PHARMACOLOGY

CVS block- Drugs summary

lectures 1,2 : adrenergic blockers
 Adrenergic neuron blockers

Adrenergic neuron blockers

• formation of false transmitters (methyl

norepinephrine)
• stimulation of presynaptic α2 receptors to
α-methyl dopa inhibit NE release (as clonidine)
• acts centrally
• Drug of choice in: hypertension in pregnancy
(pre-eclampsia - gestational hypertension)

• depletion of storage sites

Reserpine reserpine = depletes reserves

Guanethidine • inhibtion of release and enhance uptake

• stimulation of presynaptic α2 receptors to

inhibit NE release (as α-methyl dopa)
• acts centrally (on the brain)
Clonidine
• little used as antihypertensive agent due to
rebound hypertension upon abrupt
withdrawal. This can be treated with labetalol.

• used in open angle glaucoma. Acts by

Apraclonidine decreasing aqueous humor formation.
 α adrenergic antagonists

Drug Receptor action: Therapeutic use

selectivity
Phenoxybenzamine  Postural hypotension Used Before surgical
Non-selective  Decrease peripheral removal of
(irreversible-long
(α1 – α2) vascular resistance Pheochromocytoma
acting 24h)  Increase cardiac output to protect against
Phentolamine (α2 block) hypertensive crisis.
(reversible-short  Precipitate in Contraindicated in:
arrhythmias Patient with
acting 4h)
and angina decreased coronary
perfusion
Prazosin α1 selective • Vasodilatation due to 1-Benign prostatic
blockers relaxation of arterial and hyperplasia
(short half-life)
venous smooth muscles
Doxazosin  Fall in arterial pressure 2-Hypertension with
(long half-life) with less tachycardia prostate enlargement
Terazosin than with non-selective α
blockers 3-Reynaud’s disease
(long half-life)
Tamsulosin α1A  Relaxation of smooth
(present in muscles of bladder neck
prostate) and prostate → improve Benign prostatic
urine flow hypertrophy (BPH)
 Minimal effect on blood
pressure
Yohimbine α2 ↑nitric oxide in corpus Aphrodisiac in
cavernosum → vasodilatation erectile dysfunction
→ erectile process

Adverse effects* of non-selective α blockers

(phenoxybenzamine – phentolamine):
 Postural hypotension *α1 antagonists have
 Tachycardia the same adverse effects
 Headache but to a lesser degree.
 Nasal stuffiness and congestion
 Vertigo and drowsiness
 Male sexual dysfunction (inhibits ejaculation)
 - Adrenoceptors blockers

DISEASE DRUG (s) mechanism of action

• ↓ cardiac output
• ↓ renin and RASS system
Labetalol (by injection)
• Inhibition of presynaptic NE release
Hypertension Atenolol, Bisoprolol >
• Inhibition of sympathetic outflow in CNS
Metoprolol, Propranolol
• Treatment of hypertensive pregnant & hypertensive
crisis

Esmolol (ultra-short • Propranolol: Membrane stabilization (block Na

𝟏 channel local anesthetic effect/ antiarrhythmic
acting, T𝟐 = 𝟏𝟎 𝒎𝒊𝒏),
Cardiac effect: ↓ excitability, ↓automaticity , ↓
Arrhythmias Atenolol, Propranolol conductivity)
(Bisoprolol and • treatment of supraventricular & ventricular
CVS

carvedilol are preferred) arrhythmias

Beta blockers • anti -ischemic action : ↓heart rate, ↓ cardiac work &
Angina pectoris
e.g. propranolol oxygen demand, ↓the frequency of angina episodes.
Carvedilol (antioxidant
Congestive • Decrease myocardial remodeling
action)
Heart Failure • decrease risk of sudden death.
Bisoprolol, Metoprolol
• Have cardio-protective effect: ↓ infarct size ,↓
Myocardial Atenolol, Metoprolol, morbidity & mortality ,↓ myocardial O2 demand.
Infarction Propranolol • Anti-arrhythmic action (Quinidine-like action)
• Decrease the incidence of sudden death .
Timolol (eye drop) , ↓aqueous humor production from ciliary body
Chronic Glaucoma
propranolol ↓intraocular pressure (IOP)
• Protect the heart against sympathetic
Hyperthyroidism Beta blockers
overstimulation
(thyrotoxicosis) (e.g. Propranolol)
• Controls symptoms; tachycardia, tremors, sweating.
• Propranolol is Lipid soluble , thus has CNS effect
Anxiety (Social and Propranolol (orally or
sedative action  Control anxiety symptoms
performance type) parenteral)
(tachycardia, tremors, sweating)
reduce episodes of chronic migraine
Migraine (prophylaxis) propranolol catecholamine-induced vasodilatation in the brain
vasculature (antagonize the sympathetic effect)

