EMQs in Clinical Medicine.pdf - Peshawar Medical College

240 Miscellaneous
When cyclophosphamide is broken down, its toxic metabolites (e.g.
acrolein), which are irritant to the lining of the urinary tract, give rise to
a haemorrhagic cystitis. Mesna is a drug that is prescribed with
cyclophosphamide to protect the uroepithelium. It acts by inhibiting the
decomposition of intermediate metabolites to acrolein and also binds
directly with acrolein to prevent its toxic effect.
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A 25-year-old man on treatment for seizures complains of acne and
gum hypertrophy.
Acne, gum hypertrophy, nausea, vomiting and tremor are all recognized
adverse effects of phenytoin treatment. Blurred vision, ataxia or
peripheral neuropathy are signs of drug toxicity. Phenytoin has a narrow
therapeutic index and toxicity may easily occur.
Adjustment of dose of phenytoin is complicated by the fact that it has zeroorder
kinetics. This means that relatively small increases in dose can give
rise to large increases in plasma concentration and consequently toxicity.
A 24-year-old woman on treatment for epilepsy is admitted with
acute pancreatitis.
Acute pancreatitis is a rare adverse effect of valproate therapy but
patients should be informed of the symptoms and advised to seek
immediate medical attention if these develop.
95 Adverse drug reactions
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A 32-year-old man on treatment for pulmonary TB presents with
reduced sensation in a glove-and-stocking distribution.
Isoniazid is metabolized in the liver by acetylation. Toxicity in the form
of peripheral neuropathy is more common in patients with a slow
acetylator status, whereas fast acetylators are more likely to suffer from
an isoniazid-related hepatitis. Rapid acetylator status is extremely common
in the Japanese population (over 90 per cent). In the European population
slow acetylator status is slightly more common (55–60 per cent).
This is an example of a genetic polymorphism affecting drug metabolism
and toxicity.
Sensitivity to ethanol and suxamethonium are other examples of variations
in drug metabolism caused by genetic polymorphism.
A 65 year old develops a photosensitive rash after being prescribed an
additional drug for hypertension. Antinuclear antibody test is positive.
An SLE-like syndrome with a positive antinuclear antibody test can be
caused by a number of drugs, including hydralazine, procainamide, isoniazid,
griseofulvin, chlorpromazine and anticonvulsants. The symptoms
usually disappear on removal of the drug.