Pyrazolones
Phenylbutazone
was introduced in 1949, followed soon there- after by its metabolite
oxyphenbutazone. Both are potent anti- inflammatory drugs, but are associated
with significant adverse effects, and hence have been withdrawn from routine
use in several countries. They are still available in India. Their use should
be restricted to acute gout and acute exacerbations of rheumatoid arthritis and
ankylosing spondylitis.
Related
drugs include aminopyrine, antipyrine, amidopy- rine, azapropazone, dipyrone,
noramidoprine, phenazone, and sulfinpyrazone.
Phenylbutazone
interferes with prostaglandin synthesis via inhibition of the cyclo-oxygenase
pathway. It is irritating to the mucosa of the gastrointestinal tract.
·
Main features of overdose with
phenylbutazone/oxyphenbuta- zone include vomiting, abdominal pain, acid-base
and elec- trolyte disturbances, pulmonary oedema, vertigo, seizures,
hypotension, coma, and respiratory and cardiac arrest.
·
Salicylate-like symptoms including
stimulation of the respiratory center, respiratory alkalosis, and metabolic
·
Other reported effects include
hyperglycaemia, hypocal- caemia, cyanosis, paraesthesias, tinnitus,
erythematous rash, profuse sweating, and dyspnoea.
·
Renal, hepatic, and haematological
complications soon follow. Renal dysfunction is common, including protein-
uria, haematuria, anuria, oliguria and in one fatal case, acute nephritis.
Urine may be red due to a pyrazolone metabolite.
·
Blood dyscrasias (agranulocytosis,
thrombocytopenia, aplastic anaemia) are more common with dipyrone.
Methaemoglobinemia has been reported with antipyrine. Pancytopenia has been
reported after overdose with phenylbutazone and oxyphenbutazone.
·
Moderate to marked hepatocellular
injury has been reported with chronic ingestion (less than 6 weeks) of
therapeutic doses. Gastric ulceration was reported in a few patients.
·
Fatal dose is highly variable (4 to
40 gm).
·
Phenylbutazone enhances the effects
of tolbutamide and other sulphonylurea antidiabetic agents, and coumarin
anticoagulants, and may enhance the effects of phenytoinand some sulfonamides.
·
Ferric chloride test.
·
Obtain a baseline CBC, renal and
liver function tests, and urinalysis in symptomatic patients.
·
After 24 hours, a red discolouration
of the urine may be seen, due to rubazonic acid, a pyrazolone metabolite.
·
Stomach wash, activated charcoal.
Ipecac-induced emesis is not recommended because of the potential for CNS
depres-sion and seizures.
·
Treat convulsions in the usual
manner.
·
It is postulated that the excretion
of phenylbutazone, like salicylate, may be enhanced in an alkaline urine. This
may be considered in very severely intoxicated patients. However, alkaline
diuresis is of questionable value since pyrazoles are extensively metabolised,
and only 1 to 5% of the drug is eliminated unchanged by the kidneys.
·
Haemoperfusion in life-threatening
cases. Because of the low water solubility and high protein binding,
haemodi-alysis is not likely to be effective.
·
Plasmapheresis is claimed to be
beneficial in severe poisoning, and has been tried successfully in a case of
phenylbutazone overdose.
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