Labetalol (has to be
Hypertensive crisis of -blockers lower the elevated blood pressure.
combined with 
Pheochromocytoma -blockers protect the heart from NE.
blockers)
 - Adrenoceptors blockers
• Most of them are lipid soluble (Metoprolol, propranolol, timolol, labetalol, carvedilol),
Pharmaco-

these are well absorbed orally, rapidly distributed, cross readily BBB & Have CNS
kinetis

depressant actions
• Most of them have a half-life from 3-10 hrs except Esmolol (10 min. given by I.V.).
• Most of them metabolized in liver & excreted in urine.
selective β1-blockers (Due to blockade of 1- receptor):
Bradycardia, hypotension, heart failure
Since there is NO change in lipid or glucose & NO bronchoconstriction, they’re SAFE FOR:
• Asthma & COPD
• Raynaud’s phenomenon and PVD
• Diabetics/ Dyslipidemias
• Variant Angina
Note: Selectively present in low doses, Lost in high doses
Non selective β-blockers (Due to blockade of 2- receptor):
Adverse Effects:

• Depression + Hallucinations
• GI disturbances ( Intestinal motility)
• Bronchoconstriction, specially in susceptible patients
• Sodium retention 2ndry to BP renal perfusion
• hypoglycemia,  Lipolysis , ↑TG (hyperglyceridemia)
•  peripheral resistance (PR) by blocking vasodilatory effect  Vasoconstriction  blood
flow to organs except brain  cold extremities & intermittent claudication ( 2)
• Erectile dysfunction & impotence
• Coronary spasm (in variant angina patients)
Mixed alpha & beta receptor blockers:
• Carvedilol: Edema
• Labetalol (membrane stabilizing effect with ISA): Orthostatic hypotension, Sedation and
dizziness
All β-blockers:
• Masked hypoglycemic manifestations i.e. tachycardia, sweating… Coma
• Heart Block (because beta blockers can precipitate heart block).
• Bronchial Asthma, emphysyma & Peripheral vascular disease (safer with cardio-selective
indications

1 blockers).
Contra-

• Diabetic patients  Masking of hypoglycaemia / must be GIVEN CAUSIOUSLY

• Hypotension
• Alone in pheochromocytoma (must be given with -blockers).
• peripheral diseases like Reynaud's disease
Precautions

Sudden stoppage will give rise to a withdrawal syndrome:

Rebound angina, arrhythmia, myocardial infarction & Hypertension
WHY ? Due to Up-regulation of -receptors (increase number of -receptors)
To prevent withdrawal manifestations  drug withdrawn gradually.
Mind map- lectures 3,4: Antiarrhythmic Drugs

Note: Class 5 aren’t Calcium channel blockers. Class 4 are.

For a better version, click here
 Drugs summary- lectures 3,4:
ANTIARRHYTHMIC DRUGS
Antiarrhythmic Drugs
Uses: Mechanism of action:
-atrial flutter & fibrillation (common use). Cardiac ( Direct):
-Can be used in ventricular tachycardia. (Membrane stabilizing effect)
-maintaining sinus rhythm after D.C. cardio - Block K+ channel
version. - Prolong PR & QT intervals

(Given orally)
Quinidine
- Widens QRS complex.
Action: ADRs:
-Prolong - quinidine syncope due to torsades de ANS ( Indirect):
action pointes -Anticholinergic effect (Increase
IA potential - Dry mouth. conduction through the A.V.
- Blurred vision.
duration by: node)
- Urinary retention.
Slow phase 0. *α-adrenergic blocking effect
- Constipation.
- Hypotension.
- Slow
conduction Similar to quinidine except :
- less toxic on the heart.
ADRs:
- Lupus erythematosus-like
Procainamide
(Can be given IV)

- More effective in ventricular than in

atrial arrhythmia. syndrome ( in long term
therapy).
CLASS I (Na+ channel blockers)

- No anticholinergic or α-blocking actions - Hypotension .

- Torsades de pointes.
- Hallucination & psychosis .

Uses: ADRs:
(given IV bolus or slow

Treatment of emergency ventricular -Hypotension

arrhythmia (e.g. during surgery, following -Similar to other local anesthetics.
Lidocaine

acute myocardial infarction). CNS adverse effects:

infusion)

Not effective in: -paresthesia.

- tremor.
Action: - Oral administration.
- In atrial arrhythmia. - Dysarthria.
- Decrease T1/2: - tinnitus.
IB action
potential
2 hours - confusion.
- Convulsion.
duration by ADRs:
shortening
Uses:
- Nausea
- Ventricular arrhythmia.
( effective orally)

phase 3 - Vomiting
Mexiletine

(repolarizatio - Digitalis-induced arrhythmia. - Tremor

n) - Drowsiness
T1/2: - Diplopia
- Arrhythmia
- 10 hours - Hypotension

Action: Uses: ADRs:

- Slow phase 0
Flecainide

- Supraventricular arrhythmia. - Proarrhythmia.

(depolarization
- Wolff-Parkinson-White syndrome - Heart failure due to -ne
IC - No effect on - Very effective in ventricular inotropic effect.
action potential arrhythmia. - CNS adverse effects:
duration. - Should be reserved for ventricular Dizziness, tremor, blurred
arrhythmia. vision, abnormal taste
sensation, paraesthesia.
 Drugs summary- lectures 3,4: Antiarrhythmic Drugs
Action: Very short acting (half- Uses:
(β- ADRENOCEPTOR BLOCKERS)

Esmolol
a- Block β1 receptor in life= 9min.) - Atrial arrhythmia associated with
the heart. Given IV fro rapid control emotion.
b- Reduce sympathetic of ventricular rate ( atrial
CLASS II

effect on the heart.

