepressants
patient knowledge about drug therapy and to promote & antipsychotic drug levels may increase if
compliance. these agents are combined with ranolazine; if they are
Monitor patient response to combined, the dose of these drugs may need to be
the drug (alleviation of signs decreased.
and symptoms of angina, Drug-Food Interactions Grapefruit juice should be avoided while
prevention of angina). taking this drug
Part 6: Lipid Lowering Agents
Lipid-Lowering Agents atment of CAD
• Sometimes called Fats & Biotransformation (Metabolism)
Antihyperlipidemic agents. Fat intake
• Used to treat as dietary
hyperlipidemia— Fats
an increase in the Broken into:
level of lipids in Fatty Acids
the blood. Lipids
• CAD - higher Cholesterol
among people (Duodenum)
with high serum Lipoproteins
lipid levels. Produced in liver, with clinical
Coronary Artery Disease implications: low-density lipoproteins
• Decreasing (LDLs) & high-density lipoproteins
dietary fats (HDLs).
• Lose weight • Eliminating LDLs enter circulation as tightly packed
smoking cholesterol, triglycerides, and lipids to
• Increase exercise be broken down for energy or stored
levels for future use as energy.
• Decreasing stress • Treating HDLs enter circulation as loosely
hypertension, packed lipids that are used for energy &
diabetes, & gout. to pick up remnants of fats and cholesterol that are left in the
Tre periphery by

15
106 BY TONS AND MADS
LDL breakdown. alertness, to determine any central nervous system effects.
Hyperlipidemias Monitor pulse and blood pressure for changes related to
Fats needed by the body to changes in CAD risk factors.
maintain normal function. Inspect the abdomen for distention and auscultate bowel
The base unit for formation of sounds for changes in gastrointestinal motility.
steroid hormones (sex & adrenal Assess bowel elimination patterns, including frequency of stool
cortical hormones). passage and stool characteristics, to identify possible
Also a basic unit in formation & constipation and fecal impaction.
maintenance of cell membranes. Monitor the results of laboratory tests, including serum
Provided thru diet & fat cholesterol and lipid levels, to evaluate the effectiveness of
metabolism. drug therapy.
Cholesterol Acute Pain related to
Increase levels of lipids in blood. headache and GI
Result from excessive dietary intake of effects
fats or from genetic alterations in fat Constipation related
metabolism leading to a variety of to GI effects
elevated fats in the blood. Risk for Injury related
Treatment: Dietary modifications - if to CNS changes and
caused by excessive dietary intake of potential for
fats; Drug therapy - if genetically linked. bleeding
Deficient Knowledge
Bile Acid Sequestrants regarding drug
Therapeutic therapy
Actions
Bind w/ bile acids in intestine to form an insoluble complex that Bile Acid Sequestrants
is then excreted in feces. Implementation with Rationale Evaluation
Bile acids contain high levels of cholesterol. As a result, liver Do not administer powdered agents in dry form; these drugs
must use cholesterol to make more bile acids. must be mixed in fluids to be effective.
Hepatic intracellular cholesterol level falls, leading to an Mix with fruit juices, soups, liquids, cereals, or pulpy fruits. Mix
increased absorption of cholesterol-containing LDL segments colestipol, but not cholestyramine,
from with carbonated beverages. Stir, and encourage the patient to
circulation to replenish cell’s cholesterol. Serum levels of swallow all of the dose.
cholesterol & LDL decrease as circulating cholesterol is used to If the patient is taking tablets, ensure that tablets are not cut,
provide the cholesterol that the liver needs to make bile acids. chewed, or crushed because they are
Indications designed to be broken down in the GI tract; if they are crushed,
Used to reduce serum cholesterol in patients w/ primary the active ingredients will not be
hypercholesterolemia (manifested by high cholesterol & high effective. Urge the patient to swal- low tablets whole with plenty
LDLs) of fluid.
as an adjunct to diet & exercise. Give the drug before meals to ensure that the drug is in the GI
Cholestyramine is also used to treat pruritus associated with tract with food.
partial biliary obstruction. Administer other oral medications 1 hour before or 4 to 6 hours
Pharmacokinetics after the bile sequestrant to avoid
Bile acid sequestrants are not absorbed systemically. They act drug–drug interactions.
while in the intestine & are excreted directly in the feces. Arrange for a bowel program as appropriate to effectively deal
Their action is limited to their effects while they are present in with constipation if it occurs.
the intestine. Provide comfort measures to help the patient tolerate the drug
Cholestyramine is a powder that must be mixed w/ liquids & effects. These include small, frequent
taken up to six times a day. meals to reduce the risk of nausea; ready access to bathroom
Colestipol is available in both powder & tablet form & is taken facilities to prevent constipation;
only four times a day. safety precautions to prevent injury if dizziness, central nervous
Colesevelam is available in tablet form and is taken once or system (CNS) changes, or bleeding
twice a day. is a problem; replacement of fat-soluble vita- mins; skin care as
Contraindications needed; and analgesics for
& Cautions headache.
Allergy to bile acid sequestrant; Complete biliary obstruction, Offer support and encouragement to help the patient deal with
(would prevent bile from being secreted into the intestine); the diagnosis and the drug regimen
abnormal intestinal function, (could be aggravated by presence and lifestyle changes that may be necessary; refer the patient to
of these drugs); pregnancy or lactation because the potential ser- vices that might help with the
decrease in the absorption of fat & fat-soluble vitamins could high cost of these drugs.
have a detrimental effect on the fetus or neonate. If a Provide thorough patient teaching, including the name of the
lipidlowering drug is needed, however, a bile acid seques- trant drug, dosage prescribed, and schedule
is the drug of choice. for administration; method to administer the drug, such as
Adverse Effects mixing the powder form in fluids or taking
Headache, anxiety, fatigue, & drowsiness, w/c could be related tablets whole (with- out crushing, chewing, or cutting);
to changes in serum cholesterol levels. Direct GIT irritation, appropriate fluids for mixing drug; measures
including nausea, constipation that may progress to fecal to avoid adverse effects, warning signs of problems, and the
impaction, & aggravation of hemorrhoids. need for follow-up laboratory testing to
Other effects: increased bleeding times related to decreased monitor cholesterol and lipid levels; dietary and lifestyle changes
absorption of vit K & consequent decreased production of for risk reduction; and monitoring
clotting factors; vit A & D deficiencies related to decreased and evaluation to enhance patient knowledge about drug
absorption of fat-soluble vits; rash; & muscle aches & pains. therapy and to promote compliance.
Drug-drug Monitor patient response to
Interactions the drug as appropriate
Malabsorption of fat-soluble vits occurs when they are combined (reduction in serum
w/ these drugs. These drugs decrease/delay absorption of cholesterol levels).
thiazide diuretics, digoxin, warfarin, thyroid hormones, & Monitor for adverse effects
corticosteroids. (headache, vitamin
Any of these drugs should be taken 1 hour before or 4 to 6 deficiency, increased
hours after the bile acid sequestrant. bleeding times,
Drug-Food constipation, nausea, rash).
Interactions Evaluate the effectiveness
Give the drug before meals to ensure that the drug is in the GI of the teaching plan (patient
tract with food. can name drug, dosage,
Bile Acid Sequestrants adverse effects to watch for,
Nursing Considerations Nursing Diagnosis Planning and specific measures to
Assess for contraindications or cautions. avoid them; patient
Perform a physical assessment to establish a baseline before understands the importance
beginning therapy and during therapy to determine the of continued follow-up).
effectiveness of therapy and evaluate for any potential adverse Monitor the effectiveness of
effects. comfort measures and
Weigh the patient to establish a baseline and evaluate for compliance with the
changes reflecting lifestyle changes that accompany drug regimen.
therapy. HMG-CoA Reductase Inhibitors
Inspect the patient’s skin for color, bruising, and rash to Therapeutic
evaluate for possible adverse effects. Actions
Assess neurological status, including level of orientation and

16
106 BY TONS AND MADS
Blocks HMG-CoA reductase from completing the synthesis of Gustatory) related to
cholesterol making serum cholesterol & LDL levels decrease bec CNS effects
more Risk for Injury related
LDLs are absorbed by the cells for processing into cholesterol. to CNS, liver, and
Exact mechanism of action is not understood. renal effects
In contrast, HDL levels increase slightly with this alteration in fat Acute Pain related to
metabolism. Frequently referred to as “Statins”. headache, myalgia,
Indications and GI effects
Indicated as adjuncts w/ diet & exercise for treatment of Deficient Knowledge
increased cholesterol & LDL levels that are unresponsive to regarding drug
dietary therapy
restrictions alone. Pravastatin, lovastatin (oldest), & simvastatin
are indicated for documented CAD to slow dse progression. HMG-CoA Reductase Inhibitors
These 3 agents & atorvastatin are used to prevent 1st MI in Implementation with Rationale Evaluation
patients who have multiple risk factors for developing CAD. Administer the drug at bedtime because the highest rates of
Pharmacokinetics cholesterol synthesis occur between midnight and 5 AM, and the
Statins are all absorbed from GIT & undergo 1st- pass drug should be taken when it will be most effective; give
metabolism in liver. Excreted thru feces & urine. atorvastatin at any time during the day.
Peak effect is usually seen within 2 to 4 weeks. Most effective Monitor serum cholesterol and LDL levels before and period-
when taken at night when the liver is processing the most lipids. ically during therapy to evaluate the effectiveness of this drug. •
Crosses placenta, & most have been found in breast milk. Arrange for periodic ophthalmic examinations to monitor
Contraindications for cataract development.
