Ca antagonists

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- inhibits slow inward calcium mediated current with resultant slight negative inotropic effect and decreased arterial and venous smooth muscle tone.

- angina especially Prinzmetal. Should not be used without a beta blocker in unstable angina as reflex tachycardia may result in worsening angina or infarction.
- hypertension including pre-ecplampsia. Does not decrease uterine perfusion nor cause fetal deterioration
- mild achalasia in patients unfit for surgery
- oesophageal spasm

- admin: PO/SL. Slow releases preparation available. No longer licensed for sublingual use in Australia
- distrib: peak concentration 1-2 hours after oral admin. 90% plasma protein bound.
- plasma half-life: 4-5 hours but duration of effect may be 8-12 hours
- elim: metabolised in the liver to inactive metabolites

- small risk of heart failure
- worsening angina/cerebral ischaemia in some
- headache 6%
- nausea, flushing, dizziness - tolerance usually develops in 1-2 weeks
- ankle oedema due to increased proximal capillary pressure due to dilatation of resistance vessels. Does not usually respond to diuretics
- in hypertensive patients already receiving beta blockers for angina may produce severe hypotension without improving angina
- similar effect sometimes seen in early days after MI
- hepatitis and glucose intolerance rare
- relaxes uterine muscle. May increase risk of post-partum haemorrhage

- beta blockers as above
- exaggerated hypotensive response may occur when used with magnesium due to latter's Ca blocking effects

- for pre-eclampsia: 10 mg SL/PO, repeated if necessary after 30 min. BP usually reduced after 10-20 min and duration of action 3-4 h

- well abs PO
- T1/2 same as nifedipine
- extensively metab. in liver
- in equipotent (wrt hypertension) dose fewer side effects than nifedipine (8/55 patients vs 21/55)

- longer duration of action than isradipine or nifedipine - allows once daily dosage
- well abs PO with peak concs 6-12 hrs after oral dosing
- t1/2 35-50 hrs so steady state levels not achieved until 6-10 days when peak adverse effects can be expected.
- metab in liver
- sim efficacy to atenolol or hydrochlorthiazide and slightly gtr. than verapamil
- unwanted vasodilator effects in 43/92 patients but only necessitated withdrwal of drug in 2 patients
? sim incid with diltiazem.
- does not seem to depress myocardium but data sheet does not make it clear whether it can be used safely in patients with cardiac failure.

- pure arteriodilator
- increases coronary and cerebral blood flow
- minimal myocardial depression but may induce reflex tachycardia
- IV administration results in fall in BP in 5-15 min
- IV infusion can be as easily titrated as SNP
- loading infusion of 10-15 mg/h until target reached and then maintenance of 2-5 mg/h
- adverse effects include headache, nausea and vomiting

- blocks intracellular influx of calcium that is thought to be a central to ischaemic neuronal damage
- moderate cerebral vasodilator but does not reduce the incidence of angiographic spasm after SAH

Absorption: rapidly absorbed from GI tract with peak plasma levels within 1 hour. Levels similar to those achieved during intravenous infusion
Distribution: levels in CSF << plasma but within the range that inhibits cerebral vasoconstriction in vitro

IV nimodipine has no proven benefit over oral

- prevention of delayed ischaemic damage following SAH
- given IV shown to improve outcome in patients with either a delayed ischaemic deficit or angiographically proven vasospasm
- no proven benefit in patients with moderate to severe head injury, stroke or following VF cardiac arrest
- some evidence to suggest that it may ameliorate the most common symptoms of cognitive dysfunction in dementing elderly patients

- uncommon
- small reduction in BP usual but may be severe in some patients treated with IV nimodipine. Maintenance of cerebral perfusion takes precedence and dose should be reduced
- headaches
- flushing
- LFT abnomalities and jaundice reported occasionally

- selectively taken up into AVN

- less negative inotropic effect than nifedipine or verapamil
- causes less vasodilatation than nifedipine
- high first pass metabolism
- parenteral dose 75-150 mcg/kg

- appear to have specific renal vascular and tubular effects not seen with other vasodilators
- increase RBF and GFR, urine output and electrolyte excretion. Decrease in afferent arteriolar resistance may be the mechanism for the enhancement of RBF but angiotensin II induced and norepinephrine induced vasoconstriction may also be reversed by Ca antagonists
- renal vascular response depends on resting renal vascular tone. Thus conditions generally associated with renal vasoconstriction favour the vasodilatory response
- no long term clinical trials yet to show whether renal effects are sustained nor whether Ca antagonists attenuate the natural progression of advanced renal disease in hypertensive patients

© Charles Gomersall December 1999

©Charles Gomersall, September, 2008 unless otherwise stated. The author, editor and The Chinese University of Hong Kong take no responsibility for any adverse event resulting from the use of this webpage.
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