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8/8/2019 21998897 Calcium Channel Blockers
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Calcium Channel Blockers
Vanessa Ting Ching Ching
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L-type Calcium Channels
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Mechanism of Action
CCBs block initial Ca2+ entry
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Calcium Channel Blockers
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Calcium Channel BlockersAgent Indication Dose Onset of BP
effectDuration of BP
effect
Half Life
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
- 180 mg/day
Within 20
mins
- 2-5
Nimodipine Subarachnoid
haemorrhage
2 mg/hr. IV for 7 days
followed by oral at 60 mg
every 4 hrs for 14 days
- 4-6h 1-2h
Verapamil SVT (IV), SVT
prophylaxis &
angina (oral
40 - 80 mg tds qid.
Max: 480mg/day
30min 6-8h 4.5-
12
Diltiazem Angina
pectoris
60mg tds (Elderly initially
bd).Max 360mg/day
30-60min 6-8h 3-
4.5h
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Hypertension
NIFEDIPINE AMLODIPINE FELODIPINE
VERAPAMIL
DILTIAZEM
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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 supraventriculartachycardia (SVT) ± Verapamil as treatment of choice
± Avoid in unstable pts with haemodynamic compromise & widecomplex tachycardia
Slow ventricular response in atrial fibrillation (AF) and atrialflutter ± Verapamil & diltiazem impair conduction and prolong
refractoriness in the AV node, thus resting and the exercise-induced increases in heart rate
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Angina Pectoris
All CCBs are effective in treatment of stable angina
pectoris, although nitrates & -blockers are 1st-line
frequency of angina & exercise timeNifedipine 20mg bd (ACTION trial)Amlodipine 5-10mg od (Taylor)
Verapamil (Brodsky et al)
Diltiazem (Hossack et al)
Side effects with diltiazem compared to nifedipineNifedipine causes reflex tachycardia
Verapamil more effective than nifedipine
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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 inpreventing reinfarction
Diltiazem cardiac events in patients with preservedLV function ± reccurent ischaemia & revascularisation
± event & mortality rate in patients with low LVEF
Similarly, verapamil is beneficial in non-HF patients
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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 diltiazemMDPIT - 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 & Q OL but no difference in
survival rates (V-HeFT III trial)
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Subarachnoid Haemorrhage
Causes delayed cerebral ischaemia (DCI) in 2 weeksaf ter aneurysm rupture ± Vasospasm of cerebral blood vessels occur between D4 &
D21, peaking at D5 D9
Nimodipine incidence & severity of neurologicdeficits ± 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
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Drug Interactions
CCBs are major substrate of CYP3A4 ± Except amlodipine
± Other CYP3A4 inhibitors: macrolides, azole antifungals, 1-
blockers, doxycycline, quinidine
±CYP3A4 inducers: barbiturates, carbamazepine, phenytoin,rifampicin
± Grapefruit juice inhibits CYP3A4
Avoid alcohol
±
hypotensive effects AV block & bradycardia
± amiodarone, flecainide, -blockers, digoxin
Additive hypotensive effects
±
General anaesthetics, sildenafil, other antihypertensives
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Adverse Effects
Headache, dizziness, flushing,peripheral oedema
cardiac contractility & slows
cardiac conduction
Known
risk of AMI in HPT use
mortality in post-MI use Unestablished:mortality, GI
bleeding & cancer
Serious
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Toxicity
Dihydropyridines: arterial vasodilation, reflex tachycardia
Non-Dihydropyridines:peripheral vasodilation, bradycardia,cardiac inotropy
effects
Hypotension, bradycardia (verapamil)
ECG: PR interval, bradyarrhythmias
HF: rales, jugular venous distension
Hyperglycaemia, mental changes
diagnosis
Hypotension: IVF, may require intubation & ventilation
Lavage w/in 1-2h activated charcoal, whole bowelirrigation
Atropine, IV calcium, glucagon, noradrenaline
management
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References
KKMDrug Formulary 2008
DiPiro et al. Pharmacotherapy: A Pathophysiologic Approach. 6th edition,McGraw-Hill 2005
American Pharmacists Association. Drug InformationHandbook. Lexicomp2008
Rosenson et al. Calcium channel blockers in acute myocardial infarction.2007
Colucci WS. Calcium channel blockers in heart failure due to systolicdysfunction. 2007
Kannam et al. Calcium channel blockers in the management of stableangina pectoris 2007
Podrid PJ. Calcium channel blockers in the treatment of cardiacarrhythmias 2007
Kaplan et al. Choice of therapy in essential hypertension: Clinical trials2007
Barrueto F. Calcium channel blocker toxicity. 2007