Pharmacology for Anaesthesia and Intensive Care

P1: PSB Printer: Yet To Come
9780521704632c18 CUFX213A/Peck 9780521618168 December 28, 2007 13:51

Section IVOther important drugs

Table 18.1.Groups of phenothiazines.

Propylamine chlorpromazine

Piperidine thioridazine

Piperazine prochlorperazine, perphenazine

Mechanism of action

Chlorpromazine antagonizes the following receptor types: dopaminergic (D 2 ), mus-

carinic, noradrenergic (α 1 andα 2 ), histaminergic (H 1 ) and serotinergic (5-HT). It

also has membrane-stabilizing properties and prevents noradrenaline uptake into

sympathetic nerves (uptake 1).

Effects


Central nervous system – extrapyramidal effects are due to central dopamine antag-

onism. The neuroleptic malignant syndrome occurs rarely. It has variable effects on

hypothalamic function, reducing the secretion of growth hormone while increas-

ing the release of prolactin (dopamine functions as prolactin release inhibitory

factor). Temperature regulation is altered and may result in hypothermia.


Cardiovascular – it antagonizesα-adrenoceptors resulting in peripheral vasodila-

tion, hypotension and increased heat loss.


Anticholinergic – it has moderate anticholinergic effects.


Gut–appetite is increased and patients tend to gain weight (exacerbated by inac-

tivity). While it has been shown to be an adequate antiemetic, its other effects have

limited this role.


Miscellaneous – contact sensitization. Direct contact should be avoided unless

actually taking chlorpromazine. Cholestatic jaundice, agranulocytosis, leucope-

nia, leucocytosis and haemolytic anaemia are all recognized.

Kinetics

Absorption from the gut is good but due to a large hepatic first-pass metabolism

(limiting its oral bioavailability to about 30%), it is often given parenterally. The large

number of hepatic metabolites is excreted in the urine or bile, while a variable but

small fraction is excreted unchanged in the urine.

Thioridazine

Thioridazine is not used to treat nausea and vomiting. It is used in schizophrenia and

other psychoses where it is favoured in the elderly as it is only moderately sedative

and is only rarely associated with extrapyramidal effects (Table18.2).