Drugs used for the treatment of myocardial ischemia

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Drugs used for the treatment of myocardial ischemia

  1. 1. Drugs used for the treatment ofmyocardial ischemia Presented by Sk.yasmeen I/II M.Pharmacy Department of pharmacology Hindu college of pharmacy Guntur Under the Guidance of Mrs.G. Sumalatha,M.Pharm(PhD) Department of pharmacology Hindu college of pharmacy Guntur
  2. 2. myocardial ischemia Myocardial ischemia:o Myocardial ischemia also known angina is a heart condition caused by a temporary lack of oxygen-rich blood to the heart.o The sudden severe, pressing chest pain occurs, starting from substernal and radiate to left arm.o The inadequate blood flow is caused by narrowed coronary arteries, which are the vessels that supply blood to the heart
  3. 3. Myocardial ischemia
  4. 4. Myocardial infraction
  5. 5. Understanding the heart and coronary arteries Like any muscle, the heart needs a constant supply of oxygen and nutrients Which are carried to it by the blood in the coronary arteries similar to other muscle. The harder the heart is working the more oxygen &nutrients it needs The coronary arteries can become narrowed or clogged, which can decrease the amount of blood that goes to the heart muscle
  6. 6. Types of myocardial ischemia Stable (typical angina) Unstable (crescendo angina) Varient (prinzmetal’s angina) Stable MI It is a most common type Occurs when heart is working harder than usual Regular pattern to this condition After several episodes, patient learns to recognize &predict Pain goes away in a few min by taking rest & medicine
  7. 7.  variant MI• It is rare and occurs at rest• Pain associated with this can be severe and usuallyoccurs between midnight and early morning• Pain relieved by medicines unstable MI• it is dangerous condition & requires emergencytreatment• it is a sign that heart attack could occur soon• it does not follow a pattern• occurs without physical exertion & not relieved by rest& medicine
  8. 8. Conditions that increases o2 supply1. Stress2. Exercise3. During increased heart rateConditions that decrease o2 supply1. Coronary arteries diseases Accumulation of plaques Platelets aggregation Stenosis or spasm or constriction or narrowing2. Reduction in blood flow to heart Due to constriction of blood vessels3. Reduction in o2carrying capacity of blood Decrease Hb levels (in anemic conditions) Normal blood flow and supply but decrease in o2 carrying capacity
  9. 9. Symptoms Some people have “silent ischemia” MI with sign & symptoms include 1. Chest pain (left side) 2. Neck or jaw pain 3. Shoulder or arm pain 4. Clammy skin 5. Nausea &vomitingCauses1. Coronary artery diseases2. Blood clot3. Coronary spasm4. Sever illness
  10. 10. Risk factors1. Tobacco 2. Diabetis 3. High B.P 4. High blood cholesterol or triglyceride levels 5. Lack of physical activity 6. Obesity 7. Family history Complications Irregular heart rhythms (arrhythmia) Heart attack (myocardial infarction)
  11. 11. Classification coronary vasodilators1. Nitrites & nitrates according to duration of action Shot acting (3 to 60 min) Amyl nitrite, nitroglycerin(sublingual), isosorbide dinitrate Intermediate acting(3 to 6hrs) Isosorbide dinitrate ,nitroglycerin(ointment) Long acting(6 to 10 hrs) Erythirtyl tetranitrate, nitroglycerin (trans-cutaneous
  12. 12. Beta adrenergic blocking agents Atenolol Propranolol NadololCalcium Channel Blockers Amlodipine , Bepridil Diltiazem , Felodipine Isradipine, Nicardipine, Nifedipine Nimodipine, Verapamil
  13. 13. Potassium Channel Activators: Nicorandil, PinacidilAntiplatelet Drugs : Aspirin ClopidogrelAngiotensin-Converting enzyem Inhibitor:captopril, enalapril, lisinoprilCholesterol Lowering Medication : Atorvastatin, Fenofivrate
  14. 14. Further treatment surgical procedures for MI1. Angioplasty and stenting2. Coronary artery bypass surgery
  15. 15. stenting Angioplasty
  16. 16. Organic nitrates
  17. 17. Biochemical role of nitrates Release of Nitric oxide radical  Activation of Guanylate cyclase  Accumulation of cGMP  Activation of cGMP dependent Kinases  Dephosphorylation of myosin light chain  Vasodilatation of Venules and Arterioles
  18. 18. 1. Hemodynamic role of nitrates 1. Venodilatation   Preload 2 . Arteriolar dilatation  After load 3. Redistribution of blood in myocardinm 4. Increase PGE1, PGI2 Decrease in platelet aggregation
  19. 19. •Pharmacokinetics -Extensive first pass metabolism. - Metabolized by denitration & conjugation -Low bioavailability only 20% -Unchanged nitrate has half life of 2-8min -Excretion : renal route.Clinical uses of Nitrates: For treatment & prophylaxis of classical angina pectoris Treatment of Variant Angina Treatment of Unstable Angina
  20. 20. Adverse effects of Nitrates In therapeutic doses:-1. Throbbing Headache2. Flushing3. Syncope  In high doses:-4. Drug rash 1. Reflex sympathetic over activity5. Tolerance leading to tachycardia which6. Constipation. increases work load on heart. 2. Fall in blood pressure 3. Methemoglobinemia
  21. 21. Ca+2 Channel Blockers
