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Slide 1: Calcium channel blocker Dr Iqbal khan
Slide 2: Outline of Topics Introduction Classification Pharmacology of Ca++ Channel Blockers • Effects on Vascular Smooth Muscle • Effects on Cardiac Cells • Hemodynamic Effects • Drug-Specific Effects Therapeutic Uses Toxicities and Side Effects
Slide 3: Introduction Calcium regulate contraction of myocardium and smooth muscle and participate the aggregation of platelet, et al. pass into cells via calcium channel.
Slide 4: Introduction Calcium channel blockers (CCB)  a group of medicines which affect the way calcium passes into certain cells  medications that may decrease the heart's pumping strength and relax blood vessels.  used to treat various conditions including high blood pressure, angina, Raynaud's phenomenon, and some arrhythmias.
Slide 5: Classification Three major classes of Ca++ channel blockers 1. Dihydropyridines: nifedipine, nicardipine, nimodipine and many others 2. Benzothiazepines: Diltiazem 3. Phenylalkylamines: Verapamil
Slide 6: Pharmacology of Ca++ Channel Blockers • • • • Effects on Vascular Smooth Muscle Effects on Cardiac Cells Hemodynamic Effects Drug-Specific Effects
Slide 7: Pharmacology of Ca++ Channel Blockers The heart is mainly made of special muscle cells which contract to pump blood into the arteries.  The walls of the arteries also contain 'smooth' muscle cells which contract to make the artery narrow.  Calcium-channel blockers reduce the amount of calcium that goes into these muscle cells. This causes these muscle cells to relax. 
Slide 8: 1.Effects on Vascular Smooth Muscle • Relaxation in arterial smooth muscle → decreased cardiac afterload (aortic pressure) Little effect on venous beds → no effect on cardiac preload (ventricular filling pressure) • * Specific dihydropyridines may exhibit greater potencies in some special vascular beds (e.g.nimodipine more selective for cerebral blood vessels, nicardipine for coronary vessels)
Slide 9: 2. Effects on Cardiac Cells (1)Negative inotropic effects --reducing the force of the heart * Are seen with Verapamil (and to a lesser extent diltiazem) * Dihydropyridines have very modest negative inotropic effects
Slide 10: (2) Negative chronotropic/dromotropic effects-decreasing rate and conduction * Verapamil (and to a lesser extent diltiazem) act directly to depress SA node pacemaker activity and slow conduction . * Nifedipine do not have direct effects on conduction or automaticity but can cause reflex increases in heart rate because of their potent vasodilating effects.
Slide 11: 3. Hemodynamic Effects * Decrease coronary vascular resistance and increase coronary blood flow * Decrease peripheral resistance via vasodilatation of arteries * No significant effect on venous tone at normal doses
Slide 12: 4. Drug-Specific Effects Dihydropyridines (e.g. nifedipine, nicardipine, and nimodipine)    Vasodilatation of arterial resistance vessels a reflex increase in sympathetic response The overall hemodynamic effect is a drop in blood pressure, an increase in heart rate and contractility, and an increase in cardiac output.
Slide 13: Verapamil  has greater direct negative effects than the dihydropyridines resulting in a drop in heart rate resulting in a lowering of myocardial contractility  
Slide 14: Diltiazem The hemodynamic effects of diltiazem are intermediate between the dihydropyridines and verapamil  The drug causes a modest lowering of heart rate and modest decrease in myocardial contractility, both of which are less than verapamil for a given drop in blood pressure
Slide 15: Therapeutic Uses The primary indications for CCB 1. Angina: (1)variant angina nifedipine (contraction of coronary artery) (2)Effort angina(cardiac overload) (3) unstable angina Diltiazem\ Verapamil\ nifedipine with β-blocker
Slide 16: Therapeutic Uses 2. Arrhythmias: • Supraventricular tachycardias • diltiazem & verapamil • decrease automaticity & conduction in SA & AV nodes • nifedipine • potent decrease smooth muscle tone
Slide 17: Therapeutic Uses 3. Hypertension • • • decrease myocardial contractility decrease smooth muscle tone decrease PVR(pulmonary vascular resistance )
Slide 18: Less Common Uses * Treatment of migraine * Raynaud's phenomenon * Cerebral vasospasm * Inhibition of platelet aggregation * Slow development of atherosclerosis * Hypertrophic cardiomyopathy
Slide 19: Toxicities and Side Effects The calcium channel blockers are generally well-tolerated . The most common side effects, particularly with dihydropyridines, are due to excessive vasodilatation (i.e.- dizziness, hypotension, headache, flushing, edema, etc.)
Slide 20: Aggravation of myocardial ischemia due to a. excessive hypotension resulting in decreased coronary perfusion b. selective vasodilation in non-ischemic regions ("coronary steal") c. increased oxygen demand due to reflex tachycardia Verapamil and diltiazem are less likely to aggravate myocardial ischemia
Slide 21: Serious toxic effects bradycardia, transient systole, exacerbation of heart failure are rare can not be used ?