part 6 antianginal drugs 抗心绞痛药 organic nitrates organic nitrates  receptor blockers...

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  • Part 6 Antianginal Drugs Organic nitrates receptor blockers Calcium channel blockers

  • Coronary vessels: blood supply for the heart1. OVERVIEW

  • Coronary atherosclerosis: cause of cardiac ischemia

  • Distribution of coronary arteries in the heart

  • Ischemia (angina pectoris ): imbalance between oxygen demand and supply

  • Classification of angina pectoris :

    Exertional angina () Stable angina () Initial onset angina () Accelerated angina ()

    Spontaneous angina () Angina decubitus () Variant [or vasospastic] angina ([]) Acute coronary insufficiency () Postinfarction angina ()

    Mixed angina ()

    Unstable angina (): link of stable angina and myocardial infarction1. OVERVIEW

  • Myocardial oxygen demand is chiefly determined by:

    Contractility Heart rate Wall tension Preload (venous return ) Afterload (arteriolar resistance) 1. OVERVIEW

    preloadafterload

  • Myocardial oxygen demand is diminished by: Reducing contractility Reducing heart rate Reducing the preload Reducing the afterload 1. OVERVIEWWall tension

  • Myocardial oxygen supply is chiefly determined by: AV oxygen difference Regional myocardial distribution coronary blood flow: vascular resistance, artery pressure 1. OVERVIEW

  • Effects of antianginal drugs :

    Reducing oxygen demands Reducing heart rate and contractility Dilating systemic arteries and veins ( wall tension by lowering heart loads)Increasing oxygen supply Dilating conduct coronary arteries ( coronary blood flow) Promoting regional distribution ( in ischemic regions)Others : Anti-platelet coagulation and thrombus formation 1. OVERVIEW

  • 2.1 Nitrates

    Nitroglycerin ()

    A. Pharmacological actions

    Dilating vessels and reducing heart loads wall tension ; reflex tachycardia Redistribution of coronary circulation dilating conduct artery: collateral circulation reducing wall tension: blood flow in ischemic subendocardial area 2. Antianginal drugs

  • Influence of organic nitrates and dipyridamole on the blood supply of ischemic area2. Antianginal drugs

  • Mechanism of the effect of nitroglycerin and other nitrates

  • Mechanism of the effect of nitroglycerin and other nitrates

  • B. Clinical uses Angina pectoris: all kinds, especially stable type Heart failurereducing heart loads due to vasodilation

    C. Adverse reactions Increase in heart rate and contractility Symptoms due to vasodilation: headache, flash, postural hypotension, collapse, ect. Others: methaemoglobinaemia Tolerance : avoiding steady-state plasma concentration; supplement of agents containing SH (captopril) 2. Antianginal drugs

  • 2.1 Other nitrates Isosorbide dinitrate () 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

  • 2.2 receptor blockers

    A. Pharmacological action Reducing oxygen demand: heart rate and contractility Increasing oxygen supply: diastolic period : perfusion time vascular tone in normal regions : blood flow in ischemic regions Others: Improving myocardial metabolism Inhibiting coagulation of platelets2. Antianginal drugs

  • B. Clinical uses 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 Withdraw gradually and slowly: symptom rebound Combination with nitroglycerin but without verapamil Contraindicated in heart depression, asthma, and so on2. Antianginal drugs

  • 2.3 Calcium channel blockers

    2. Antianginal drugs

  • 2.3 Calcium channel blockers

    A. Pharmacological actions

    Reducing myocardial oxygen remand: heart loads : nifedipine heart rate and contractility : verapamil and diltiazem Increasing myocardial blood supply Protecting ischemic myocardial cells Inhibiting coagulation of platelets2. Antianginal drugs

  • Actions of calcium channel blockers

  • Selective calcium channel blockers

    Dihydropyridines (): nifedipine rapid, hypotension, reflex tachycardia amlodipine high bioavailability, t1/2 40-50 h, long-acting, less influences on heart rate and blood pressure

    Phenylalkylamines (): verapamil reducing oxygen demands, antiarrhythmia

    Benzothiazepines (): diltiazem weaker for heart depression and vasodilation; suitable for variant angina pectoris

  • B. Clinical uses

    stable and variant type: nifedipine, verapamil, diltiazem unstable type: verapamil, diltiazem2. Antianginal drugsActions of DHP (like nifedipine) are similar to those of nitroglycerinActions of verapamil are similar to those of blockersActions of diltiazem are intermedial in both above drugs

  • nitroglycerin blockers Ca2+ 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 Ca2+ antagonists (nifedipine; combination with verapamil/diltiazem not be recommendated)Caution: Combination may potentiate the antianginal effects, but may induce severe hypotension3. Summary of antianginal drugs

  • 2.4 Other drugs

    ACEIs Treating hypertension and preventing ischemic heart disease Reducing heart loadsInhibiting cardiac remodeling

    Nicorandil

    Opening ATP-sensitive K+ channel (KATP) Lowering intracellular Ca2+ Providing NO (like nitroglycerin)Inducing ischemic preconditioning 2. Antianginal drugs

  • Molsidomine Promoting collateral circulation Similar to nitroglycerinUsed in stable angina

    Dipyridamole

    Inhibiting adenosine uptake and cAMP degradationInhibiting pletelet aggregationSmall doses, long-term oral administration2. Antianginal drugs

  • SummaryCardiovascular pharmacology

  • Overview of Cardiovascular DiseasesCommon Cardiac DiseasesAbnormal contractilityHeart failuresAbnormal rhythmsArrhythmiasAbnormal blood supplyIschemic heart diseases Myocardial disorders

    Common vascular diseasesAbnormal systematic resistanceHypertensionDysfunction of coronary vesselsCoronary vascular diseasesDysfunction of cerebral vesselsCerebral ischemia, hemorrhageDysfunction of pulmonary vesselsPulmonary hypertensionDysfunction of peripheral vessels: Peripheral vascular disorderArteriosclerosis: basis of most CVS diseases

  • Overview of Cardiovascular Drugs Classification based on target organs/tissuesHeartHeart failures, arrhythmias, cardiac ischemiaVesselsVasodilatation, vasoconstriction, arteriosclerosis

    Classification based on the mechanismsIon channelsCa2+, Na+, K+ channelsReceptorsAdrenoceptors, AT1 receptors, etc.EnzymesACEI, Na+-K+-ATPase, HMG-CoA reductaseOthersDiuretics

  • Cardiovascular Drugs Antiarrhthemic drugsClassification; Typical drugs and their properties

    Antihypertensive drugsClassification; Properties of 6 main drug classes

    Drugs for treating heart failureClassification; ACEIs, blockers, cardiac glycoide

    Antiatheroscleotic drugsHMG CoA reductase inhibitors (statins)

    Antianginal drugsNitroglycerin; blockers; Ca2+ antagonists

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