Pharmacology for Anaesthesia and Intensive Care

P1: PCX Printer: Yet To Come
9780521704632c09 CUFX213A/Peck 9780521618168 December 28, 2007 11:33

Section IICoredrugs in anaesthetic practice


Pulmonary oedema (due to increased capillary permeability)


Coagulopathy


Hypokalaemia


Hypo- or hyperglycaemia


Encephalopathic, unconscious

Treatment


Activated charcoal


Forced alkaline diuresis


Haemofiltration/haemodialysis

Reye’ssyndrome is uncommon and affects mainly children. Its aetiology has been

linked to aspirin. It causes widespread mitochondrial damage, fatty changes in the

liver progressing to hepatic failure, encephalopathy with cerebral oedema and has

amortality rate of up to 40%. Therefore, aspirin is only recommended for children

below 12 years of age when specifically indicated, for example, for juvenile arthritis

(Still’s disease).

Kinetics

Aspirin is a weak acid with a pKa= 3 and is present essentially in the unionized form

in the stomach allowing gastric absorption, but due to the relatively alkaline nature

of the mucosal cells salicylate ions may become trapped and unable to reach the

systemic circulation. However, due to total surface area the small bowel absorbs more

drug. Once in the systemic circulation, 85% is protein bound, mainly by albumin. It is

rapidly hydrolyzed by intestinal and hepatic esterases to salicylate, which undergoes

further hepatic metabolism to salicyluric acid and glucuronide derivatives. Salicylate

and its metabolites are excreted in the urine (enhanced under alkaline conditions).

The elimination half-life varies because glycine conjugation (converting salicylate to

salicyluric acid) may become saturated in overdose resulting in zero-order kinetics.

Para-aminophenols

Paracetamol

While paracetamol has essentially no effect on cyclo-oxygenase in vitro it has been

classified as a NSAID because of its moderate analgesic and antipyretic properties. It

has been proposed that its antipyretic actions are due to inhibition of prostaglandin

synthesis within the central nervous system, by inhibition of COX-3, a COX-1

variant.

Presentation and uses

Paracetamol is presented as 500 mg tablets alone and in combination with weak

opioids. Suppositories contain 125 mg and 1 g and the paediatric elixir contains