& Cautions Monitor liver function tests before and periodically dur- ing
Allergy to statins or fungal byproducts or compounds. Statins therapy to monitor for liver damage; consult with the prescriber
C/Is: active liver disease or history of alcoholic liver disease, w/c to
could discontinue the drug if the aspartate amino- transferase (AST)
be exacerbated, leading to severe liver failure; pregnancy or or alanine aminotransferase (ALT) level increases to three times
lactation, bec of the potential for adverse effects on fetus or normal.
neonate. Ensure that the patient has attempted a cholesterol-lowering
Labeled as pregnancy category X. diet and exercise program for at least 3 to 6 months before
Atorvastatin levels are not affected by renal disease, but beginning therapy to ensure the need for drug therapy.
patients w/ renal impairment who are taking other statins Encourage the patient to make the lifestyle changes necessary
require close to decrease the risk of CAD and to increase the effectiveness
monitoring. Caution should be used in patients with impaired of drug therapy.
endocrine function because of the potential alteration in the Withhold lovastatin, atorvastatin, or fluvastatin in any acute,
formation of serious medical condition (e.g., infection, hypotension major
steroid hormones. surgery or trauma, metabolic endocrine disorders, seizures) that
Adverse Effects might suggest myopathy or serve as a risk factor for the
GI system: flatulence, abdominal pain, cramps, nausea, development of renal failure.
vomiting, & constipation. CNS effects: headache, dizziness, Suggest the use of barrier contraceptives for women of
blurred vision, childbearing age because there is a risk of severe fetal
insomnia, fatigue, & cataract development & may reflect abnormalities if
changes in the cell membrane & synthesis of cholesterol. these drugs are taken during pregnancy.
Increased Provide comfort measures to help the patient tolerate drug
concentrations of liver enzymes commonly occur, & acute liver effects. These include small, frequent meals to minimize nausea
failure has been reported with the use of atorvastatin & and vomiting; access to bathroom facilities to ensure adequate
fluvastatin. bowel evacuation; bowel program as needed to address
Lovastatin, pravastatin, and simvastatin are not associated w/ constipation; use of food with the drug if GI upset is severe to
some of severe liver toxicity that is seen w/ other agents. decrease direct irritating effects; environmental controls, such
Rhabdomyolysis, a breakdown of muscles whose waste products as temperature and lighting controls, to help deal with
can injure the glomerulus & cause acute renal failure, has also headaches; and safety precau- tions, such as lighting control
occurred with the use of all of these drugs. and
Drug-drug activity restrictions, to protect the patient if vision changes and
Interactions muscle effects occur.
Risk of rhabdomyolysis increases if any of these drugs is Offer support and encouragement to help the patient deal with
combined w/ erythromycin, cyclosporine, gemfibrozil, niacin, or the diagnosis, needed lifestyle changes, and the drug regimen.
antifungal Provide thorough patient teaching, including the name of the
drugs; such combinations should be avoided. Increased serum drug, dosage prescribed, and administration at bedtime for best
levels & resultant toxicity occur if combined w/ digoxin or effectiveness; measures to avoid adverse effects, warning signs
warfarin; if of problems, and the need for fol- low-up laboratory testing
this combination is used, serum digoxin levels and/or clotting to monitor cholesterol and lipid levels; importance of follow-up
times should be monitored carefully & consult physician for renal and liver funcion testing; dietary and lifestyle changes for
appropriate risk reduction; and monitoring and evaluation, to enhance
dose changes. Increased estrogen levels can occur if taken with patient knowledge about drug therapy and to promote
oral contraceptives; monitor carefully if this combination is used. compliance.
Serum levels and the risk of toxicity increase if these drugs are
combined with grapefruit juice. Cholesterol Absorption Inhibitors
Drug-Food Therapeutic
Interactions Actions
None is mentioned. Ezetimibe works in the brush border of small intestine to
HMG-CoA Reductase Inhibitors decrease absorption of dietary cholesterol from small
Nursing Considerations Nursing Diagnosis Planning intestine. As a result, less dietary cholesterol is delivered to the
Assess for contraindications and cautions. liver, & liver increases clearance of cholesterol from
Perform a physical assessment to establish a baseline before serum to make up for the drop in dietary cholesterol, causing
beginning therapy and during therapy to determine its total serum cholesterol level to drop.
effectiveness and evaluate for any potential adverse effects. Indications
Weigh the patient to establish a baseline and evaluate for Adjunct to diet & exercise to lower serum choesterol levels; in
changes reflecting lifestyle changes that accompany drug combination w/ atorvastatin or simvastatin for the
therapy. treatment of homozygous familial hypercholesterolemia; with
Assess the patient’s neurological status, including level of diet for the treatment of homozygous sitosterolemia to
orientation, affect, and reflexes, which show early changes lower sitosterol and campesterol levels.
related to CNS function, to evaluate for possible CNS effects Pharmacokinetics
of the drug. Ezetimibe is absorbed well after oral administration, reaching
Obtain vital signs, including pulse and blood pressure, to peak levels in 4 to 6 hours. It is metabolized in the liver
identify changes. and the small intestine, with a half-life of 22 hours. Excretion is
Inspect the abdomen for distention and auscultate bowel through feces and urine. It is not known whether the
sounds for changes in gastrointestinal motility. drug crosses the placenta or enters breast milk.
Assess bowel elimination patterns, including frequency of Contraindications
stool passage and stool characteristics, to identify possible & Cautions
constipation. Allergy to any component of the drug. If used in combination w/
Monitor the results of laboratory tests, including renal and a statin, it should not be used during pregnancy or
liver function tests, to identify possible toxicity and serum lactation or w/ severe liver disease bec of the known effects of
lipid levels to evaluate the drug’s effectiveness. statins, including possible liver problems & renal
Disturbed Sensory failure.
Perception (Visual, Used w/ caution as monotherapy during pregnancy or lactation
Kinesthetic, bec the effects on the fetus or neonate are not

17
106 BY TONS AND MADS
known & w/ elderly patients or patients with liver disease changes for reducing the risk of CAD and increasing the
because of the potential for adverse reactions. effectiveness of drug therapy; and
Adverse Effects monitoring & evaluation to enhance patient knowledge about
Mild abdominal pain & diarrhea; not associated w/ bloating & drug therapy & to promote
flatulence that occurs w/ bile acid sequestrants & compliance.
another class of lipid-lowering drugs called fibrates.
Other adverse effects: headache, dizziness, fatigue, URI, back Other Lipid-Lowering Agents
pain, & muscle aches and pains. Fibrates
Drug-drug - Stimulate breakdown of lipoproteins from tissues & their
Interactions removal from plasma.
Risk of elevated serum levels of ezetimibe increases if it’s given - Lead to decrease in lipoprotein & triglyceride synthesis
w/ cholestyramine, fenofibrate, gemfibrozil, or & secretion.
antacids. If used in combination, it should be taken at least 2 - Absorbed from GIT & are metabolized in liver &
hours before or 4 hours after the other drugs. Risk of excreted in urine.
toxicity also increases if it’s combined w/ cyclosporine. If this 1. Fenofibrate (TriCor, others) inhibits triglyceride
combination cannot be avoided, the patient should be synthesis in liver, resulting in reduction of LDL levels;
monitored very closely. increases uric acid secretion; & stimulate triglyceride
If combined w/ any fibrate, the risk of cholethiasis increases, breakdown. Used for adults w/ very high triglyceride
monitor patient closely. levels who are not responsive to strict dietary measures
Warfarin levels increase in patient who is taking ezetimibe; if & who are at risk for pancreatitis. Peak effects are
this combination is used, monitored very closely. usually seen within 4 weeks, and the patient’s serum
Drug-Food lipid levels should be reevaluated at that time.
Interactions 2. Gemfibrozil (Lopid) inhibits peripheral breakdown of
None is mentioned. lipids, reduces production of triglycerides & LDLs, &
Cholesterol Absorption Inhibitors increases HDL concentrations. It’s associated with GI
Nursing Considerations Nursing Diagnosis Planning and muscle discomfort. Should not be combined w/
Assess for contraindications or cautions. statins. There’s an increased risk of rhabdomyolysis
Perform a physical assessment to establish a baseline from 3 weeks to several months after therapy if this
before beginning therapy and during therapy to combination is used. If this combination cannot be
determine its effectiveness and evaluate for any avoided, the patient should be monitored very closely.
potential adverse effects. 3. Fenofibric acid (Trilipix) - peroxisome
Monitor orientation and reflexes to detect changes in proliferator–activated receptor alpha agonist. Activate a
CNS function, such as dizziness, that could require specific hepatic receptor that results in increased
safety measures. breakdown of lipids, elimination of triglyceride-rich
Monitor respirations and auscultate lungs for evidence particles from the plasma, & reduction in production of
of adventitious sounds to monitor changes in cardiac enzyme that naturally inhibits lipid breakdown. The
output. result is seen as a decrease in triglyceride levels,
Inspect the abdomen for distention and auscultate changes in LDL production that makes them more easily
bowel sounds for changes in gastrointestinal motility. broken down in the body, & an increase in HDL levels.
Assess bowel elimination patterns, including Used as adjunctive therapy to reduce triglyceride levels,
frequency of stool passage and stool characteristics, decrease LDL, & increase HDL levels in patients w/
to identify possible changes that could require mixed lipid disorders & primary hypercholesterolemia.
intervention. Slowly absorbed from GIT, w/ peak levels occurring in 4
Monitor the results of laboratory tests, including to 5 hours; metabolized in the liver, it has a half-life of
serum cho- lesterol and lipid levels, to evaluate the 20 hours & is excreted in the urine. Use w/ caution: in
effectiveness of drug therapy, and liver function patient w/ renal impairment; should be avoided if w/
studies to monitor for toxic effects. severe renal impairment. Adverse effects: headache,
Disturbed Sensory back pain, nausea, diarrhea, muscle pain, runny nose, &
Perception (Visual, respiratory infections. Gallstones have also been
Kinesthetic, reported with this drug. Patients complaining of
Gustatory) related to gallstone-type pain should be screened carefully. There
CNS effects is an increased risk of muscle breakdown &
Acute Pain related to rhabdomyolysis if taken with a statin, & patients using
headache, myalgia, this combination need to be monitored closely. Caution
and GI effects must be used with warfarin anticoagulants; increased
Deficient Knowledge bleeding can occur. The patient should be monitored
regarding drug closely and the dose of the anticoagulant regulated to
therapy achieve therapeutic anticoagulation.
