REVIEWER IN PHARMA LEC G Cells Gastrin (stimulates

acid secretion)
ANTI-ULCER DRUGS
PEPTIC ULCER DISEASE
GASTROINTESTINAL SYSTEM
✓ Lesion is located in either the stomach or
Two Basic Anatomical Divisions
small intestine (duodenum)
1. Alimentary Canal
✓ Duodenum is the most common site
✓ GI Tract
✓ Mouth to Anus
Risk Factors
2. Accessory Organs
✓ Close family history of PUD
✓ Salivary Glands
✓ Blood Group O
✓ Liver
✓ Smoking tobacco (Increases gastric acid
✓ Gallbladder
secretion)
✓ Pancreas
✓ Consumption of beverages that contain
caffeine
IMPORTANT POINTS IN DIGESTION
✓ Excessive psychological stress
❖ Peristalsis – Rhythmic contractions of
✓ Drugs: Corticosteroids, NSAIDs, and
the layers of the smooth muscle of the GI
platelet inhibitors (aspirin and clopidogrel)
tract which propels food and medications
➢ Most common cause of noninfected PUD
along the tract
✓ Infection with Helicobacter pylori
❖ Mucosa Layer – Provides surface area
➢ Primary cause of PUD
for the various acids, bases, mucus, and
➢ 50% of population has H. pylori present
enzymes to break down food
in their stomach and SI
❖ Villi/ Microvilli – Tiny projections in
the SI which provides huge surface area for
the absorption of food and medications

GASTRIC CELLS

Cells Type Substance Secreted

Goblet Cells Mucus (protects

gastric lining)

Parietal Cells Gastric Acid (e.g

hydrochloric acid)

Chief Cells Pepsinogen (protease

precursor)

D Cells Somatostatin(inhibits
acid secretion)

1
SYMPTOMS OF PEPTIC ULCER ✓ CAUSE - Weakening of the lower
esophageal sphincter (may not close tightly
Duodenal Ulcer and stomach contents backflow when
✓ Gnawing or burning upper abdominal stomach contracts)
pain ✓ Complications (if untreated) –
✓ Occurs 1-3 hours after a meal Esophagitis, esophageal ulcers or strictures
✓ Pain is worse when stomach is empty and ✓ Associated with obesity
disappears on ingestion of food
✓ If erosion progresses deeper into the Life-style changes to improve GERD
mucosa, bleeding occurs (manifests bright ➢ Losing weight
red vomit or black tarry stools) ➢ Elevating the head when sleeping
✓ May heal spontaneously, but recur ➢ Avoiding fatty or acidic foods
✓ Long-term follow-up is not necessary ➢ Eating smaller meals at least 3 hours
✓ More common in males 30-50 year age before sleep
group ➢ Eliminating tobacco and alcohol use
✓ H. pylori - related ❖ Patients self-treat with OTC drugs but
surgery may be necessary if it is
Gastric Ulcer persistent
✓ Less common
✓ Relieved by food but pain may continue
even after a meal
✓ Anorexia (loss of appetite), weight loss,
and vomiting are common accompanying
symptoms
✓ Remissions may be infrequent or absent
✓ Medical follow-up should continue for
years because small erosions become
cancerous
✓ Severe ulcers penetrate the wall of the
stomach and cause death
✓ More common in women over age 60 GOALS OF PUD
✓ NSAID-related PHARMACOTHERAPY
✓ Relief of symptoms
GASTROESOPHAGEAL REFLUX ✓ Promote of healing of the ulcer
(GERD) ✓ Prevent future recurrence of the
✓ Common condition in which the acidic disease
contents of the stomach move upward
into the esophagus Treatment of Most Causes
✓ Produces an intense burning (heartburn) ✓ Advise lifestyle changes (for obese or
sometimes accompanied by belching smoking patients)

2
✓ Switch alternative medications (for ✓ Heals more than 90% of duodenal ulcers
people taking NSAIDs for chronic within 4 weeks and about 90% of gastric
conditions) ulcers in 6-8 weeks
✓ Elimination of H. pylori if it is the cause ✓ Used only in short-term control of PUD
and GERD (Typical length of therapy is 4
Drugs weeks)
1. Proton-pump inhibitors (PPI) ✓ Should be taken 20-30 minutes before
2. H2-receptor antagonists major meal of the day
3. Antacids ✓ Omeprazole and lansoprazole are used
4. Antibiotics concurrently with antibiotics to eradicate H.
5. Miscellaneous drugs pylori
✓ Esomeprazole and pantoprazole used
MECHANISMS OF ACTION as once-a-dose dosing
✓ AE: Headache, abdominal pain, diarrhea,
nausea and vomiting. Long-term use may
cause osteoporosis-related fractures (Give
calcium supplements to prevent this.)

PROTON PUMP INHIBITORS

H2-RECEPTOR ANTAGONIST

✓ Omeprazole, lansoprazole,
esomeprazole, pantoprazole
✓ MOA: Reduce acid secretion by binding
irreversibly to H+, K+-ATPase, the enzyme
that acts as a pump to release acid (H+ or
protons)
✓ Reduce acid secretion and have longer ✓ Ranitidine, cimetidine, famotidine
duration than H2-receptor antagonists ✓ Histamine has two types of receptors:

3
➢ H1 – Produces inflammation and allergy
➢ H2 – Responsible for increasing acid
secretion
✓ MOA: Suppresses the volume and
acidity of parietal cell secretion
✓ Drugs are available OTC
✓ Used short-term (2 weeks) for
treatment of GERD
✓ For duodenal ulcers 6-8 weeks/
Gastric ulcers up to 12 weeks of therapy
ANTACIDS
✓ AE: Minor and rarely causes
discontinuation of therapy. In high doses
or in patients with renal or hepatic disease, it
may cause confusion, restlessness,
hallucinations, or depression
✓ Cimetidine is the 1st drug but used less
frequently because can cause drug-drug
interactions and should be taken up to 4
times a day
✓ DI: Antacids diminish effectivity of
H2 receptor antagonists ✓ Alkaline, inorganic compounds of
aluminum, magnesium, sodium and calcium
✓ The most common type of combinations
are of aluminum hydroxide and magnesium
hydroxide
✓ MOA: Neutralize stomach acid
✓ Mainstays of PUD and GERD therapy
because they are inexpensive OTC drugs
✓ But not recommended as primary drug
class for PUD because they do not
promote healing of ulcer or eradicate H.
pylori
✓ Chewable tablets and liquid formulations
are available
✓ Simethicone is sometimes added to
antacid preparation because it reduces gas
bubbles that cause bloating and
discomfort. Simethicone is classified as an
anti-flatulent because it reduces gas.
✓ Self-medication is safe

4
✓ Antacids act within 10-15 minutes but
duration is only 2 hours so it should be
taken often
✓ CI: Patients on sodium-restricted diet
or with diminished renal function because it
could result to accumulation of calcium or
magnesium
✓ AE: Constipation or kidney stones (due
to calcium); Milk-alkali syndrome –
Administration of milk with calcium
carbonate antacids or any items with
Vitamin D which cause hypercalcemia
(headache, urinary frequency, anorexia,
nausea, and fatigue). May cause permanent
renal damage

PHARMACOTHERAPY WITH
COMBINATION ANTIBIOTIC
THERAPY

✓ H. pylori devised ways to neutralize high

acidity and make chemicals called adhesins,
which allow it to stick tightly to the GI
mucosa
✓ Infections can remain for life if not
treated
Prototype Drug: Aluminum hydroxide ✓ Elimination of this bacteria allows ulcers
(AlternaGEL,others) to heal more rapidly thus antibiotics must be
used
❖ Note: People with noninfected PUD
should be screened first and not given
antibiotics because it worsens their
condition
Regimens
✓ Given usually 7-14 days
✓ Two or more antibiotics are given with
antiulcer drugs to increase effectiveness of
therapy and lower bacterial resistance

5
Initial: Omeprazole + clarithromycin + ✓ AE: CNS effects such as drowsiness,
amoxicillin fatigue, confusion, and insomnia; Can cause
Alternatives: tardive dyskinesia in long term therapy
1. Omeprazole (or other PPI) + ✓ Metozolv ODT – oral-disintegrating
clarithromycin + metronidazole tablet form for treatment of GERD and
2. Omeprazole (or other PPI) + bismuth diabetic gastroparesis
subsalicylate + metronidazole + tetracycline

