Pharmacology for Anaesthesia and Intensive Care

P1: PSB Printer: Yet To Come
9780521704632c17 CUFX213A/Peck 9780521618168 December 28, 2007 13:44

17 Centralnervous system

amine neurotransmitters, which is thought to be the basis of their central activity.

MAO-A preferentially deaminates 5-HT and catecholamines, while MAO-B prefer-

entially deaminates tyramine and phenylethamine.

There are now two generations of MAOIs. The original generation inhibit MAO

irreversibly and non-selectively (i.e. MAO-A and -B) while the new generation selec-

tively and reversibly inhibit only MAO-A (RIMA). Neither group is used as first line

therapy because of the potential for serious side effects and hepatic toxicity.

Non-selective irreversible MAOIs (phenelzine,

isocarboxazid, tranylcypromine)

Phenelzine and isocarboxazid are hydrazines while tranylcypromine is a non-

hydrazine compound. Tranylcypromine is potentially the most dangerous as it pos-

sesses stimulant activity.

Effects

Inaddition to controlling depression they also produce sedation, blurred vision,

orthostatic hypotension and hypertensive crises following tyramine rich foods

(cheese, pickled herring, chicken liver, Bovril and chocolate) and indirectly acting

sympathomimetics. Hepatic enzymes are inhibited and the hydrazine compounds

may cause hepatotoxicity. Interaction with pethidine may precipitate cerebral irri-

tability, hyperpyrexia and cardiovascular instability. Interaction with fentanyl has

also been reported.

Selective reversible MAOIs – RIMA (moclobemide)

Moclobemide causes less potentiation of tyramine than the older generation MAOIs

and in general patients do not need the same level of dietary restriction. How-

ever, some patients are especially sensitive to tyramine and so all patients should

be advised to avoid tyramine-rich foods and indirect-acting sympathomimetic

amines.

Itis completely absorbed from the gut but undergoes significant first-pass

metabolism resulting in an oral bioavailability of 60–80%. It is metabolized in the

liver by cytochrome P450 and up to 2% of the Caucasian and 15% of the Asian pop-

ulation have been shown to be slow metabolizers. The metabolites are excreted in

the urine.

Linezolidis a new antibiotic indicated for methacillin-resistantStaphlococcus

aureusand vancomycin-resistant enetrococci. It is also a MAOI and as such has the

typical range of cautions and contraindications.

MAOIs and general anaesthesia

Those patients taking MAOIs and presenting for emergency surgery should not be

given pethidine or any indirectly acting sympathomimetic amines (e.g. ephedrine).

Ifcardiovascular support is indicated, direct-acting agents should be used but