1. Angina pectoris Sudden,severe,pressing chest pain starting substernal &radiate to left arm. Due to imbalance between myocardium oxygen requirement and oxygen supply. Risk factors : Age,sex,obesity.smoking,diabetes.

2. Classification of angina 1. Exertional angina, Stable,Atherosclerotic,Classic, Due to obstruction of coronaries by atheroma. 2. Variant, Vasospastic angina due to Spasm of coronaries. 3- Unstable angina. Due to spasm and partial obstruction of coronaries.

3. 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

4. 2- Long acting Nitroglycerine, Isosorbide dinitrate, Isosorbide mononitrate,Erythrityl – Tetranitrate. Action of all start withen hours and continue for hours. They are given : Orally,Ointment,Buccal,Transdermal patch,Parenteral.

5. Absorption Well absorbed according to the route: GIT for the long acting short acting Sublingual Transdermal for long acting inhaLation

6. Metabolism Through first pass hepatic metabolism. Short acting have a low oral bioavailability (10-20%),so not given orally to avoid first pass metabolism. Nitroglycerine metabolites( two dinitro And two mononitro forms). The dinitro forms are active metabolites and have significant vasodilator effect.

7. Metabolism Isosorbide dinitrate metabolite (5- mononitrate) is an active metabolite used clinically. Excretion As metabolites through kidney.

8. Mechanism of action Glutathione S-transferase Nitroglycerine ————————  No. guanylyl cyclase and NO activates increase c GMP c GMP dephosphorelate myosin light chain (Myosin-LC-po 4 ) to myosin- LC Causing muscle relaxation.

9. Pharmacological actions Nitrates relax all types of smooth muscles vascular or non vascular. Relax both arteries and veins but more effective on veins. They have no direct effect on cardiac or skeletal muscles. NO released stimulate guanylyl cyclase In platelets causing increase cGMP that decrease platelet aggregation.

10. Clinical uses Short acting for acute attacks Long acting for prophylactic. Treatment of all types of angina.

11. 1- Angina of effort A) Decrease venous return B) Decrease ABP Both A&B decrease myocardial oxygen requirement.

12. 2-Variant angina Relax smooth muscle of epicardial coronary artery and relief coronary spasm.

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

14. Adverse effects Orthostatic hypotension Throbbing headache Tachycardia Facial or cutaneous flushing Tolerance (Tachyphylaxis) Salt and water retention Carcinogenicity Methaemoglobinemia only with nitrities

15. Contraindication Nitrates are contraindicated in increase intracranial pressure. Nitrates can be used safely in increase of intraocular pressure (Glucoma).

16. Calcium channel blockers 1- They block calcium entry in myocardium causing ; A) decrease myocardium contractility & myocardium oxygen requirement. B) decrease heart rate causing decrease in myocardium oxygen requirement.

17. 2-Block calcium entry in vascular smooth muscles (arterioles) causing a)decrease in peripheral resistance( after load)------ decrease in oxygen requirement. b)Relief of coronary spasm.

18. Clinical uses In all types of angina but very effective in variant angina. Used mainly in prophylactic therapy.

19. β-Adrenoceptor blocking drugs They are not vasodilators They are used in treatment of angina : They decrease both heart rate & myocardial contractility that decrease in myocardial oxygen requirement at rest & in exercise so improve exercise tolerance.

20. Clinical uses They are effective in the prophylactic treatment of classic & unstable angina. They are not used in variant angina. They are effective in treatment of silent or ambulatory angina (no pain ). Decrease mortality of patients with recent myocardial infarction.

21. Potassium channel openers (Nicorandil ) Activation of potassium channels. Nitric oxide release. Arterio & venodilators. Used as prophylactic therapy. May cause : Headache,flushing,dizziness.

22. Drug treatment of angina 1- Acute attack : Short acting nitrates or nitritis. 2- Prophylactic therapy ; Long – acting nitrates. Calcium channel blockers. β- adrenoceptors blockers. Potassium channel openers.

23. Combination therapy Nitrates and β-adrenoceptors blockers. Calcium channel blockers and β- adrenoceptor blockers.? ? Calcium channel blockers and nitrates. Calcium channel blockers, β- adrenoceptor blockers, nitrates.

24. Surgical therapy Ballon Coronary by pass.