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  • Slide 1
  • Part 6 Antianginal Drugs Organic nitrates Organic nitrates receptor blockers receptor blockers Calcium channel blockers Calcium channel blockers
  • Slide 2
  • Coronary vessels: blood supply for the heart 1. OVERVIEW
  • Slide 3
  • Coronary atherosclerosis: cause of cardiac ischemia cause of cardiac ischemia
  • Slide 4
  • Distribution of coronary arteries in the heart
  • Slide 5
  • Ischemia (angina pectoris): Ischemia (angina pectoris ): imbalance between oxygen demand and supply imbalance between oxygen demand and supply
  • Slide 6
  • Classification of angina pectoris: Exertional angina ( ) Stable angina ( ) Stable angina ( ) Initial onset angina ( ) Initial onset angina ( ) Accelerated angina ( ) Accelerated angina ( ) Spontaneous angina ( ) Angina decubitus ( ) Angina decubitus ( ) Variant [or vasospastic] angina ( [ ] ) Variant [or vasospastic] angina ( [ ] ) Acute coronary insufficiency ( ) Acute coronary insufficiency ( ) Postinfarction angina ( ) Postinfarction angina ( ) Mixed angina ( ) Unstable angina ( ): link of stable angina and myocardial infarction Unstable angina ( ): link of stable angina and myocardial infarction 1. OVERVIEW
  • Slide 7
  • Myocardial oxygen demand is chiefly determined by: Contractility Contractility Heart rate Heart rate Wall tension Wall tension Preload (venous return ) Preload (venous return ) Afterload (arteriolar resistance) Afterload (arteriolar resistance) 1. OVERVIEW preloadafterload
  • Slide 8
  • Myocardial oxygen demand is diminished by: Reducing contractility Reducing contractility Reducing heart rate Reducing heart rate Reducing the preload Reducing the preload Reducing the afterload Reducing the afterload 1. OVERVIEW Wall tension
  • Slide 9
  • 1. OVERVIEW Myocardial oxygen supply is chiefly determined by:Myocardial oxygen supply is chiefly determined by: AV oxygen difference AV oxygen difference Regional myocardial Regional myocardial distribution distribution coronary blood flow: coronary blood flow: vascular resistance, artery pressure
  • Slide 10
  • Effects of antianginal drugs: Reducing oxygen demands Reducing heart rate and contractility Reducing heart rate and contractility Dilating systemic arteries and veins ( wall tension by lowering heart loads) Dilating systemic arteries and veins ( wall tension by lowering heart loads) Increasing oxygen supply Dilating conduct coronary arteries ( coronary blood flow) Dilating conduct coronary arteries ( coronary blood flow) Promoting regional distribution ( in ischemic regions) Promoting regional distribution ( in ischemic regions)Others: Anti-platelet coagulation and thrombus formation Anti-platelet coagulation and thrombus formation 1. OVERVIEW
  • Slide 11
  • 2.1 Nitrates Nitroglycerin ( ) A. Pharmacological actions Dilating vessels and reducing heart loads Dilating vessels and reducing heart loads wall tension ; reflex tachycardia wall tension ; reflex tachycardia Redistribution of coronary circulation Redistribution of coronary circulation dilating conduct artery: dilating conduct artery: collateral circulation collateral circulation reducing wall tension: reducing wall tension: blood flow in ischemic subendocardial area blood flow in ischemic subendocardial area 2. Antianginal drugs
  • Slide 12
  • Influence of organic nitrates and dipyridamole on the blood supply of ischemic area 2. Antianginal drugs
  • Slide 13
  • Mechanism of the effect of nitroglycerin and other nitrates [Ca 2+ ]i
  • Slide 14
  • B. Clinical uses Angina pectoris: all kinds, especially stable type Angina pectoris: all kinds, especially stable type Heart failure reducing heart loads due to vasodilation Heart failure reducing heart loads due to vasodilation C. Adverse reactions Increase in heart rate and contractility Symptoms due to vasodilation: headache, flash, postural hypotension, collapse, ect. Symptoms due to vasodilation: headache, flash, postural hypotension, collapse, ect. Others: methaemoglobinaemia Others: methaemoglobinaemia avoiding steady-state plasma concentration; Tolerance : avoiding steady-state plasma concentration; supplement of agents containing SH (captopril) supplement of agents containing SH (captopril) 2. Antianginal drugs
  • Slide 15
  • 2.1 Other nitrates ( ) Isosorbide dinitrate ( ) (5- ) Isosorbide-5-mononirate (5- ) Compared with nitroglycerin: Orally active Similar but weaker effect Acting slowly but lasting longer Larger individual variation and more adverse effects 2. Antianginal drugs
  • Slide 16
  • Slide 17
