Antianginal drugs (VK)
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Transcript of Antianginal drugs (VK)
When the supply of oxygen and nutrients
in the blood is insufficient to meet the
demands of the heart, the heart muscle
aches.
The heart demands a large supply of
oxygen to meet the demands placed on it.
Oxygen demand
Oxygen supply=
>
Coronary blood flow
Regional myocardial distribution
Ventricular volume
LV pressure
Wall tension
Heart rate
Contractile state
Aortic pressure
Coronary vascular resistance
Chronic stable angina (also called classic or effort angina)
Unstable angina(also called preinfarction or crescendo angina)
Vasospastic angina(also called Prinzmetal’s or variant angina)
The goal of therapy with antianginal
agents is to restore the balance
between oxygen supply and demand in
the ischemic region of the myocardium.
CLASSIFICATION1.Nitrates Short acting: Glyceryl trinitrate (GTN, Nitro glycerine) Long acting: Isosorbide dinitrate (short acting by S.L
route), Isosorbide mononitrate, Erythrityl tetranitrate, Pentaerythritol tetranitrate
2.β-Blockers
Propranolol, Metoprolol, Atenolol and others.
3.Calcium channel blockers Phenyl alkylamine : Verapamil Benzothiazepine : Diltiazem Dihydropyridines : Nifedipine, Felodipine, Amlodipine,
Nitrendipine, Nimodipine, Lacidipine, Benidipine
4.Potassium channel opener
Nicorandil, Pinacidil
5.Others Dipyridamole, Trimetazidine,
Oxyphedrine
Clinical Classification
(A)Used to abort or terminate attack GTN,
Isosorbide dinitrate (sublingually).
(B)Used for chronic prophylaxis All other drugs.
Therapeutic Objectives Increase blood flow to ischemic heart muscle and/or
Decrease myocardial oxygen demand
Minimize the frequency of attacks and decrease the
duration and intensity of anginal pain
Improve the patient’s functional capacity with as few side
effects as possible
Prevent or delay the worst possible outcome, MI
Available forms:
Sublingual Ointments
Buccal Transdermal patches
Chewable tablets Inhalable sprays
Capsules Intravenous solutions
Dila of coronary vessels
Dila of coronary vessels
Arterial dilatation Arterial dilatation
Mainly vasodilatation Mainly vasodilatation
Relaxation of vascular smooth muscle fibres
Relaxation of vascular smooth muscle fibres
Increased cGMP Increased cGMP
Dephosphorylation of myosin light chain (reduced ca+ conc in the cytosol)
Dephosphorylation of myosin light chain (reduced ca+ conc in the cytosol)
Nitrates Nitrates
Stimulate Guanylyl cyclase
Stimulate Guanylyl cyclase
Release nitric oxide Release nitric oxide
Denitrated in the smooth muscle cell
Cause vasodilation due to relaxation of smooth muscles
Potent dilating effect on coronary arteries
Used for prophylaxis and treatment of angina
Nitroglycerin Prototypical nitrate
Large first-pass effect with PO forms
Used for symptomatic treatment of ischemic heart
conditions (angina)
I.V form used for BP control in perioperative
hypertension, treatment of CHF, ischemic pain, and
pulmonary edema associated with acute MI
isosorbide dinitrate
(Isordil, Sorbitrate, Dilatrate SR)
isosorbide mononitrate
(Imdur, Monoket, ISMO)
Used for: Acute relief of angina
Prophylaxis in situations that may provoke angina
Long-term prophylaxis of angina
Side Effects Headache
Usually diminish in intensity and frequency
with continued use
Tachycardia, postural hypotension
Tolerance may develop (Monday disease)
Isosorbide dinitrate
Isosorbide dinitrate has active initial
metabolites.
This drug is administered orally or sublingually;
it has better oral BA and a longer half-life (up to
1 h) than nitroglycerin.
Timed-release oral preparations are available
with durations of action up to 12 hours.
Therapeutic uses
1. Sublingual nitroglycerin is most often used for
severe, recurrent Prinzmetal's angina.
