Anti-anginal drugs

ANTI-ANGINAL DRUGSAnginal pain occurs when the coronary blood flow is insufficient to meet the hearts metabolic requirements: - spasm of coronary artery - fixed narrowing of coronary artery due to an atheromatous plaque,some times complicated by platelet-fibrin thrombus.

DRUGS THAT ARE USED IN ANGINA

Organic nitratesCalcium antagonists- adrenoceptor antagonists

Organic nitratesPowerful vasodilators,acting mainly on capacitance vessels to reduce preload.Act by intracellular production of NO, which stimulates cGMP formation, affecting both contractile proteins and Calcium regulation.Tolerance occurs experimentally,but not thought to be important clinically.

Effectiveness in angina is due partly to reduced cardiac load,partly to dilatation of collateral coronary vessels,causing more effective distribution of coronary flow. In variant angina,dilatation of constric- ted coronary vessels is beneficial. Important compound are: Glyceryl trinitrate,used sublingually for rapid anti-anginal effect;

-Isosorbide dinitrate,used sublingualy or orally for prophylaxis and more sustained effect Nitroprusside,used for rapid lowering of blood pressure,acts in the same way.No serious unwnted effects; headache postural hypotension may occur initi- ally,but tolerance develops. In overdose,may cause methaemoglobinaemia.

CALCIUM ANTAGONISTS

Three main types,typified by Verapamil, Diltiazem ,Dihydropyridines (e.g. nifedi- pine) respectively.Act by preventing opening of voltage- gated Ca channels (L-type).Mainly affect heart and smooth muscle, causing inhibition of Ca2+ entry associated with depolarisation.

Selectivity between heart and smooth muscle varies: Verapamil is relatively cardioselective. Nifedipine is relatively smooth-musle- selective and Diltiazem is intermediateVasodilator effect (mainly Dihydropyri- dine ) is mainly on resistance vessels, causing reduced afterload. Calcium antagonists also dilate coronary vessels,but this is not clinic- ally important except in Variant angina.

Clinical uses include: Antidysrhythmic therapy (mainly verapamil,diltiazem,especilly atrial ta- chycardias),heart failure (dihydropyri- dines), Angina (by reducing cardiac work) and Hypertension.Unwanted effects (headache,constipation) are generally minor.There is a risk of causing cardiac failure or heart block with verapamil and diltiazem.

Dari Medical Pharmacology at a Glance , M.J. NEAL ,second ed. 1995

Anti-anginal therapyUnstable angina is caused by platelet- fibrin thrombus on coronary artery atheroma.The most important drug is aspirin,because it reduces the incidence of myocardial infarction. Glyceryl trinitrate as an intravenous infusion is very effective in relieving in this setting.

Stable angina is caused by fixed coro nary artery narrowing due to atheroma. Drugs and other measures to prevent progression of atheroma and cause it regression are important long-term me- asures.Duration of pain in stable angina is usually only a few minutes on stopping exercise; this can be reduced by sub- lingual glyceryl trinitrate.

The frequency of anginal attacts can be reduced by regular use of: -organic nitrates (e.g. isosorbide mono nitrate given regularly by mouth or glyceryl trinitrate administered trans dermally via a patch,or sublingually immediately before exertion). - - adrenoceptor antagonists (e.g. atenolol,metoprolol). - calcium antagonists (diltiazem,amlo dipine)

Clinical uses of organic nitratesStable angina - Prevention (e.g. regular isosorbide mono-nitrate; or glyceryltrinitrate sub- lingually immediately before exertion) - Treatment ( sublingual glyceryltrini trate).

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Unstable angina: Intravenous glyceryl trinitrate (as supplement to aspirin)To reduce cardiac pre-load in patients with heart failure,especially those un able to take ACE inhibitors.Uses related to relaxation of other smooth muscles (e.g. uterine,billiary) are being investigated).

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