P1: PSB Printer: Yet To Come
9780521704632c16 CUFX213A/Peck 9780521618168 December 28, 2007 13:34
Section IIICardiovascular drugs
Drug interactions – drugs that block uptake 1 (tricyclic antidepressants, cocaine)
prevent guanethidine from entering the nerve terminal and disrupting nora-
drenaline storage. They therefore antagonize guanethidine.Up-regulation of adrenoceptors follows the long-term use of guanethidine so that
these patients are very sensitive to direct-acting sympathomimetic amines.Kinetics
Following oral administration, guanethidine is variably and incompletely absorbed.
Hepatic first-pass metabolism results in an oral bioavailability of 50%. It is not bound
byplasma proteins and does not cross the BBB. It has an elimination half-life of
several days. Elimination is by hepatic metabolism and excretion of unchanged drug
and its metabolites in the urine.Reserpine
Reserpine is no longer available in the UK. It is a naturally occurring alkaloid that was
widely used to treat hypertension that failed to respond toβ-blockers or diuretics.Mechanism of action
Reserpine acts centrally and peripherally by preventing storage vesicles incorporat-
ing noradrenaline from neuronal cytoplasm leading to rapid de-amination by mito-
chondrial MAO and noradrenaline depleted neurones. Serotonin is also depleted.Effects
Cardiovascular – hypotension is mainly a result of a reduced cardiac output and
systemic vascular resistance. Postural hypotension is rarely a problem, but nasal
congestion is less well tolerated.
Central nervous system – depression, lethargy, and nightmares are caused by reser-
pine’s ability to cross the BBB. Extrapyramidal effects may also be seen. General
anaesthetic requirements are decreased.
Gut–diarrhoea and increased gastric acid secretions may lead to epigastric pain.
Miscellaneous – sexual dysfunction, hyperprolactinaemia, gynaecomastia and
galactorrhoea are seen rarely.
Drug interactions – patients taking reserpine will exhibit increased sensitivity to
direct-acting sympathomimetic amines (adrenoceptor up-regulation) but reduced
sensitivity to indirect-acting sympathomimetic amines (depleted noradrenaline
stores).Kinetics
Following absorption from the gut, reserpine is metabolized slowly in the liver. Some
metabolic products are excreted in the urine while most appear to be excreted