MISCELLANEOUS DRUGS
CARDIAC DRUGS
Sucralfate
✓ Consists of sucrose plus aluminum ANTI-HYPERTENSIVE DRUGS
hydroxide
✓ MOA: Produces a thick, gel-like Regulation of Blood Pressure by Kidneys
substance which coats the ulcer, protecting it & Blood Vessels
against further erosion and promote healing +Kidneys regulate blood pressure by
✓ AE: Constipation control of fluid volume and via the
✓ Must be taken four times daily renin-angiotensin-aldosterone system
(RAAS)
Misoprostol (Cytotec) +Kidneys control Na+ and water
✓ MOA: Inhibits gastric acid secretion and elimination and retention which affects
stimulates production of protective mucus cardiac output and systemic arterial blood
✓ I: Prevention of PUD in patients taking pressure
high doses of NSAIDS or corticosteroids RAAS
✓ AE: Abdominal cramping +Renin (from renal cells) – stimulates
✓ CI: Pregnancy (sometimes it is used to production of Angiotensin II (potent
terminate pregnancies) vasoconstrictor)
+Angiotensin II – causes release of
Metoclopramide aldosterone
✓ I: Used for short-term therapy of +Aldosterone (from adrenal cells) -
symptomatic PUD who fail to respond to promotes sodium retention → causes water
first-line drugs; Used for nausea and retention → increase in fluid volume →
vomiting related to surgery or cancer elevate BP
chemotherapy; GERD
✓ MOA: Causes muscles in the upper Renin Angiotensin Aldosterone System
intestine to contract which results in faster
emptying of the stomach and blocks food
from refluxing to the esophagus
✓ Available oral, IM, or IV routes

6
 recepto
r

Sympa Effecto Adrene Norepi Antiadre

thetic r cells rgic or nephrin nergic
non e, drugs
adrener epineph (adrener
gic rine, gic
(Alpha and blockers
or Beta) adrener – alpha
gic or beta
Other Regulatory Methods agonist blockers
drugs
+ Baroreceptors (aorta and carotid sinus) Parasy Locate Choline Acetylc Choliner
+ Vasomotor center in the medulla mpathe d rgic/mu holine gic
+ Hormones tic betwee scarinic or antagoni
+ Antidiuretic hormone (ADH) n choline st drugs
+ Atrial natriuretic peptide (ANP) postgan rgic
glionic agonist
+ Brain natriuretic peptide (BNP)
fiber s drugs
+ Catecholamines increase blood pressure and
through vasoconstriction effector
+ Norepinephrine from sympathetic cells
terminals
+ Epinephrine from adrenal medulla Blood Pressure Regulation

Autonomic Nervous System

What is Hypertension?
+Increase in BP with systolic pressure
greater than 140 mmHg and diastolic
pressure greater than 90 mmHg
ANS Locatio Recepto Stimula Inhibitio
n of r tion n

7
+ Most common condition leading to
myocardial infarction (MI), stroke, renal
failure, and death
Recommended Therapies for
Hypertension

Non-Pharmacologic Management of
Hypertension
Types of Hypertension
Primary (Essential) Hypertension
+Most common (90% of HBP)
+Contributing factors: Hyperlipidemia,
AfricanAmerican race, diabetes, aging,
stress, excessive alcohol ingestion, smoking,
obesity, and a family history of hypertension

Secondary Hypertension
+Only 10% of HBP
+Related to renal and endocrine disorders

+ Limit intake of alcohol

+ Restrict sodium consumption
+ Reduce intake of saturated fat and
cholesterol and increase consumption of
fresh fruits and vegetables
+ Increase aerobic physical activity
+ Discontinue use of tobacco products
+ Reduce sources of stress and learn to
implement coping strategies
+ Maintain optimum weight

8
Pharmacologic Therapy for Hypertension Indications
- Antihypertensives Hypertension, various forms of glaucoma,
benign prostatic hypertrophy (BPH) –
alpha1 blockers, management of severe HF
+ cardiac glycosides and diuretics

Contraindications
Drug allergy, acute HF, concurrent use of
MAOIs, peptic ulcer, severe liver or kidney
disease, asthma –contraindicated if using
non cardioselective beta blocker like
carvedilol

Adverse Effects
Bradycardia with reflex tachycardia,
postural and postexercise hypotension, dry
mouth, drowsiness, dizziness, depression,
edema, constipation, and sexual dysfunction
(i.e. impotence)

Other Effects
Headache, sleep disturbances, nausea, rash,
and palpitations

Interactions
Alcohol, benzodiazepines, and opioids –
CNS depression

Alpha2-Adrenergic Receptor Stimulators

(Agonists)
Adrenergic Drugs + Clonidine and Methyldopa
+ Methyldopa is used to treat hypertension
in pregnancy
+ Not first-line antihypertensive drugs –
high incidence of unwanted effects
(orthostatic hypertension, fatigue, and
dizziness)

9
+Adjunct drugs in hypertension +Matrix of the capsule is expelled in the
stool (inform patients)

Clonidine (Catapres)
+Prototype drug
+ Decrease blood pressure and manage
opioid withdrawal
+Better safety profile
+Oral and topical preparations (patch)
+ Must not be discontinued abruptly or
cause rebound hypertension

Dual-Action Alpha1 and Beta Receptor

Blockers / Beta-Blocker

+ Carvedilol
+ Dual-Action Alpha1 and beta receptor
blocker
+ Widely used drug and well tolerated by
patients
+ Used for hypertension, mild to moderate
HF (in conjunction with digoxin, diuretics,
and ACE inhibitor treatment)
+ CI: Drug allergy, cardiogenic shock,
severe bradycardia or decompensated HF,
Alpha1 Blockers bronchospastic conditions like asthma, and
+Doxazosin, prazosin, tamsulosin, and cardiac problems involving the conduction
terazosin system
+Contraindicated in patients who have
hypersensitivity to them Nebivolol
+Available only as oral preparations + Newest beta blocker (2008)
+Tamsulosin – not used for control of + Beta1-selective beta blocker used for
blood pressure but indicated solely for hypertension; Also used for HF
control of BPH + Produces vasodilatation which results in
decrease in SVR
Doxazosin + Promoted as causing less sexual
+Most commonly used alpha1 blocker dysfunction
+Dilates both arteries and veins + Should not be stopped abruptly and must
+Available in immediate and extended be tapered over 1-2 weeks
release form

10
 breakdown of bradykinin (vasodilator),
substance P (vasodilator), and preventing
formation of Angiotensin II
ACE Inhibitors (-pril group) + Renal – Good for HF; Prevent sodium and
water resorption by inhibiting aldosterone
+ Captopril, benazepril, enalapril, fosinopril, secretion → diuresis → decrease blood
lisinopril, moexipril, perindopril, quinapril, volume → decreases work required of the
ramipril, and trandolapril heart
+ Used as first-line drugs for hypertension INDICATIONS
+ Most are prodrugs (except for captopril + Hypertension
and lisinopril) + Adjunct to Heart Failure treatment
+ Captopril has the shortest half-life and + Stop progression of Ventricular
must be dosed more frequently Hypertrophy (ventricular remodeling) after
+Enalapril is the only ACE inhibitor that is MI
available in parenteral preparation + Choice for DM patients with HTN
+ Can be combined with other (decrease glomerular filtration pressure) and
antihypertensives prevent diabetic nephropathy (reduce
proteinuria)

ACE Inhibitors
Mechanism of Action and Drug Effects
+ Inhibits ACE (enzyme responsible for
converting Angiotensin I to Angiotensin II)
to prevent elevation of blood pressure
Primary Effects CONTRAINDICATIONS
+ Cardiovascular – Decrease SVR (systemic + Known drug allergy, hyperkalemia,
vascular resistance) by preventing pregnant and lactating women, in children,

11
and patients with bilateral renal artery
stenosis
+ Angioedema (inflammation of
submucosal tissues)
Angiotensin II Receptor Blockers or
Adverse Reactions
ARBs (-sartan group)
+ Fatigue, dizziness, mood changes, and
+ Losartan, eprosartan, valsartan, irbesartan,
headaches. Hyperkalemia, angioedema,
candesartan, Olmesartan, telmisartan,
renal impairment
azilsartan
+ Dry, nonproductive cough → reversible
Mechanism of Action and Drug Effects\
with D/C
+ Block the binding of angiotensin II to
Toxicity and Management
type 1 angiotensin II receptors (Selective)
+ OD: Hypotension
+ Affect vascular smooth muscle and the
+ Treatment: Symptomatic and supportive –
adrenal gland
IVF to expand blood volume; Hemodialysis
+ Block vasoconstriction
to remove captopril and lisinopril
+ Block secretion of aldosterone
+ Indications
Captopril
+ Hypertension
+ Prototype drug for the class
+ Adjunct to HF treatment
+ Not a prodrug
Contraindications
+ Minimize or prevents left ventricular
+ Known drug allergy, pregnancy and
dilatation and dysfunction (ventricular
lactation; Use cautiously in older patients
remodeling) after MI (improve patient’s
with renal dysfunction; BP and PR should
chances for survival)
be assessed before drug therapy
+ Reduce HF
Adverse Effects
+ Shortest half-life; should be given 3-4
+ Chest pain, fatigue, hypoglycemia,
times a day
diarrhea, UTI, anemia, and weakness
Toxicity and Management
+ OD: Hypotension and tachycardia
+ Treatment: Symptomatic and supportive
Enalapril – give IVF to expand blood volume
+ Available in both oral and IV preparation
+ IV enalapril given for patients who cannot ARBs
tolerate oral medications; does not require
monitoring
+ Prodrug – patients must have a
functioning liver
+ Improved patient’s chances of survival
after MI and reduce HF