Cholesterol Absorption Inhibitors Vitamin B
Implementation with Rationale Evaluation Vitamin B3, known as niacin (Niacor, Niaspan) or nicotinic acid,
Monitor serum cholesterol, triglyceride, and LDL levels before inhibits release of free fatty acids from adipose tissue,
and periodically during therapy increases rate of triglyceride removal from plasma, & generally
to evaluate the effectiveness of this drug. reduces LDL & triglyceride levels & increases HDL
Monitor liver function tests before and periodically during levels. It may also decrease levels of apoproteins needed to
therapy to detect possible liver form chylomicrons.
damage. Initial effect on lipid levels is usually seen w/in 5 to 7 days, w/
Ensure that the patient has attempted a cholesterol- lowering maximum effect occurring in 3 to 5 weeks.
diet and exercise program for at Niacin is associated w/ intense cutaneous flushing, nausea, &
least several months before beginning therapy to ensure the abdominal pain, making its use somewhat limited.
need for drug therapy. Also increases the serum levels of uric acid & may predispose
Encourage the patient to make the lifestyle changes nec- essary patients to development of gout.
to decrease the risk of CAD Niacin is often combined w/ bile acid sequestrants for increased
and to increase the effectiveness of drug therapy. effect. Given at bedtime to make maximum use of
Suggest the use of barrier contraceptives for women of nighttime cholesterol synthesis, & must be given 4 to 6 hours
childbearing age if the drug is being after the bile sequestrant to ensure absorption.
used in combination with a statin because there is a risk of Omega-3
severe fetal abnor- malities if these Fatty
drugs are taken during pregnancy. Acids
Provide comfort measures to help the patient tolerate drug Omega-3-acid ethyl esters (Lovaza) are a combination of
effects. These include readily omega-3 fatty acids & an activator that inhibits liver enzyme
available access to bathroom facilities to help with episodes of systems to decrease the synthesis of triglycerides, a risk factor
diarrhea; safety precau- tions in metabolic syndrome, lowering serum triglyceride
to protect the patient if dizziness is an issue; and anal- gesics levels. Approved to lower triglycerides in adults w/ high
for headache and muscle aches triglyceride levels. Should be combined w/ appropriate diet &
if appropriate. exercise to help keep overall lipid levels lower.
Offer support and encouragement to help the patient deal with Not recommended in pregnancy or lactation. There’s substantial
the diagnosis, needed lifestyle research evidence to support the effects of this
changes, and the drug regimen. drug, unlike research on over-the-counter fish oil products,
Provide thorough patient teaching, including name of the drug, which does not support effectiveness in lowering lipid
dosage prescribed, & schedule levels. This drug may prolong bleeding time so caution must be
for administration; measures to avoid adverse effects, warning used with any other drugs that affect bleeding.
signs of problems, & the need Adverse Effects: Diarrhea, nausea, abdominal pain.
for follow-up laboratory testing to monitor cholesterol and lipid Omega-3-carboxylic acids (Epanova) are a fish oil mixture of
levels; dietary and lifestyle free fatty acids approved as an adjunct to diet to reduce

18
106 BY TONS AND MADS
triglyceride levels in adults with severe hypertriglyceridemia Therapies
(500 mg/dL or over). In some patients, this drug New drugs are being investigated:
increases LDL levels, which need to be closely monitored. Endocannabinoids are substances present in the body that
Caution needs to be used in patients with hepatic impairment or activate various neurological receptors that seem to be very
allergy to fish or shellfish. These capsules have to important in the body’s regulation of appetite, satiety, and lipid
be swallowed whole, not cut, crushed, or chewed. This drug metabolism. With blocking of the endocannabinoid system, a
may prolong bleeding time so caution must be used series of changes occur that would seem to have a very
with any other drugs that affect bleeding. Diarrhea, nausea, profound effect on many components of the metabolic
abdominal pain, and discomfort are the most common syndrome.
adverse effects. Blocking the endocannabinoid system results in feelings of
satiety and decreased appetite, leading to weight loss;
Other Lipid-Lowering Agents decreased
Other Therapies release of growth hormone, increased oxygen and glucose use
2 drugs approved in 2014 specifically treatment of homozygous in the muscle, decreased fat synthesis in the liver, decreased
familial hypercholesterolemia: 1.) Mipomersen (Kynamro) & 2.) levels
lomitapide (Juxtapid) are both agents approved as adjuncts to of triglycerides and LDLs, and increased levels of HDLs,
diet, exercise, & other lipid-lowering therapies. improving the lipid profile; increased sensitivity of insulin
Both have black box warnings regarding the potential for serious receptor sites,
hepatotoxicity, and because of this risk, both are available only leading to decreased blood glucose levels; decreased fat
through a limited-access program. production and storage; increased levels of adiponectin; and
Mipomersen inhibits apoprotein B synthesis and lomitapide decreased
inhibits the triglyceride transfer protein. Both drugs are indicated activity of tumor necrosis factor, a proinflammatory agent, and
only decreased activity of C-reactive protein, which is associated with
for use with familial hypercholesterolemia, and neither drug has proinflammatory and prothrombotic states.
any evidence of any effect on CV morbidity or mortality. Rimonabant is an endocannabinoid blocker that has been used
Combination in Europe as a weight loss agent. In early studies in the United
Therapy States, it has been shown to significantly reduce weight and
Frequently, if the patient shows no response to strict dietary abdominal adiposity and improve lipid profiles while increasing
modification, exercise, and lifestyle changes with the use of one insulin
lipidlowering agent, combination therapy may be initiated to sensitivity and reducing the proinflammatory and prothrombotic
achieve desirable serum LDL & cholesterol levels. markers. Approval of the drug was denied at one point because
For example, a bile acid sequestrant might be combined with of
niacin; the combination would decrease the synthesis of LDLs some significant CNS changes that occur, leading to questions of
while safety. In April 2008 preliminary studies of the drug were
lowering the serum levels of LDLs. This combination is thought published that reported no change in atherosclerosis and
to help slow the progression of CAD. Numerous disease progres- sion, despite improvement in metabolic
fixed-combination syndrome
therapies are markers, thus showing again that there is no real understanding
Future of the process of CAD and risk modification.
Part 7: Drugs Affecting Bood Coagulation
Blood Coagulation DISORDERS AFFECTING BLOOD COAGULATION
Balance of procoagulants & Thromboembolic Disorders
anticoagulants. Conditions that predispose a person to
Vascular system maintain a balance the formation of clots and emboli.
between coagulation (solid state) & Thrombi tend to form along the
need to unclot (reverse damaged endothelial lining.
coagulation). If vessels are completely occluded,
People injure their blood vessels anoxia occurs, followed by infarction &
sometime in life. necrosis.
Drugs affecting blood coagulation These disorders are treated w/ drugs that
work at various steps in bloodclotting & clot-dissolving processes interfere w/ the normal coagulation
to restore balance needed to process to prevent the formation of clots
maintain the CV system. in the system.
Clotting Process Hemorrhagic Disorders
Local Vasoconstriction - 1st Excess bleeding w/c include:
reaction to blood vessel injury. A. Hemophilia - a genetic lack of clotting
Platelet Aggregation factors;
Injury exposes blood to collagen & B. Liver disease - clotting factors & proteins
other substances under endothelial needed for clotting are not produced; &
lining of vessel causing platelets in C. Bone marrow disorders - platelets are not
circulating blood to stick (release ADP) formed in sufficient quantity to be effective.
or adhere to the site of the injury. These disorders are treated w/ clotting factors & drugs that
Intrinsic Pathway promote the coagulation
Hageman Factor (factor XII) is activated process.
(factor XIIa).
Factor XIIa: activates clot formation &
clot-dissolving processes, & starts
inflammatory process.
Extrinsic Pathway Antiplatelet Agents
Injured cells released Thromboplastin w/c Therapeutic
activates clotting factors to form a clot on Actions
the outside of blood vessels. Inhibit platelet adhesion & aggregation by blocking receptor
Clot Resolution and Anticlotting sites on platelet membrane, preventing platelet–platelet
Process interaction or the interaction of platelets w/ other clotting
Antithrombin III chemicals.
Prevents formation of thrombin, Anagrelide - blocks production of platelets in bone marrow.
thus stopping breakdown of Indications
fibrin Used effectively to treat cardiovascular diseases that are prone
threads. to produce occluded vessels; for maintenance of venous &
Plasmin or Fibrinolysin arterial grafts; to prevent cerebrovascular occlusion; & as
Dissolves clots to ensure free adjuncts to thrombolytic therapy in treatment of MI &
movement of blood thru the system. prevention of
A protein-dissolving substance that reinfarction after MI.
breaks down Prescriber’s choice of drug depends on intended use & patient’s
fibrin framework of tolerance of the associated adverse effects.
blood clots & opens up vessels. Pharmacokinetics
Plasminogen - precursor of Plasmin. Abciximab, eptifibatide, & tirofiban are administered IV.
Plasmin Antiplatelet agents that are administered orally include
helps to keep anagrelide,
blood vessels aspirin, cilostazol, clopidogrel, sulfin- pyrazone, and ticlopidine.
open and Dipyridamole is used orally or as an IV agent.
functional. These drugs are generally well absorbed & highly bound to
Found in lungs plasma proteins.
& uterus in high Metabolized in liver & excreted in urine, & they tend to enter
level. breast milk.

