Angina Pectoris & It's Updated Management.pptx

ngina Pectoris & It's Updated Management.

1. Drugs Presented by: DR . For Angina Pectoris

2. ANGINA PECTORIS Angina: a strangling Pectoris: of the chest Pain syndrome due to induction of an adverse oxygen supply & demand in portion of myocardium Pain radiates (left side) – Jaw, neck, shoulder, arm (occasionally back) Tight, squeezing, chocking Breathlessness

3. Myocardial O 2 Demand Myocardial O 2 Supply NO pain (Normal) Pain Heart Rate Contractility Preload Afterload Coronary & Regional blood flow ANGINA PECTORIS

4. Types of Angina Pectoris 1 . Stable (Classical/ Typical) Angina 2. Unstable Angina 3. Variant ( Prinzmetal ) Angina

5. Stable Angina Unstable Angina Fixed stenosis Dynamics stenosis Symptom appear on exertion, stress Symptoms m ay even appear at rest Symptom r elief on r est May not relief on rest Predictable unpredictable

6. Prinzmetal , variant or rest-angina Prinzmetal angina is an uncommon pattern of episodic angina that occurs at rest and is due to coronary artery spasm Symptoms are caused by decreased blood flow to the heart muscle from the spasm of the coronary artery Prinzmetal angina generally responds promptly to coronary vasodilators, such as nitroglycerin and calcium-channel blockers

7. ANGINA PECTORIS

8. Classification of drugs: Nitrates: Short acting: Glyceryl trinitrate (GTN, Nitroglycerine), Isosorbide dinitrate (Sublingually) Long acting: Isosorbide dinitrete (orally), Isosorbide mononitrate , β - Blocker: Propranolol , Metoprolol , Atenolol etc Calcium Channel Verapamil, Diltiazem, Blocker : Nifedipine , Amlodipine, Felodipine Pot. Channel opener : Nicorandil Other: Dipyridamole , Trimetazidine

9. Clinical Classification: Used to abort or terminate attack: Glyceryl trinitrate (GTN), Isosorbide dinitrate (Sublingually) Used for chronic prophylaxis: All other drugs

10. NITRATES: All share same action differ in time course only Pharmacological actions: - Relax vascular & other ( oesophageal , biliary etc) smooth muscles

11. Mechanism of action of Nitrates:

12. MOA: Nitrates inhibit coronary vasoconstriction or spasm, increasing perfusion of the myocardium and, thus, relieving vasospastic angina. In addition , nitrates relax the veins ( venodilation ), decreasing preload and myocardial oxygen consumption. Organic nitrates , such as nitroglycerin , relax vascular smooth muscle by their intracellular conversion to nitrite ions and then to nitric oxide, which, in turn, activates guanylate cyclase and increases the cells’ cyclic guanosine monophosphate ( cGMP ). Elevated cGMP ultimately leads to dephosphorylation of the myosin light chain, resulting in vascular smooth muscle relaxation

13. How Nitrates help (relieve pain) in angina pectoris? Reduce cardiac oxygen consumption by reducing cardiac preload and after load Redistribution of coronary flow towards ischaemic areas via collaterals Relief of coronary spasm

14. Reduce cardiac oxygen consumption Dilates vein → ↑ peripheral pooling of blood → ↓ venous return → ↓ preload → reduce cardiac oxygen consumption b. Dilates arteries → ↓ t.p.r → ↓ afterload → ↓ cardiac work → reduce cardiac oxygen consumption

15. Redistribution of coronary flow a. Nitrates preferentially relax bigger coronary arteries than arterioles and also the collateral circulation b. Ischaemia induce dilation of arterioles in the ischaemic zone Both actions (a & b) preferentially increase blood flow to ischaemic area

16. Redistribution of coronary flow

17. Pharmacokinetics of Nitrates Lipid soluble, undergo high first pass metabolism (except mononitrate ) Onset of action depend on route of administration

18. Adverse effects of nitrates a. Throbbing headache Flushing, sweating, hypotension, palpitation, dizziness & fainting High dose- Methemoglobinemia Tolerance: - on continuous use (oral, transdermal , i.v .) - Nitrate free interval is created every day to overcome: eccentric administration e. Dependence: so slow withdrawal with addition of other drugs

19. Glyceryl trinitrate (GTN) Volatile liquid: adsorbed on inert matrix of tablet Stored in air tight glass container protecting from light Given SL: acts within 1-2 min, t 1/2 = 2 min Sublingual spray act more rapidly than tab Can also be given transdermally or i.v .

20. Isosorbide dinitrate SL for acute attack and oral for prophylaxis High and variable first pass metabolism when given orally, t 1/2 = 40 min Last dose should not be given later than 6 pm

21. Isosorbide mononitrate Active metabolite of isosorbide dinitrate Low first pass metabolism- orally t 1/2 =4-6 hours Last dose should be given in the afternoon; SR tablet OD in the morning

22. Uses of nitrates 1. Stable angina: For acute attack: - Sublingual GTN or Dinitrate is taken sos preferably in sitting posture - produce relief within 3 min; if not it can be repeated for 2 more times For chronic prophylaxis: - long acting preparation of GTN or other nitrates are given orally

23. Uses of nitrates Unstable angina and Myocardial Infarction CHF and acute Left ventricular failure Biliary colic Esophageal spasm

24. Beta Blockers  Heart rate  Contractility  BP  Myocardial O 2 demand Increase exercise tolerance Lower risk of sudden cardiac death in IHD patient Decrease frequency and severity of attack : Prophylactic use Worsen variant angina Selective beta blocker are preferred, taken regularly & NOT withdrawn abruptly Do not dilate coronaries

25. Calcium Channel Blockers  Heart rate  Contractility  Myocardial O 2 demand Effective in classical as well as variant angina Non Dihydropyridine mainly: Dihydropyridines (DHPs): Arteriolar dilation → ↓ afterload →↓work load →↓myocardial oxygen demand Short acting DHPs (e.g. Nifedipines ) may aggravate myocardial ischaemia CCBs prevent arterial spasm which have additional beneficial effect in variant angina

26. Combination Therapy Used when monotherapy fails to provide adequate relief Nitrates + β blockers in stable angina (decrease side effect of each other) β blockers + slow acting DHPs Nitrates (↓preload ) + slow acting DHPs(↓ afterload ): valuable in severe variant angina Nitrates + DHPs + β blockers: Supraaddative , useful in Severe & resistant cases Verapamil / Diltiazem + β blockers should be AVOIDED: both depress – SA & AV node https://www.slideshare.net/slideshow/drugs-for-angina-pectoris/107867918

27. Thank You