Pharmacology for Anaesthesia and Intensive Care

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15 Vasodilators

Table 15.3.Main cardiovascular effects of some Ca^2 +channel antagonists.

Blood

pressure Heart rate

AVconduction

time

Myocardial

contractility

Peripheral and

coronary artery

vasodilation

Verapamil ↓↓ ↑ ↓↓ ↑

Nifedipine ↓→↑→↑ →↑↑↑↑

Diltiazem ↓↓ ↑ ↓ ↑↑

Kinetics

Diltiazem is almost completely absorbed from the gut but hepatic first-pass

metabolism reduces the oral bioavailability to 50%. Hepatic metabolism produces an

active metabolite, desacetyldiltiazem, which is excreted in the urine. The urine also

eliminates 40% of diltiazem in the unchanged form. Approximately 75% is plasma

protein-bound.

Miscellaneous

Hydralazine

Presentation and uses

Hydralazine is available as 25–50 mg tablets and as a powder containing 20 mg for

reconstitution in water before intravenous administration (5% dextrose should be

avoided as it promotes its rapid breakdown). Hydralazine is used orally in the control

of chronic hypertension and severe chronic heart failure in conjunction with other

agents. It is used intravenously in acute hypertension associated with pre-eclampsia

at 10–20 mg. This may take up to 20 minutes to work and repeat doses may be

required.

Mechanism of action

The exact mechanism of action is uncertain but involves the activation of guanylate

cyclase and an increase in intracellular cGMP. This leads to a decrease in available

intracellular Ca^2 +and vasodilation.

Effects


Cardiovascular – its main effect is to reduce arteriolar tone and systemic vascular

resistance, whereas the capacitance vessels are less affected. As a result postural

hypotension is not usually a problem. Reflex tachycardia and an increase in cardiac

output ensue but may be effectively antagonized byβ-blockade.


Central nervous system – cerebral artery blood flow increases as a result of cerebral

artery vasodilation.