CALCIUM CHANNEL BLOCKERS
CALCIUM CHANNEL BLOCKERS
- Drugs blocking L-type of voltage-gated calcium channels, present in blood vessels & heart.
- Three groups of drugs:
- Phenylalkylamines –
- Verapamil, nor-verapamil.
- Benzothiazepines –
- Dihydropyridines –
- Nifedipine, nicardipine, nimodipine, nisoldipine, nitrendipine, isradipine, lacidipine, felodipine & amlodipine.
Drug actions of CCB’s:
- Inhibits calcium channels & reduces frequency of Ca+ channels opening –> Results in vasodilation.
- Smooth muscle relaxation in blood vessels & extravascular organs (bronchus, GIT, urinary bladder, uterus).
CCB’s & cardiac activity:
- Decreased cardiac activity –
- Decreased heart rate, AV conduction & contractility.
- Little direct cardiac activity:
- Dihydropyridine (DHP) group.
- Acts mainly on blood vessels – Hence, called peripherally acting CCBs.
- Strong direct cardiac activity:
- Verapamil & diltiazem (verapamil > diltiazem).
- Strong cardiodepressant activity.
Effect of different CCBs on HR & BP:
|Verapamil||Vasodilation||Decreases BP||Strong reduction||Increases HR||Mild reduction|
|Diltiazem||Vasodilation||Decreases BP||Mild reduction||Increases HR||Little reduction|
|DHP||Vasodilation||Decreases BP||No effect||Increases HR||Increases HR|
General indications of CCB’s:
- Used in angina (both classical & variant angina)
- Mainly Verapamil, diltiazem & long acting DHPs.
- DOC for hypertensive patients with migraine.
- Eg: Flunarizine (weak CCB) – For prophylaxis of migraine.
- In hypertensive patients with PVD (peripheral vascular diseases – Raynaud’s phenomena).
General contraindications of CCB’s:
- In sick sinus syndrome –
- Because of CCB’s reflex tachycardia.
- In angina –
- Precipitates acute attack of angina
- Accentuates angina symptoms by causing tachycardia (Except short-acting DHPs like nifedipine).
- In Hyperglycemia (mainly Nifedipine):
- By decreasing insulin release.
- CCB’s along with β-blockers.
General adverse effects of CCB’s:
- Reflex tachycardia:
- Caused due to vasodilatory action.
- Mainly by DHP’s drugs.
- Nifedipine (short half-life) – More marked tachycardia.
- Amlodipine – Long-acting drugs (maximum half-life) – Less tachycardia.
- This effect nullified by direct cardiodepressant action (except DHPs).
- Voiding difficulty in elderly:
- Due to urinary bladder relaxation.
- Constipation & ankle edema (particularly verapamil).
- Increases plasma digoxin concentration –
- By decreasing its excretion.
Individual drug description:
- Maximum cardio-depressant action.
- Causes vasodilation – By blocking calcium channel.
- Maximum effect on cardiac conduction.
- Increases PR interval.
- Metabolic properties:
- Maximum plasma protein-bound drug.
- CYP3A inhibitor.
- Has racemic mixture of two enantiomers with different pharmacokinetic & pharmacodynamic properties.
- Treatment of angina, PSVT, hypertension & hypertrophic obstructive cardiomyopathy (HOCM).
- Lesser effect on heart than verapamil.
- Same indication as verapamil.
- Suitable for elderly patients, low renin hypertension cases, asthma, migraine or peripheral vascular disease & isolated systolic hypertensive cases.
3. Dihydropyridine drug group:
- Safe in pregnancy.
- Predominant peripheral action.
- Increases angina risk.
- Increases heart rate & thus cardiac work.
- Prevented by sustained-release preparation of nifedipine & amlodipine.
- Possesses natriuretic property.
- Interferes with anesthesia.
- Nifedipine & beta-blocker given together – To overcome nifedipine’s increased sympathetic activity.
- Previously used sublingually for hypertensive emergencies.
- Banned due to increased risk of MI & mortality.
- For Achalasia cardia.
- Longest acting parenteral CCB.
- DOC for hypertensive emergencies.
- Combined with beta blockers to avoid tachycardia.
- Shortest acting CCB’s
- Relatively Cerebro-selective vasodilator.
- Used for reversal of compensatory vasoconstriction after subarachnoid hemorrhage.
- Ultrashort-acting DHP.
- Recently approved for hypertensive emergencies.
- DOC for managing asthmatic patient with hypertension.
- Rebound hypertension is seen.
CALCIUM CHANNEL BLOCKERS
- Calcium channel blockers block L-type of voltage-gated calcium channels present in blood vessels & heart.
- CCB’s causes vasodilation by inhibits calcium channels & reduces frequency of Ca+ channels opening.
- CCB’s reduces cardiac activity including heart rate, AV conduction & contractility.
- Dihydropyridine (DHP) group of CCB drugs are referred to as peripherally acting CCB’s.
- Strong cardio-depressant activity is mainly exhibited by verapamil & diltiazem (verapamil > diltiazem).
- CCB’s are indicated for both classical & variant angina, mainly verapamil, diltiazem & long acting DHPs.
- DOC for hypertensive patients with migraine is calcium channel blocker.
- Flunarizine is weak CCB used for prophylaxis of migraine.
- CCB’s are used in hypertensive patients with PVD (Raynaud’s phenomena).
- CCB’s are contraindicated in sick sinus syndrome, as it causes reflex tachycardia.
- Short-acting DHPs like nifedipine accentuates angina symptoms, by causing tachycardia & precipitates acute anginal attack.
- Nifedipine causes hyperglycemia by decreasing insulin release.
- CCB’s along with β-blockers are contraindicated.
- Nifedipine shows marked tachycardia.
- Long-acting CCB’s like Amlodipine will show less tachycardiac effects.
- CCB’s causes urinary bladder relaxation, resulting in voiding difficulty in elderly.
- CCB’s increases plasma digoxin concentration, by decreasing its excretion.
- Verapamil shows maximum cardio-depressant action.
- Verapamil exhibits maximum effect on cardiac conduction.
- Verapamil increases PR interval.
- CCB with maximum plasma protein-bound nature is verapamil.
- Verapamil has racemic mixture of two enantiomers with different pharmacokinetic & pharmacodynamic properties.
- Verapamil is used for treatment of angina, PSVT, hypertension & hypertrophic obstructive cardiomyopathy (HOCM).
- Among CCB’s, dihydropyridine drugs are safer in pregnancy.
- Nifedipine has predominant peripheral action.
- Nifedipine by increases angina risk by increasing heart rate & thus cardiac work.
- Nifedipine interferes with anesthesia.
- Mostly Nifedipine & beta-blocker are given together, to overcome nifedipine’s increased sympathetic activity.
- Nifedipine is banned for sublingual usage for hypertensive emergencies, due to increased risk of MI & mortality.
- Nifedipine is also used for achalasia cardia.
- Longest acting parenteral CCB is Nicardipine.
- DOC for hypertensive emergencies is Nicardipine.
- Nimodipine is shortest acting CCB’s with relatively cerebro-selective vasodilating nature.
- Nimodipine is used for reversal of compensatory vasoconstriction after subarachnoid hemorrhage.
- Clevidipine is an ultrashort-acting DHP.
- Clevidipine is recently approved for hypertensive emergencies.
- Amlodipine is DOC for managing asthmatic patient with hypertension.
- Rebound hypertension is seen with Amlodipine.