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106 BY TONS AND MADS
Contraindications Fondaparinux I(newest)inhibits factor Xa & blocks the clotting
& Cautions cascade to prevent clot formation, supplied in prefilled
Allergy to the drug; pregnancy bec of potential for increased syringes, making it convenient for patients who self- administer
bleeding; (be used during pregnancy only if benefits to the the drug at home.
mother clearly outweigh the potential risks to the fetus); Indications
lactation bec of potential adverse effects on fetus or neonate; if Warfarin: maintain a state of anticoagulation in situations in w/c
they patient is susceptible to potential dangerous clot formation.
are needed by a breast-feeding mother, she should find another Heparin: for acute treatment & prevention of venous thrombosis
method of feeding the baby. & pulmonary embolism; treatment of atrial fibrillation w/
Caution should be used: presence of any known bleeding embolization; prevention of clotting in blood samples & in
disorder bec of risk of excessive blood loss; recent surgery bec dialysis & venous tubing; & diagnosis & treatment of
of disseminated
risk of increased bleeding in unhealed vessels; & closed head intravascular coagulation (DIC). Because heparin must be
injuries bec of risk of bleeding from injured vessels in the brain. injected, it’s often not the drug of choice for outpatients, who
Anagrelide should be used: history of thrombocytopenia bec it would be responsible for injecting the drug several times during
decreases production of platelets in bone marrow. Platelet the day. Patients may be started on heparin in the acute
levels should be checked regularly to monitor for situation & then switched to the oral drug warfarin.
thrombocytopenia if a patient is on this drug. Pharmacokinetics
Adverse Effects Heparin is injected IV or subcu & has almost immediate onset of
Bleeding, (often occurs as increased bruising & bleeding while action. It’s excreted in urine. Warfarin is used orally. All
brushing teeth), headache, dizziness, & weakness; the cause other drugs in this class (heparin, antithrombin, argatroban,
of these reactions is not understood. Nausea & GI distress may desirudin, fondaparinux, and bivalirudin) are given parenterally.
occur bec of direct irritating effects of the oral drug on the GI Warfarin is readily absorbed thru GIT, metabolized in liver, &
tract. Skin rash, another common effect, may be related to excreted in urine & feces.
direct drug effects on the dermis. Warfarin’s onset of action is about 3 days; its effects last for 4 to
Drug-drug 5 days. Because of the time delay, warfarin is not the drug
Interactions Risk of excessive bleeding increases if any of these of choice in an acute situation, but it is convenient & useful for
drugs is combined with another drug that affects blood clotting. prolonged effects.
Drug-Food Because antithrombin is an exogenous form of a naturally
Interactions occurring anticoagulant, the body handles it in the same way
None is mentioned. that
Antiplatelet Agents it handles naturally occurring antithrombin.
Nursing Considerations Nursing Diagnosis Planning Argatroban is given as a continuous IV infusion.
Assess for cautions or contraindications. Desirudin and fondaparinux are absorbed quickly from SC sites
Assess baseline status before beginning and metabolized and excreted by the kidneys.
therapy to determine any potential adverse Bivalirudin is given IV and is excreted through the kidneys.
effects. This includes body temperature; skin Anticoagulants
color, lesions, and temperature; affect, Contraindications
orientation, and reflexes; pulse, blood & Cautions
pressure, and perfusion; respirations and Allergy to the drugs. Should not be used w/ any conditions that
adventitious sounds; complete blood count could be compromised by increased bleeding tendencies,
(CBC); and clotting studies. including hemorrhagic disorders, recent trauma, spinal puncture,
Risk for Injury related GI ulcers, recent surgery, intrauterine device placement,
to bleeding effects or tuberculosis, presence of indwelling catheters, & threatened
CNS effects • Acute abortion.
Pain related to GI or Warfarin is contraindicated in pregnancy bec fetal injury & death
CNS effects have occurred; in lactation, because of potential risk to the
Deficient Knowledge baby; & in renal or hepatic disease, which could interfere w/ the
regarding drug metabolism & effectiveness of these drugs.
therapy Although some adverse fetal effects have been reported with its
use during pregnancy, heparin does not enter breast milk,
Antiplatelet Agents and so it is the anticoagulant of choice if one is needed during
Implementation with Rationale Evaluation lactation.
Provide small, frequent meals to relieve GI discomfort if GI Caution should be used in patients w/ heart failure,
upset is a problem. thyrotoxicosis, senility, or psychosis bec of potential for
Provide comfort measures and analgesia for headache to relieve unexpected
pain and effects & in patients with diarrhea or fever, w/c could alter
improve patient compliance with the drug regimen. normal clotting process by, respectively, loss of vitamin K from
Suggest safety measures, including the use of an electric razor the
and avoidance intestine or activation of plasminogen.
of contact sports, to decrease the risk of bleeding. Caution should be used in pregnancy with anticoagulants other
Monitor platelet count if the patient is using anagrelide to detect than warfarin because of the potential for adverse effects;
thrombocytopenia and increased risk of bleeding. benefit should outweigh potential risks.
Provide increased precautions against bleeding during invasive Adverse Effects
procedures; Bleeding, ranging from bleeding gums w/ tooth brushing to
use pressure dressings and ice to decrease excessive blood loss severe internal hemorrhage. Patients need teaching about
caused by administration, disposal of the syringes, & signs of bleeding to
anticoagulation. watch for.
Mark the chart of any patient receiving this drug to alert medical Periodic blood tests will be needed to assess the effects of the
staff that there drug on the body. Clotting times should be monitored closely
is a potential for increased bleeding. to avoid these problems. Patient should also be monitored for
Provide thorough patient teaching, including the name of the warfarin overdose.
drug, dosage Serious adverse effects may occur when adding or taking away
prescribed, measures to avoid adverse effects, warning signs of a drug from the regimen of a patient receiving warfarin w/o
problems, the careful patient monitoring & adjustment of warfarin dose .
need for periodic monitoring and evaluation, and the need to Warfarin has been associated w/ alopecia & dermatitis, as well
wear or carry a as
MedicAlert notification, to enhance patient knowledge about bone marrow depression &, less frequently, prolonged & painful
drug therapy and erections.
to promote compliance with the drug regimen. Nausea, GI upset, diarrhea, and hepatic dysfunction also may
Offer support and encouragement to help the patient deal with occur secondary to direct drug toxicity.
the diagnosis Drug-drug
and the drug regimen. Interactions
Increased bleeding can occur if heparin is combined w/ oral
Anticoagulants anticoagulants, salicylates, penicillins, or cephalosporins.
Therapeutic Decreased anticoagulation can occur if heparin is combined with
Actions nitroglycerin.
Interfere w/ normal cascade of events involved in the clotting Warfarin has documented drug–drug interactions w/ a vast
process. Warfarin, the only oral drug in this class, causes a number of other drugs. It is a wise practice never to add or take
decrease in the production of vitamin K–dependent clotting away a drug from the regimen of a patient receiving warfarin
factors in the liver. The eventual effect is a depletion of these without careful patient monitoring & adjustment of the warfarin
clotting factors & a prolongation of clotting times. dose to prevent serious adverse effects.
Heparin, argatroban, & bivalirudin block the formation of Drug-Food
thrombin from prothrombin. Interactions None is mentioned.
Antithrombin interferes w/ the formation of thrombin from Anticoagulants
prothrombin; it is a naturally occurring anticoagulant. Nursing Considerations Nursing Diagnosis Planning

20
106 BY TONS AND MADS
Allergies to these drugs. upset, rash).
Screen for conditions that could be exacerbated by increased
bleeding tendencies, including hemorrhagic disorders, recent Thrombolytic Agents
trauma, spinal puncture, GI ulcers, recent surgery, intrauterine Therapeutic
device placement, tuberculosis, presence of indwelling Actions
catheters, and threatened abortion. Also screen for pregnancy To activate the natural anticlotting system—conversion of
to ensure that benefits outweigh any potential risks plasminogen to plasmin. The activation of this system breaks
(contraindicated with warfarin); lactation, because of the down fibrin threads & dissolves any formed clot.
potential for risks to the baby (use of heparin is suggested if an Thrombolytics are effective only if the patient has plasminogen
anticoagulant is needed during lactation); renal or hepatic in the plasma.
disease, which could interfere with the metabolism and Indications Refer to table 48.1.
effectiveness of these drugs; HF; thyrotoxicosis; senility or Pharmacokinetics Given IV and are cleared from the body after
psychosis because of the poten- tial for unexpected effects; liver metabolism. They cross the placenta, but it is not known
and diarrhea or fever, which could alter the normal clotting whether they
process. enter breast milk
Assess baseline status before beginning therapy to deter- mine Contraindications
any potential adverse effects. This includes body temperature; & Cautions
skin color, lesions, and temperature; affect, orientation, and Presence of allergy to any of these drugs.
reflexes; pulse, blood pressure, and per- fusion; respirations Any condition that could be worsened by the dissolution of clots,
and adventitious sounds; clotting studies, renal and hepatic including recent surgery, active internal bleeding,
function tests, CBC, and stool guaiac; and electrocardiogram cerebrovascular accident (CVA) within the last 2 months,
(ECG), if appropriate. aneurysm, obstetrical delivery, organ biopsy, recent serious GI
Risk for Injury related bleeding, rupture of a noncompressible blood vessel, recent
to bleeding effects major trauma (includng cardiopulmonary resuscitation), known
and bone marrow blood clotting defects, cerebrovascular disease, uncontrolled
depression hypertension, and liver disease (which could affect normal
Disturbed Body clotting factors and the production of plasminogen).
Image related to These drugs are also contraindicated in pregnancy because of
alopecia and skin the possible adverse effects on the fetus or neonate. These
rash drugs should not be used during pregnancy unless the bene- fits
Ineffective Tissue to the mother clearly outweigh the potential risks to the
Perfusion (Total Body) fetus. Caution should be used during lactation because of the
related to blood potential risk for bleeding effects in the nursing baby.
loss Adverse Effects
Deficient Knowledge The most common adverse effect associated with the use of
regarding drug thrombolytic agents is bleeding. Patients should be monitored
therapy closely for the occurrence of cardiac arrhythmias (with coro-
nary reperfusion) and hypotension. Hypersensitivity reac- tions
Implementation with Rationale Evaluation are not uncommon; they range from rash and flushing to
Evaluate for therapeutic effects of warfarin—prothrombin time bronchospasm and anaphylactic reaction.
(PT) 1.5 to 2.5 times the control value or ratio Drug-drug
of PT to INR (International Normalized Ratio) of 2 to 3—to Interactions The risk of hemorrhage increases if thrombolytic
evaluate the effectiveness of the drug dose. agents are used with any anticoagulant or antiplatelet drug.