  22. 22. Ca+2 Channel Blockers Ca+2 channel blockers protect tissue by inhibiting the entrance of Ca+2 into cardiac and smooth muscle cells of the coronary and systemic arterial beds. All Ca+2 channel blockers produce some vasodilatation (↓ PVR) Some agents also slow cardiac conduction particularly through the AV node thus serving to control cardiac rhythm. Some agents have more effect on cardiac muscle than others but all serve to lower blood pressure. They are useful in Prinzmetal angina in conjunction with nitrates.
  23. 23. pharmacokinetics•Administration: orally well absorbed•Undergoes first pass metabolism•Half life : 3 to 5 hrsSide effects•Swelling of legs•Excess lowering of heart rate and blood pressure•Depressing heart muscle function
  24. 24. β-Blockers These decrease O2 demands by lowering the heart rate & contractility (decrease CO) particularly the increased demand associated with exercise. They also reduce PVR by direct vasodilation of both arterial & venous vessels reducing both pre- and after load. These effects are caused by blocking β1 receptors, selective β1 antagonistso atenolol,o metoprolol ando acebutolol lose their selectivity at high doses and at least partially block β2 receptors (a concern for bronchospastic disease). β1 antagonists reduce the frequency and severity of anginal episodes particularly when used in combination with nitrates.
  25. 25. β-Blockers
  26. 26. • There are a number of contraindications for β blockers: asthma, diabetes, bradycardia. Pharmacokinetics: • GI • 30-50% metabolized in the first-pass in liver. • T1/2: 3-5 hours,Side effects•Worsening of asthma•Depression, fatigue•Impotence•Increased cholesterol levels•Shortness of breath due to diminished heart muscle function
  27. 27. Potassium channel opener’s mechanism Potassium channel openers Activate potassium channel increase potassium permeability in cell l Hyperpolarisation occurs Closer of L-type calcium channels Reduced intracellular free calcium Leads to vasodilatation
  28. 28. Nicorandil•Administration : orally•Bioavailability : 75 to 80%•Protein binding : 25%•Metabolism : hepatic•Half life : 1hr•Excretion : renal Adverse effect •Headaches •Nausea •Vasodilatation •Vomiting •Decrease B.P •Stomach pain
  29. 29. Antiplatelet drugsMechanism of action• prostacyclin (PGI2) & thromboxane (TXA2) are derived from archedonicacid.•PGI2 is formed from vascular endothelium•TXA2 is generated by platelets is a vasoconstrictor•PGI2 is important for natural resistance to arterial thrombosis•TXA2 and vascular PGI2regulates the the platelet aggreability•Collagen form sub endothelial matrix of damaged vessel initiates theattachment•TXA2 inhibits the adenylyl cyclase and lowers the cAMP concentration•Low concentration of cAMP accelerates platelets aggregation-Aspirin inhibits cyclo-oxygenase-Inhibits the TXA2 synthesis-Prevention of platelet aggregations
  30. 30. Pharmacokinetics•Administration : orally•Bioavailability : rapidly and completely absorbed•Protein binding : 99.6%•Metabolism : hepatic•Half life : 5-9hr•Excretion : renal•Adverse effects•Nausea•Rashes and diarrohea•Peptic ulceration
  31. 31. Angiotensin converting enzyme inhibitorsMechanism: inhibit ACE low circulating Ang II decreased PVRPharmacokineticsBioavailability : 60% (oral)Metabolism : hepaticHalf life : 11 hrsExcretion : renalMain effects: decreased PVR  decreased BPAdverse effects: skin rash, taste, cough, hyperkalemia
  32. 32. Cholesterol lowering drugsMechanism of action•Competitively inhibiting HMG-CoA reductase firstenzyme of HMG-CoA reductase pathway•Statins are similar to HMG-CoA•They take the place of HMG-CoA in the enzymeand reduce the rate by which it is able to producemevalonate which is used in production ofcholesterol•Reduce LDL levels by 30% to40%•Reduce HDL levels by 2% to 15%•Reduce triglycerides by 10% to30%
  33. 33. Atrovastatin•absorption :rapid oral absorption•T max 1 to 2 hours•High intestinal clearance &first pass metabolism•Protein binding >98%•Excretion: hepatic biliary excretion Fenofivrate •absorbtion : oral absorbtion •Half life :20 hrs •Protein binding >99%Adverse effects •Excretion: renalexcretion•Mild transient GI disturbances•Rash headache•Myopathy (muscle pain)•Elevation of liver diseases
  34. 34. Contraindication•Interaction with anti arrhythmic drugs Antidepressantso Failure of sublingual tablets of nitrates to dissolve•Interactions with corticosteroids NSAIDSo Hypotensive action is antagonized•Interaction with beta blockers and calcium channel blockersoThey can cause the excessive hypotension
  35. 35. Additional MI treatment Stop smoking Eliminate alcohol Manage any underlying disorders, such as, high B.P high levels of serum cholesterol,
  36. 36. Newer antianginal drugsBecause of high prevalence of angina ,new drugs are actively sought for its treatmentSome of the drugs or groups currently under investigation are listedDrugs•Potassium channel activators : nicorandil•Metabolic modulators : trimetazidine, ronolazine•Direct bradycardic agents : ivabradine•Protein kinase Gfacilitators : detanonoate•Sulfonyl ureas : glybenclamide•Nitric oxide donors : L-arginine•Capsaicin•amiloride•Thiazolidinediones•Vasopepdidase inhibitors
  37. 37. REFERENCE•RANG &DALE’S pharmacology 6th edition•BERTRAM G.KATZUNG BASIC AND CLINICALPHARMACOLOGY•ROBBIN AND COTRON PATHOLOGIC BASIS OF DISEASE•PRINCIPLES OF PHARMACOLOGY HL.SHARMAKK.SHARMA•PHARMACOLOGY AND PHARMACOKINETICSR.S.Satoskar S.D.Bhandarkar
  38. 38. Thank you

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