Antianginal drugs

Antianginal drugs class lecture ppt

1. Antianginal Drugs Suresh Kumar Ghritlahare Assist. Professor SRU, Raipur, (C.G.)

2. Antianginal drugs Antianginal drugs: Antianginal drugs are those that prevent, abort or terminate attacks of angina pectoris. Angina pectoris: It 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: Classical angina: (common form) (b)Variant/ Prinzmeta / Vasospastic angina: (uncommon form)

3. Types of Angina 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provoked (stable angina) by exercise, emotion, eating or coitus and subside when the increased energy demand is withdrawn. 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.) which may be superimposed on arteriosclerotic coronary artery disease.

4. Fig.: Diagrammatic representation of coronary artery calibre changes in classical and variant angina

5. 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: 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

6. Mechanism of action 1. Nitrates: Organic nitrates are rapidly denitrated enzymatically in the smooth muscle cell to release the reactive free radical nitric oxide (NO) which activates cytosolic guanylyl Increased cGMP causes dephosphorylation of myosin light chain kinase (MLCK) through a cGMP dependent protein kinase . Reduced availability of phosphorylated (active) MLCK interferes with activation of myosin it fails to interact with actin to cause contraction. Consequently relaxation occurs. Raised intracellular cGMP may also reduce Ca2+ entry contributing to relaxation.

7. Adverse effects : These are mostly due to vasodilatation. 1. Fullness in head, throbbing headache; some degree of tolerance develops on continued use. 2. Flushing, weakness, sweating, palpitation, dizziness and fainting; these are mitigated by lying down. Erect posture and alcohol accentuate these symptoms. 3. Methemoglobinemia : is not significant with clinically used doses. However, in severe anaemia , this can further reduce O2 carrying capacity of blood. 4. Rashes are rare, though relatively more common with pentaerythritol tetranitrate .

8. Uses: Angina pectoris Acute coronary syndromes (ACS) Myocardial infarction (MI) CHF Cyanide poisoning

9. 2. β BLOCKERS: β - blocker reduce cardiac work load and oxygen conjumption This drug do not dilate coronaries blood vessel, total coronary flow is reduced due to blockage of β 2 receptor Β eta-blocker increase exercize tolerance in classical angina Decrease frequency and severity of attack

10. 3. CALCIUM CHANNEL BLOCKERS: Three important classes of calcium channel blockers are examplified by: Verapamil —a phenyl alkylamine , hydrophilic papaverine congener. Nifedipine —a dihydropyridine ( lipophilic ). Diltiazem —a hydrophilic benzothiazepine . Calcium channels: Three types of Ca2+ channels have been described in smooth muscles (other excitable cells as well): (a) Voltage sensitive channel : Activated when membrane potential drops to around –40 mV or lower. (b) Receptor operated channel: Activated by Adr and other agonists—independent of membrane depolarization (NA contracts even depolarized aortic smooth muscle by promoting influx of Ca2+ through this channel and releasing Ca2+ from sarcoplasmic reticulum). (c) Leak channel: Small amounts of Ca2+ leak into the resting cell and are pumped out by Ca2+ATPase. Mechanical stretch promotes inward movement of Ca2+, through the leak channel or through separate stretch sensitive channel.

11. MOA: Smooth muscle Smooth muscles depolarize primarily by inward Ca2+ movement through voltage sensitive channel. These Ca2+ ions trigger release of more Ca2+ from intracellular stores and together bring about excitation-contraction coupling through phosphorylation of myosin light chain as depicted in Fig. The CCBs cause relaxation by decreasing intracellular availability of Ca2+. They markedly relax arterioles but have mild effect on veins. Extravascular smooth muscle (bronchial, biliary , intestinal, vesical , uterine) is also relaxed.

12. Use: Hypertension Angina pectoris Cardiac arrhythmias Hypertropic cardiopathy Other use: Nifedipine - premature labour

13. 4. POTASSIUM CHANNEL OPENERS: Nicorandil This dual mechanism antianginal drug activates ATP sensitive K+ channels ( KATP) thereby hyperpolarizing vascular smooth muscle. The vasodilator action is partly antagonized by K + channel blocker glibenclamide . Like nitrates it also acts as a NO donor—relaxes blood vessels by increasing cGMP . Thus, arterial dilatation is coupled with venodilatation . 5. OTHER ANTIANGINAL DRUGS: Trimetazidine This antianginal drug acts by nonhaemodynamic mechanisms. There is no effect on determinants of myocardial O2 consumption, such as HR and BP, both at rest as well as during exercise , but angina frequency is reduced and exercise capacity is increased.

14. References Tripathi KD, “Essentials of Medical Pharmacology” published by Jaypee Brothers Medical Publishers (P) Ltd, Seventh Edition: 2013, New Delhi, p.p. no-539-555.

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