26. Nicorandil : mode of action Nitrate-like action K + channel opener ATP Dilates epicardial Coronary arteries Venodilatation Dilates peripheral arterioles Dilates coronary Resistance vessels Decreased Preload Decreased afterload ↑ coronary blood flow ↓ Myocardial O 2 requirement ↓ Myocardial O 2 requirement ↑ coronary blood flow Nicorandil dual action
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33. In Aerobic Condition (60-90%) Fatty Acid Myocytes Palmitate ATP Mitochondria TCA Cycle Acetyl Co A Palm-Co A Glucose Pyruvate Myocytes Pyruvate ATP Mitochondria TCA Cycle Acetyl Co A (10-40%)
34. In Ischemic Conditions Fatty acid oxidation out-competes glucose oxidation for the energy production Glucose Pyruvate Myocytes Glycogen Lactate H + Pyruvate ATP Mitochondria TCA Cycle Acetyl Co A ADP ATP Fatty Acid Myocytes Palmitate ATP Mitochondria TCA Cycle Acetyl Co A Palm-Co A
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37. 1. Cardiovasc Drugs Ther 1994: 8 741-747 2. JAMA 2004: 291: 309 – 316 3. J AM Coll Cardiol 2004: 43 : 1375 - 1382 Nicorandil Ranolazine Hybrid between organic nitrate and ATP - sensitive K + Channel Activator (Opener) Metabolic modulator Vasodilation is achieved by Nitrate like action and through the opening of potassium channels Inhibits the late Na+ current and thus reduces the Calcium overload Direct Cardioprotective Action like Ischemic preconditioning and also prevents No Reflow Phenomenon Does not exhibit any direct cardioprotective action Does not have any significant effect on exercise tolerance Improves exercise tolerance and reduces the frequency of angina attacks in patients with ischemic heart disease 1-3 Initial dosage- 5 mg/ day Maximum dosage- 40 mg/ day (O.D/ B.I.D) Initial dosage- 500 mg/ day Maximum Dosage- 1000 mg/ day (B.I.D)
38. * Eur Heart J. 2006 Jan;27(1):42-8 . Nicorandil can be coprescribed with antiarrhtyhmic agents like Amiodarone and Diltiazem Ranolazine cannot be coprescribed with antiarrhythmic agents because of induction of torsade points due to prolongation of QT interval Nicorandil IV is indicated in Acute Coronay Syndrome Ranolazine is not indicated in Acute Coronary Syndrome Nicorandil has no effect on diabetic patients Ranolazine significantly improved glycaemic control in diabetic patients.* Nicorandil Ranolazine
It is proposed that Na + -related Ca 2+ overload mediates a vicious cycle of ischemia begetting more ischemia. Ca 2+ overload may result in increased left ventricular diastolic tension. As a result, myocardial O 2 consumption increases and intramural small vessels are compressed, causing increased O 2 demand and decreased O 2 supply, respectively. Positive feedback during ischemia increases the imbalance between myocardial oxygen supply and demand. Na + /Ca 2+ overload and ischemia
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