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. Risk Factors Age Sex Obesity Smoking Diabetes

4. Classification of angina 1. Exertional angina, Stable, Atherosclerotic or Classic, Due to obstruction of coronaries by atheroma. 2. 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 (Glyceryl trinitrate) Used as sublingual tablets. B) Isosorbide dinitrate As sublingual spray. C) Amyl nitrite Inhalation

7. Continue 2- long acting Nitroglycerine, Isosorbide dinitrate,Isosorbide mononitrate. Delayed onset of action and continue for hours. Given : Given : Orally,Ointment,Transdermal patch, Intravenous.

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

9. Continue Metabolism Through first pass hepatic metabolism. Short acting not given orally to avoid first pass metabolism. Nitroglycerine & Isosorbide dinitrate 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 increase c GMP c GMP dephosphorylate myosin 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 attacks Long 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 coronary artery 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 myocardium causing : decrease in myocardium contractility & heart rate Causing decrease in myocardium oxygen requirement.

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

21. Classification of calcium channel blockers DihydropyridineNifedipine 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 prophylactic treatment of all types of angina Except in variant angina. Decrease mortality of patients with recent myocardial infarction, heart failure & hypertension.

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

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 and nitrates. Calcium channel blockers, β-adrenoceptor blockers, nitrates, antiplateles or anticoagulants.

33. Surgical therapy Ballon Coronary by pass.