- WBW.
flutter or fibrillation). - Digitalis-induced arrhythmia.
c- 1-decrease
automaticity of SA node used in patients who had

Propranolol
Metoprolol
Atenolol
and ectopic pacemaker. myocardial infarction to
2-prolong refractory
period of AV node. reduce incidence of
sudden death due to
ventricular arrhythmias.
pharmacological actions: Adverse effects:
Action: - prolongs action potential - bradycardia & heart block, heart failure
- pulmonary fibrosis
Prolong the action duration and therefore
- hyper- or hypothyroidism
prolongs refractory period (
potential duration Main effect )
- photodermatitis & skin deposits
by prolong phase 3. ( patients should avoid exposure to the sun)
- additional class Ia, II & IV - may cause bluish discoloration of the skin.
effects - CNS: tremor, headache, ataxia, paresthesia
- vasodilating effects - constipation
( due to its α- & β- - corneal micro deposits
adrenoceptor blocking effects - hepatocellular necrosis
and its calcium channel - peripheral neuropathy
blocking effects )
Pharmacokinetics: Drug Interactions:
- long t1/2 = (13 - 1 - As amiodarone is
Amiodarone

103 days) metabolized by

CYP3A4 & CYP2C8.
Therapeutic uses: - metabolized to
drugs (or substances)
its major active
1- main use : serious that inhibit these
metabolite
resistant ventricular N-
enzymes will increase
serum concentration
CLASS III

arrhythmias desethylamiodaro of amiodarone

2- maintenance of sinus n-e by cytochrome e.g. : Loratadine,
rhythm after D.C. cardio P450 3A4 Ritonavir, Trazodone,
version and CYP2C8 Cimetidine, Grapefruit
3- resistant - eliminated juice.
primarily by 2 - drugs that are
supraventricular
hepatic inducers of these
arrhythmias ( e.g. WPW ). enzymes will decrease
metabolism
serum concentration
- cross placenta
of amiodarone
and appear in e.g. : Rifampin
breast milk 3 - Reduces clearance
of several drugs e.g.
quinidine, warfarin,
procaiamide,flecainide

•Given by rapid I.V. infusion.

Ibutilide

•Used for the acute conversion of atrial flutter or fibrillation to normal sinus
rhythm.

•Causes QT interval prolongation.

•May cause torsades de pointes.

 Drugs summary- lectures 3,4: Antiarrhythmic Drugs
Action:
Therapeutic uses :

Diltiazem Verapamil
calcium channel blockers.
main site of action is A.V 1- atrial arrhythmias
Class IV

node & S.A node. 2- re-entry supraventricular arrhythmias. e.g. WPW

cause: 3- NOT effective in ventricular arrhythmias
- slowing of conduction
- prolongation of effective
refractory period

Drugs: Mechanism of action : (of Therapeutic uses : (of Adenosine)

CLASS V (MISCELLENIOUS

Adenosine) ■ half-life = less than 10 sec.

ANTIARRHYTHMIC DRUGS)

■ drug of choice for acute management of

-inhibits cAMP by binding to adenosine
paroxysmal supraventricular tachycardia
Adenosine A1 receptors, causing the following ■ preferred over verapamil – safer
actions: and does not depress contractility
1 - Opening of potassium channels
Digitalis (hyperpolarization). Adverse effects: (of Adenosine)
2 - decreasing conduction velocity ■ flushing in about 20% of patients
mainly at AV node. ( negative ■ shortness of breath and chest burning in
10%
dromotropic effect )
of patients ( bronchospasm )
3- inhibiting phase 4 pacemaker action ■ brief AV block ( contraindicated in heart
potential ( SA node). block)
( negative chronotropic effect ).
Drugs summary
 mind map- lectures 5,6: treatment of heart failure

For a more detailed mind map (therapeutic use), click here.

 Drugs summary- lectures 5,6: Treatment of heart failure

Veno- Aldosterone Arterio-

Group Diuretics
dialators antagonists dialators

Decrease
Action Decrease preload
afterload
• reduce salt and water
retention antagonist of dilate arterial
Mechan • which decrease ventricular
Dilate venous
aldosterone blood vessels to
blood vessels
ism of preload and venous pressure
and ↓
↓ peripheral
receptor vascular
action • reduction of cardiac size preload
• Improvement of cardiac resistance
performance

1-Spironolactone
1- Chlorothiazide • nonselective
first-line agent in heart antagonist of
failure therapy Nitroglyceri aldosterone
used in volume overload receptor
ne
(pulmonary and/ or • a potassium
& Isosorbide
peripheral edema) sparing diuretic Hydralazine
used in mild congestive dinitrate used in Used when
heart failure used I.V. for congestive the main
Drugs 2- Furosemide severe heart heart failure symptom is
a potent diuretic used for failure when • improves Rapid fatigue
immediate reduction of the main survival in due low
pulmonary congestion & symptom is advanced heart cardiac output
severe edema associated dyspnea due failure
with : to pulmonary 2- Eplerenone
- acute heart failure congestion a new selective
- moderate and severe aldosterone
chronic failure receptor
antagonists
 Drugs summary- lectures 5,6: Treatment of heart failure

