Pharmacology for Anaesthesia and Intensive Care

P1: PSB Printer: Yet To Come
9780521704632c15 CUFX213A/Peck 9780521618168 December 28, 2007 13:25

Section IIICardiovascular drugs

Table 15.2.Various pharmacological properties of some Ca^2 +channel antagonists.

Absorbed

(%)

Oral bioavail-

ability (%)

Protein

binding (%)

Active

metabolites Clearance

Elimination

half-life (h)

Verapamil 95 20 90 yes renal 6–12

Nifedipine 95 60 95 no renal 2–5

Diltiazem 95 50 75 yes 60% hepatic,

40% renal

3–6

coronary artery blood flow and reflex increases in heart rate and contractility. The

cardiac output is increased. Occasionally these reflex changes worsen the oxygen

supply/demand ratio.

Kinetics

Nifedipine is well absorbed following oral administration although hepatic first-

pass metabolism reduces its oral bioavailability to 60%. It is 95% plasma protein-

bound and has an elimination half-life of 5 hours following oral administration. It is

predominantly excreted as inactive metabolites in the urine (Table15.2).

Nimodipine

Nimodipine is a more lipid-soluble analogue of nifedipine and as such can penetrate

the BBB. It is used in the prevention and treatment of cerebral vasospasm follow-

ing subarachnoid haemorrhage and in migraine. It may be administered orally or

intravenously.

Its action may be dependent on blocking a Ca^2 +-dependent cascade of cellular

processes that would otherwise lead to cell damage and destruction.

Diltiazem

Presentation and uses

Diltiazem is available as 60–200 mg tablets, some of which are available as slow

release. It is also available in combination with hydrochlorothiazide. It is used for

the prophylaxis and treatment of angina and in hypertension.

Effects


Cardiovascular – diltiazem has actions both within the heart and in the peripheral

circulation. It prolongs AV conduction time and reduces contractility but to a lesser

extent than verapamil. It also reduces the systemic vascular resistance and the

blood pressure falls although a reflex tachycardia is not usually seen. Coronary

blood flow is increased due to coronary artery vasodilation.