Antianginal Dr ugs

1. Antianginal Drugs Prof.AzzaEL-Medany

2. Angina pectoris • Sudden,severe,pressing chest pain starting substernal &radiate to left arm. • Due to imbalance between myocardium oxygen requirement and oxygen supply.

3. RiskFactors • Age • Sex • Obesity • Smoking • Diabetes

4. Classification of angina • Exertional angina, Stable, Atherosclerotic or Classic, Due to obstruction of coronaries by atheroma. • Prinzmetal(Variant or vasospastic ) Due to Spasm of coronaries.

5. Continue 3- Unstable angina Due to spasm and partial obstruction of coronaries 4- Silent angina

6. Nitrates & Nitrites • Preparations : 1- Short acting: Start within few minutes and total duration of action 15-30 minutes. A) Nitroglycerine (Glyceryltrinitrate) Used as sublingual tablets. B) Isosorbidedinitrate As sublingual spray. C) Amyl nitrite • Inhalation

7. Continue 2- long acting Nitroglycerine, Isosorbidedinitrate,Isosorbidemononitrate. • Delayed onset of action and continue for hours . • Given : Orally,Ointment,Transdermalpatch, Intravenous.

8. Pharmacokinetics • Absorption Well absorbed according to the route of administration

9. Continue • Metabolism Through first pass hepatic metabolism. Shortacting not given orally to avoid firstpass metabolism. Nitroglycerine & Isosorbidedinitrate have active metabolites.

10. Continue • Excretion Through the kidney.

11. Mechanism of action Glutathione S-transferase • Nitroglycerine———————— Nitric oxide ( NO). • NO activates guanylyl cyclase and increasec GMPc GMP dephosphorylatemyosin light chain • Causing smooth muscle relaxation.

12. Pharmacological actions • Nitrates relax all types of smooth muscles vascular or non vascular . • Potent venodilator. • Have no effect on cardiac or skeletal muscles. • NO released stimulate guanylyl cyclase in platelets causing increase cGMP that decrease platelet aggregation.

13. Clinical uses • Effective in all types of angina: Short acting for acute attacksLong acting for prophylactic. • Severe heart failure.

14. Angina of effort • Decrease preload ( increase venous capacitance ) • Decrease afterload decrease myocardial oxygen requirement. • Redistribution of coronary blood flow. • Prevent platelet aggregation

15. Variant angina • Relax smooth muscle of epicardial coronaryartery and relief coronary spasm.

16. Unstable angina • Decrease myocardial oxygen requirement. • Relief coronary spasm. • Decrease platelet aggregation.

17. Adverse effects • Orthostatic hypotension & syncope • Palpitation & Tachycardia • Salt & water retention • Throbbing headache • Facial flushing • Tolerance • Carcinogenicity • Methemoglobinemia only with nitrites

18. Contraindication • Nitrates are contraindicated in increase intracranial pressure. • Notice: Nitrates can be used safely in increase of intraocular pressure (Glucoma).

19. Calcium channel blockers • Block calcium entry in myocardiumcausing : • decrease in myocardium contractility & heart rate Causing decrease in myocardium oxygen requirement.

20. Continue • Block calcium entry in vascular smoothmuscles ( arteries & arterioles) causing : Decrease inperipheral resistance (after load)------decrease in oxygen requirement. Relief of coronary spasm.

21. Classification of calcium channel blockers Dihydropyridine Nifedipine More selective as vasodilator Verapamil & Diltiazem More selective as cardiac depressant

22. Pharmacokinetics • Given orally • Verapamil & Diltiazem can be given intravenously • Excreted in urine

23. Clinical uses • In all types of angina but very effective in variant angina . Used in prophylactic therapy. • Hypertension • Supraventricular tachycardia • Peripheral vascular disease

24. Adverse effects • Cardiac arrest, bradycardia ( verapamil & diltiazem ) • Reflex tachycardia ( nifedipine) • Fatigue & headche • Ankle edema • Constipation ( verapamil)

25. Drug interaction • Verapamil or diltiazem with β-blockers causing bradycardia or cardiac arrest

26. β-Adrenoceptor blocking drugs • Not vasodilators • Used in prophylactic treatment of angina through : Decrease in both heart rate & myocardial contractility that decrease myocardial oxygen requirement at rest & in exercise so improve exercise tolerance.

27. Continue • Effective in the prophylactictreatment of all types of angina Except in variant angina. • Decrease mortality of patients with recentmyocardial infarction, heart failure & hypertension.

28. Potassium channel openers Nicorandil Activation of potassium channels. Nitric oxide release. Arterio & venodilator. • Used as prophylactic therapy . • Side effects : Headache, flushing, dizziness.

29. Fatty Acid Oxidase Inhibitors • Oxidation of fatty acids as a source of energy needs more oxygen than oxidation of carbohydrate. • Drugs that shift myocardial metabolism toward use of glucose (fatty acid oxidase inhibitors) have the potential of reducing the oxygen demand without change hemodynamics , e.g. trimetazidine

30. Anticoagulants & Antiplatelets • Aspirin & Heparin decreasing the risk in unstable angina & acute coronary syndrome.

31. Drug treatment of angina • Acute attack : Short acting nitrates or nitrites. • Prophylactic therapy ; • Long –acting nitrates. • Calcium channel blockers. • β- adrenoceptor blockers. • Potassium channel openers. • Fatty acid oxidase inhibitors

32. Combination therapy • Nitrates and β-adrenoceptor blockers. • Calcium channel blockers( dihydropyridine) and β-adrenoceptor blockers . • Calcium channel blockers andnitrates. • Calcium channel blockers, β-adrenoceptorblockers, nitrates , antiplateles or anticoagulants.

33. Surgical therapy • Ballon • Coronary by pass.