2. Continuous infusion or slowly absorbed
preparations of nitroglycerin (including the
transdermal patch) or derivatives with longer half-
lives have been used for unstable angina and
for CHF in the presence of MI.
Adverse effects
Nitrates and nitrites produce vasodilation,
which can lead to orthostatic hypotension, reflex
tachycardia, throbbing headache (may be dose
limiting), blushing, and a burning sensation.
Tolerance.
Large doses produce methemoglobinemia and
cyanosis.
Atenolol (Tenormin)
Metoprolol (Lopressor)
Propranolol (Inderal)
Nadolol (Corgard)
Mechanism of Action Decrease the HR, resulting in decreased myocardial
oxygen demand and increased oxygen delivery to
the heart
Decrease myocardial contractility, helping to
conserve energy or decrease demand
Therapeutic Uses Antianginal
Antihypertensive
Cardioprotective effects, especially after MI
Side Effects
Body System Effects
Cardiovascular bradycardia, hypotension
second- or third-degree heart block
heart failure
Metabolic Altered glucose and lipid
metabolism
Side Effects
Body System Effects
CNS dizziness, fatigue,
mental depression, lethargy,
drowsiness, unusual dreams
Other impotence
wheezing, dyspnea
Phenyl alkylamine:
Verapamil Benzothiazepine:
Diltiazem Dihydropyridines:
Nifedipine,Felodipine,Amlodipine, Nitrendipine,Nimodipine,Lacidipine
Mechanism: Calcium channel-blocking agents produce a
blockade of L-type (slow) calcium channels, which decreases contractile force and oxygen requirements.
Agents cause coronary vasodilation and relief of spasm
they also dilate peripheral vasculature and decrease cardiac afterload.
Preload refers to total volume of blood in the left ventricle of the heart and the pressure it exerts before the left ventricle contracts. Afterload then is the amount of pressure exerted by the left ventricle when it does contract.
Pharmacologic properties
C C blocking agents can be admi orally.
When admi intravenously, they are effective within minutes.
The therapeutic use of these drugs in angina is generally reserved for instances in which nitrates are ineffective or when β-Blks C/I.
Serum lipids are not increased.
These drugs produce hypotension.
Verapamil Verapamil produces slowed
conduction through the AV node (predominant effect); this may be an unwanted effect in some situations (especially in the treatment of hypertension).
Verapamil may produce AV block when used in combination with β-blks.
The toxic effects of verapamil include myocardial depression, heart failure, and edema.
Verapamil also has peripheral vasodilating effects that can reduce afterload and BP
The peripheral effects of verapamil can produce headache, reflex tachycardia, and fluid retention.
These dihydropyridine CCBls have predominant actions in the peripheral vasculature; they decrease afterload and to a lesser extent preload and lower blood pressure.
These drugs have significantly less direct effect on the heart than verapamil.
Diltiazem Diltiazem, a benzothiazepine, is
intermediate in properties between verapamil and the dihydropyridines.
Diltiazem is used to treat variant (Prinzmetal's) angina, either naturally occurring or drug-induced and stable angina.
Bepridil Bepridil blocks both slow and fast sodium
channels and both voltage-dependent and receptor-mediated calcium channels.
Bepridil is used only when other agents have failed or have elicited intolerable A/E.
Bepridil may cause ventricular arrhythmias.
Therapeutic Uses First-line agents for treatment of angina,
hypertension, and supraventricular tachycardia
Short-term management of atrial fibrillation and
flutter
Several other uses
Their efficacy is similar to nitrates, beta
blockers, CCBs
Main advantages of Nicorandil, it has
longer DOA and does not cause
tolerance
Administered orally
Arterial dilators Arterial dilators
↓Preload↓Preload
VenodilatorsVenodilators
Hyperpolarization of the membrane
Hyperpolarization of the membrane
K+ efflux
K+ efflux
Open ATP-dependent K+ channels
Open ATP-dependent K+ channels
Nicorandil & Pinacidil
Nicorandil & Pinacidil
↓ Afterload ↓ Afterload
Headache Hypotension Palpitation Flushing N,V