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Myocardial Ischemia

Myocardial Ischemia. Manifests in Different Forms:. Stable Angina (atherosclerotic block of coronary artery) Unstable Angina (rupture of atherosclerotic plaque) Silent / Effort Ischemia (Often induced by exercise) Variant Angina (focal/diffuse coronary vasospasm)

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Myocardial Ischemia

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  1. Myocardial Ischemia

  2. Manifests in Different Forms: • Stable Angina(atherosclerotic block of coronary artery) • Unstable Angina(rupture of atherosclerotic plaque) • Silent / Effort Ischemia(Often induced by exercise) • Variant Angina(focal/diffuse coronary vasospasm) • Myocardial Infarction(Heart Attack, death of tissue)

  3. Pathophysiology:Etiology Atherosclerosis: Deposition of Fatty Substances esp. cholesterol or fatty acids in arteries Risks Factors include: Hypertension Hyperlipidemia Obesity Carbon Monoxide in Smoke Sedentary life-style

  4. Coronary Artery Spasm: Cause Unknown. May occur in patients with or without atherosclerosis Risks Factors include: Smoking Stress

  5. Pharmacological Intervention • Symptomatic(Angina) • Nitrates • Ca2+ Channel Blockers • β-Blockers • Prophylactic • Lipid Lowering Drugs • Anti-Coagulants • Fibrinolytic • Anti-platelet

  6. Determinants of Oxygen Demand Need to improve ratio Coronary blood flow / cardiac work or Cardiac O2 Supply / Cardiac O2 Requirement

  7. Coronary artery with partial blockage When a clogged artery keeps the heart from getting enough blood and oxygen, angina can occur

  8. Angina – Surgical Treatment(Coronary bypass, angioplasty, stents)

  9. Pharmacological Intervention:Drug Types • Drug Types Currently Used Reduce O2 Demand and/or Improve Coronary Flow Reduce BP Venous Return Force/Rate of Heart 1. Nitrates 2. Ca2+ Channel Blockers 3. β-Blockers Targeted towards reducing plaque formation 4. Lipid Lowering Drugs 5. Drugs Affecting Coagulation, Fibrinolysis & Platelet Aggregation Slower development of ischemia

  10. Drugs Affecting Plaque Formation

  11. Anti-thrombotic drugs There are three main classes of anti-thrombotic drugs Anti-coagulant drugs Fibrinolytic drugs Anti-platelet drugs

  12. Anti-thrombotic drugs Anticoagulant and antiplatelet drugs inhibits the coagulation process and administered to prevent the initial formation of thrombi/recurrence of thrombi. Fibrinolytic drugs act by dissolving existing thrombi or emboli and play an important role in the acute treatment of thrombosis.

  13. Anti-thrombotic drugs The principal indications of anti-thrombotic drugs are– The prevention and treatment of venous thromboembolism (VTE) The prevention of stroke in patients with atrial fibrillation The prevention and treatment of acute coronary syndrome (ACS)

  14. Anti-coagulants There are three principal classes of anticoagulants: Heparins Vitamin K antagonists Direct thrombin inhibitors

  15. Anti-coagulants Heparin: Heparin is a heterogenous polysaccharide with a unique pentasaccharide sequence responsible for its activity. Unfractionated heparin Low molecular weight heparin

  16. Anti-coagulants Heparin : Mechanism of action : All heparins act by enhancing the activity of the endogenous anticoagulant, antithrombin by increasing its affinity for thrombin The heparin-antithrombin complex also inhibits factors Xa, IXa and XIa. Thrombin and Factor Xa are most sensitive to inhibition.