12
 ● Used in the treatment of
hypertension and other
cardiovascular diseases (angina
pectoris, dysrhythmias)
● Useful in treating elderly and
African Americans, who are
sometimes less responsive to drugs
in other hypertensive classes

Losartan
✓Prototype drug of the class
✓Hypertension and heart failure treatment
✓CI: hypersensitivity; breastfeeding
✓Use with caution in patients with renal or
hepatic dysfunction and in patients with
renal artery stenosis Vasodilators
✓Not to be used in pregnancy ● Act directly on arteriolar and/or
venous smooth muscle to cause
relaxation
● Do not work through adrenergic
receptors
● Minoxidil, hydralazine, diazoxide,
Diuretics
and nitroprusside
● First-line drugs for hypertension
● Mechanism of Action and Drug
● Produce few adverse effects
Effects
● Effective in controlling mild to
● Direct-acting vasodilators → cause
moderate hypertension
peripheral vasodilation →reduction
● Thiazide diuretics reduce
in SVR → hypotension
hypertension-related morbidity and
● Minoxidil (topical form) – restore
mortality; Combined with other
hair growth
antihypertensive classes to enhance
● Diazoxide, hydralazine, and
effectiveness; Also used to treat
minoxidil – work through arteriolar
kidney diseases and heart failure
vasodilation
● Nitroprusside – work on both
Calcium Channel Blockers or CCBs
arteriole and veins
● Exert beneficial effects on the heart
and blood vessels by blocking
Indications
calcium ion channels

13
 + Hypertension, hypertensive emergencies therapy in the hospital and for hypertensive
(nitroprusside and diazoxide IV) emergencies
Contraindications +New combo with antianginal drugs: 37.5
+ Known drug allergy, hypotension, cerebral mg hydralazine
edema, acute MI, and coronary artery + 20 mg isosorbide dinitrate = for adjunct
disease. Also in heart failure that is HF in African American patients
secondary to diastolic dysfunction

Adverse Effects
+ Diazoxide – many undesirable AEs
+ Hydralazine – dizziness, headache,
anxiety, tachycardia, edema, dyspnea,
Sodium nitroprusside
nausea, vomiting, diarrhea, hepatitis, SLE.
+Used in intensive care setting for severe
Vit. B6 deficiency, and rash
hypertensive emergencies
+ Minoxidil – T-wave ECG changes,
+Titrated to effect by IV infusion
pericardial effusion, angina, breast
tenderness, rash, and thrombocytopenia
+ Sodium nitroprusside – bradycardia,
decreased platelet aggregation, rash,
hypothyroidism, hypotension,
methemoglobinemia, and rarely cyanide
toxicity (cyanide ions are a by-product of
nitroprusside metabolism)
+ Toxicity and Management of Overdose
+ Hydralazine – Supportive and
symptomatic (IV fluids, digitalization if
needed, and beta blockers to control
tachycardia)
+ Sodium nitroprusside – D/C of the
infusion, cyanide antidote kit (sodium nitrite
and sodium thiosulfate injection and amyl
nitrite for inhalation
+ Interactions
+ Hydralazine – additive hypotensive effects
with adrenergics or other antihypertensives

Miscellaneous Drugs
Hydralazine
Eplerenone
+Oral – for routine cases of essential HTN
✓ Selective aldosterone blockers
IV – for patients who cannot tolerate oral

14
 ✓ Blocks aldosterone at its receptors in the
kidney, heart, blood vessels, and brain
✓ For routine treatment of hypertension
and for post-MI heart failure
✓ Contraindicated in patients with known
drug allergy, elevated serum potassium
levels, severe renal impairment, and those
taking cytochrome P-450 enzyme 3A4
inhibitors
Bosentan
✓ Blocks receptors of hormone endothelin
(hormone stimulates the narrowing of blood
vessels by binding to endothelin receptors)
✓ For treatment of pulmonary artery
hypertension with moderate to severe HF Nursing Process
✓ Hepatotoxic and teratogenic
✓ CI: known drug allergy, pregnancy,
significant liver impairment, and concurrent
drug therapy with cyclosporine or glyburide

Treprostinol
✓ Dilates pulmonary and systemic blood
vessels and inhibit platelet aggregation
✓ For patients with pulmonary artery
hypertension with moderate to severe HF
✓ CI: known drug allergy
✓ Routes: Oral, inhalational, or infusion

Human Needs Statements

15
 Cholesterol – used to make steroid
hormones, cell membranes, and bile acids
❖Both are water-insoluble fats and must be
bound to specialized lipid-carrying proteins
called APOLIPOPROTEINS
LIPOPROTEIN – triglycerides/ cholesterol
+ apolipoproteins; transports lipids via blood

Cholesterol Homeostasis
Fats in Diet → Triglycerides →
incorporated into Chylomicrons and
absorbed into the lymphatic system →
transported to the intestines → LIVER (to
make steroid hormones, lipid structural
components, and bile acids)

VLDL – produced by the liver from both

endogenous and exogenous sources; cleaved
by lipoprotein lipase and lose triglycerides
→

IDL – cleaved by lipoprotein lipase →

LDL – cholesterol remains in LDL after

these processes; absorbed by peripheral cells
with LDL receptors such as endocrine cells
to produce hormones

HDL – produced in the liver and intestines

and formed when chylomicrons are broken
down; lipids not used by peripheral cells are
transferred here as cholesterol esters

ANTILIPEMICS DRUGS

Primary Forms of Lipids

Triglycerides – function as an energy
source and stored in adipose tissues

16
 from circulating lipoproteins → gets filled
with fat → become FOAM CELLS →
FATTY STREAK

Hyperlipidemia

❖Hypercholesterolemia
✓Excess amount of cholesterol which can
cause death and disability related to
coronary heart disease
✓Number of LDL receptors decreases
which results in accumulation of LDL in the
blood

A N A T O M Y – CORONARY
ARTERIES

Atherosclerotic Plaque Formation

Increase serum cholesterol level →
circulating monocytes adhere to the smooth
C O M P L I C A T I O N S OF H Y P E
endothelial surfaces of the coronary
RLIPIDEMIA:MYOCARDIA
vasculature → burrow into the
LINFARCTIONANDSTROK
subendothelial tissues → change into
E
macrophage cells → take up cholesterol

17
 ✓ 1 st -line drug therapy for
Pharmacologic Treatment of hypercholesterolemia, and types IIa and IIb
Hyperlipidemia hyperlipidemia
Contraindications
1. Hydroxymethylglutaryl-coenzyme A ✓ Drug allergy and pregnancy
(HMG-CoA) reductase inhibitors (statins) ✓ Liver disease or elevation of liver
2. Bile acid sequestrants enzyme Adverse Effects (see table)
3. B-vitamin Niacin (Vitamin B3/Nicotinic Toxicity and Management
Acid) ✓ Supportive based on presenting
4. Fibric Acid Derivatives symptoms Interactions (see table)
5. Miscellaneous: ✓ Oral anticoagulants
✓Cholesterol absorption inhibitor – ✓ Drugs metabolized by cytochrome P-450
Ezetimibe (Zetia) enzyme 3A4 (CYP3A4)
✓Vytorin (ezetimibe + simvastatin) ✓ Grape juice – inactivate enzyme
✓Mipomersen (adjunct drug used once CYP3A4 ✓ Gemfibrozil – Increase risk of
weekly via subcutaneous injection) rhabdomyolysis
✓Microsomal triglyceride transfer protein ✓ Lab tests – Abnormal liver function tests
inhibitor - Lomitapide
✓Proprotein convertase subtilisn kexin 9
(PCSK9) inhibitors – Alirocumab and
Evolocumab

HMG-CoA Reductase Inhibitors (statins)

