Calcium Channel Blockers

Vanessa Ting Ching Ching

L-type Calcium Channels
Mechanism of Action

CCBs block initial Ca2+ entry

Calcium Channel Blockers
 Calcium Channel Blockers
Agent Indication Dose Onset of BP Duratio Half
effect n of BP Life
effect
Amlodipine hypertension 5-10mg od 30-50 mins 24h 30-
50h
Felodipine hypertension 5-10mg od 2-5h 24h 11-
16h
Nifedipine hypertension 10 - 30mg tds. Max : 120 Within 20 - 2-5
- 180 mg/day mins
Nimodipine Subarachnoid 2 mg/hr. IV for 7 days - 4-6h 1-2h
haemorrhage followed by oral at 60 mg
every 4 hrs for 14 days
Verapamil SVT (IV), SVT 40 - 80 mg tds – qid. 30min 6-8h 4.5-
prophylaxis & Max: 480mg/day 12
angina (oral
Diltiazem Angina 60mg tds (Elderly initially 30-60min 6-8h 3-
pectoris bd). Max 360mg/day 4.5h
 Hypertension
NIFEDIPINE AMLODIPINE FELODIPINE

VERAPAMIL

DILTIAZEM
 Cardiac Arrhythmias
• CCBs preferentially affect slow response myocardial tissue
– sinoatrial and atrioventricular nodes
– AMI may convert fast conducting tissue (ventricular myocardium,
Purkinje fibers) into slow response tissue
• Terminate & prevent recurrence of supraventricular
tachycardia (SVT)
– Verapamil as treatment of choice
– Avoid in unstable pts with haemodynamic compromise & wide
complex tachycardia
• Slow ventricular response in atrial fibrillation (AF) and atrial
flutter
– Verapamil & diltiazem impair conduction and prolong
refractoriness in the AV node, thus ↓resting and the exercise-
induced increases in heart rate
 Angina Pectoris
All CCBs are effective in treatment of stable angina
pectoris, although nitrates & β-blockers are 1st-line
↓frequency of angina & ↑exercise time
•Nifedipine 20mg bd (ACTION trial)
•Amlodipine 5-10mg od (Taylor)
•Verapamil (Brodsky et al)
•Diltiazem (Hossack et al)

↓ Side effects with diltiazem compared to nifedipine

•Nifedipine causes reflex tachycardia

Verapamil more effective than nifedipine

 Myocardial Infarction
• Avoid short-acting dihydropyridines in AMI
– Nifedipine ↑ early mortality
– Due to repeated hypotension & reflex tachycardia, &
negative inotropic effects
• Long-acting dihydropyridines as an adjunct to control
hypertension in AMI
– Role in AMI not directly studied but may not be harmful
• Negative chronotropic CCBs may be useful in
preventing reinfarction
• Diltiazem ↓ cardiac events in patients with preserved
LV function
– ↓reccurent ischaemia & revascularisation
– ↑event & mortality rate in patients with low LVEF
• Similarly, verapamil is beneficial in non-HF patients
 Systolic Heart Failure
CCBs should be avoided in HF
•Nifedipine ↑hospitalization, worsening HF & early discontinuation
due to adverse events
•Verapamil shows neither benefit or increased mortality
•Conflicting results with diltiazem
MDPIT - ↑mortality & reinfarction in LV dysfunction
DiDi trial – improved CI, exercise tolerance & wellbeing but no
improvement in survival

Long-acting CCBs have little negative inotropic activity

Amlodipine: established safety but no appreciable benefit in HF

(PRAISE & PRAISE 2 trial)
Felodipine: prevent ↓exercise tolerance & QOL but no difference in
survival rates (V-HeFT III trial)
 Subarachnoid Haemorrhage
• Causes delayed cerebral ischaemia (DCI) in 2 weeks
after aneurysm rupture
– Vasospasm of cerebral blood vessels occur between D4 &
D21, peaking at D5 – D9
• Nimodipine ↓incidence & severity of neurologic
deficits
– Preferential CCB action on cerebral arterials due to
lipophilicity
– Initiate upon diagnosis & continue for 21 days
• Administration is complicated by hypotension
– May ↓dosing interval (30mg q2h) or ↓total daily dose
(60mg q4h)
– Maintain intravascular volume & pressor therapy
 Drug Interactions
• CCBs are major substrate of CYP3A4
– Except amlodipine
– Other CYP3A4 inhibitors: macrolides, azole antifungals, α1-
blockers, doxycycline, quinidine
– CYP3A4 inducers: barbiturates, carbamazepine, phenytoin,
rifampicin
– Grapefruit juice inhibits CYP3A4
• Avoid alcohol
– ↑hypotensive effects
• AV block & bradycardia
– amiodarone, flecainide, β-blockers, digoxin
• Additive hypotensive effects
– General anaesthetics, sildenafil, other antihypertensives
Adverse Effects
Toxicity
 References
• KKM Drug Formulary 2008
• DiPiro et al. Pharmacotherapy: A Pathophysiologic Approach. 6th edition,
McGraw-Hill 2005
• American Pharmacists Association. Drug Information Handbook. Lexicomp
2008
• Rosenson et al. Calcium channel blockers in acute myocardial infarction.
2007
• Colucci WS. Calcium channel blockers in heart failure due to systolic
dysfunction. 2007
• Kannam et al. Calcium channel blockers in the management of stable
angina pectoris 2007
• Podrid PJ. Calcium channel blockers in the treatment of cardiac
arrhythmias 2007
• Kaplan et al. Choice of therapy in essential hypertension: Clinical trials
2007
• Barrueto F. Calcium channel blocker toxicity. 2007