Evaluate for therapeutic effects of heparin—whole blood clotting Drug-Food
time (WBCT) 2.5 to 3 times control or Interactions None is mentioned
activated partial thromboplastin time (APTT) 1.5 to 3 times the Thrombolytic Agents
control value—to evaluate the effectiveness Nursing Considerations Nursing Diagnosis Planning
of the drug dose. Assess for any known allergies to these drugs
Evaluate the patient regularly for any sign of blood loss & contraindications.
(petechiae, bleeding gums, bruises, dark-colored Assess baseline status before beginning
stools, dark-colored urine) to evaluate the effectiveness of the therapy to determine any potential adverse
drug dose and to determine the need to effects. Assess the following: body
consult with the prescriber if bleeding becomes apparent. temperature; skin color, lesions, and
Establish safety precautions to protect the patient from injury. temperature; affect, orientation, and reflexes;
Provide safety measures, such as use of an electric razor and pulse, blood pressure, and perfusion;
avoidance of contact sports, to decrease the respirations and adventitious sounds; and
risk of bleeding. clotting studies, renal and hepatic function
Provide increased precautions against bleeding during invasive tests, CBC, guaiac test for occult blood in
procedures; use pressure dressings; avoid intramuscular stool, and ECG.
injections; and do not rub SQ injection sites Risk for Injury related
because the state of anticoagulation increases the risk of blood to clot-dissolving
loss. effects
Mark the chart of any patient receiving this drug to alert the Ineffective Tissue
medical staff that there is a potential for Perfusion (Total Body)
increased bleeding. related to possible
Maintain antidotes on standby (protamine sulfate for heparin, blood loss
vitamin K for warfarin) in case of overdose. Decreased Cardiac
Monitor the patient carefully when any drug is added to or Output related to
withdrawn from the drug regimen of a patient bleeding and
taking warfarin because of the risk of drug–drug interactions arrhythmias
that would change the effectiveness of the Deficient Knowledge
anticoagulant. regarding drug
Make sure that the patient receives regular follow-up and therapy
monitoring, including measurement of clotting
times, to ensure maximum therapeutic effects. Implementation with Rationale Evaluation
Provide thorough patient teaching, including the name of the Arrange to administer tenecteplase or streptokinase to reduce
drug, dosage prescribed, measures to avoid mortality associated with acute MI as
adverse effects, warning signs of problems, the need for periodic soon as possible after the onset of symptoms because the
monitoring and evaluation, and the need timing for the administration of tenecteplase
to wear or carry a MedicAlert notification, to enhance patient or streptokinase is critical to resolve the clot before permanent
knowledge about drug therapy and to promote damage occurs to the myocardial cells.
compliance with the drug regimen. Discontinue heparin if it is being given before administra- tion of
Offer support and encouragement to help the patient deal with a thrombolytic agent, unless
the diagnosis and the drug regimen. specifically ordered for coronary artery infusion, to prevent
Monitor patient response to excessive loss of blood.
the drug: increased Evaluate the patient regularly for any sign of blood loss
bleeding time (warfarin, PT (petechiae, bleeding gums, bruises, darkcolored stools,
1.5 to 2.5 times the control dark-colored urine) to evaluate drug effectiveness and for the
value or PT/INR ratio of 2 to need to consult with the
3; heparin, WBCT of 2.5 to prescriber if blood loss becomes apparent.
3 times the control value or Monitor coagulation studies regularly; consult with the prescriber
APTT of 1.5 to 3 times the to adjust the drug dose appropriately.
control value). Institute treatment within 6 hours after the onset of symptoms
Monitor for adverse effects of acute MI to achieve optimum
(bleeding, bone marrow therapeutic effectiveness.
depression, alopecia, GI

21
106 BY TONS AND MADS
Arrange to type and cross-match blood in case of serious blood Replace clotting factors that are either genetically missing or low
loss that requires whole-blood in a particular type of hemophilia. The drug of choice
transfusion. depends on the particular hemophilia that is being treated.
Monitor cardiac rhythm continuously if the drug is being given Indications
for acute MI because of the risk of Antihemophilic factor is factor VIII, the clotting factor that is
alteration in car- diac function; have life support equipment on missing in classic hemophilia (hemophilia A). This agent is used
standby as needed. to correct or prevent bleeding episodes or to allow necessary
Provide increased precautions against bleeding during invasive surgery.
procedures, use pressure dressings and Coagulation factor VIIa and factor IX complex are used for
ice, avoid intramuscular injections, and do not rub SQ injection patients with hemophilia A or B.
sites because of the risk of increased Factor IX complex contains plasma fractions of many of the
blood loss in the anti- coagulated state. clotting factors & increases blood levels of factors II, VII, IX, &
Mark the chart of any patient receiving this drug to alert medical X.
staff that there is a potential for Factor XIII replaces factor XIII in patients w/ congenital
increased bleeding. deficiency. Anti-inhibitor coagulant complex is used to control
Provide thorough patient teaching, including the name of the spontaneous bleeding or to cover surgical procedures in patients
drug, dosage prescribed, measures to w/ hemophilia A & B w/ inhibitors.
avoid adverse effects, warning signs of problems, and the need Antihemophilic factor Fc fusion protein is used to prevent &
for peri- odic monitoring and evaluation, control bleeding episodes in adults & children w/ hemophilia A
to enhance patient knowledge about drug therapy and to (factor VIII deficiency), & antihemophilic factor porcine
promote compliance with the drug regimen. sequence is used for treating bleeding episodes in adults w/
Offer support and encouragement to help the patient deal with acquired
the diagnosis and the drug regimen. hemophilia A. The drug of choice for any given patient is
determined by his or her particular coagulation abnormalities.
Other Drugs Affecting Clot Formation Pharmacokinetics Replace normal clotting factors & are
Low-MolecularWeight Heparins processed as such by the body. They must be given IV & are
Inhibit thrombus & clot formation by blocking factors Xa and IIa. processed by the body in
Because of the size & nature of the molecules, these drugs the same way that naturally occurring clotting factors are
do not greatly affect thrombin, clotting, or the PT; therefore, processed in the plasma, usually with a half-life of 24 to 36
they cause fewer systemic adverse effects. hours.
Have been found to block angiogenesis, the process that allows Contraindications
cancer (CA) cells to develop new blood vessels; studied as & Cautions
possible adjuncts to CA chemotherapy. Known allergy to mouse proteins. Factor IX is contraindicated in
Indicated for specific uses in prevention of clots & emboli the presence of liver disease w/ signs of intravascular
formation after certain surgeries or prolonged bed rest. coagulation or fibrinolysis to prevent serious aggravation of
Nursing care to be given is similar to that of a patient receiving these disorders. Coagulation factor VIIa is contraindicated with
heparin. The drug is given just before (or just after) the known allergies to mouse, hamster, or bovine products to
surgery and then is continued for 7 to 14 days during the prevent hypersensitivity reactions.
postoperative recovery process. Not recommended for use during lactation, & caution should be
Caution must be used to avoid combining these drugs w/ used during pregnancy bec of potential for adverse effects
standard heparin therapy; serious bleeding episodes & deaths on the baby or fetus. May be used during pregnancy only if
have been reported when this combination was inadvertently benefit to the mother outweighs potential risk to the fetus. It’s
used. Low-molecular-weight heparins include dalteparin & recommended that another method of feeding the baby be used
enoxaparin. if these drugs are needed during lactation. Because these
Anticoagulant drugs are used to prevent serious bleeding problems or treat
Adjunctive bleeding episodes, there are few contraindications to their use.
Therapy Adverse Effects Headache, flushing, chills, fever, and lethargy
Include lepirudin, protamine sulfate, prothrombin complex may occur as a reaction to the injection of a foreign protein.
concentrate, & vit K. The “Safe Medication Administration” box Nausea and
under “Adverse Effects” for anticoagulants provides additional vomiting may also occur, as may stinging, itching, and burning
information about vitamin K and protamine sulfate. at the site of the injection.
Lepirudin (Refludan) is an IV drug developed to treat a rare Drug-drug
allergic reaction to heparin. An allergy to heparin precipitates a Interactions
heparin-induced thrombocythemia w/ associated None is mentioned.
thromboembolic disease. Drug-Food
Lepirudin directly inhibits thrombin, blocking thromboembolic Interactions None is mentioned.
effects of this reaction. A 0.4-mg/kg initial IV bolus followed by Antihemophilic Agents
a continuous infusion of 0.15 mg/kg for 2 to 10 days is the usual Nursing Considerations Nursing Diagnosis Planning
treatment. Monitored patient for bleeding from any site and Assess for the following conditions, which
for the development of direct hepatic injury. could be cautions or contraindications to use
Hemorrheologic of the drug: any known allergies to these
Agent drugs or to mouse proteins with
Pentoxifylline (generic) is known as a hemorrheologic agent, or antihemophilic factor and liver disease.
a drug that can induce hemorrhage. It is a xanthine that, like Assess baseline status before beginning
caffeine and theophylline, decreases platelet aggregation and therapy to determine any potential adverse
decreases the fibrinogen concentration in the blood. These effects.
effects can decrease blood clot formation and increase blood Assess body temperature; skin color, lesions,
flow through narrowed or damaged vessels. The mechanism and temperature; affect, orientation, and
of action by which pentoxifylline does these things is not known. reflexes; pulse, blood pressure, and perfusion;
It is one of the few drugs found to be effective in treating respirations and adventitious sounds; clotting
intermittent claudication, a painful vascular problem of the legs. studies; and hepatic function tests.
Because pentoxifylline is a xanthine, it is associated with many Ineffective tissue
CV stimulatory effects; patients with underlying CV problems perfusion (total body)
need to be monitored carefully when taking this drug. related to changes in
Pentoxifylline can also cause headache, dizziness, nausea, and coagulation
upset Acute pain related to
stomach. It is taken orally three times a day for at least 8 weeks GI, CNS, or skin
to evaluate its effectiveness. See Table 48.1 for additional effects
information about this drug. Anxiety or fear related
Drugs Used to Control Bleeding to the diagnosis and
Hemophilia - in which there is a genetic lack of clotting factors use of blood-related
that leaves the products
patient vulnerable to excessive bleeding with any injury. Deficient knowledge
Liver disease - in which clotting factors and proteins needed for regarding drug
clotting are not therapy
produced.