✓ Pravastatin, simvastatin, atorvastatin,
fluvastatin, rosuvastatin and pitavastatin
✓ Reduce plasma concentrations of LDL
cholesterol by up to 50%; Increase HDL HMG-CoA Reductase Inhibitors (statins)
2-15%
❖HMG-CoA reductase– rate-limiting Atorvastatin
enzyme in cholesterol synthesis ✓Used to lower total and LDL cholesterol
Mechanism of Action levels as well as triglyceride levels
✓ Inhibit HMG CoA reductase and ✓Raise levels of HDL
decrease rate of cholesterol production ✓Given once daily usually at evening
✓ Less cholesterol = Increase LDL meal or at bedtime (correlates better with
receptors to recycle LDL from circulation the diurnal cholesterol production in the
back into the liver (to make steroids, bile body)
acids, and cell membranes) ✓Not given to pregnant women
❖Start of maximum effects 6-8 weeks after
the start of therapy
Indications

18
 Simvastatin ✓ Primary or adjunct drug for type II
✓One of the 1st statins to become generic hyperlipoproteinemia; Used with statins as
✓Lower total and LDL cholesterol as well additive effect to lower LDL
as triglyceride levels ✓ Cholestyramine – used to relieve pruritus
✓Modestly raised HDL associated with partial biliary obstruction
✓Not given to pregnant women Contraindications
✓Use of 80 mg dose is limited because it ✓ Drug allergy, biliary or bowel
can cause myopathy ✓Have a lot of drug obstruction, PKU
interactions Adverse Effects
✓ May cause mild increase in triglyceride
levels
✓ Constipation is a common problem
accompanied by heartburn, nausea,
Bile Acid Sequestrants belching, and bloating (disappear over time)
✓Bile-acid binding resins and ionexchange ✓ Colesevelam – have fewer AEs
resins ✓ Patients are instructed to take drugs with
✓Cholestyramine, colestipol, and meals, increase dietary fiber or take fiber
Colesevelam supplement, increase fluid intake
✓Proven efficacy but powdered forms are Toxicity and Overdose
somewhat inconvenient to use ✓ OD: Obstruction of GI tract
✓Second-line drugs after statins ✓ Treatment: Restore gut motility
✓Lower LDL by 15-30%; Increase HDL by Interactions
3-8%; Increase hepatic VLDL production → ✓ Limited to effects on the absorption of
10-50% increase in Triglyceride level concurrently administered drugs
Mechanism of Action ✓ All drugs must be taken at least 1 hour
✓Bind bile and prevent resorption of bile before or 4-6 hours after bile acid
acids from the small intestine sequestrant administration
✓Insoluble bile acid + resin (drug) is ✓ Decrease absorption of fat-soluble
formed then excreted in the stool vitamins (ADEK)
✓Decrease in bile acid prompts liver to
produce more bile acids from cholesterol
thus bringing down cholesterol levels in the
circulation
✓To compensate for decrease in
cholesterol, liver then increases LDL
receptors where LDL bind thus lowering Cholestyramine
LDL in the bloodstream ✓Prescription-only drug
Indications ✓CI: hypersensitivity to the drug, complete
biliary obstruction, and PKU ✓Interfere
with fat-soluble vitamin distribution to the

19
fetus or nursing infant of pregnant or ✓Release histamine – increase gastric
nursing woman motility and acid secretion
✓Used for its constipating effect, given as ✓Stimulate fibrinolytic system to break
needed for LBM down fibrin clots
✓Available in dry powder Indications
✓Pose as a choking hazard if not diluted ✓Used to lower lipid levels, including
before administration triglycerides, total serum cholesterol, and
LDL cholesterol levels
✓Increase HDL cholesterol levels
✓Lower levels of lipoprotein A (except in
patients with severe hypertriglyceridemia
✓Treatment of types IIa, IIb, III, IV, and V
hyperlipidemia
✓Effects begin to be noticed 1-4 days of
therapy with maximum effects seen after 3-5
weeks of continuous therapy
Contraindications
✓Known drug allergy, liver disease, peptic
ulcer, presence of any active hemorrhagic
process, pregnant and lactating women
Adverse Effects
Niacin (Nicotinic acid, Vitamin B3)
✓Flushing, pruritus, and GI distress
✓Take aspirin or NSAIDs 30 minutes
✓Unique lipid-lowering drug but also a
before niacin dose to minimize cutaneous
vitamin
flushing
✓Large doses are required to lower lipids
✓Start on low initial dosage to minimize
✓OTC medication
AEs
✓Not 1st line therapy; given with other
✓Take with meals
antilipemic drugs
Interactions
Mechanism of Action and Drug Effects
✓Minimal
✓Exact mechanism is unknown; but
✓HMG-CoA reductase inhibitors – may
believed to its ability to inhibit lipolysis in
cause myopathy
adipose tissue, decrease esterification of
Notes
triglycerides in the liver and increase the
✓Use extended-release and immediate
activity of lipoprotein lipase
release forms → less hepatotoxicity and
✓Drug activity limited to reduction of the
flushing of skin
metabolism or catabolism of cholesterol and
✓Not recommended for patients with gout
triglycerides
✓Produce vasodilatation in cutaneous
vessels (large doses – induced by
prostaglandins)

20
 ✓Enhance action of oral anticoagulants
✓Myositis, myalgias, and rhabdomyolysis
with statins
✓Raise ezetimibe level if used concurrently
✓Lab tests – Decreased hemoglobin level,
hematocrit value, and WBC count; Increased
AST, clotting time, lactate dehydrogenase
and bilirubin level

Fibric Acid Derivates (Fibrates)

✓Gemfibrozil and fenofibrate
✓Affect triglyceride levels but also lower
total and LDL cholesterol levels and raise Gemfibrozil
HDL (25%) ✓Prescription-only drug
Mechanism of Action and Drug Effects ✓Decreases synthesis of apolipoprotein B
✓Activate lipoprotein lipase (breaks down and lowers VLDL level
cholesterol) ✓Increase HDL level (25%)
✓Suppress release of free fatty acid from ✓Effective in lowering plasma triglyceride
adipose tissue, inhibit synthesis of level
triglycerides in the liver, and increase the ✓Treatment of type IIb, IV, and V
secretion of cholesterol in the bile hyperlipidemia
✓Induce changes in blood coagulation –
decrease platelet adhesiveness and increase
plasma fibrinolysis (breaks down clots)
Indications
• Decrease LDL concentrations – type IIb,
III, IV, and IV hyperlipidemia MISCELLANEOUS DRUGS
Contraindications Ezetimibe
✓Drug allergy and severe liver or kidney ✓Cholesterol absorption inhibitor
disease, cirrhosis, and gall bladder disease ✓MOA: Selectively inhibits absorption of
Adverse Effects cholesterol and related sterols in the SI
✓Abdominal discomfort, diarrhea, nausea, ✓I: Hyperlipidemia and to patients with
headache, blurred vision, increased risk for moderate to severe chronic kidney disease –
gall stones, and prolonged prothrombin time reduce vascular events
Toxicity and Management of Overdose ✓CI: hypersensitivity, active liver disease
✓Toxicity and OD – uncommon ✓DI: Decrease effects if used with bile acid
✓Supportive care based on presenting sequestrants
symptoms ✓Taken with or without food
Interactions ✓Dosed as the same time with statin if used

21
 Flax Seeds

Alirocumab
✓PCSK9 inhibitor
❖PCK9 – serine protease enzyme which
increases LDL-C levels
✓MOA: PCSK9 inhibitors are monoclonal
antibodies that inhibit PCK9 to reduce
LDL-C by 70%
✓I: Hyperlipidemia
✓CI: Hypersensitivity
✓DI: Belimumab
✓AE: diarrhea, increased negative liver
function tests, influenza, hypersensitivity
reaction, injection-site reaction, myalgia,
and cough Omega-3 Fatty Acids
✓Dosage: Subcutaneous injection every 2-4
weeks

Supplements

Garlic

Nursing Process

22
 Diuretic Drugs

Human Needs Statement

✓Major excretory organ = urine formation

✓Other homeostatic functions:
1. Primary organ for regulating fluid
balance, electrolyte composition, and
acid-base balance of body fluids
2. Secrete enzyme RENIN, which helps in
regulation of blood pressure
3. Secrete ERYTHROPOIETIN, a
hormone that stimulates RBC production
4. Responsible for the production of
CALCITRIOL, active form of Vitamin D

