ANGINA
Dr.Fatima
Antianginal Drugs
Angina pectoris :Is characterized by sudden, sever, pressing chest pain radiating to the neck, jaw, back and
arms. It’s caused by coronary blood flow that is insufficient to meet the oxygen demand of the
myocardium, the imbalance between oxygen delivery and utilization may result from a spasm of
the vascular smooth muscle or from obstruction of blood vessels caused by atherosclerosis.
3 classes of drugs are effective in the treatment of stable angina :Organic nitrates, β-blockers and calcium channel blockers in addition to lifestyle especially
cessation of smoking.
Antianginal Drugs
β-blockers:
Organic nitrate:
Calcium channel blockers :
Isosorbide dinitrate
Acebutolol
Amlodipin
Isosorbide mononitrate
Atenolol
Diltiazem
Nitroglycerin
Metoprolol
Felodipine
Propranolol
Nicardipine
Nifedipine
Verapamil
TYPES OF ANGINA
-Stable
A
angina:- called
typical angina pectoris, characterized by burning ,heavy feeling in the chest. It’s caused by the reduction of coronary atherosclerosis, ischemia result from increase demand by physical activity or emotional excitement.
Treated or relieved by rest or nitroglycerin.
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ANGINA
Dr.Fatima
-Unstable
B
angina:- lies between stable angina and myocardial
infarc-
tion (M.I).
Chest pains occur with increased frequency and precipitated with less effort.
Unstable angina requires hospital admission and more aggressive therapy to
prevent death and progression to M.I.
c
-Prinzmetal’s
or variant or vasospastic angina:- occurs at rest
due to coronary artery spasm and it responds to vasodilators,such as nitroglycerin
and calcium channel blockers (CCB).
D
-mixed
form angina: -occurs during efforts and rest due the presence
of mixed obstruction associated with endothelial dysfunction.
Organic nitrates:They are effective in stable, unstable and vasospastic angina, they are simple nitric or nitrous
acid esters of glycerol including:



NITROGLYCERIN(glyceryl trintrate): given sublingually or via transdermal patch,
or spray
ISOSORBIDE DINITRATE AND MONONITRATE: can be given orally.
AMYL NITRITE.
MECHANISM OF ACTION:Organic nitrates are thought to relax vascular smooth muscle by their intracellular conversion to
nitrite ions, and then nitric oxide Activate guanylate cyclase
increase guanosin monophosphate
( c GMP )
dephosphorylation of myosin light chain
vascular smooth muscle relaxation
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ANGINA
Dr.Fatima
EFFECTS ON THE CARDIOVASCULAR SYSTEM:
Nitroglycerin has two major effects:1. It causes dilation of large veins, resulting in pooling of blood in veins so diminished preload (venous return to the heart )and decrease cardiac work (decrease
oxygen demand).
2. It dilates the coronary vasculatures, lead to increase blood supply to the heart
muscle.
PHARMACOKINETICS:
The onset of action is (1min.) for nitroglycerin and more than 1 hour for isosorbide mononitrate. Significant first pass metabolism of nitroglycerin occurs in the liver so its given either
sublingually or via a transdermal patch.
Isosorbide mononitrate can be given orally because of its stability against hepatic break down,
oral isosorbide dinitrate undergo denitration to 2 mononitrates.
ADVERSE EFFECTS:
Headache in 30-60 % of patients. High dose can also cause postural hypotension, facial
flushing and tachycardia.
TOLERANCE:
Tolerance to the action of nitrates develops rapidly, the blood vessels become desensitized to
vasodilatation, tolerance can be overcome by providing a daily “nitrate-free interval” to restore
sensitivity to the drug its typically 10-12 hrs usually at night because demand on the heart is decreased at that time except variant angina in which nitrate free period occurs in late afternoon
because this angina worsen early in the morning. Patient who did not respond to nitrate may
benefit by addition of other class of drugs.
β- adrenergic blockers:
β- adrenergic blocking agents decrease the oxygen demand of the myocardium they suppress
activation of the heart by blocking β1 receptors and they decrease the work of the heart by decrease heart rate, contractility, cardiac out put and blood pressure.
Propranolol is not cardio selective, thus other selective β1-blockers such as metoprolol or
atenolol are preferred. those with intrinsic sympathomimetic activity should be avoided.
Β-blockers can be combined with nitrates to treat angina.
They are contraindicated in patients with asthma, diabetes, sever bradycardia, peripheral vascular disease or chronic obstructive pulmonary disease.
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ANGINA
Dr.Fatima
CALCIUM CHANNEL BLOCKERS (CCB):
Calcium is essential for muscular contraction. The calcium channel blockers inhibit the entrance of calcium into cardiac and smooth muscle cells of coronary and systemic arterial beds.
All CCBs are arteriolar vasodilators and decreased vascular resistance, with negative inotropic
effect. Verapamil affects the myocardium; whereas nifedipine affect peripheral vascular smooth
muscle, Diltiazcm is intermediate in its action. Variant angina caused by spontaneous coronary
spasm rather than by increased myocardial oxygen demand so its controlled by organic nitrates
or CCBs; but β-blockers are contraindicated.
A. NIFEDIPINE
It’s arteriolar vasodilator, has minimal effect on cardiac conduction or heart rate. It’s
administered orally, metabolized in the liver and excreted both in urine and feces. Nifedipine is useful in the treatment of variant angina.
SIDE EFFECTS: Flushing, headache, hypotension and peripheral edema and tachycardia
due to vasodilation.
B. VERAPAMIL: It slows cardiac atrioventricular (AV) conduction directly and decrease
heart rate, contractility, blood pressure and oxygen demand, it causes greater negative inotropic effects than nifedipine, it is contraindicated in patient with preexisting depressed cardiac function or AV conduction abnormalities; and is used with caution in patients taking
digoxin because verapamil increases digoxin levels. It is extensively metabolized in the liver
and it causes constipation.
C. Diltiazem: it is similar to verapamil, both drugs slow AV conduction and decrease the
rate of firing of the sinus node pacemaker. Diltiazem reduces heart rate to a lesser extent
than verapamil, it is useful in patients with variant angina because it can relieve coronary artery spasm. It’s metabolized in the liver with same side effects and drug interaction of verapamil.
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