Angiotensin converting Angiotensin α-adrenoceptor Direct

Group enzyme inhibitors receptor blockers vasodilators
blockers

Action Decrease both ( preload and after load )

1st line for hypertension &
chronic heart failure therapy
Blocks AT1 receptors
along with diuretics.
Mechanism decrease the action of block α- receptors in
inhibit ACE  reduce synthesis
AgII
of action of AgII  activation of arterioles and venules
(more potent effect
Bradykinin system which is a
than ACE)
potent vasodilator.
↓ preload and afterload

1-Decrease peripheral resistance (Afterload ) reduce blood pressure by

Useful 2-Decrease Venous return (Preload) decreasing both afterload
Effects 3- Decrease sympathetic activity & preload which help
4- Inhibit cardiac and vascular remodeling heart failure patients

Losartan, Valsartan, Sodium

Captopril Enalapril Rampril
Irbesartan Prazosin nitroprusside
Rapidly absorbed from GIT after
oral administration
Food reduce their bioavailability
- I.V acute or
Prodrugs converted severe
Short
to their active refractory HF
Drugs duration
metabolites in the
of action
liver -Acts
Not a
Long T1/2 immediately
prodrug
(given once daily)
- Effect lasts
Enalaprilat 1 – 5 min
(active metabolite of Enalapril )
Used I.V in hypertensive
emergency

1- acute renal failure

2- hyperkalemia
3-hypotension in hypovolemic
Adverse
patients
effect
4- Dry cough
5- angioneurotic edema
6-Dysgeusia

• during the second and third

Contra-
trimesters of pregnancy
indications
• renal artery stenosis
 Drugs summary- lectures 5,6: Treatment of heart failure

β – adrenocepters
Group Cardiac glycosides (Digitalis) Phosphodiesterase-III inhibitors
agonists

action Increase contractility (+ve inotropic)

Amrinone / Milirone Dobutamine
Drugs Digoxin
Enoximone / vesnarinone (new drugs) (selective β1 agonist)

Inhibit Phosphodiesterase isoenzyme

Inhibit NA/K ATPase enzyme (the
3 in cardiac and blood vessels to
Sodium pump)
inhibit cAMP degradation (↑cAMP)
1- inhibit Na/K pump directly
Mechanis 2- indirect inhibition of Na/Ca exchange
1- in heart: ↑ Ca which ↑
m of action 3- facilitate Ca influx contraction
4- ↑ Ca release from ER & T tubules
2- in peripheral vessels dilatation of
Net result : increase the intracellular
arteries and veins (reduction of
Calcium
preload and afterload)

1- increase the force of myocardial

Pharmacol contraction to increase cardiac output
- ogical ( +ve inotropic effect )
action 2- slow heart rate by vagal stimulation
(-ve chronotropic effect)

- narrow therapeutic index

Pharmaco- - 40-80 % absorbed orally (variable
kinetics bioavailability)
- 85% excreted unchanged in urine

Milrinone : Acute heart failure

- congestive heart failure Treatment of acute
- Atrial arrhythmias: (intravenously), not safe nor effective
Therapeuti heart failure in
• Atrial flutter in the longer treatment (> 48hours)
c uses • Atrial fibrillation Cardiogenic shock
Amrinone not used now because it
• Supraventricular tachycardia (I.V in severe cases)
causes thrombocytopenia

1) digitalis-induced arrhythmias
(any type of arrhythmias for example
bigeminal rhythm )
2) GIT side effects (The earliest signs of 1) GIT upsets (Nausea ,vomiting)
toxicity) 2) thrombocytopenia
Adverse 3) live toxicity
3) CNS side effects especially in old age
effects (Milrinone has LESS hepatotoxic and
Factors that increase toxicity: less bone marrow depression than
- Renal diseases amrinone)
- Hypokalemia
- Hypomagnesemia
- Hypercalemia
 Drugs summary- lectures 5,6: Treatment of heart failure

Group β-adrenoceptor blockers Natriuretic Peptides

Second generation: Bisoprolol, Metoprolol

β1 receptors blockers (cardio selective)
Drugs Nesiritide
Third generation: Carvedilol , Nebivolol
have vasodilator actions ( α- blocking)

Nesiritide is a purified preparation of human

β-blockers:
BNP (which is normally secreted by the
1- attenuate cardiac remodeling
ventricular myocardium in response to stretch)
(cardiac dilatation & hypertrophy)
manufactured by recombinant DNA
Mechanism of 2- slow heart rate, which allows the left
technology.
action ventricle to fill more completely
It increases cyclic-GMP in vascular smooth
3- decrease renin release
muscle, leading to smooth muscle relaxation
reduce mortality and morbidity of
and reduction of preload and afterload
patients with HF

indicated for the treatment of patients with

Therapeutic reduce the progression of chronic heart
acutely decompensated heart failure who have
uses failure, not used in acute heart failure
dyspnea at rest or with minimal activity