RENAL DRUGS Parts and Function

23
 Part Function Others
✓ Best marker for estimating kidney
Proximal Reabsorbs Reabsorbs function
Convoluted 60-70% of sugars and ✓ Volume of filtrate passing through the
Tubule sodium and proteins Bowman’s capsule per minute
water back
✓ Used to predict the onset and progression
to
bloodstream of kidney failure
✓ Provides an indication of the ability of
Descending Active Passive the kidneys to excrete drugs from the body
Loop of reabsorption reabsorption ✓ Progressive decline in GFR = decline in
Henle of Na+ of Cl-, number of functioning nephrons
water, K+
✓ Significant kidney damage may exhibit
Ascending Active Active no symptoms until 50% or more of nephrons
Loop of reabsorption reabsorption have been nonfunctional and GFR falls to
Henle of Na+ of Cl less than half its normal value
(20-25%)

Distal Active Regulated

Convoluted reabsorption by
Tubule of Na+ (5- aldosterone
10%),
sometimes
in exchange
for H+ or
K+

Collecting Reabsorptio ADH acts to

ducts n of water, increase
electrolytes, water
and absorption
secretion of back into
K+ bloodstream

DIURETICS
Glomerular Filtration Rate (GFR) ✓Drugs that accelerate the rate of urine
formation
✓Exert their effects on the nephron
✓Goal: Reverse abnormal fluid retention in
the body
✓Use of diuretics results in REMOVAL of
sodium and water from the body
✓Developed between 1950 and 1970, and

24
remain among the most commonly
prescribed drugs in the world
✓Role: Among the first-line treatment for
hypertension (BP > 120/80)
✓Mechanisms of Diuretic Hypotension
`1. Cause direct arteriolar dilation →
decrease in peripheral vascular Sites of Action of Diuretics
resistance
`2. Reduce extracellular fluid
volume, plasma volume, and cardiac
output → decrease in blood pressure
✓2 Advantages:
1. Low Cost
2. Favorable safety profile
✓Main problem: Metabolic adverse effects
that can result from excessive fluid and
electrolyte loss (dose-related, controllable
with titration)

General Mechanism of Action and

Mechanisms of Actions of Different
Indications
Classes of Diuretics
Mechanism of Action:
1. Block sodium (Na+) reabsorption in the
nephron, thus sending more Na+ to the urine
2. Water follows Na+ = increase in volume
in urination or diuresis
3. May affect the renal excretion of other
ions (Mg++, K+, PO4, Ca++, bicarbonate
ions)
General Indications
1. Hypertension
2. Heart failure
3. Kidney failure
4. Liver failure or cirrhosis Carbonic Anhydrase Inhibitors (CAIs)
5. Pulmonary edema ✓Chemical derivatives of sulfonamide
antibiotics
CLASSIFICATION OF DIURETICS ✓Inhibit the activity of the enzyme carbonic
anhydrase (found in the kidneys, eyes, and
other parts of the body)
Mechanism of Action:

25
✓Acts on the Carbonic Anhydrase ✓Metabolic abnormalities such as acidosis
System ✓Carbonic Anhydrase (CA ) - and hypokalemia, drowsiness, anorexia,
located in the proximal tubules where 2/3 of paresthesia, hematuria, urticaria,
the Na+ and water is reabsorbed; Hydrogen photosensitivity, and melena (blood in stool)
must be exchanged in order for it to be Interactions:
reabsorbed; CA makes hydrogen available Digoxin, corticosteroids = toxicity due to
for this exchange induced hypokalemia /Increased effects of
✓CAIs prevents reabsorption of water and drugs such as amphetamines,
Na+ in the blood, thus they are eliminated in carbamazepine, cyclosporine, phenytoin,
the urine and quinidine
✓CAIs reduce formation of hydrogen and
bicarbonate ions = induce respiratory and
metabolic acidosis → increase
oxygenation in hypoxia by increasing Acetazolamide (Diamox)
ventilation, cerebral blood flow, and ✓Prototype drug for CAIs
dissociation of oxygen from ✓Dose: 500-1,000 mg/day (oral or IV)
oxyhemoglobin (BENEFICIAL)
Indications: Loop Diuretics
✓Adjunct drug in treatment of open-angle ✓Bumetanide, ethacrynic acid, furosemide,
glaucoma → CAIs increase the outflow of and torsemide
aqueous humor; can also be given along ✓Potent diuretics = rapid onset and long
with miotics in preparation for ocular duration (effective as a single daily dose)
surgery ✓Bumetanide, furosemide, and torsemide
✓Acetazolamide is used to manage edema are chemically related to the sulfonamide
secondary to heart failure that has been antibiotics
resistant to other diuretics, but less potent ✓Have renal, cardiovascular, and metabolic
and effectiveness diminishes in 2-4 days effects
because they induce metabolic acidosis Mechanism of Action:
✓Acetazolamide is effective in both ✓Act along the thick ascending limb of the
prevention and treatment of symptoms of loop of Henle
high-altitude sickness (symptoms: ✓Activate renal prostaglandins → causes
headache, nausea, shortness of breath, dilation of blood vessels of the kidney,
dizziness, drowsiness, and fatigue) lungs, and the rest of the body (decrease
Contraindications: vascular resistance)
✓Drug allergy, hyponatremia, Effects:
hypokalemia, severe renal or hepatic ✓Potent diuresis and subsequent loss of
dysfunction, adrenal gland insufficiency, and fluid → decreased fluid volume →
cirrhosis decreased return to the heart or decreased
Adverse Effects: filling pressures leading to:
➢Reduction of blood pressure

26
 ➢Reduction of pulmonary vascular ✓ Neurotoxic and nephrotoxic properties →
resistance additive effects when given in combination
➢Reduction of systematic vascular with drugs that have similar toxicities
resistance ✓ Affect laboratory results: INCREASE in
➢Reduction of central venous serum levels of uric acid, glucose, ALT,
pressure ➢Reduction of left AST
ventricular end-diastolic pressures ✓ If combined with thiazides (metolazone)
✓Metabolic effects: Secondary to cause sequential nephron blockade
electrolyte losses (Na+, K+, Ca++) (blockade of sodium and water resorption at
✓Changes in plasma levels of insulin, multiple sites in the nephron
glucagon, and growth hormone ✓ NSAIDs: Have opposite effects on
Indications: prostaglandin activity; diminish activity of
✓Manage edema associated with heart loop diuretic
failure and hepatic or renal disease
✓Control hypertension
✓Increase renal excretion of calcium in
patients with hypercalcemia
Contraindications:
✓Drug allergy, hepatic coma, and severe
electrolyte loss Adverse Effects:
✓Hypokalemia (give potassium
supplements as prevention)
✓Torsemide – blood disorders, including
thrombocytopenia, agranulocytosis,
leukopenia, and neutropenia; also Prototype Drug: Furosemide (lasix)
Stevens-Johnson syndrome
Toxicity:
✓Electrolyte loss and dehydration →
circulatory failure
Treatment: Electrolyte and fluid
replacements

Adverse Effects of Loop Diuretics

Osmotic Diuretics
✓Mannitol, urea, organic acids, and
glucose ✓Mannitol = nonabsorbable solute;
Interactions of Loop Diuretics most commonly used drug
Mechanism of Action: (mainly Mannitol)

27
✓Works along the nephron; Major sites are ✓Percentage indicates the number of grams
the proximal tubule and descending limb of per 100 mL of fluid (always double check
the loop of Henle calculations in infusions)
✓Not absorbed = Increases osmotic ✓Crystallizes in low temperature (occur if
pressure in the glomerular filtrate → pulls concentrations exceed 15%)
water into renal tubules from surrounding ✓Before administering mannitol, visually
tissues ✓Inhibits tubular resorption of water inspect the mannitol container for
and solutes → rapid diuresis precipitants
Effects:
✓Reduces cellular edema and increases
urine production
✓Induce vasodilation → increase
glomerular filtration and renal plasma flow Potassium-Sparing Drugs
(prevents kidney damage during acute renal ✓Amiloride, spironolactone, and
failure) triamterene ✓Aldosterone-inhibiting
Other Uses: diuretics because they block aldosterone
✓Reduce intracranial pressure and cerebral receptors ✓Spironolactone – competitive
edema resulting from head trauma antagonist of aldosterone; causes sodium,
✓Reduce intraocular pressure and water to be excreted and potassium
Indications: retained; most commonly used among the 3
✓Treatment for patients in early oliguric drugs Mechanism of Action and Drug
phase of acute renal failure (as long as renal Effects: ✓Work in the collecting ducts and
blood flow and glomerular filtration is distal convoluted tubules → interfere with
enough) sodium-potassium exchange
✓Promote excretion of toxic substances, ✓Spironolactone competitively binds to
reduce intracranial pressure, and treat aldosterone receptors and aldosterone effects
cerebral edema in the distal tubules
Contraindications: ✓Amiloride and triamterene inhibit
✓Drug allergy, pulmonary edema, and aldosterone-induced and basal sodium
active intracranial bleeding resorption in the distal tubule and collecting
Adverse Effects ducts
✓Convulsions, thrombophlebitis, and ✓Prescribed for children with heart failure
pulmonary congestion Interactions: None because the cause is usually excess secretion
of aldosterone
Mannitol ✓Weaker than thiazide and loop diuretics
✓Prototypical osmotic diuretic ✓Used as adjuncts in thiazide treatment
✓Available only in parenteral form as 5%, (both have synergistic effects and counteract
10%, 15%, 20%, and 25% solutions for each other’s adverse metabolic effects)
intravenous injection Indications:
✓Spironolactone and triamterene –
hyperaldosteronism and hypertension, and to

