antianginal CHF antihyperlipidemic drugs.pptx

A detail discussion on antianginal drugs

1. ANTIANGINAL DRUGS

2. Antianginal drugs are those that prevent, abort or terminate attacks of angina pectoris.

3. Classification of antianginal drugs: A) Nitrates : a) short-acting: 1) Glyceryl trinitrate 2) Isosorbide dinitrate (by sublingual route)

4. b) long-acting: 1) Isosorbide dinitrate (by oral route) 2) Isosorbide mononitrate 3) Erythrityl tetranitrate 4) Pentaerythritol tetranitrate

5. B) Beta ( β ) – blockers 1) Metoprolol 2) Atenolol 3) Propranolol 4) Others

6. C) Calcium channel blockers a) Phenyl alkalamines : Verapamil b) Benzothiazepine : Diltiazem c) Dihydropyridines : Amlodipine, Nifedipine , Felodipine , Nitrendipine , Nimodipine , Lacidipine , Lercanidipine , Benidipine .

7. D) Potassium channel opener : Nicorandil E) Other antianginal drugs: 1) Trimetazidine 2) Ranolazine 3) Ivabradine 4) Dipyridamole

8. Clinical classification of antianginal drugs : a) Used to abort or terminate attack: GTN, Isosorbide dinitrate (sublingually) b) Used for chronic prophylaxis: All other antianginal drugs.

9. Nitrates GTN ( Glyceryl trinitrate / nitroglycerin) is the prototype antianginal nitrate . Available as sublingual, oral and transdermal patches

10. Mechanism of action Nitrate enters smooth muscle cell Nitrate is enzymatically converted to NO (nitric oxide) NO activates guanylyl cyclase which produces cGMP from GTP cGMP prevents phosphorylation of MLCK (Myosin light chain kinase) as well as prevents intracellular influx of Ca 2+

11. Dephosphorylated MLCK is unable to activate myosin Myosin and actin interaction needed for contaction cannot occur Smooth muscle relaxation occurs; In addition, reduced Ca 2+ entry into the smooth muscle cell also contributes to relaxation. Vasodilation occurs

12. Vasodilation of veins more prominent than arteries  reduces cardiac output  reduced oxygen consumption by the cardiac muscles Vasodilation of coronary arteries  increases blood flow to heart muscles. Both of these lead to relief from A.P.

13. Uses/Indications of Nitrates In Angina pectoris: for aborting any acute episode, as well as for chronic prophylaxis Acute coronary syndrome (ACS ): in unstable angina (UA ) and non-ST segment elevation myocardial infarction (NSTEMI). Myocardial infarction (MI ): during evolving MI Congestive heart failure and acute left ventricular failure.

14. 5) Biliary colic due to galI stone or morphine 6) Esophageal spasm 7) Cyanide poisoning: may be used

15. Adverse effcts Fullness in head, throbbing headache : which may decrease with continuous use. Flushing, weakness, sweating, palpitation, dizziness and fainting : Due to postural hypotension. Methemoglobinaemia leading to reduced oxygen carrying capacity in severe anaemia . Rashes (more common with pentaerythritol tetranitrate ).

16. 5) Dependence: Sudden withdrawal after prolonged exposure has resulted in spasm of coronary and peripheral blood vessels . Withdrawal of nitrates should be gradual . 6 ) Tolerance: when GTN is used orally , transdermally or by continuous i.v. infusion , as well as with the use of long acting agents, especially sustained release formulations . provide nitrate free intervals everyday.

17. Drugs Used In Heart Failure

18. Heart failure (HF) is a complex, progressive disorder in which the heart is unable to pump sufficient blood to meet the needs of the body. Goals of treatment are to alleviate symptoms, slow disease progression, and improve survival.

19. Drugs that can be used :

20. ARNI = angiotensin receptor neprilysin i nhibitor

21. HCN = hyperpolarization- activated cyclic nucleotide gated

22. DIGOXIN They are cardiac glycosides cardiac glycosides is a group of chemically similar compounds that can increase the contractility of the heart muscle and, therefore, are used in treating HF. have a low therapeutic index, with only a small difference between a therapeutic dose and doses that are toxic or even fatal.

23. Mechanism of action

24. Indications/Uses 1) In congestive heart failure (CHF): used in conjunction with other drugs. 2) In cardiac arrythmias : in cases of atrial fibrillation , atrial flutter, paroxysmal supraventricular tachycardia(PSVT). Digoxin slows conduction velocity through the AV node.

25. Adverse effects Anorexia, nausea, vomiting, blurred vision, or yellowish vision Fatigue, malaise, headache, mental confusion, restlessness, disorientation, psychosis and visual disturbances. I ncreasing the risk of arrhythmias: When Na+/K+- ATPase is markedly inhibited by digoxin, the resting membrane potential may increase, which makes the membrane more excitable, increasing the risk of arrhythmias

26. Antihyperlipidemic drugs

27. Antihyperlipidemic drugs : lower plasma lipids The major conventional risk factors for ASCVD are elevated LDL-C and reduced HDL-C. High LDL-CH ( >= 160 mg/dl) or total CH >= 240 mg/dl

28. Atorvastatin This is a high efficacy and one of the most commonly used statin capable of lowering LDL-CH by 55-60%. Atorvastatin has a much longer plasma t½ of 14-18 hr , and has additional antioxidant property. Dose: 10-40 mg/day (max. 80 mg)

29. Mechanism of action are competitive inhibitors of HMG CoA (3-Hydroxy-3-methyl glutaryl - coenzyme A) reductase , the rate-limiting step in cholesterol synthesis.

30. Acetyl coenzyme A multi steps 3-Hydroxy-3-methyl glutaryl -CoA (HMG-CoA) HMG-CoA reductase Mevalonate multi steps Cholesterol

31. By inhibiting de novo cholesterol synthesis, they deplete the intracellular supply of cholesterol. Depletion of intracellular cholesterol causes the cell to increase the number of cell surface LDL receptors that can bind and internalize circulating LDL-C. Thus, plasma cholesterol is reduced, by both decreased cholesterol synthesis and increased LDL-C catabolism.

32. uses Atorvastatin is often the statin of choice for patients with severe renal dysfunction as it does not require dose adjustment. 1) first-line treatment for patients with elevated risk of ASCVD (atherosclerotic cardiovascular diseases) to reduce the occurrence of ASCVD events: ASCVD includes CAD, stroke and peripheral artery disease. 2 ) in children >11 years with hereditary Familial Hypercholesterolemia.

33. A/E Myopathy: ranging from mild muscle soreness or weakness (myalgia) to life-threatening rhabdomyolysis Hepatotoxicity Gastro intestinal complaints and headache: usually mild. May precipitate DM

34. Precautions and contraindications c/I in pregnancy Avoid in patients with active liver disease Avoid in breastfeeding mothers Should not be used along with drugs like: fibrates (esp. gemfibrozil ), niacin, cyclosporine, digoxin, warfarin, macrolide antibiotics, and azole antifungals  increases the risk of myopathy

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