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Calcium channel Blockers

Dr S A Jayaratne

Dept 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 effects
Cardiac effects Cause AV block
Cardiac slowing due to its action on
conducting tissue

Pharmacological effects contd--

Vascular effects
Generalised arterial /arteriolar dilatation
reduce BP (not much effect on veins)
Cause coronary vasodilatation
Also used in patients with coronary artery
vasospasms (variant angina)

Types of calcium channel blockers


3 structurally different types depending on the
binding to different parts of L-type calcium
channels
-Dihydropyridinese.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 effects
Causes arteriolar vasodilation
Some venodilator effect
.Contraindicated in heart failure, bradycardia,
heart block
Indication-cardiac arrythmia

Dihydropyridines- Nifedipine, amlodipine


Dilates artries (little effect on veins)
Less ve inotropic & chronotropic effects
T1/2 2hrs
Sustained release preparations are available
(once daily dosing)
Can be taken sublingually (absorption is mainly
from stomach)

Adverse effects of Nifedipine


Short acting preparations
Risk of MI & cardiac death
Hazard of activating the sympathetic system
every time a dose is taken

Amlodipine
Has a long t1/2
not contraindicated in heart failure

Types of calcium channel blockers contd

Diltiazem Intermediate in its effect. Causes less cardiac


depression & less reduction in AV conduction
than verapamil
But C/I in heart failure & bradycardia

Nimodipine
Moderate cerebral vasodilating effect
In subarachnoid Haemorrhage ischaemia is due
spasm
Nimodipine selective for cerebral vasculature
Given iv

Action of calcium channel blockers in angina


Coronary vasodilatation -increases oxygen
supply to myocardium
Dilatation of arteries/arterioles reduce
peripheral resistance
reduce work load
on heart
reduce myocardial demand for
oxygen
Reduce heart rate by its effect on conducting
tissues
reduce myocardial oxygen
demand

Short acting dihydropyridines should be


avoided
Long acting preparations, slow release
preparations & nondihydropyridines are used

Pharmacokinetics of calcium channel blockers


Given orally (except Nimodipine
in subarachnoid haemorrhage given iv)
Undergoes first pass metabolism to varying
extents in gut wall & liver
Dose change is unnecessary in renal failure
Metabolised by cytochrome p-450 enzyme
Verapamil is inhibitor of metabolising
enzymes

Clinical uses of calcium channel blockers


Angina-amlodipine,verapamil
Hypertension-amlodipine, diltiazem,
nifedipine, verapamil
Cardiac arrhythmia-verapamil
Reynauds disease nifedipine
Subarachnoid haemorrhage-nimodipine

Adverse effects of CCBs


Headache, flushing dizziness, hypotension
(dihydropyridines)
Palpitations
Ankle oedema
Bradycardia, heart block
Constipation, (verapamil) nausea , vomiting

Contraindications for CCBs

Hypotension
Sinus bradycardia
AV conduction defects
Severe cardiac failure

Calcium channel blockers have no role in the


treatment of heart failure
Depressant effect on the heart may worsen
heart failure