Mind map – drugs for heart failure

 mind map- lectures 7,8: Antihypertensive Drugs
Antihypertensive Drugs
DIURETICS
Potassium-sparing diuretics
Loop diuretics
Thiazides
Amiloride as well as
Furosemide spironolactone
Hydrochlorothiazide
-Sever & Moderate hypertension - Not potent antihypertensive,
In Mild hypertension -Sever heart failure mainly used in Heart failure)

β- Adrenoceptor monotherapy in mild to moderate hypertension, In

Blockers severe cases used in combination with other drugs.

non cardio selective(β1 & β2) cardio selective(β1) α–β adrenergic blockers
Propranolol Bisoprolol
Nadolol Labetalol
Atenolol
carvidalol
metoprolol
contraindicated in asthmatic patients

α1-Adrenoceptor •Added to β- blockers for treatment of

hypertension of pheochromocytoma
blockers
Prazosin & Terazosin Doxazosin
Due to the postural hypotension, α1-adrenoceptor blockers are not commonly used for Rx of HTN

Ca++ CHANNEL
Treatment of chronic hypertension with oral preparation
•Nifedipine used for Raynaud’s phenomena
•Nicardipine can be given by I.V. route & used in hypertensive
BLOCKERS emergency

Dihydropyridine Verapamil Diltiazem

It is more selective as vasodilator than a It is more effective as cardiac Intermediate action. Used
cardiac depressant. This group is depressant , therefore mainly for angina pectoris
specifically used for treatment of commonly used as
hypertension. antiarrhythmic .
e.g. Nifedipine, Nicradipine,
Amlodipin (Ankmlor)
 mind map- lectures 7,8: Antihypertensive Drugs
Antihypertensive Drugs
Centrally acting α methyl dopa
sympatholytic drugs
Indirect α 2 agonist
Clonidine
Direct α2-agonist Safely used in hypertensive pregnant
women
Sudden withdrawal causes rebound hypertension

Minoxidil K- channel opener, Arteriodilator

Vasodilators 1.severe hypertension
2.correction of baldness (by Hypertrichosis)

Na nitropruside Hydralazine
Direct , Arteriodilator
Diazoxide
Release of (NO), Arterio & venodilator
1.Hpertensive
1.Hpertensive emergency 1.Moderate -severe hypertension. emergency
2.Severe heart failure 2.Hypertensive pregnant woman 2. Treat hypoglycemia
3. Heart failure (CHF) (contraindicated for
ADRs: cyanide toxicity,
methemoglobinemia diabetics
Cause lupus-erythematosus-like syndrome

Note that ACE I all end with USES:

ACE INHIBITORS the suffix “-pril” - Hypertension
•Drugs include captopril, - Heart failure
Cause Acute renal failure, lisonopril, enalapril, ramipril, - Diabetic
contraindicated in renal fisonopril nephropathy
artery stenosis

Note that all end with the

BLOCKERS OF AT1 suffix “-sartan” Clinical Uses:
RECEPTOR •Drugs include: hypertension.
losartan (Especially in
Adverse effects: asthmatic patients)
As ACEI except cough ,wheezing, valosartan
and angioedema. Because it has no irbesartan
effect on bradykiniin
 Drugs summary- lectures 7,8: Antihypertensive Drugs

Classification Examples Important notes

Hydrochlorothiazide, • K-sparing diuretics reduce K loss in the urine

Diuretics
Furosemide ,potassium • Hydrochlorothiazide & Furosemide
sparing diuretics decrease the B.P by decreasing
(Amiloride, & volume of blood & cardiac output
spironolactone) • Furosemide is indicated for
hypertension with renal impairment
captopril, lisonopril, • Cause and increase the risk of renal failure
ACE Inhibitor enalapril, ramipril,& thus contradiction in patient with renal
fisonopril diseases & Pregnant women
Angiotensin Losartan, valosartan, & Same ADRs & contraindications as ACEI, except
receptor Blockers irbesartan for cough and angioedema, thus indicated for
asthmatic hypertensive patients.
• Treat chronic hypertension
Calcium channel Verapamil, Diltiazem, • Nicardipine is used in hypertensive
blockers Nicardipine & emergency
Nifedipine • side effects :
Verapamil  Constipation
Nifedipine  reflex tachycardia.
• Hydralazine used in Hypertensive pregnant
woman. ADRs: lupus erythematous like
syndrome.
Vasodilators Hydralazine, Minoxidil,
• Minoxidil Cause: (Hypertrichosisis)
Diazoxide, & Na
increase hair growth, That’s why it is
nitropruside
contradicted in female.
• Na nitropruside Cause: Cyanide toxicity &
used in hypertensive emergency
Nadolol, Bisoprolol, • In severe cases used in combination with
β- Adrenoceptor Atenolol, metoprolol, other drugs.
Blockers Labetalol, & carvidalol • They decrease cardiac output & renin
release
• Mask the symptoms of Hypoglycemia in
diabetic patients.
• Prazosin is short-acting, causes first dose
α- Adrenoceptor Prazosin, Doxazosin & hypotension & postural hypotension
Blockers Terazosin • Doxazosin is Preferred, because of its long
half- life
clonidine can lead to rebound hypertension
Centrally acting Clonidine & α methyl α methyl dopa : Safe in Pregnant woman
sympatholytic dopa
 Drugs summary – lectures 9,10: Antihyperlipidemic drugs
1. Drugs targeting exogenous pathways
Ezetimibe Bile acid sequestrants (resins)
Cholestyramine, Colesevelam and Colestipol
Drug
Selectively inhibits absorption of dietary and (Bind bile acids [BA]preventing their
Mechanis biliary cholesterol in the small intestine  pool enterohepatic recycling &  fecal excretion
m of cholesterol available to the liver upregulate LDL (10 folds). that will hepatic C uptake &
receptor. plasma & tissue C .