Bone marrow disorders - in which platelets are not formed in Implementation with Rationale Evaluation
sufficient Ensure that appropriate clotting factor is being used for the
quantity to be effective. patient to ensure
Note: Bleeding disorders are treated w/ clotting factors & drugs therapeutic effectiveness and prevent inappropriate increase in
that promote other clotting
the coagulation process. These include antihemophilic agents & factors.
hemostatic Administer by the IV route only to ensure therapeutic
agent. effectiveness. Monitor clinical
response and clotting factor levels regularly to arrange to adjust
Antihemophilic Agents dose as needed.

22
106 BY TONS AND MADS
Monitor the patient for any sign of thrombosis to arrange to use acid is associated
comfort and w/ development
support measures as needed (e.g., support hose, positioning, of hyper
ambulation, exercise). coagulation
Decrease the rate of infusion if headache, chills, fever, or states if it is
tingling occurs to prevent combined w/ oral
severe drug reaction; in some individuals, the drug will need to contraceptives or
be discontinued. estrogens.
Arrange to type and crossmatch blood in case of serious blood Risk of bleeding
loss that will require increases if it is
whole-blood transfusion. given with
Mark the chart of any patient receiving this drug to alert medical heparin.
staff that there is a Topical (Local)
potential for increased bleeding. Hemostatic
Provide thorough patient teaching Agents
Offer support and encouragement Use thrombin w/ caution for those patients who are
allergic to bovine products. Because thrombin comes
from animal sources, it may precipitate an allergic
HEMOSTATIC response; the patient needs to be carefully monitored
AGENTS THERAPEUTIC ACTIONS & INDICATIONS for such a reaction.
PHARMACOKINETICS Many of potential allergic reactions associated with
Systemic bovine thrombin will be decreased as a result of
Hemostatic approval for thrombin recombinant to be made using
Agents recombinant DNA technology. Safety for use of
Used to prevent body-wide or systemic clot thrombin recombinant in children has not been
breakdown, thus preventing blood loss in situations established.
in w/c serious systemic bleeding could occur, or Use of absorbable gelatin and
hyperfibrinolysis. microfibrillar collagen can pose a risk of
Aminocaproic acid inhibits plasminogen-activating infection because bacteria can become
substances & has some antiplasmin activity. When trapped in the vascular area when the
taking the oral form of aminocaproic acid, take 10 sponge is applied.
tablets in the first hour & then continue taking the Immediate removal of the sponge and
drug around the clock. See Table 48.4 for usual cleaning of the area can help to decrease
indications for aminocaproic acid. this risk.
Aminocaproic acid is available in oral and IV forms. It is rapidly There are no
absorbed and widely distributed throughout the body. It is reported drug–
excreted largely unchanged in urine, with a half-life of 2 hours. drug interactions
Topical (Local) with the topically
Hemostatic applied
Agents hemostatic
Use for surface injuries that involve so much damage agents.
to small vessels in the area that clotting does not SYSTEMIC HEMOSTATIC AGENTS
occur & blood is slowly & continually lost. Nursing Considerations Nursing Diagnosis Planning
Absorbable gelatin & microfibrillar collagen are available in Assess for cautions & contraindications.
sponge form & are applied directly to the injured area until the Assess baseline status before beginning
bleeding stops. therapy to determine any potential adverse
Human fibrin sealant (Artiss) is available in spray form & applied effects.
in a thin layer onto the graft bed. Assess body temp; skin color, lesions,
Evicel is sprayed directly onto any active bleeding site. temperature; affect, orientation, & reflexes;
Thrombin, w/c is derived from bovine sources, is a solution that pulse, BP, & perfusion; respirations &
is adventitious sounds; bowel sounds & normal
applied topically & mixed in w/ the blood. output; urinalysis & clotting studies; & renal &
Thrombin recombinant is also a solution & is applied directly to hepatic function.
the bleeding site surface in conjunction w/ absorbable gelatin Disturbed sensory
sponge; the amount needed varies w/ the area of tissue to be perception related to
treated. CNS effects Acute
HEMOSTATIC AGENTS CONTRAINDICATIONS & CAUTIONS pain related to GI,
ADVERSE EFFECTS DRUG-DRUG CNS, or muscle
INTERACTION effects
Systemic Risk for injury related
Hemostatic to CNS or bloodclotting effects
Agents Deficient knowledge
Aminocaproic acid is contraindicated in the presence of regarding drug
allergy to the drug to prevent hypersensitivity reactions & therapy
w/ acute DIC bec of risk of tissue necrosis.
Caution should be used in cardiac disease bec of the risk SYSTEMIC HEMOSTATIC AGENTS
of arrhythmias & in renal & hepatic dysfunction, w/c could Implementation with Rationale Evaluation
alter excretion of this drug & normal clotting processes. Monitor clinical response and clotting factor levels regularly to
Although safety for use of this drug during pregnancy has arrange to adjust
not been established, it should be used only if benefits to dose as needed.
mother clearly outweigh the potential risks to neonate Monitor the patient for any sign of thrombosis to arrange to use
bec of the potential for adverse effects on the fetus. comfort and
It is recommended that nursing mothers use a different support measures as needed (e.g., support hose, positioning,
method for feeding the baby if this drug is used because ambulation, exercise).
of the potential for adverse effects on the baby. Orient the patient and offer support and safety measures if
Most common adverse effect associated with hallucinations or
systemic hemostatic agents is excessive psychoses occur to prevent patient injury.
clotting. Offer comfort measures to help the patient deal with the effects
CNS effects of aminocaproic acid can include of the drug. These
hallucinations, drowsiness, dizziness, headache, include small, frequent meals, mouth care, environmental
and psychotic states, all of w/c could be related controls, and safety
to changes in cerebral blood flow associated measures.
with changes in clot dissolution. Provide thorough patient teaching, including the name of the
GI effects, including nausea, cramps, and drug, dosage
diarrhea, may be related to excessive clotting in prescribed, measures to avoid adverse effects, warning signs of
the GI tract, causing reflex GI stimulation. problems, and the
Weakness, fatigue, malaise, and muscle pain can need for periodic monitoring and evaluation, to enhance patient
occur as small clots build up in muscles. knowledge about
Intrarenal obstruction and renal dysfunction drug therapy and to promote compliance with the drug regimen.
have also been reported. Offer support and encouragement to help the patient deal with
Aminocaproic the diagnosis and
the drug regimen.
Part 8: Drugs Used to Treat Anemia
Anemia alteration in erythropoiesis (process
Low levels of RBC resulting from of RBC production), w/c occurs in the

23
106 BY TONS AND MADS
myeloid tissue of the bone marrow. Darbepoetin alfa: for anemias associated w/ chronic renal
Erythrocytes (RBCs) - carry O2 to failure, including patients receiving dialysis, &
tissues & remove CO2 for delivery to anemia induced by CA chemotherapy.
the lungs. Methoxy polyethylene glycolepoetin beta is an injection indicated
Lifespan of mature RBC - 120 days to stimulate erythropoiesis in people w/
RBC are lysed in the liver, spleen, or chronic renal disease. Adults may be on or off dialysis
bone marrow. treatments. Also indicated for pedia patients 5 to 17
To produce healthy RBCs, bone marrow y.o on hemodialysis when converting from another stimulating
must have: agent.
A. Adequate iron - used in forming hgb Pharmacokinetics
rings to carry O2. Given IV or subcu injection.
B. Minute amounts of Vit B12 & folic acid - Epoetin alfa is metabolized in the serum thru normal process
to form strong supporting structure that the body uses to clear erythropoietin. It
that survive being battered thru blood has a slow onset & peaks in 5 to 24 hours, & its duration of
vessels for 120 days effect is usually 24 hours. It has a half-life of 4 to
C. Essential amino acids & carbohydrates 13 hours & is excreted in the urine.
- to complete the hgb rings, cell Darbepoetin alfa has a half-life of 21 hours after IV
membrane, & basic structure. administration or 49 hours after subcu administration. It
TYPES OF ANEMIA reaches peak effects in 14 hours (if given IV) or 34 hours
1. Iron (subcutaneously). Duration of effects is 24 to 72
Deficiency hours, and excretion is through the urine.
Anemia It is not known whether epoetin alfa enters breast milk. Methoxy
Lack of adequate healthy RBCs. Usually treated with iron polyethylene glycolepoetin beta has a long
replacement therapy. half-life: 119 hours (IV) and 124 hours (subcutaneously). The
Person with this type of anemia may complain of being tired due onset of hemoglobin increase after
to insufficient O2 delivery to the tissues. administration is 7 to 15 days after the first dose. Steady-state
Commonly seen in: Menstruating women, who lose RBCs levels are achieved with dosing every 2 wks.
monthly; Pregnant & lactating women, who have increased Drugs Used to Treat Anemias
demands for iron; Rapidly growing adolescents, esp those who Contraindications
do not have nutritious diet; Persons w/ GI bleeding, & Cautions
including individuals w/ slow bleeding associated with use of Uncontrolled hypertension bec of risk of even further
nonsteroidal antiinflammatory drugs. hypertension when RBC numbers increase & pressure
2. Megaloblastic w/in the vascular system increases, w/ known hypersensitivity to
Anemias any component of the drug to avoid
A condition in w/c the bone marrow produces unusually large, hypersensitivity reactions, & w/ lactation because of potential for
structurally abnormal, immature RBCs (megaloblasts). allergic-type reactions w/ neonate.
Characterized by very large RBCs. Large RBCs crowded in bone No adequate studies in pregnancy, so use should be limited to
marrow & fewer RBC are produced, increasing the amount those situations in w/c benefit to mother
of immature cells in circulation. clearly outweighs the potential risk to fetus.