28
reverse potassium loss caused by
potassium-wasting due to loop or thiazide Prototype Drug:
diuretics Spironolactone(Aldactone)
✓Spironolactone – cardioprotective due to
aldosterone-inhibiting activity = prevents
remodeling process
❖Heart failure → caused by
hyperactive
renin-angiotensin-aldosterone system
→ causative factor in permanent
damage to the ventricular myocardial
wall (remodeling) following
myocardial infarction
✓Amiloride – same uses as triamterene and Triamterene
spironolactone but less effective in treatment ✓ Pharmacologic properties similar to
of metabolic alkalosis; primarily used for amiloride
heart failure ✓ Acts directly on the distal renal tubule of
Contraindications: the nephron to depress the resorption of
✓ Drug allergy, hyperkalemia (serum K+ sodium and excretion of potassium and
level exceeding 5.5 mEq/L), and severe hydrogen ions
renal failure or anuria ✓ Has little or no antihypertensive effect
Adverse Effects: ✓ Available only in oral form
✓ Spironolactone – gynecomastia, ✓ Also available in combination with
amenorrhea, irregular menses, and HCTZ (a thiazide diuretic)
postmenopausal bleeding
✓ Triamterene (rare) – reduce folic acid
levels and cause formation of kidney stones
and urinary casts; precipitate megaloblastic Thiazide and Thiazide-Like Diuretics
anemia ✓Thiazide diuretics are benzothiadiazines,
✓ Hyperkalemia when used with other which are chemical derivatives of
potassium-sparing drugs such as ACE sulfonamide antibiotics - Chlorothiazide and
inhibitors HCTZ
Interactions: ✓HCTZ – most commonly prescribed and
✓ ACE inhibitors, and potassium least expensive; combined with
supplements = hyperkalemia antihypertensive drugs
✓ Lithium = lithium toxicity ✓Thiazide-like diuretics – similar to
✓ NSAIDS = diminished diuretic response thiazides; chlorthalidone, indapamide;
metolazone; Metolazone is most effective in
this class in the treatment of patients with
renal dysfunction

29
Mechanism of Action:
✓Primary site of action is at the distal
convoluted tubule
✓Inhibit the resorption of sodium,
potassium, and chloride = results in water
loss
✓Cause direct relaxation of the arterioles
which reduces peripheral resistance
❖As renal function decreases, efficacy
diminishes because delivery of the drug to
site is impaired
❖Thiazides are not to be used if creatinine
clearance is less than 30 to 50 mL (N=125 Drug Interactions of Thiazide and
mL/min depending on age of the patient) Thiazide-Like Diuretics
❖Metolazone remains effective to a
creatinine clearance of 10 mL/min, thus
used in cases of renal failure
Indications:
✓Treatment of edema of various origins,
idiopathic hypercalciuria, and diabetes
insipidus in addition to hypertension
✓Adjunct drugs in management of heart
failure and hepatic cirrhosis
✓May be used in heart failure due to
diastolic dysfunction
Contraindications:
✓Drug allergy, hepatic coma (metolazone),
anuria, and severe renal failure
Toxicity and Management of Overdose: Prototype drug: Hydrochlorothiazide
✓OD and toxicity: Electrolyte imbalance (Microzide)
resulting from hypokalemia
✓Treatment: Electrolyte replacement

Adverse Effects of Thiazide and

Thiazide-Like Diuretics

Metolazone

30
✓Thiazide-like diuretic
✓More potent than thiazide diuretics
✓Important in patients with renal
dysfunction
✓Effective to a creatinine clearance as low
as 10 mL/min
✓May be given with loop diuretics for
patients with moderate to severe heart
Skin Turgor
failure
✓More efficacious when given 30 minutes
before loop diuretics
✓Available only in oral form

Dosages of Thiazide and Thiazide-Like

Diuretics
Capillary Refill Time

NURSING PROCESS (Diuretics)

Important Considerations
Details of Information Card

31
32
 Goal: Maintain homeostasis

Homeostasis
✓Fluid intake is equal to fluid output
✓Fluid intake: liquids, solid foods, IV
fluids, or parenteral fluids
✓Fluid output: urine, emesis, or feces
✓Insensible losses: skin, lungs, GI tract
✓Measurable losses: fistulas, drains, or GI
suction
✓Overhydration: sudden weight gain is
strong indicator
Fluids and Electrolytes
✓Edema: Fluid excesses that accumulate in
interstitial spaces, such as the pericardial
sac, joint capsules, and lower extremities
✓Dehydration: Quantity of water lost
exceeds water gained; water deficit; Death
occurs when 20-25% of TBW is lost
✓Sodium is the principal extracellular
electrolyte that plays primary role in water
concentration

Types of Dehydration
Hypertonic
Fluid and Electrolyte Management
Occurs when water loss is greater than
✓ One of the cornerstones of patient care
sodium loss, which results in a concentration
✓ Body fluids provide transportation of
of solutes outside the cells and causes the
nutrients to cells and carry waste products
fluid inside the cells to move to the
away from the cells
extracellular space, thus dehydrating the
✓ Approximately 60% of adult human body
cells. Example: Elevated temperature
weight is composed of water
resulting in perspiration.
✓ Percent BW is higher in infants and
Hypotonic
lower in older adults
Occurs when sodium loss is greater than
Functions of Water
water loss, which results in higher
✓Acts as a solvent to dissolve solutes
concentrations of solute inside the cells and
✓Acts as a medium for metabolic reactions
causes fluid to be pulled from outside the
Internal Control Mechanisms for Fluid
cells (plasma and interstitial spaces) into the
Balance
cells. Examples: Renal insufficiency and
✓Thirst
inadequate aldosterone secretion.
✓Antidiuretic hormone (ADH)
Isotonic
✓Aldosterone

33
Caused by a loss of both sodium and water ✓ Used in reference to body fluids and is
from the body, which results in a decrease in the concentration of the particles in a
the volume of extracellular fluid. Examples: solution
Diarrhea and vomiting. ✓ Normal osmolality of body fluids:
290-310 mOsm/kg
Conditions Leading to Dehydration Tonicity
✓ Used in reference to IV fluids and is the
Conditions Leading to Fluid Loss or
Dehydration and Associated measurement of the concentration of the IV
Corresponding Symptoms fluids as compared with the osmolality of
body fluids
✓ Measure of osmotic pressure
❖ Isotonic – osmotic pressure inside and
outside the cell is equal; normal saline (0.9%
Condition Associated NaCl) or lactated Ringers solution; no net
Symptoms fluid movement
❖ Hypotonic – solution outside the cell has
lower osmotic pressure than inside the cell;
Bleeding Tachycardia and 0.45% NaCl solution; causes fluid to move
hypotension out of the vein and into the tissues and cells
❖ Hypertonic – solution outside the cell has
Bowel Reduced perspiration higher osmotic pressure than inside the cell;
obstruction and mucous 3% NaCl injection; causes fluid to move
secretions from ISF into the veins

Solutions
Diarrhea Reduced urine output
(oliguria)

Fever Dry skin and mucous

membranes

Vomiting Reduced lacrimal

(tears) and salivary
secretions
*There may be overlap involving more than
one of the symptoms depending on the
patient's specific condition.

