Monoamine oxidase inhibitors

A 54-year-old male requires emergency laparotomy. He has long-standing depression

and is taking a monoamine oxidase inhibitor. Which one of the following monoamine

oxidase inhibitors is LEAST LIKELY to cause incident during conduct of general

anaesthesia?

a) Moclobemide

b) Phenelzine

c) Isocarboxazid

d) Tranylcypromine

e) Iproniazid

Answer: A

Explanation:

The popularity of monoamine oxidase inhibitors (MAOIs) for the treatment of depressive

disorders, obsessive syndromes and chronic back pain rose in the 1970s and 1980s

but has subsequently declined due to the emergence of superior medications with more

favourable side-effect profiles. Nevertheless, patients still taking these medications will

be encountered and awareness of the potential interactions should be maintained.

Amine neurotransmitters and neurohumoural messengers are metabolised by monoamine

oxidase (MAO) and catechol-O-methyl transferase (COMT). Inhibition of MAO

causes indiscriminate increase in concentration of amines in the central nervous system

and elsewhere. Co-administration with agents that rely on MAO for their metabolism

(e.g. indirectly acting sympathomimetics, ephedrine) or agents that also increase concentration

of amines (notably pethidine, which blocks neuronal reuptake of serotonin)

can produce dramatic clinical syndromes. The type I reaction is excitatory and involves

hypertension, hyperpyrexia, convulsions, coma and can be fatal. The type II reaction is

depressive, producing respiratory depression, hypotension and coma essentially

resembling opioid overdose. Iproniazid was the prototype MAOI, originally introduced

in the 1950s as a treatment for tuberculosis for which its efficacy was limited.

Tranylcypromine is the most hazardous as it possesses stimulant activity independent

of its enzyme inhibition properties. Moclobemide is a selective reversible inhibitor of

monoamine oxidase-A, thus is devoid of many of the side-effects and interactions of its

historical counterparts. Unlike the older agents, which form covalent bonds with the

enzyme, moclobemide’s action is reversible spontaneously with a half-life of two to

four hours. It may be continued peri-operatively but pethidine and indirectly acting

sympathomimetics should still be avoided. Carefully titrated morphine would be the

opioid of choice where regional anaesthesia cannot be employed.