Pharmacology for Anaesthesia and Intensive Care

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15 Vasodilators

Table 15.1.Chemical classification of Ca^2 +channel antagonists.

Class I phenylalkylamines verapamil

Class II dihydropyridines nifedipine, amlodipine, nimodipine

Class III benzothiazepines diltiazem

Mechanism of action

Thel-isomer has specific Ca^2 +channel blocking actions with a particular affinity

for those at the SA and AV node, whereas thed-isomer acts on fast Na+channels

resulting in some local anaesthetic activity.

Effects


Cardiovascular – verapamil acts specifically to slow the conduction of the action

potential at the SA and AV node resulting in a reduced heart rate. To a lesser extent

it produces some negative inotropic effects and vasodilates peripheral vascular

smooth muscle. It is a mild coronary artery vasodilator. Blood pressure falls. It may

lead to various degrees of heart block or cardiac failure in those with impaired

ventricular function and ventricular fibrillation in those with WPW syndrome.


Central nervous system – it vasodilates the cerebral circulation.


Miscellaneous – following chronic administration it may potentiate the effects of

non-depolarizing and depolarizing muscle relaxants.

Kinetics

Verapamil is well absorbed from the gut but an extensive first-pass hepatic meta-

bolism reduces the oral bioavailability to 20%. Demethylation produces norver-

apamil, which retains significant anti-arrhythmic properties. It is 90% plasma

protein-bound and is mainly excreted in the urine following metabolism, although

up to 20% is excreted in bile.

Nifedipine

Presentation and uses

Nifedipine is available as capsules containing 5–10 mg, the contents of which may

be administered sublingually, and tablets containing 10–60 mg, some of which are

available as sustained release. The onset of action is 15–20 minutes following oral

and 5–10 minutes following sublingual administration. Swallowing the contents of

an opened capsule may further reduce the onset time. It is used in the prophylaxis

and treatment of angina, hypertension and in Raynaud’s syndrome.

Effects


Cardiovascular – nifedipine reduces tone in peripheral and coronary arteries,

resulting in a reduced systemic vascular resistance, fall in blood pressure, increased