Toxic Effects of Phenylbutazone

Léonard, J.C.

doi:10.1136/bmj.1.4823.1311

Cited by 38 publications

(8 citation statements)

References 4 publications

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“…The total assessed (89 patients) is 42.40o of the whole series. This figure is higher than tha't obtained by Leonard (1953). who found an average incidence of 220x' in figures obtained from the literature; it agrees with figures obtained by Hart (1953) and by Freeland et al (1953); 25% of my cases have been forced to stop taking the drug owing to side-effects.…”

Section: Resultssupporting

confidence: 89%

“…The total assessed (89 patients) is 42.40o of the whole series. This figure is higher than tha't obtained by Leonard (1953 shows that there is a definite increase in the incidence of reactions as the dosage is increased, and that, as has been generally agreed, 1,200 mg. daily is a dangerous dosage; at this level 75% of patients have a reaction. The relationship between dosage and the incidence of reactions is statistically significant; using the \2 test, P is much less than 0.01 (n=5, x2=21.56).…”

Section: Resultscontrasting

confidence: 48%

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Use of Phenylbutazone in Rheumatoid Arthritis

Pemberton¹

1954

BMJ

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Section: Resultssupporting

confidence: 89%

Section: Resultscontrasting

confidence: 48%

Use of Phenylbutazone in Rheumatoid Arthritis

Pemberton¹

1954

BMJ

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“…The pathological examinations of the killed ani mals indicated that the cause of death presumably might be diffuse bleeding in the adrenal cortex. The evidence for the role of aminopyrine and phenylbutazone in the pro duction of clinical leucopenias was repoted by Kracke (4), Etess et al (5) and Leonard (6). It was demonstrated that the gastric ulcer with massive hemorrhage occurred in a patient treated with phenylbutazone (7).…”

Section: Pathohistological Findingsmentioning

confidence: 99%

HYPERSENSITIVE TOXICITY OF 5-n-BUTYL-1-CYCLOHEXYL-2, 4, 6-TRIOXOPERHYDROPYRIMIDINE IN THE PREGNANT RAT

Tanabe

1967

Jpn.J.Pharmacol

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5-n-Butyl-l-cyclohexyl-2,4,6-trioxoperhydropyrimidine (BCP), a new antipyretic antiphlogistic agent, has been reported to differ from aminopyrine and phenylbutazone in lack of central convulsion in mice and rats as well as in mildness of the convulsion caused by the toxic doses in rabbits and dogs (1). Respiratory depression was the usual cause of death following excessive doses of BCP. The oral subchronic toxicity of BCP, amino pyrine and phenylbutazone in rats was reported by Okamoto (2) and Araki (3). Accord ing to their results, BCP in the daily doses above 800 mg/kg produced slight degeneration and destruction of the convoluted tubular epithels in the kidney, while phenylbutazone in the lesser doses resulted not only in the similar changes in the kidney, but also in obvious degeneration of the liver cells and the cardiac muscle fibers.The necessary prerequisite of a clinically available drug should be superiority of the main pharmacological effects and also minority of the side effects. During the toxicolo gical studies of the anti phlogistics, the present author found that the lethal dose of BCP in the pregnant rats was markedly different from that in the non-pregnant ones. There fore, attemt has been made in the present report whether the lethal response to the com pound is conditioned by sex or gestation. METHODSAdult male and female rats (4-5 months of age) of Wistar strain were used. The animals were housed in the individual cage at room temperature of 22±2°C and at humidity of 40-70%, and were fed a commercial powdered diet (CLEA OA-2, supplied by the Japan CLEA Co.) and water ad libitum.Pregnant rats : Previously unmated two female rats were placed in a cage with a male overnight. Those found to have vaginal plugs were isolated and the day when the females showed the positive smear was regarded as zero day of pregnancy.Drug administration : BCP, aminopyrine and phenylbutazone were suspended in water at various concentration with carboxymethyl cellulose and administerd via stomach tube. The non-pregnant rats were treated with a single dose of 1.0, 1.5 and 2.0 g/kg of BCP and were observed for 7 days. In next series of experiments, BCP in doses of 100

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“…Similarly, a risk of phenylbutazone is peptic ulceration (Raffensperger, 1953), which can be fatal from perforation (Shield et al, 1953;Beutler and Bergenstal, 1954) or from haemorrhage (Stephens et al, 1952;Benstead, 1953). Phenylbutazone has other complications, such as depression of the bone-marrow and agranulocytosis (Dilling, 1953;Leonard, 1953), skin rashes (Cudkowicz and Jacobs, 1953), stomatitis (Freeland et al, 1953); visceral lesions (MacCarthy and Jackson, 1955), and water retention (Wilkinson and Brown, 1953), which may precipitate cardiac failure in the elderly. However, the toxicity of any drug must be weighed against the benefits conferred by it, and we believe that its use is justified in carefully selected cases of the painful and crippling rheumatic disorders.…”

Section: Conclusion and Summarymentioning

confidence: 99%