Calcium channel Blockers Dr S A JayaratneDept of Pharmacology

Mechanism of action

Mechanism of action contd--They bind to the L-type calcium channels Block the inward movement of calcium In heart and in vascular smooth muscles.Three classes of CCBs binds to three different sites in the calcium channel

Pharmacological effectsCardiac effects-Cause AV blockCardiac slowing due to its action on conducting tissue

Pharmacological effects contd--Vascular effectsGeneralised arterial /arteriolar dilatationreduce BP (not much effect on veins)

Cause coronary vasodilatationAlso used in patients with coronary artery vasospasms (variant angina)

Types of calcium channel blockers3 structurally different types depending on the binding to different parts of L-type calcium channels -Dihydropyridines- e.g Nifedipine, amlodipine - Phenylalkylamines e.g Verapamil -Benzothiazepines- e.g Diltiazem

Types of calcium channel blockers contd Phennylalkylamine (Verapamil)greater effect on heart -vly inotropic effect & chronotropic effectsCauses arteriolar vasodilation Some venodilator effect.Contraindicated in heart failure, bradycardia, heart blockIndication-cardiac arrythmia

Dihydropyridines- Nifedipine, amlodipineDilates artries (little effect on veins) Less ve inotropic & chronotropic effectsT1/2 2hrs Sustained release preparations are available (once daily dosing)Can be taken sublingually (absorption is mainly from stomach)

Adverse effects of NifedipineShort acting preparations Risk of MI & cardiac death

Hazard of activating the sympathetic system every time a dose is taken

AmlodipineHas a long t1/2 not contraindicated in heart failure

Types of calcium channel blockers contdDiltiazem-Intermediate in its effect. Causes less cardiac depression & less reduction in AV conduction than verapamil

But C/I in heart failure & bradycardia

NimodipineModerate cerebral vasodilating effect

In subarachnoid Haemorrhage ischaemia is due spasmNimodipine selective for cerebral vasculature

Given iv

Action of calcium channel blockers in anginaCoronary vasodilatation -increases oxygen supply to myocardiumDilatation of arteries/arterioles reduce peripheral resistance reduce work load on heart reduce myocardial demand for oxygenReduce heart rate by its effect on conducting tissues reduce myocardial oxygen demand

Short acting dihydropyridines should be avoidedLong acting preparations, slow release preparations & nondihydropyridines are used

Pharmacokinetics of calcium channel blockersGiven orally (except Nimodipine in subarachnoid haemorrhage given iv)Undergoes first pass metabolism to varying extents in gut wall & liverDose change is unnecessary in renal failureMetabolised by cytochrome p-450 enzymeVerapamil is inhibitor of metabolising enzymes

Clinical uses of calcium channel blockersAngina-amlodipine,verapamilHypertension-amlodipine, diltiazem, nifedipine, verapamilCardiac arrhythmia-verapamilReynauds disease nifedipineSubarachnoid haemorrhage-nimodipine

Adverse effects of CCBsHeadache, flushing dizziness, hypotension (dihydropyridines)PalpitationsAnkle oedemaBradycardia, heart blockConstipation, (verapamil) nausea , vomiting

Contraindications for CCBsHypotensionSinus bradycardiaAV conduction defectsSevere cardiac failure

Calcium channel blockers have no role in the treatment of heart failureDepressant effect on the heart may worsen heart failure