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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 Duratio Half
BP 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 : Within 20 - 2-5
120 - 180 mg/day mins
Nimodipine Subarachnoi 2 mg/hr. IV for 7 days - 4-6h 1-2h
d followed by oral at 60
haemorrhage mg every 4 hrs for 14
days
Verapamil SVT (IV), SVT 40 - 80 mg tds – qid. 30min 6-8h 4.5-12
prophylaxis Max: 480mg/day
& angina
(oral
Hypertension
NIFEDIPIN AMLODIPI FELODIPIN
E NE E

VERAPAM
IL

DILTIAZE
M
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 & ↑exercise
↓frequency of angina
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