Pharmaco- LDL 20% LDL 15-30%

 TG 8%  HDL 3-5%
logical  HDL 1-4%  TG & VLDL
action
As Monotherapy, Primary prevention of low risk As Monotherapy: rarely, if statin is
of CHD , contraindicated
Indications As Combination Therapy; is safe (With statinsOr As combination with statins in type IIa
With other lipid lowering drugs As fibrates ). Hyperlipoproteinemia
• GIT disturbance, headache, fatigue, • clinically safe as they are not systemically
• artheralgia and myalgia. absorbed, but May  absorption of fat
ADRs & soluble vitamins ( A, D, E, K)
Interaction • They also  absorption of some drugs,
except for Colesevelam
• Biliary obstruction
Contra-
• Chronic constipation
indications • Severe hypertriglyceridemia

Adjuvants in Hyperlipidemia
Omega -3-FA β---Sitosterol
The adjuvant (found in fish oils containing (found in plants with structure similar to
highly unsaturated FA)
cholesterol)
decreases TG & gives Some Compete with dietary & biliary cholesterol
Mechanism &
vascular protection Absorption.
Effect decrease LDL levels +10%
treatment of very high TGs Given as food supplement before meal in
Indication Hypercholesterolemia

Antihyperlipidemic drugs Combinations

Synergistic combination Contraindicated combination Should be taken with breaks in
between.
Statin & ezetimibe. Statins & Fibrates, because the Resins: decreases the absorption
incidence of myopathy may of statins and ezetimibe.
increase
 Drugs summary – lectures 9,10: Antihyperlipidemic drugs

2. Drugs targeting endogenous pathways

Statins Fibrates
Drug Simvastatin- Lovastatin Clofibrate, Fenofibrat,
Niacin (Nicotinic Acid)
Atorvastatin - Pravastatin Gemfibrozil
Rosuvastatin
competitive inhibitors of HMG- promotes hepatic apoA-I They increase gene
CoA reductase, which catalyzes a production and slows transcription for
Mechanism
rate-limiting step in de novo hepatic clearance of lipoprotein lipase (LPL) →
hepatic cholesterol synthesis apoA-I and HDL ↑catabolism of TG

LDL 18-55% LDL (15-30), LDL (5-20),

Pharmaco-  HDL (15-35) HDL (10-20)
logical  HDL 5-10%
action  Triglyceride (20-50) Triglyceride (20-50)
 TG & VLDL 10-30%

first-line drugs when LDL-lowering • Type llA 1st-line defense for:

drugs are indicated, as they have hypercholestrolemia – • Mixed dyslipidemia
additional Pleiotropic effects. Type llB (i.e. raised serum TG
 Monotherapy : hypercholesterolemia and C )
1. Type IIa Hyperlipoprotinemia. & any combined • Patients with low HDL
If there is no control, hyperlipidemia and high risk of
combine (sequestrants / • Patient with atheromatous disease
Indications ezatimibe, niacine,.. ) to hypertriglyceridemia & ( often type 2 diabetic
decrease cholesterol . low HDL-C. patients )
2. In all ischemic insults • Hyperchylomicronemia. • Patients with severe
 Combination therapy • mixed dyslipidemia resistant dyslipidemia
1. Mixed dyslipidemias ( combination with
2. In diabetics and patients with other lipid lowering
insulin resistance drugs ).

• Hepatotoxicity, raised • Sensation of warmth & • Myositis:

concentrations of liver cutaneous flushing (can Rhabdomyolysis
Acute renal failure,
enzymes ( serum be avoided by low dose especially in alcholics &
aminotransferases) of Aspirin). patients with renal
ADRs • Teratogenicity, statins should • reactivation of peptic impairment.
be avoided during pregnancy ulcer • Gallstones, especially
Clofibrate
• Myalgia & Myopathy ( • hepatotoxicity.
Creatine kinase) • Hyperglycemia
• ↑ uric acid.
Pravastatin and fluvastatin are the - increase risk of
statins of choice in patients taking myopathy when
Drug
other drugs metabolized by combined with statins
interaction
cytochrome 3A4 system. - Displace drugs from
plasma proteins
 Drugs summary – lecture 11: Thrombolytic drugs

Thrombolytic drugs (plasminogen activators)

Types Fibrin Specific Non fibrin-specific
AKA: Tissue plasminogen Activators (t-PA)

Action They activate mainly plasminogen bound to Activate both plasminogen bound to clot
clot surface (non-circulating plasminogen in surface and circulating plasminogen in
tissue). blood.

