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Anti-anginal drugs:- Hand written Notes

ANTIANGINAL DRUGS
Antianginal drugs are those that prevent, abort or terminate attacks of angina pectoris. Angina pectoris Is a pain syndrome due to induction of an adverse oxygen supply/demand
situation in a portion of the myocardium. Two principal forms are recognized:
(a) Classical angina (common form) Attacks are predictably provoked (stable angina) by exercise, emotion, eating or coitus and subside when the increased energy demand is withdrawn. The underlying pathology is—severe arterio-
sclerotic affliction of larger coronary arteries (conducting vessels) which run epicardially and send perforating branches to supply the deeper tissue (Fig. 39.1). The coronary obstruction is
‘fixed’; blood flow fails to increase during increased demand despite local factors mediatedndilatation of resistance vessels (Fig. 39.2) and ischaemic pain is felt. Due to inadequacy of ischaemic left ventricle, the end diastolic left ventricular pressure rises from 5 to about 25 mm Hg—produces subendocardial ‘crunch’ during
diastole (blood flow to the subendocardial region occurs only during diastole) and aggravates the
ischaemia in this region. Thus, a form of acutely developing and rapidly reversible left ventricular failure results which is relieved by taking rest and reducing the myocardial workload.
Drugs that are useful, primarily reduce cardiac work (directly by acting on heart or indirectly by reducing preload hence end diastolic pressure, and afterload). They may also cause favourable redistribution of blood flow to the ischaemic areas.
(b) Variant/Prinzmetal/Vasospastic angina (uncommon form) Attacks occur at rest or during sleep and are unpredictable. They are due to recurrent localized (occasionally diffuse) coronary
vasospasm (Fig. 39.2) which may be superimposed on arteriosclerotic coronary artery disease. Abnormally reactive and hypertrophied segments
in the coronary arteries have been demonstrated. Drugs are aimed at preventing and relieving the
coronary vasospasm. Unstable angina (UA) with rapid increase in duration and severity of attacks is mostly due to rupture of an atheromatous plaque attracting platelet deposition and progressive occlusion of the coronary artery; occasionally with associated
coronary vasospasm. Chronically reduced blood supply causes atro-
phy of cardiac muscle with fibrous replacement (reduced myocardial work capacity → CHF) and may damage conducting tissue to produce unstable
cardiac rhythms. Antianginal drugs relieve cardiac ischaemia but do not alter the course of coronary
artery pathology: no permanent benefit is afforded. On the other hand, aspirin, ACE inhibitors and statins (hypocholesterolaemic) can modify
coronary artery disease and improve prognosis. Glyceryl trinitrate, the drug unsurpassed in its ability to abort and terminate anginal attack, was introduced by Murrell in 1879. Other organic nitrates were added later, but a
breakthrough was achieved in 1963 when propranolol was used for chronic prophylaxis. The calcium channel blockers have been a major contribution of the 1970s. A number of vasodilator and other drugs have been promoted from time to time, but none is as uniformly effective. Some potassium channel openers (nicorandil), metabolic modulator (trimetazidine) and late Na+
current inhibitor (ranolazine) have been introduced lately.
CLASSIFICATION
1. Nitrates
(a) Short acting: Glyceryl trinitrate (GTN,
Nitroglycerine)
(b) Long acting: Isosorbide dinitrate (short acting by sublingual route), Isosorbide mononitrate, Erythrityl tetranitrate, Pentaerythritol tetranitrate
2. β Blockers Propranolol, Metoprolol, Atenolol and others.
3. Calcium channel blockers
(a) Phenyl alkylamine: Verapamil
(b) Benzothiazepine: Diltiazem
(c) Dihydropyridines: Nifedipine, Felodipine, Amlodipine, Nitrendipine, Nimodipine, Lacidipine, Lercanidipine, Benidipine
4. Potassium channel opener Nicorandil
5. Others Dipyridamole, Trimetazidine,
Ranolazine, Ivabradine, Oxyphedrine
Clinical classification
A. Used to abort or terminate attack GTN, Isosorbide dinitrate (sublingually).
B. Used for chronic prophylaxis All other drugs.

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