Presentation is loading. Please wait.

Presentation is loading. Please wait.

Antianginal Drugs 抗心绞痛药 Antianginal Drugs. What’s Angina pectoris Cause and the classification of angina pectoris : – Atheromatous obstruction of the.

Similar presentations


Presentation on theme: "Antianginal Drugs 抗心绞痛药 Antianginal Drugs. What’s Angina pectoris Cause and the classification of angina pectoris : – Atheromatous obstruction of the."— Presentation transcript:

1 Antianginal Drugs 抗心绞痛药 Antianginal Drugs

2 What’s Angina pectoris Cause and the classification of angina pectoris : – Atheromatous obstruction of the large coronary vessels (atherosclerotic angina, classic angina); 劳累性心绞痛:稳定型,初发型,恶化型 – Transient spasm of localized portions of the large coronary vessels (angiospastic or variant angina); 自发性心绞痛:卧位型,变异型,急性冠脉功能不全,梗死后心绞痛 – Both causes 混合性心绞痛 Unstable angina pectoris: initial onset type; accelerated type; spontaneous type initial onset type; accelerated type; spontaneous type associated with atheroscleosis plaque and thrombus formation associated with atheroscleosis plaque and thrombus formation may lead to myocardial infarction may lead to myocardial infarction Overview

3 Coronary vessels: blood supply for the heart Overview

4 Coronary atherosclerosis: cause of cardiac ischemia cause of cardiac ischemia Overview

5

6 Distribution of coronary arteries in the heart

7 Primary cause of angina pectoris: – In classic angina, the imbalance occurs when the myocardial oxygen requirement increases; “angina of effort” – In variant angina, oxygen delivery decreases as a result of reversible coronary vasospasm. “vasospastic or Prinzmetal's angina” oxygen requirement  oxygen supply  imbalance Overview

8 preloadafterload

9 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 Myocardial oxygen supply is increased by: Dilating conduct coronary arteries Dilating conduct coronary arteries (  coronary blood flow) (  coronary blood flow) Promoting regional distribution Promoting regional distribution (  in ischemic regions) (  in ischemic regions) Treatments: Non-drug treatment: 经皮冠状动脉成形术 (percutaneous transluminal coronary angioplasty, PTCA), 冠脉搭桥术 ( coronary artery bypass graft surgery, CABG ) Drug treatment Wall tension  Overview

10 Antianginal Drugs Antianginal drugs: Organic nitrates Organic nitrates   receptor blockers   receptor blockers Calcium channel blockers Calcium channel blockers Anti-platelet agents ACEIs Fish oil Effects of antianginal drugs: Reducing oxygen demandsReducing oxygen demands Increasing oxygen supplyIncreasing oxygen supply Others: Anti- platelet coagulation and thrombus formationOthers: Anti- platelet coagulation and thrombus formation

11 Nitrates & Nitrites Quick tolerance and cross-tolerance; Pharmacokinetic factors determine the selection; nitroglycerin

12 - Pharmacokinetics Low oral bioavailability (eg, nitroglycerin and isosorbide dinitrate, typically < 10–20%). Sublingual is normally used. Transdermal and buccal absorption from slow release preparations. Amyl( 戊基 ) nitrite and related nitrites can be used with inhalation route. Duration of effect is very brief (Unchanged nitrate t1/2=2-8 minutes, partially denitrated metabolites longer t1/2= 3 hrs). So micro-pump is very common in hospital usage. Nitrates & Nitrites

13 - 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  Alleviating ischemic injury Alleviating ischemic injury Anti- platelet coagulation Anti- platelet coagulation Nitrates: Nitroglycerin ( 硝酸甘油 )

14 Influence of organic nitrates and dipyridamole on the blood supply of ischemic area Nitrates: Nitroglycerin ( 硝酸甘油 )

15 Intracellular Ca 2+ release ↓ , extracellular Ca 2+ influx ↓ Intracellular [Ca 2+ ] ↓ The production of PGE or PGI2 and membrane hyper-polarization may also be involved. Mechanism of the effect of nitroglycerin and other nitrates

16 - Clinical uses Angina pectoris: all kinds, especially stable type Angina pectoris: all kinds, especially stable type Heart failure Heart failure - Adverse reactions Symptoms due to vasodilation: headache, postural Symptoms due to vasodilation: headache, postural hypotension, etc. hypotension, etc. Increase in heart rate and contractility Others: methaemoglobinaemia (高铁血红蛋白) Others: methaemoglobinaemia (高铁血红蛋白) avoiding steady-state plasma concentration; Tolerance : avoiding steady-state plasma concentration; supplement of agents containing – SH supplement of agents containing – SH (captopril, NAC), VitC (captopril, NAC), VitC Nitrates: Nitroglycerin ( 硝酸甘油 )

17 Other nitrates ( 硝酸异山梨酯 ) Isosorbide dinitrate ( 硝酸异山梨酯 ) (5- 硝酸异山梨酯 ) Isosorbide-5-mononirate (5- 硝酸异山梨酯 ) Compared with nitroglycerin: Similar but weaker effect Acting slowly but lasting longer Larger individual variation and more adverse effects Nitrates

18 - 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 Increase oxygen supply Increase oxygen supply Inhibiting coagulation of platelets Inhibiting coagulation of platelets  receptor blockers

19 - 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 - 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 Cardiac depression Cardiac depression Inducing asthma Inducing asthma Combination with nitroglycerin Combination with nitroglycerin  receptor blockers

20 - 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 Inhibiting coagulation of platelets Inhibiting coagulation of platelets Protecting ischemic myocardial cells Protecting ischemic myocardial cells - Clinical uses stable and variant type: stable and variant type: nifedipine, verapamil, diltiazem nifedipine, verapamil, diltiazem unstable type: unstable type: verapamil, diltiazem verapamil, diltiazem Calcium channel blockers

21

22 - Toxicity Cardiac depressionCardiac depression, including cardiac arrest, bradycardia, atrioventricular block, and heart failure. Relatively short-acting calcium channel blockers have the potential to enhance the risk of adverse cardiac events. Slow-release and long-acting vasoselective calcium channel blockers are usually well tolerated. Patients receiving  -adrenoceptor-blocking drugs are more sensitive to the cardiodepressant effects of calcium channel blockers. Tolerable toxicity: flushing, dizziness, nausea, constipation, and peripheral edema. Calcium channel blockers

23 Other drugs Angiotensin converting enzyme inhibitors (ACEI) Nicorandi ( 尼可地尔 ) a potassium channel opener Molsidomine (吗多明) Producing NO → stimulate guanylyl cyclase (GC) →increase cGMP → relaxes vascular smooth muscle Dipyridamole (双嘧达莫,潘生丁) Inhibiting adenosine uptake and cAMP degradation Inhibiting adenosine uptake and cAMP degradation Inhibiting pletelet aggregation Inhibiting pletelet aggregation

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 Summary of antianginal drugs

25

26 Thanks!


Download ppt "Antianginal Drugs 抗心绞痛药 Antianginal Drugs. What’s Angina pectoris Cause and the classification of angina pectoris : – Atheromatous obstruction of the."

Similar presentations


Ads by Google