21998897 calcium channel blockers

8/8/2019 21998897 Calcium Channel Blockers

http://slidepdf.com/reader/full/21998897-calcium-channel-blockers 1/15

Calcium Channel Blockers

Vanessa Ting Ching Ching



L-type Calcium Channels



Mechanism of Action

CCBs block initial Ca2+ entry



Calcium Channel Blockers



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



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 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



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



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



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)



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



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



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



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



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

21998897 calcium channel blockers

Documents