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Calcium Channel Blockers (CCB)
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  1. Calcium Channel Blockers (CCB) Huang zhanqin

  2. OUTLINE • Background • Ca2+ channel • Classification of CCB • Mechanisms • Pharmacological effects • Clinical use • Adverse drug reactions (ADR) • Review & Questions

  3. BACKGROUND • Function of Ca2+ • Muscle gland Inflammatory cells Contraction secretiondegranulation • Cardiac cells Plt. Coagulation Neurocyte A.Paggregationkey factortransmiter releasing • Calcium channel blockers : CCBs are drugs which decrease the intracellular calcium concentration via reducing the calcium influx by selectively blocking the voltage dependent calcium channel on the cellular membrane, hence influence the cellular function.

  4. Ca2+ Channel is transmembrane protein .

  5. Ca2+ Channel • Classification according to the activated method • VDC • L(long-lasting) • T(transient) N(non L non T) P Q R • ROC Activation -10mV -70mV E.g. DHPs,dil, ver, aml Mibefradil Flunarizine Distribution Cardiovascular Sys. SM,Glands,NC

  6. Classification of CCB • According to the selectivity • selectivity nonselectivity • PAAs: Ver. BPPs:Flu. • DHPs: Nif,Nim Prenylamine • Diltiazem OTHERS:

  7. Classification of CCB • According to the mainly acting sites • Target Agents • Heart PAAs: Ver. • Vessel DHPs: Aml,Nif,Nim • Intermediate Diltiazem

  8. Effects of CCB • Heart: negative inotropic;frequency;conduction Cardiac Output HR P-R • Mechanism constriction 0,4 phase of AP • Protecting the ISC myocardium: Ca-overload necrosis and/or apoptosis • Vessel(vascular smooth mucle): dilatation • Mechanism constriction • Prevention of Coronary Heart Disease: • Mechanism Ca-overload; Platelet;RBC • Anti-oxydation, anti-proliferation • SM: relaxing • Glands: secreting Athero- sclerosis

  9. Clinic use of CCB

  10. ADR of CCB • Nifedipine: Dizzy, ankle edema, palpitation, flushing • Verapamil: constipation,dizzy, bradycardia, AVB • Diltiazem: headache,edema, dizzy

  11. Points & Questions • Block Ca entry by preventing opening of voltage-gated L-,T-type Ca channels • Three main L-type antagonists,typified by verapamil, diltiazem and dihydropyidines • Selectivity between heat and smooth mucle varies: Ver is relatively cardioselective;Nif is relatively smooth muscle selective and Dil is intermediate • Vasodilator effect (mainly DHPs)is mainly on resistance vessels,causing reduced afterload. Calcium antagonists also dilate coronary vessels, which is important in variant angina.

  12. Points & Questions • Effects on heart(Ver,Dil): antidysrhythmic action ( mainly atrial tachycardias) because of impaired AV conduction, and reduced contractility • Clinic uses include:antidysrhythmic therapy (mainly Ver,especially atrial tachycardias), angina(by reducing cardiac work) and hypertension. • Unwanted effects include headache, constipation (Ver), and ankle edema (DHPs). There is a risk of causing cardiac failure or heart block, especially with Ver and Dil.