2.
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.
8.
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)
9.
10.
The goal of therapy with antianginal agents is
to restore the balance between oxygen supply
and demand in the ischemic region of the
myocardium.
12. 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.
13. 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
15. Nitrates
Nitrates
Denitrated in the smooth muscle cell
Release nitric oxide
Release nitric oxide
Stimulate Guanylyl cyclase
Stimulate Guanylyl cyclase
Increased cGMP
Increased cGMP
Dephosphorylation of myosin light
Dephosphorylation of myosin light
chain (reduced ca+ conc in the cytosol)
chain (reduced ca+ conc in the cytosol)
Relaxation of vascular
Relaxation of vascular
smooth muscle fibres
smooth muscle fibres
Mainly vasodilatation
Mainly vasodilatation
Arterial dilatation
Arterial dilatation
Dila of coronary vessels
Dila of coronary vessels
16.
Cause vasodilation due to relaxation of smooth
muscles
Potent dilating effect on coronary arteries
Used for prophylaxis and treatment
of angina
17. 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
18.
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
20.
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.
21.
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.
22.
Adverse ef fects
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.
24. 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
29. Mechanism:
Calcium channel-blocking agents produce a blockade
of L-type (slow) calcium channels, which decreases
contractile force and oxygen requirements.
Agents
cause coronar y 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.
30.
31.
Pharmacologic proper ties
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.
32.
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.
33.
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.
34.
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
ef fect on the hear t than verapamil.
35.
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.
36.
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.
37. Therapeutic Uses
First-line agents for treatment of angina, hypertension,
and supraventricular tachycardia
Short-term management of atrial fibrillation and flutter
Several other uses
38.
Their efficacy is similar to nitrates, beta
blockers, CCBs
Main advantages of Nicorandil, it has longer
DOA and does not cause tolerance
Administered orally
39. Nicorandil &
Nicorandil &
Pinacidil
Pinacidil
Open ATP-dependent K+ channels
Open ATP-dependent K+ channels
K+ efflux
K+ efflux
Hyperpolarization of the membrane
Hyperpolarization of the membrane
Venodilators
Venodilators
Arterial dilators
Arterial dilators
↓Preload
↓Preload
↓ Afterload
↓ Afterload
In cardiac physiology, preload is the end volumetric pressure that stretches the right or left ventricle of the heart to its greatest geometric dimensions under variable physiologic demand. [1] In other words, it is the initial stretching of the cardiomyocytes prior to contraction; therefore, it is related to the sarcomere length at the end of diastole. Parameters such as ventricular end diastolic volume or pressure are used to measure preload since the ideal length of the cardiac sarcomere cannot be measured. Passive filling of the (heart) ventricle and subsequent atrial contraction thus allows an echocardiographically volumetric measurement. Preload is theoretically most accurately described as the initial stretching of a single cardiomyocyte prior to contraction. This cannot be measured in vivo and therefore other measurements are used as estimates. Estimation may be inaccurate, for example in a chronically dilated ventricle new sarcomeres may have formed in the heart muscle allowing the relaxed ventricle to appear enlarged. The term end-diastolic volume is better suited to the clinic, although not exactly equivalent to the strict definition of preload. Atrial pressure is a surrogate for preload.