Tonicity and Osmolality Acid-Base Balance

Osmolality

34
✓ Regulated by the respiratory system and
kidneys
✓ Acid – substance that can donate or
release H+
✓ Base – substance that can accept H+,
such as bicarbonate
✓ pH – measure of the degree of acidity
and alkalinity; inversely related to hydrogen
ion concentration
✓ Normal pH range – 7.35 to 7.45;
Acidosis pH below 7.35 and alkalosis pH
above 7.45
Acid-Base Disorders and Compensation
Regulation of Acid-Base Balance
✓Respiratory system compensates for
metabolic problems and pH imbalances by
regulation of carbon dioxide (CO2)
✓Kidney compensates for metabolic
problems by regulating of reabsorption of Crystalloids
bicarbonate (HCO3-) and excretion of ✓Fluids given by IV injection that supply
hydrogen ion (H+) water and sodium to maintain osmotic
Laboratory Tests gradient between the extravascular and
✓Arterial Blood Gas (ABG) – influence of intravascular compartments
the respiratory system ✓ Short-term plasma volume – expander
✓Blood Test to determine Acid-Base (related to their sodium concentration)
balance – measures total body CO2 and is ✓Normal saline (0.9% NaCl) and lactated
usually represented as HCO3 Ringers solution
❖Serum is a term closely related to plasma
Acid-Base Imbalance

Causes of Acid-Base Imbalance

35
 Adverse Effects:
✓Do not stay within the blood vessels and
can leak out of the plasma into the tissues
and cells (because they don’t have large
particles like proteins) → peripheral edema
and pulmonary edema
✓Dilute proteins in the plasma → reduces
colloid oncotic pressure
✓Prolonged use can cause fluid overload
✓Effects are relatively short-lived
Interactions:
✓Rare

Sodium Chloride
- Physiological electrolyte
Mechanism of Action: - No hypersensitivity reactions to it; safe
✓ Contain fluids and electrolytes that are during pregnancy
normally found in the body - Contraindicated to patients with
✓ Do not contain proteins (colloids) hypernatremia and/ or hyperchloremia
✓ Distributed faster into the interstitial and - Available in several concentrations in
intracellular compartments than colloids solutions and available in 650 mg tablets
✓ Better for treating dehydration than
expanding plasma volume alone
✓ Much less expensive than colloids and
blood products NaCl solutions
✓ No risk for viral transmission or ISOTONIC
anaphylaxis and no alteration of coagulation - 0.9% is the most common
profile associated with blood products - Physiologically normal concentration of
Indications: sodium chloride
✓ Maintenance fluids - Referred to normal saline (NS)
✓ Compensate for insensible fluid losses, to - Contains 154 mEq of sodium per liter
replace fluids, and to manage specific fluid
and electrolyte disturbances HYPOTONIC
✓ Promote urinary flow - 0.45% and 0.25
✓ Used for liver failure, burns, - Correcting to rapidly can cause hemolysis
cardiopulmonary bypass surgery, of RBC
hypoproteinemia, renal dialysis, and shock
Contraindications: HYPERTONIC
✓ Drug allergy to a specific product, - 3% and 5%
hypovolemia, and electrolyte disturbance - High-alert drug
depending on the crystalloid used

36
- Contraindicated in increased, normal, or quickly while the large particles maintain
slightly decreased sodium concentrations the plasma volume
- Correcting to rapidly can lead to osmotic Mechanism of Action and Drug Effects:
demyelination syndrome (fatal) ✓PLASMA EXPANDERS - Colloids
cannot pass into extravascular space and has
Colloids the ability to increase the colloid oncotic
pressure → moves water from extravascular
space into the blood vessels in an attempt to
make blood isotonic → increase blood
volume
✓Also make up part of the total plasma
volume
✓Increase colloid oncotic pressure – move
fluid from outside to inside the blood vessels
(can maintain this for several hours)
✓ Substances that increase the colloid ✓INDICATIONS: Shock and burns or
oncotic pressure and move fluid from whenever the patient requires plasma
interstitial compartment to plasma volume expansion
compartment by pulling the fluid into the ✓Superior to crystalloids because it
blood vessels maintains plasma volume for a longer time
✓ Three blood proteins responsible: ✓More expensive and are more likely to
ALBUMIN, GLOBULIN, and promote bleeding because they dilute the
FIBRINOGEN blood
✓ Normal total body protein level: 7.4 ✓CONTRAINDICATION: Drug allergy
g/dL; if it falls below 5.3 g/dL → fluid shifts to specific product and hypervolemia, and
out of the blood vessels into the tissues severe electrolyte imbalance
✓ Colloid oncotic pressure decreases in ✓ADVERSE EFFECTS: Generally safe,
malnutrition and old age Dilutional Effect = possible bleeding;
✓ To reverse process: colloid replacement Dextran therapy can cause anaphylaxis and
therapy renal failure (rare)
✓Commonly used colloids: ALBUMIN ✓INTERACTIONS: None
(naturally-occurring), DEXTRAN
(carbohydrates) , HETASTARCH (starch)
✓ Other types of colloids come from fats
(lipid emulsion) and animal collagen
(gelatin)
✓ With the exception of albumin, most
colloids are combination of small and large
particles; small particles are eliminated

37
 ALBUMIN
✓ Natural protein produced by liver
✓ Generates 70% of colloid pressure
✓ Human albumin is a sterile solution
albumin prepared from pooled blood,
plasma, serum, or placentas obtained from
healthy human donors; pasteurized
✓ Limited supply; expensive
✓ CI: hypersensitivity, heart failure, severe
anemia, or renal insufficiency Blood Products
✓ Parenteral form only in 5% and 25% ✓ Biologic drugs
✓ Augment the plasma volume
✓ RBC-containing products: Improve tissue
oxygenation
✓ More expensive than crystalloids and
DEXTRAN colloids; less available because they require
✓ Solution of glucose human donors
✓ Available as dextran 40 and has same ✓ Indicated for patients who have lost 25%
molecular weight as albumin or more blood
✓ Actions are similar to human albumin → Mechanism of Action and Drug Effects:
expands plasma volume ✓ Plasma Expanders - ability to increase
✓ CI: hypersensitivity, heart failure, renal colloid oncotic pressure (pull water from
insufficiency, and extreme dehydration extravascular space to intravascular space)
✓ Available only in parenteral form mixed ✓ Ability to carry oxygen (RBC products)
in either 5% dextrose solution or 0.9% NaCl ✓ Administered when a person’s body is
solution deficient in these products
✓ CI: None
✓ Adverse Effects: Can be incompatible
with recipient's immune system →
anaphylaxis and rejection; transmit
pathogens (hepatitis and HIV)
Dosing Guide for Crystalloids and
✓ Interactions: Calcium and aspirin which
Colloids
affect coagulation; Blood must NOT BE
administered with any solution other than
normal saline

Indications for Use of Blood Products

38
Packed Red Blood Cells (PRBC)
✓Obtained by centrifugation of whole
blood and separation of RBC’s from plasma
and other cellular elements
✓Advantages: oxygen-carrying capacity,
less likely to cause cardiac fluid overload
✓Disadvantages: high cost, limited
shelf-life, fluctuating availability, as well as
their ability to transmit viruses, trigger Electrolytes
allergic reactions, and cause bleeding
abnormalities Potassium
✓ Most abundant electrolyte inside the
cells; 95% of K+ in the body is intracellular
✓ Normal concentration = 150 mEq/L
✓ Ratio of intracellular to extracellular
potassium is important; changes in
extracellular potassium can lead to
unwanted neuromuscular and cardiovascular
effects
✓ Obtained from diet
Fresh Frozen Plasma (FFP) ✓ Hypokalemia – serum potassium level
✓Obtained by centrifuging whole blood and less than 3.5 mEq/L; Result from decreased
removing cellular elements → resulting intake, shifting of K+ into cells, increased
plasma is frozen renal excretion and other losses such as
✓Used as adjunct to massive blood diarrhea, vomiting, or tube drainage
transfusion in the treatment of patients with ✓ Hyperkalemia – serum potassium level
underlying coagulation disorders greater than 5.5 mEq/L; Result from
✓Plasma-expanding capability is similar to increased intake, reduced renal excretion,
dextran redistribution of potassium from
✓Disadvantage: Can transmit pathogens intracellular to extracellular compartment
following burns or rhabdomyolysis; Severe
Guidelines for Use of Blood Products hyperkalemia manifests as ventricular
fibrillation and cardiac arrest

