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9780521704632c15 CUFX213A/Peck 9780521618168 December 28, 2007 13:25
15 VasodilatorsWhile vitamin B 12 is required to complex CN−to cyanocobalamin, it is of little value
in the acute setting. It is, however, sometimes used as prophylaxis.
SCN is 100 times less toxic than CN−but its toxic effects may become significant if
it is allowed to accumulate during prolonged administration especially in those with
impaired renal function. Its accumulation is also more likely in those being given
prophylactic sodium thiosulphate as it promotes the production of SCN.Nitrates
Glyceryl trinitrate (GTN)
GTN is an organic nitrate.Presentation
GTN is prepared in the following formulations: an aerosol spray delivering 400μg
per metered dose and tablets containing 300–600μg, both used as required sub-
lingually. Modified release tablets containing 1–5 mg for buccal administration are
placed between the upper lip and gum and are used at a maximum dose of 5 mg
tds while the 2.6–10 mg modified-release tablets are to be swallowed and used at a
maximum dose of 12.8 mg tds. The transdermal patch preparation releases 5–15 mg/
24 hours, and should be resited at a different location on the chest. The clear colour-
less solution for injection contains 1–5 mg.ml−^1 and should be diluted to a 0.01%
(100μg.ml−^1 ) solution before administration by an infusion pump and is used at
10–200μg.min−^1. GTN is absorbed by polyvinyl chloride; therefore, special polyethy-
lene administration sets are preferred. GTN will explode if heated so transdermal
preparations should be removed before DC cardioversion.Uses
GTN is used in the treatment and prophylaxis of angina, in left ventricular failure
associated with myocardial infarction and following cardiac surgery. It has also been
used in the control of intra-operative blood pressure and for oesophageal spasm.Mechanism of action
GTN vasodilates veins by the production of nitric oxide. This activates the enzyme
guanylate cyclase leading to increased levels of intracellular cyclic GMP. Although
Ca^2 +influx into vascular smooth muscle is inhibited, its uptake into smooth endo-
plasmic reticulum is enhanced so that cytoplasmic levels fall resulting in vasodilation
(Figure15.2).Effects
Cardiovascular – in contrast to SNP and despite a similar mechanism of action
GTN produces vasodilation predominantly in the capacitance vessels, that is, veins,
although arteries are dilated to some extent. Consequently, it produces a reduction