Examples Alteplase Reteplase Tenectepla Streptokinas Anistrepla Urokinase

se e (SK) se

Origin A modified recombinant Streptokinas acylated Human

Recombinant human t-PA e is a plasminog enzyme
Form Of Prepared By Recombinant Bacterial en obtained
Human tPA. Technology protein. combined from urine
with SK or kidney

T1/2 5 Min 15 Min. 30 Min <20 minutes 70-120 IV infusion.

min

administr IV Bolus Two I.V. Bolus Single IV I.V infusion bolus I.V. 12-20 min
Followed By Injections Bolus. injection
ation An Infusion.

Price - the cheapest more Very

expensive Expensive

ADRs • Less risk of bleeding than Non fibrin- Antigenicity More No

specific thrombolytics , because of Allergy effective anaphylaxi
selectivity to fibrin (no systemic Bleeding. and has s (not
plasminogen activation) less ADRs antigenic)
• Not antigenic: Can be used in patients than SK
with antistreptococcal antibodies (due to
either recent infection or use of SK).

Uses • ST-elevation Myocardial approved Venous or lyses of

Infarction (STEMI) for Acute arterial acute
• Pulmonary Embolism Myocardial thrombosis massive
Infarction pulmonar
(AMI) y emboli

Contraind Absolute contraindications include: Relative contraindications

 Active internal bleeding include:
ications  Cerebral hemorrhagic stroke Active peptic ulcer
 Recent intracranial trauma or neoplasm Severe uncontrolled
 Major surgery within two weeks hypertension.

Antidote Fibrinolytic Inhibitors (Antiplasmins) inhibit plasminogen activation and promote clot
stabilization. E.g. Aminocaproic Acid & tranexamic acid & Aprotinin
Drugs summary – lectures 12,13: Antianginal drugs:
Antianginal drugs
Agents that improve symptoms and ischemia Agents that improve prognosis
1. Organic nitrates
• Short acting nitrates 1. Aspirin / Other antiplatelets
• Long - acting nitrates. 2. Statins
2. Calcium channel blockers 3. ACE Inhibitors
3. Potassium channel openers 4. -AD blockers
4. -adrenoceptor blockers
5. Metabolically acting agents *They help in
6. Others (Ivabradine) 1.Halt progression
* All used for Prophylactic therapy to Halt 2.Prevent acute insult
progression, Prevent acute insults (ACSs), Improve 3.Improve survival
survival. except for Short acting nitrates which are
indicated for attacks & situational prophylaxis

For a better
version, click here
 lectures 12,13: Antianginal drugs:
1. Organic nitrates
Types Short acting Long acting

Drugs Nitroglycerine [GTN] Isosorbide mono & dinitrate

• Sublingual tablets or spray for variant

angina - Acute symptom relief of stable • For long-term Persistent prophylaxis of
angina - Situational prophylaxis “as stable angina.
Indications
before exercise” • CHF  Isosorbide mononitrate +
• I.V. Preparations: in unstable angina, hydralazine [if contraindication to ACEIs]
refractory AHF, AMI

1. Nitric oxide binds to guanylate cyclase in vascular smooth muscle cell to form cGMP.
Mechanism
2. cGMP activates PKG to produce relaxation

1. Venous vasodilation → ↓preload

Hemodynam 2. Coronary vasodilation → ↑myocardial perfusion
ic effect 3. Arteria vasodilatation → ↓afterload
4. Shunting of flow from normal area to ischemic area by dilating collateral vessel

Loss of vasodilator response of nitrates on use of long-acting preparations (oral,

transdermal) or continuous intravenous infusions, for more than a few hours without
interruption.
Mechanism:
NIRATE
1-Compensatory neurohormonal counter-regulation
TOLERANCE
2-Depletion of free-SH groups
Nitrate tolerance can be overcome by:
1.Smaller doses at increasing intervals (Nitrate free periods twice a day).
2.Giving drugs that maintain tissue SH group like Captopril.

• Throbbing headache
• Flushing in blush area
ADRs • Tachycardia & palpitation
• Postural hypotension, dizziness & syncope
• Rarely methemoglobinema

• Known sensitivity to organic nitrates, Uncorrected hypovolemia

Contra- • Glaucoma: nitrates  aqueous humour formation
indications • Head trauma or cerebral haemorrhage Increase intracranial pressure
• Concomitant administration of PDE5 Inhibitors
 lectures 12,13: Antianginal drugs:
2. Calcium channel blockers (CCBs)
Dihydropyridines: More Selective to VSMCs
Nifedipine , Nicardipine & Amlodepine
Classification
(Heterogeneous) Phenylalkylamines :Verapamil More selective to cardiomyocyte
Benzthiazepines :Diltiazem Intermediate in action
Calcium channel blockers  Bind to L Type Ca channels  decrease their frequency of
Mechanism opening in response to depolarization  entry of Ca   Ca from internal stores 
No Stimulus-Contraction Coupling  RELAXATION
 Cardiomyocyte Contraction VSMC Contraction Coronary dilatation

