You are working in the developing world and a patient with known
acute intermittent
porphyria presents for emergency surgery. Which one of the
following pharmaceuticals
would it be best to AVOID in this patient?
a) Suxamethonium
b) Halothane
c) Aspirin
d) Pancuronium
e) Ropivacaine
Answer: e
Explanation
The porphyrias are an example of pharmacogenetics in anaesthesia.
Porphyrins (of
which the most significant in humans is haem) are essential molecules
concerned with
oxygen transport and handling in the cell. They are manufactured
via a sequence of
enzyme-catalysed reactions from glycine and succinyl CoA.
Congenital deficiencies in
these enzymes lead to accumulation of porphyrin precursors, or
porphyrinogens,
which are responsible for clinical manifestations of the
condition. The porphyrin
biosynthesis pathway is very efficient and normally <2% of
the precursors are produced
in excess of that required for haem synthesis. The principal
rate-limiting enzyme
is δ-Aminolaevulinic acid (ALA) synthetase, which catalyses the
initial combination of
glycine and succinyl CoA. ALA synthetase is under tight negative
feedback control via
haem concentrations. If haem concentration falls, the enzyme is
disinhibited and the
biosynthesis pathway is encouraged. In the various types of
porphyria, there are
deficits in subsequent enzymes in the pathway. Acute attacks are
precipitated by a
drop in haem concentration prompting ALA synthetase to produce δ-ALA. Subsequent
enzymes are then unable to continue the pathway. As haem is a
pivotal component in
cytochrome P450, enzyme-inducing drugs will increase demand for
haem, drop its
concentration and thereby induce an attack of porphyria.
Unfortunately drugs to
avoid are not limited to the usual quoted ‘enzyme inducers’ because
there are a multitude
of mechanisms by which administered drugs may reduce haem
concentration or
induce ALA synthetase. Drugs are classified by international consensus
as use, avoid, use
with caution and use with extreme caution only.
Reference
James
MF, Hift RJ. Porphyrias. Br J Anaesth 2000;
85(1): 143–53.
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