  17. Anti-coagulants Heparin : Pharmacokinetics : Highly ionized and not absorbed orally Does not cross the placenta Dose dependent kinetics Heparin : Adverse effects : Bleeding Thrombocytopenia Osteoporosis Alopecia

  18. Anti-coagulants LOW MOLECULAR WEIGHT HEPARINLMWH It selectively inhibits factor Xa Better s.c bioavailability 80% than unfractionated heparin 30% Longer acting Lab monitoring is not required Lower risk of thrombocytopenia and osteoporosis E.g., Enoxaparin, Dalteparin, Tinzaparin

  19. Anti-thrombotic drugs HEPARIN ANTAGONIST Protamine sulfate: Strongly basic unit Given I.V ., 1 mg neutralizes 100 units of heparin Less effectively neutralized LMWH

  20. Anti-coagulants Direct factor Xa inhibitors: Fondaparinux(Arixtra): It is a synthetic pentasaccharide LMWH and fondaparinux have more anti-Xa activity than anti-IIa activity Lower risk for heparin-induced thrombocytopenia

  21. Anti-coagulants Direct thrombin inhibitors : These drugs directly inhibits thrombin without involving anti-thrombin and Vitamin K Used as anti-coagulants in patients with heparin induced thrombocytopenia Hirudin, Lepirudin, Argatroban

  22. Anti-coagulants Danaparoid is a heparinoid consisting of heparan sulfate, dermatan sulfate and chondroitin sulfate. It has greater specific anti-Xa activity than LMWH. It can be used as anti-coagulant in patients with heparin induced thrombocytopenia.

  23. Anti-coagulants Vitamin K antagonists The anticoagulant effect of vitamin K antagonists is due to inhibition of the synthesis of vitamin K dependent functional clotting factors II, VII, IX and X as well as anticoagulant protein C in the liver. Warfarin, Dicumoral, Phenindione

  24. Anti-coagulants Warfarin Coumadin It is an oral anticoagulant. Acts as a competitive antagonist of Vit K and reduce the functional level of clotting factors II, VII, IX and X as well as anticoagulant protein C in the liver. Anti-coagulant effect delayed for 3 days.

  25. Anti-coagulants Warfarin : Adverse effects and cautions: Bleeding is common adverse effect --- monitored by PT or INR. Skin necrosis, purple toe syndrome and alopecia rarely. Some cephalosporins like cefoperazone kills the intestine bacteria and decrease the Vit-K production and increase the anti-coagulant activity of warfarin.

  26. Anti-coagulants Warfarin : Antidote Vitamin K 1 (Phytonadione) can be used in over dosage of warfarin. Serious hemorrhage may be stopped by fresh frozen plasma or plasma concentrates of II, VII, IX and X factors.

  27. HEPARIN WARFARIN Fondaparinux

  28. Fibrinolytic drugs These are plasminogen activators which convert plasminogen into plasmin that catalyzes the degradation of fibrin. These are used for the lysis of the already formed clots – recanalize the occluded vessel. Streptokinase, Urokinase, t-PA These are indicated in the treatment of pulmonary embolism and myocardial infarction

  29. Tranexamic acid

  30. Fibrinolytic drugs Fibrinolytic drugs

  31. Anti-platelet Drugs

  32. Anti-platelet drugs ASPIRIN Dipyridamole TICLOPIDINE, CLOPIDOGREL GLYCOPROTEIN II b / III a RECEPTORS INHIBITORSAbciximab, Eptifibatide, Tirofiban Anti-platelet Drugs

  33. ASPIRIN: Irreversible inactivation of TXA2 synthetase in the platelets. Low dose spares endothelial synthesis of PGI-2 and thus better anti-platelet activity. Gastric bleeding is a disadvantage. Anti-platelet Drugs

  34. Anti-platelet Drugs LOW DOSE ASPIRIN

  35. DYRIDAMOLE : It is a vasodilator and anti-platelet agent. Inhibits phosphodiesterase and increase the cAMP – which potentiates PGI-2 and interfere with platelet aggregation. It is used with aspirin in prevention of thromboembolism in prosthetic heart valves and stroke. Anti-platelet Drugs

  36. TICLOPIDINE, CLOPIDOGREL It blocks purinergic (ADP) receptors on the platelets High oral bioavailability Less GI bleeding than aspirin Neutropenia, Thrombocytopenia Anti-platelet Drugs

  37. GLYCOPROTEIN II b / III a inhibitors : ABCIXIMAB, EPTIFIBATIDE, TIROFIBAN These drugs binds to IIb / IIIa receptors on platelets and block the binding of fibrinogen and thus inhibits aggregation of platelets. They are used in acute coronary syndrome and coronary angioplasty. Heparin / aspirin can be given with it. Anti-platelet Drugs

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