Result from insufficient amounts of folic acid or vitamin B12 to Use caution when administering any of these drugs to patients
adequately create the stromal structure needed in a healthy w/ normal renal functioning & adequate levels
RBC, causing a slowing of nuclear DNA synthesis. This effect of erythropoietin bec of rebound decrease in erythropoietin that
occurs in rapidly dividing cells such as the bone marrow. will occur & when administering them to a
2.a. Folic patient w/ anemia & normal renal function bec this can cause
Acid more severe anemia.
Deficiency Adverse Effects
Lack of folic acid (a Vit B) in the blood. Folic helps body make CNS effects of headache, fatigue, asthenia, & dizziness & the
RBCs & is essential for cell division in all types of tissue. Its potential for serious seizures. These effects
deficiencies are noticed 1st in rapidly growing cells: CA tissues,may be the result of a cellular response to the glycoprotein.
GIT, & in the bone marrow. Nausea, vomiting, & diarrhea are also common effects.
Folic acid deficiency in pregnancy will lead to neural tube defects
Cardiovascular symptoms: hypertension, edema, & possible
in fetus; treated w/ folic acid/folate admin. chest pain, all of w/c may be related to increase
Folic acid is found in green leafy vegetables, milk, eggs, & liver.
in RBC numbers changing the balance w/in CV system. Serious
2.b. Vit B12 CV effects & increased risk for deep vein
Deficiency thrombosis (DVT) have been seen when hgb becomes higher
Also known as cobalamin deficiency, a condition that develops than 11 g/dL.
when body can't make enough healthy RBCs bec of lack of Patients receiving IV administration must be monitored for
vit B12. Vit. B12 is needed to make healthy RBCs, WBCs, & possible clotting of access line r/t direct cellular
platelets. effects of the drug. Rapid growth of cancer is seen when hgb
Failure of gastric mucosa to produce Vit B12 & intrinsic factor becomes higher than 11 g/dL.
will result to PERNICIOUS ANEMIA; treated w/ parenteral or Postmarketing studies showed that pure red cell aplasia
nasal Vit B12. associated with erythropoietin-neutralizing
3. Sickle antibodies could occur with all of these products.
Cell or Drug-drug
Hemolytic Interactions Never be mixed in solution with any other drugs
Anemia because of a risk of interactions in the solution.
Characterized by a genetically inherited hemoglobin S, w/c gives Drug-Food
RBCs sickle-shaped appearance. Interactions None is mentioned.
Fewer than normal RBCs are produced w/c are unable to carry Drugs Used to Treat Anemias
O2 efficiently. Sickle-shaped RBCs can become lodged in tiny Nursing Considerations Nursing Diagnosis Planning
blood vessels, where they stack up on one another & occlude Assess for contraindications or cautions.
vessel leading to anoxia & infarction of tissue in that area, w/c Perform physical assessment to establish
is characterized by severe pain & an acute inflammatory baseline before beginning & during therapy to
reaction—a condition often called sickle cell crisis (the patient determine drug effectiveness & evaluate any
may potential adverse effects.
even have ulcers on the extremities as a result of such Assess neurological status, including affect,
occlusions). orientation, & muscle strength, to identify possible
Hydroxyurea has been found to be effective in decreasing acute adverse CNS effects.
exacerbations. Monitor v/s, including pulse & BP, for changes, &
of this disease in adults. assess CV status to identify possible CV effects, &
inspect lower extremities for evidence of edema,
Drugs Used to Treat Anemias w/c could indicate a change in CV function.
Epoetin alfa acts like the natural glycoprotein erythropoietin to Assess respirations & auscultate lung sounds for
stimulate the production of RBCs in the bone adventitious breath sounds for early detection of
marrow. Darbepoetin alfa is an erythropoietin-like protein changes in CV function.
produced in Chinese hamster ovary cells w/ the Monitor lab test results, including renal function
use of recombinant DNA technology. tests, CBC, hct, iron concentration, transferrin, &
Indications electrolyte levels, to evaluate effectiveness of
Epoetin: treatment of anemia associated w/ renal failure & for therapy & to ensure that hgb level does not
patients on dialysis, for anemia associated w/ exceed 11 g/dL. Be aware of variations in
AIDS therapy, & for anemia associated w/ CA chemotherapy hematological test results associated w/ race.
when bone marrow is depressed & kidneys may Nausea related to
be affected by toxic drugs. Not approved to treat other anemias adverse GI effects
& not a replacement for whole blood in the Diarrhea related to GI
emergency treatment of anemia. effects
Risk for injury related to

24
106 BY TONS AND MADS
CNS effects adequate dietary intake of iron. Use in pregnancy & lactation to
Risk for imbalanced fluid meet increase demand of iron.
volume related to CV Indicated for the treatment of iron deficiency anemias & may
effects Deficient also be used as adjunctive therapy in patients receiving an
knowledge regarding erythropoiesis-stimulating drug. The drug of choice depends on
drug therapy the prescriber’s personal preference and experience and often
The patient will receive on
the best therapeutic what kinds of samples are available to give the patient.
effect from the drug Pharmacokinetics
therapy. Ferrous aspartate, ferrous fumarate, ferrous gluconate, ferrous
The patient will have sulfate, & ferrous sulfate exsiccated are available for oral
limited adverse effects administration. Iron dextran is a parenteral form of iron given by
to the drug therapy. the Z-track method, w/c may be used if oral form cannot be
The patient will have an given or
understanding of the tolerated. Patients w/ severe GI absorption problems may
drug therapy, adverse require this form of iron.
effects to anticipate, Iron sucrose, ferumoxytol, & sodium ferric gluconate complex
and measures to relieve are given IV specifically for those undergoing chronic
discomfort and improve hemodialysis or
safety. who are in renal failure & not on dialysis but are receiving
Drugs Used to Treat Anemias supplemental erythropoietin therapy.
Implementation with Rationale Evaluation Iron is primarily absorbed from small intestine by an active
Confirm the chronic, renal nature of the patient’s anemia beforetransport system. Most of oral drug taken is lost in feces, but
administering the drug to slowly some
treat renal failure anemia to ensure proper use of the drug. of the metal is absorbed into the intestine & transported to bone
Give epoetin alfa three times per week, either IV or marrow. It ake 2-3 weeks to see improvement & up to 6 -10
subcutaneously, to achieve appropriate months
therapeutic drug levels. Administer darbepoetin alfa once per for a return to stable iron level once a deficiency exists.
week, subcutaneously or IV. Contraindications & Cautions
Provide the patient with a calendar of marked days to aid in Allergy (severe hypersensitivity reactions have been associated
remembering dates for injection w/ parenteral form). Hemochromatosis (excessive iron);
and promote increased compliance with the drug regimen. hemolytic
Do not mix with any other drug solution to avoid potential anemias, w/c may increase serum iron levels & cause toxicity;
incompatibilities. normal iron balance bec the drug will not be absorbed & will just
Monitor access lines for clotting and arrange to clear line as pass
needed. Ensure that prescribed thru body; & peptic ulcer, colitis, or regional enteritis bec the
laboratory testing, such as hematocrit levels, is completed drug can be directly irritating to these tissues & can cause
before drug administration to exacerbation
determine correct dose. If the patient does not respond within 8of diseases.
weeks, reevaluate the Adverse Effects
cause of anemia. Anticipate a target hemoglobin of 11 g/dL. GI irritation; includes GI upset, anorexia, nausea, vomiting,
Evaluate iron stores before and periodically during therapy diarrhea, dark stools, & constipation. W/ increasing serum
because supplemental iron may levels, iron can
be needed as the patient makes more RBCs. Monitor blood be directly toxic to CNS, causing coma & even death. Parenteral
pressure due to risk for iron is associated w/ severe anaphylactic reactions, local
hypertension. irritation,
Maintain seizure precautions on standby in case seizures occur staining of tissues, & phlebitis. Ferumoxytol is a supermagnetic
as a reaction to the drug. iron oxide that can alter MRI images & interpretation for up to 3
Provide comfort measures to help the patient tolerate the drug mos
effects. These include small, after administration; patients should be cautioned to report
frequent meals to help minimize nausea and vomiting, readily taking iron before undergoing any medical testing.
available access to bathroom Drug-drug
facilities should diarrhea occur, and analgesia for headache or Interactions
arthralgia. Absorption decreases aken w/ antacids, tetracyclines, or
Offer support and encouragement to help the patient deal with cimetidine; if these drugs must be used, they should be spaced
the diagnosis and the drug at least 2
regimen. hours apart. Antiinfective response to ciprofloxacin or ofloxacin
Provide thorough patient teaching, including the name of the can decrease if taken w/ iron bec of decrease absorption;
drug, dosage prescribed, administer
administration technique and frequency of administration, at least 2 hrs apart. Increased iron levels occur if taken w/
measures to avoid adverse chloramphenicol; patients receiving this combination should be
effects, warning signs of problems and need to notify healthcaremonitored
provider, and the need for closely for sign of iron toxicity. Effects of levodopa may decrease
follow-up laboratory testing, to enhance patient knowledge if taken w/ iron preparations; take them at least 2 hours apart.
about drug therapy and to Drug-Food
promote compliance. Interactions
Monitor patient response to the Iron is not absorbed if taken w/ antacids, eggs, milk, coffee, or
drug (alleviation of anemia, tea. These substances should not be administered concurrently.
target hemoglobin level a Acidic
maximum of 11 g/dL). liquids (vit C or juice) may enhance the absorption of iron and
Monitor for adverse effects should not be given concurrently.
(headache, hypertension, Agents Used for Iron Deficiency Anemia
nausea, vomiting, seizures, Nursing Considerations Nursing Diagnosis Planning
dizziness). Assess for contraindications or cautions.
Monitor the effectiveness of Perform a physical assessment to establish a baseline before
comfort measures and beginning therapy and during therapy to determine drug
compliance with the regimen. effectiveness and to evaluate for any potential adverse effects.