  • 2.2 receptor blockers A. Pharmacological action Reducing oxygen demand: Reducing oxygen demand: heart rate and contractility heart rate and contractility Increasing oxygen supply: Increasing oxygen supply: diastolic period : perfusion time diastolic period : perfusion time vascular tone in normal regions : vascular tone in normal regions : blood flow in ischemic regions blood flow in ischemic regions Others: Others: Improving myocardial metabolism Improving myocardial metabolism Inhibiting coagulation of platelets Inhibiting coagulation of platelets 2. Antianginal drugs
  • Slide 18
  • B. Clinical uses stable and unstable pectoris, especially associated with hypertension or arrhythmias, even with myocardial infarction ; but not used for variant angina pectoris stable and unstable pectoris, especially associated with hypertension or arrhythmias, even with myocardial infarction ; but not used for variant angina pectoris C. Notes Dose individualization: starting from small dose Dose individualization: starting from small dose Withdraw gradually and slowly: symptom rebound Withdraw gradually and slowly: symptom rebound Combination with nitroglycerin but without verapamil Combination with nitroglycerin but without verapamil Contraindicated in heart depression, asthma, and so on Contraindicated in heart depression, asthma, and so on 2. Antianginal drugs
  • Slide 19
  • 2.3 Calcium channel blockers 2. Antianginal drugs
  • Slide 20
  • 2.3 Calcium channel blockers A. Pharmacological actions Reducing myocardial oxygen remand: Reducing myocardial oxygen remand: heart loads : nifedipine heart loads : nifedipine heart rate and contractility : verapamil and diltiazem heart rate and contractility : verapamil and diltiazem Increasing myocardial blood supply Increasing myocardial blood supply Protecting ischemic myocardial cells Protecting ischemic myocardial cells Inhibiting coagulation of platelets Inhibiting coagulation of platelets 2. Antianginal drugs
  • Slide 21
  • Actions of calcium channel blockers
  • Slide 22
  • Selective calcium channel blockersSelective calcium channel blockers Dihydropyridines ( ):Dihydropyridines ( ): nifedipine rapid, hypotension, reflex tachycardia nifedipine rapid, hypotension, reflex tachycardia amlodipine high bioavailability, t 1/2 40-50 h, long-acting, less influences on heart rate and blood pressure amlodipine high bioavailability, t 1/2 40-50 h, long-acting, less influences on heart rate and blood pressure Phenylalkylamines ( ):Phenylalkylamines ( ): verapamil reducing oxygen demands, antiarrhythmia verapamil reducing oxygen demands, antiarrhythmia Benzothiazepines ( ):Benzothiazepines ( ): diltiazem weaker for heart depression and vasodilation; suitable for variant angina pectoris diltiazem weaker for heart depression and vasodilation; suitable for variant angina pectoris
  • Slide 23
  • B. Clinical uses stable and variant type: stable and variant type: nifedipine, verapamil, diltiazem nifedipine, verapamil, diltiazem unstable type: unstable type: verapamil, diltiazem verapamil, diltiazem 2. Antianginal drugs Actions of DHP (like nifedipine) are similar to those of nitroglycerin Actions of verapamil are similar to those of blockers Actions of diltiazem are intermedial in both above drugs
  • Slide 24
  • nitroglycerin blockers Ca 2+ antagonists combination* nitroglycerin blockers Ca 2+ antagonists combination* Heart rate Contractility / Wall tension / / Oxygen demand Blood pressure : increase, : markedly increase; : decrease, : markedly decrease; : variable according to the dose and effect of each drug ; * blockers combined with nitroglycerin or Ca 2+ antagonists (nifedipine; combination with verapamil/diltiazem not be recommendated) Caution: Combination may potentiate the antianginal effects, but may induce severe hypotension 3. Summary of antianginal drugs
  • Slide 25
  • 2.4 Other drugs ACEIs Treating hypertension and preventing ischemic heart diseaseTreating hypertension and preventing ischemic heart disease Reducing heart loadsReducing heart loads Inhibiting cardiac remodelingInhibiting cardiac remodeling Nicorandil Opening ATP-sensitive K + channel (K ATP ) Opening ATP-sensitive K + channel (K ATP ) Lowering intracellular Ca 2+ Lowering intracellular Ca 2+ Providing NO (like nitroglycerin) Providing NO (like nitroglycerin) Inducing ischemic preconditioningInducing ischemic preconditioning 2. Antianginal drugs
  • Slide 26
  • Molsidomine Promoting collateral circulationPromoting collateral circulation Similar to nitroglycerinSimilar to nitroglycerin Used in stable anginaUsed in stable angina Dipyridamole Inhibiting adenosine uptake

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