39
Mechanism of Action and Drug Effects: Interactions: potassium sparing diuretics,
✓Involved in muscle contraction, ACE inhibitors -= hyperkalemia; non -
transmission of nerve impulses, and potassium -sparing diuretics, amphotericin
regulation of heartbeats (pacemaker function B, and mineralocorticoids = hypokalemia
of the heart)
✓Essential for the maintenance of acid-base Dosage Guidelines for Potassium Infusion
balance, isotonicity, and electrodynamic
characteristics of the cell
✓Plays a role in many enzymatic reactions;
essential component in gastric secretion,
renal function, tissue synthesis, and
carbohydrate metabolism
Indication: Treatment or prevention of
potassium depletion Potassium supplements
CI: Allergy to specific drug product, ✓Prevent or treat potassium depletion
hyperkalemia from any cause, severe renal ✓Oral (tablets, solutions, elixirs,
disease, acute dehydration, untreated powders for solutions): acetate,
Addison disease, severe hemolytic disease, bicarbonate, chloride, citrate, and
conditions involving extensive tissue gluconate salts
breakdown (multiple trauma, severe burns) ✓IV parenteral salt forms: acetate,
Adverse Effects: diarrhea, nausea, chloride, phosphate (high-alert drugs
vomiting, GI bleeding and ulceration, pain at = cause toxicity)
injection site (parenteral administration)
❖IV potassium must not be given faster Sodium polystyrene sulfonate
than 10 mEq/hr to patients who are not (Kayexalate)
on cardiac monitors; critically ill on ✓Cation exchange resin used to treat
cardiac monitors = 20 mEq/hr hyperkalemia
Toxicity and Management ✓Administered orally via nasogastric
✓ Result from hyperkalemia tube or as an enema
✓ Symptoms: muscle weakness, ✓Works in the intestine where K+ from
paresthesia, paralysis, cardiac rhythm body are exchanged for Na+ in the
irregularities ➔ ventricular fibrillation and resin
cardiac arrest ✓Electrolytes are monitored when this
✓ Severe hyperkalemia – dextrose IV + is administered due to K+ losses
insulin, sodium bicarbonate, and calcium ❖Should not be administered in
gluconate or chloride = reduces K+ patients who do not have normal
concentration; followed by sodium bowel function; D/C if patients have
polystyrene sulfonate (Kayexalate) orally or constipation
rectally or hemodialysis to eliminate excess ✓Dosage: 15 to 30 g until desired
K+ effect on serum potassium occurs

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 CI: Drug allergy to specific product and
Sodium hypernatremia
- Counterpart of potassium; principal cation AE: Oral administration can cause gastric
outside the cells upset – nausea, vomiting, cramps: IV
- Normal concentration: 135 to 145 mEq/L - administration can cause venous phlebitis
- Hyponatremia – sodium loss or Interactions: antibiotic called
deficiency than 135 mEq/L; manifested as quinupristin/dalfopristin (Synercid)
lethargy, hypotension, stomach cramps,
vomiting, diarrhea, and seizures Sodium Chloride
-Hypernatremia – sodium excess of 145 ✓Replacement electrolyte for prevention or
mEq/L: generally, indicates deficit in total treatment of sodium loss
body water; manifested as muscle cramps, ✓Diluent for infusion of compatible drugs
headache, lethargy, seizures, coma, and and in assessment of kidney function after
possible intracranial hemorrhage fluid challenge
✓IV preparations and 650 mg tablets
Types of Hyponatremia

Type Total Total

Body Sodium Conivaptan
Water
✓ Nonpeptide dual arginine vasopressin
(TBW)
(AVP), V1A and V2 receptor antagonist
Hypovolemic Decreased Increased ✓ Inhibits the effects of ADH in the kidney
hyponatremia (to a greater ✓ Specifically indicated for treatment of
extent) hospitalized patients with euvolemic
Euvolemic Increased Normal hyponatremia, or lowserum sodium levels at
hyponatremia normal water volumes
✓ IV infusion
Hypervolemic Increased Increased ✓ AE: infusion site reactions, thirst,
hyponatremia (to a headache, hypokalemia, vomiting, diarrhea,
greater
and polyuria
extent)
✓ Monitor serum sodium levels because
can cause osmotic demyelination syndrome
Mechanism of Action and Drug Effects: ✓ Interactions: cytochrome P-450 enzyme
✓Involved in control of water distribution, inhibitors - ketoconazole, itraconazole,
fluid and electrolyte balance, and osmotic clarithromycin, ritonavir and indinavir →
pressure of body fluids increase serum Na+ levels
✓Chloride complements physiologic action
of sodium
Indications: Treatment or prevention of
sodium depletion

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Nursing Process (Fluid and Electrolytes)

Antidiabetic Drugs

Drugs for Diabetes

Pancreatic Hormones (Insulin and

Glucagon)
Insulin
• Secreted by beta cells of the pancreas
• Transporter or gatekeeper of glucose to the
cells
• Decrease blood glucose levels
(hypoglycemic effect)
Glucagon
• Secreted by alpha cells of the pancreas
• Increase blood glucose levels
(hyperglycemic effect)

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 HbA1c Test
✓ Blood test that is used to help diagnose
and monitor people with diabetes
✓ Refers to glucose and hemoglobin joined
together
✓ Measures the amount of blood sugar
attached to hemoglobin

Actions of Insulin

Diabetes Mellitus Type 1

• Accounts 5-10% of DM
• Most common disease of childhood
• Insulin-dependent DM
• Caused by autoimmune destruction of
pancreatic beta cells, resulting in lack of
insulin secretion
Blood Glucose Chart • Genetic, immunologic, and environmental
factors play a role in its development
• Prolonged DM produces long-term damage
to arteries → heart disease, stroke, kidney
disease, and blindness
• Inadequate circulation to feet can cause
gangrene in toes which require amputation
• Neuropathy (nerve degeneration) is
common with symptoms such as tingling in
the fingers to complete loss of sensation

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Symptoms ✓ More rapid onset of action
• Hyperglycemia (Humalog)
• Polyuria – excessive urination • ✓ More prolonged duration of
Polyphagia – increased hunger action (Lantus)
• Polydipsia – increased thirst • Insulin is destroyed in the GI tract, thus it
• Glycosuria – high levels of glucose in the must be given by INJECTION
urine ✓ Insulin pumps
• Weight loss • AE: Hypoglycemia, DKA
• Fatigue • Other AE: Localized allergic reaction,
generalized urticaria, and swollen lymph
Diabetic Ketoacidosis nodes: Somogyi phenomenon: rapid
• Because glucose cannot enter cells, lipids decrease in blood glucose during at night
are used as energy source • Tx: For mild to moderate hypoglycemia,
• Ketoacids are produced as waste products give food or drinks containing glucose. In
• Ketoacids give acetone-like, fruity odor of severe hypoglycemia, give IV glucose
patient’s breath dextrose solution, glucagon (IM, IV, or
• High levels of ketoacids lower the pH of subcutaneous) if cannot tolerate IV glucose
the blood
Insulin Pump

Types of Insulin: Actions and

Administration
Pharmacotherapy for Type 1 DM
• Insulin replacement therapy
• Insulin administration should be carefully
planned in conjunction with proper meal
planning and lifestyle habits
•Right amount of insulin must be available
to cells when glucose in present in the blood
• Doses of insulin is highly individualized
• Different types of insulin

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Prototype Drug
| Human Regular Insulin (Humulin R,
Novolin R)

Complementary and Alternative

Therapies

Nursing Process

Diabetes Mellitus Type 2

• More common form representing 90-96%
of DM
• Middle-aged adults, although there are
increasing numbers of children diagnosed
now with DM Type 2
• Cause: INSULIN RESISTANCE – target
cells become unresponsive due to defect in
insulin receptor function
• Activity of insulin receptors can be
increased by physical exercise and lowering
the level of circulating insulin
• Healthy diet and regular exercise program
can reverse insulin resistance and delay or
prevent type 2 DM

Hyperosmolar Hyperglycemic state

(HHS)
• Less common, but higher mortality rate
than DKA

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• Serious, acute condition with mortality rate 4. Thiazolidinediones
of 20-40% 5. Meglitinides
• Onset is gradual and sometimes mistaken 6. Incretin Enhancers and Miscellaneous
for a stroke Drugs
• Seen often in older adults wherein their
skin appears flushed, dry, and warm ANTIDIABETIC DRUGS
• Blood glucose levels may rise above 600
mg/dL
• Tx: Fluid replacement, correction of
electrolyte imbalances, and low dose insulin
given by slow IV infusion

Pharmacotherapy for Type 2 DM

• Six primary groups of antidiabetic drugs
for type 2 DM
• Classified according to their chemical
structure
• Treatment goals: Target an HbA1c of 6.5%
or less with a fasting plasma glucose level
less than 110 g/dL
• Therapy is usually initiated with a single
drug
• If glycemic control is not achieved, then a
second drug is added
• Failure to achieve glycemic control with 2
antidiabetic drugs indicates the need for Prototype Drug: Metformin
insulin to be added to the regimen
• Periodically a third non insulin drug will
be added at the same time as insulin

Six Primary Groups of Antidiabetic

Drugs
1. Sulfonylureas
✓First oral hypoglycemics available
✓1 st and 2nd generation
2. Biguanides
✓Metformin Nursing Process
✓Prototype drug
3. Alpha-Glucosidase Inhibitors
✓Acarbose

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