Evaluate the effectiveness of Inspect the color and integrity of the skin and mucous
the teaching plan (patient can membranes to identify potential signs and symptoms
name drug, dosage, adverse associated with anemia and evaluate for possible adverse
effects to watch for, and effects of the parenteral form.
specific measures to avoid Assess patient’s neurological status, including level of
them; patient understands the orientation, affect, and reflexes, to identify possible CNS effects
importance of continued followup). and early signs of possible toxicity.
Monitor pulse, blood pressure, perfusion, respirations, and
Agents Used for Iron Deficiency Anemia adventitious sounds to check CV function and detect early
Elevate the serum iron concentration. They are then either signs of toxicity.
converted to hemoglobin or trapped in reticuloendothelial cells Inspect the abdomen for distention and auscultate bowel
for storage sounds to evaluate GI motility.
and eventual release and conversion into a usable form of iron Inspect the skin integrity of the intended parenteral
for RBC production. administration site to ensure intactness and evaluate for
Indications possible staining.
Oral iron preparations - often used to help patients regain a Monitor the results of laboratory tests, including complete
positive iron balance; these preparations need to be blood count, hematocrit, hemoglobin, and serum ferritin assays,
supplemented w/ to determine drug effectiveness and identify toxic levels.
Acute pain related to

25
106 BY TONS AND MADS
CNS or GI effects or Hydroxocobalamin must be given IM every day for 5-10 days to
parenteral build up levels & then once a month for life. It cannot be taken
administration Nausea orally
related to adverse GI bec the problem w/ pernicious anemia is the inability to absorb
effects vitamin B12 secondary to low levels of intrinsic factor. It can be
Constipation related to used
adverse GI effects in states of increased demand (e.g., pregnancy, growth spurts)
Disturbed body image or dietary deficiency, but oral vitamins are preferred in most of
related to drug staining those
of the skin from cases. Cyanocobalamin is not as tightly bound to proteins and
parenteral injection does not last in the body as long as hydroxocobalamin. This
Risk for injury related to drug is
CNS effects Deficient primarily stored in the liver and slowly released as needed for
knowledge regarding metabolic functions. It is available as an intranasal gel that
drug therapy allows
vitamin B12 absorption directly through the nasal mucosa.
Agents Used for Iron Deficiency Anemia Nascobal is used once a week as an intranasal spray in one
Implementation with Rationale Evaluation nostril. Folic acid and vitamin B12 are well absorbed after
Ensure that iron deficiency anemia is confirmed before injection,
administering drugs to ensure proper use of the metabolized mainly in the liver, and excreted in the urine. These
drug. vitamins are considered essential during pregnancy and lactation
Consult with the physician to arrange for the treatment of the because of the increased demands of the mother’s metabolism.
underlying cause of anemia if possible Contraindications
because iron replacement will not correct the cause of the iron & Cautions
loss. Presence of known allergies to these drugs or to their
Administer the oral form with meals that do not include eggs, components.
milk, coffee, and tea to relieve GI Use cautiously in pregnant or lactating or those who have other
irritation and nausea if GI upset is severe and to prevent anemias to ensure that correct doses of the drug are used to
drug–food interactions; have the patient drink provide
oral solutions through a straw to prevent staining of the teeth. the best therapeutic effect & decrease the risk of toxic effects.
Caution the patient that stools may be dark or green to prevent Nasal cyanocobalamin should be used w/ caution in the
undue alarm if this occurs. presence of nasal erosion or ulcers, which could alter absorption
Take measures to help alleviate constipation to prevent of the drug.
discomfort and the adverse effects of severe Adverse Effects
constipation. With relatively few adverse effects because they are used as
Administer IM only by the Z-track technique to ensure proper replacements for required chemicals.
administration and to avoid staining of Hydroxocobalamin has been associated with itching, rash, and
the tissues brown. Warn the patient that the injection can be signs of excessive vitamin B levels, which can also include
painful. peripheral
Arrange for hematocrit and hemoglobin measurements before edema and heart failure. Mild diarrhea has been reported with
administration and periodically during these drugs.
therapy to monitor drug effectiveness. Pain and discomfort can occur at injection sites. Nasal irritation
Provide comfort measures to help the patient tolerate drug can occur with the use of intranasal spray.
effects. These include small, frequent Agents for Megaloblastic Anemias
meals to minimize nausea, readily available access to bathroom Nursing Considerations Nursing Diagnosis Planning
facilities should constipation occur, Assess for contraindications or
and increased fiber and fluid intake and increased exercise to cautions:Any known allergies to these
help alleviate constipation. drugs or drug components, other
Offer support and encouragement to help the patient deal with anemias, pregnancy, lactation, and nasal
the diagnosis and the drug regimen. erosion.
Provide thorough patient teaching, including the drug name, Assess baseline status before beginning
dosage, and route of administration; therapy to determine any potential
administration technique, such as parenteral Z-track injection or adverse effects. This includes affect,
oral solution through a straw, and orientation, and reflexes; pulse, blood
frequency of administration; foods and fluids to avoid and to pressure, and perfusion; respirations and
include to ensure proper absorption; adventitious sounds; and complete blood
need for increased fluids and fiber foods in diet and exercise to count, hematocrit, and iron levels, to
prevent constipation; notification of determine the effectiveness of drug
change in stool color and consistency; potential for pain at site therapy.
and staining of the skin with parenteral Acute pain related to
administration; measures to avoid adverse effects; warning signs injection or nasal
of problems and need to notify irritation
healthcare provider; and the need for follow-up laboratory Risk for fluid volume
testing, to enhance patient knowledge imbalance related to
about drug therapy and to promote compliance. CV effects Deficient
knowledge regarding
Agents for Megaloblastic Anemias drug therapy
Folic acid & vit B12 are essential for cell growth & division & for
production of strong stroma in RBCs. Vit B12 is also necessary Implementation with Rationale Evaluation
for Confirm the nature of the megaloblastic anemia to ensure that
maintenance of myelin sheath in nerve tissue. the proper drug
Indications regimen is being used.
Folic acid & vit B12 are given as replacement therapy for dietary Give both types of drugs in cases of pernicious anemia to ensure
deficiencies, as replacement in high- demand states such as therapeutic
pregnancy & lactation, & to treat megaloblastic anemia. effectiveness.
Folic acid is used as a rescue drug for cells exposed to some Parenteral vitamin B12 must be given IM each day for 5 to 10
toxic chemotherapeutic agents. days and then
Leucovorin is used as rescue drug following methotrexate once a month for life if used to treat pernicious anemia. Arrange
therapy to decrease toxicity of methotrexate caused by for nutritional
decreased consultation to ensure a well-balanced diet. Monitor for the
elimination or overdose of folic acid antagonists such as possibility of
trimethoprim & for treatment of various megaloblastic anemias. hypersensitivity reactions; have life support equipment on
Levoleucovorin (newest drug in this class) only approved to standby in case
decrease toxicity of methotrexate caused by decreased reactions occur.
elimination or Arrange for hematocrit readings before and periodically during
overdose of folic acid antagonists in the treatment of therapy to
osteosarcomas. monitor drug effectiveness.
Pharmacokinetics Provide comfort measures to help the patient tolerate drug
Folic acid can be given oral, IM, IV, & subcu forms. Parenteral effects. These
drugs are preferred for patients w/ potential absorption include small, frequent meals, access to bathroom facilities, and
problems; all analgesia for
other patients should be given oral form if at all possible. muscle or nasal pain.
Leucovorin is a reduced form of folic acid that is available for Provide thorough patient teaching, including the name of the
oral, IM, and IV use. Levoleucovorin is only available in an IV drug, dosage
form. prescribed, measures to avoid adverse effects, warning signs of
problems, and

26
106 BY TONS AND MADS
the need for periodic monitoring and evaluation, to enhance should be used with caution in the presence of impaired liver or
patient knowledge renal function, which could interfere with
about drug therapy and to promote compliance with the drug metabolism and excretion of the drug, and it should only be
regimen. used in pregnancy and lactation if the benefit to
Offer support and encouragement to help the patient deal with the mother clearly outweighs the potential risk to the fetus or
the diagnosis baby because this drug crosses the placenta
and the drug regimen. and enters breast milk and could cause serious effects in the
fetus or baby.
Agents for Sickle Cell Anemia Adverse Effects
Hydroxyurea, taken for several months, increases the amount of Hydroxyurea is cytotoxic and is associated with adverse effects
fetal hemoglobin produced in the bone associated with the death of cells, especially
marrow and dilutes the formation of the abnormal hemoglobin S in cells that are rapidly turning over. GI effects include anorexia,
in adults who have sickle cell anemia. This nausea, vomiting, stomatitis, diarrhea, or
results in less clogging of small vessels and the painful, anoxic constipation; dermatological effects include rash or erythema;
effects associated with RBC sickling or and bone marrow suppression usually occurs.
stacking. Headache, dizziness, disorientation, fever, chills, and malaise
Indications See Table 49.3 have been reported, possibly related to the
Pharmacokinetics effects of cell death in the body. As with other cytotoxic drugs,
Given orally, hydroxyurea is absorbed well from the GI tract, there is an increased risk of cancer
reaching peak levels in 1 to 4 hours. It is development.
metabolized in the liver and excreted in the urine with a half-life Drug-drug
of 3 to 4 hours. It is known to cross the Interactions
placenta and to enter breast milk. There is an increased risk of uric acid levels if this drug is
Contraindications combined with any uricosuric agents; if this
& Cautions combination must be used, dose adjustments will be needed for
Hydroxyurea is contraindicated with known allergy to any the uricosuric agent.
component of the drug to prevent hypersensitivity Drug-Food
reactions and with severe anemia or leukopenia because it can Interactions
cause further bone marrow suppression. It None is mentioned.
Drugs Acting on the Renal System pp. 849-878.
Drugs Acting on the Gastrointestinal System
To be continued sa next lyf
STRUCTURE AND FUNCTION OF GI SYSTEM - responsible for only very small part of waste
- only system in the body open to external excretion (kidneys and lungs excrete most)
environment: begins at the mouth; progresses - Accessory organs: pancreas, liver, and gallbladder
through the esophagus, stomach, and small and
large intestines; and ends at the anus..
OTHER DRUGS

27

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