Antianginal cardiac work through their –ve 1- After load  myocardial O2 supply
actions inotropic & chronotropic action cardiac work 
(verapamil & diltiazem)  myocardial oxygen
myocardial oxygen demand demand
 IN STABLE ANGINA; Regular prophylaxis
 IN VARIANT ANGINA Attacks prevented
Indications  IN UNSTABLE ANGINA Seldom added in refractory cases
 Long acting Dihydropyridene (Amlodepine) is a useful antianginal if with CHF, because
the don’t decrease cardiac contractility.
• Short acting dihydropyridine (Nifedipine , Nicardipine) should be AVOIDED  BP 
Precaution symathetic activation reflex tachycardia + syncope impair coronary filling
ischemia …..
• nitrates + Verapamil & diltiazem
Combinations
• beta-adrenoceptor blockers + Long acting dihydropyrdine (amlodepine)

3. K+ CHANNEL OPENERS
Drugs Nicorandil
1.Opening of KATP channels (more arteriolar 2. Acting as NO donner; as it has a
dilator) nitrate moiety (more venular dilator)
Mechanism On VSMCs :K+ channel opening 
(dual) Hyperpolarization VASODILATATION On VSMCs :
NO donner  cGMP/ PKG
On Cardiomyocyte : K channel opening  VASODILATATION
Repolarization  Cardiac work
1. Prophylactic 2nd line therapy in stable angina
Indications
2. refractory variant angina
• Flushing, headache,
ADRs • Hypotension, palpitation, weakness
• Mouth & peri-anal ulcers, nausea and vomiting
 lectures 12,13: Antianginal drugs:
4. β1 Adrenergic Blockers
β1 Blockers Atenolol, Bisoprolol, Metoprolol
 Heart rate by Heart contractility by
Antianginal 1- Duration of diastole 1.Workload
mechanism 2- Coronary blood flow 2.O2 consumption
3-oxygen supply
1-Regular prophylaxis  Cardio-selective are better to spare b2-AR
Stable 2-They are 1st choice on prolonged use   incidence of sudden death specially due
to ventricular tachycardia  by their antiarrhythmic action.

1-Indication contraindicated  as it has no vasodilator action. They may worsen symptoms

Variant
and aggravate condition.
Unstable halts progression to AMI  improve survival
AMI Reduce infarct size, reduce morbidity & mortality
- blockers should be withdrawn gradually. sudden stoppage  give rise to withdrawal
manifestations: Rebound angina, arrhythmia, myocardial infarction & hypertension Due 
Precautions Up-regulation of -receptors.
Given to diabetics with ischemic heart disease if Benefits are more than hazards

5. Metabolically Acting Agents

1.O2 requirement of glucose pathway is lower than FFA pathway
Mechanism 2.During ischemia, oxidized FFA levels rise, blunting the glucose pathway
3.Reduces O2 demand without altering hemodynamics
Trimetazidine

Indication Used whenever needed as add-on therapy

ADRs GIT disturbances
1-Hypersensitivity reaction
Contraindications
2-In pregnancy & lactation
Ranolazine

Mechanism Inhibits the late sodium current which increases during ischemia
1-It prolongs the QT interval so not given with Class Ia & III antiarrhthmics
Contraindications
2-Toxicity develops due to interaction with CYT 450 inhibitors

6. Others (Ivabradine)
Selectively blocks If (If is an inward Na+/K+ current that activates pacemaker cells of the
Ivabradine SA node)
Reduces slope of depolarization, slowing HR, reducing myocardilal work & O2 demand
‫‪THANK YOU FOR CHECKING OUR WORK‬‬
‫‪435 PHARMACOLOGY TEAM‬‬
‫عبدالرحمن السياري‬
‫أحمد اليحيى‬
‫شماء السعد‬ ‫لولوه الصغير‬
‫خالد الزهراني‬
‫عبدهللا الجنيدل‬ ‫رهف بن عبّاد‬ ‫شادن العمران‬
‫أحمد المصعبي‬ ‫سارة الخليفة‬ ‫لمى الزامل‬
‫عبدالرحمن الزامل‬ ‫ساره المطوع‬ ‫كوثر الموسى‬
‫عبدالرحمن الشمري‬ ‫فاطمة الدين‬ ‫ديمه الراجحي‬
‫معاذ باعشن‬ ‫آية غانم‬ ‫جواهر الحربي‬
‫عبدالعزيز الشعالن‬
‫أسرار باطرفي‬ ‫دالل الحزيمي‬
‫محمد السحيباني‬
‫فارس المطيري‬ ‫نوف العبدالكريم‬ ‫رنيم الدبيخي‬
‫فوزان العتيبي‬ ‫وضحى العتيبي‬ ‫نورة الصومالي‬
‫محمد ابونيان‬ ‫ريما الحيدان‬ ‫منيرة السلولي‬
‫عمر القحطاني‬ ‫منيرة العمري‬ ‫نورة البصيص‬
‫يوسف الصامل‬
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