Opçöes para a utilizaçåo dos antiinflamatórios nåo-esteróides no manejo da psoríase artropática / The management of arthropatic psoriasis with nonsteroidal antiinflammatory

Os antiinflamatórios nåo-esteróides såo fármacos nåo-esteroidais que inibem a via da ciclooxigenase no metabolismo do ácido aracdônio, suprimindo a síntese das prostaglandinas. Algumas destas drogas exacerbam as lesöes cutâneas da psoríase (indometacina, ácido acetilsalicílico). Outros antiinflamatórios nåo-esteróides apresentam uma boa açåo farmacológica sem exacerbarem o quadro dermatológico da moléstia (naproxeno, ibuprofeno e fenilbutazona). Estas drogas proporcionaråo novas opçöes na terapêutica da psoríase artropática. Os autores relatam sua experiência no manejo da psoríase artropática com os antiinflamatórios nåo-esteróides

Genetic susceptibility to fixed drug eruption: evidence for a link with HLA-B22.

BACKGROUND: Our observation of familial cases of fixed drug eruption (FDE) prompted us to consider a genetic predisposition to this disease. OBJECTIVE: Our purpose was to determine whether there is any association between FDE and any of the major histocompatibility complex class I or II alleles. METHODS: HLA class I and II typing was performed by lymphocytotoxicity assay in 36 unrelated patients with FDE. RESULTS: Significantly higher (p < 0.0001) frequencies of the B22 and Cw1 antigens were found in the 36 patients with FDE. CONCLUSION: Our data are the first to suggest a genetic predisposition to FDE.

Cutaneous reactions to analgesic-antipyretics and nonsteroidal anti-inflammatory drugs. Analysis of reports to the spontaneous reporting system of the Gruppo Italiano Studi Epidemiologici in Dermatologia.

We analyzed the cutaneous reactions to systemic analgesic-antipyretics and non-steroidal anti-inflammatory drugs reported to the spontaneous reporting system of the Gruppo Italiano Studi Epidemiologici in Dermatologia (GISED). The system has been active since 1988, with periodic intensive surveillance exercises, and 202 dermatologists have collaborated. Up to December 1991, 2,137 reactions had been collected, of which 713 were reactions to systemic analgesic-antipyretics and nonsteroidal anti-inflammatory drugs. A general profile of the reactions was identifiable. It included, in order of frequency, urticaria/angioedema, fixed eruptions, exanthemas, erythema multiforme and Stevens Johnson syndrome. Fixed eruptions and Stevens Johnson syndrome were reported with exceedingly high frequency in association with feprazone. Our system also revealed previously unreported reactions, including fixed eruption to nimesulide, fixed eruption to piroxicam and fixed eruption to flurbiprofen.

Familial occurrence of fixed drug eruptions.

Fixed drug eruptions following the use of pyrazolone derivatives occurred in 4 members of the same family: a 12-year-old girl, her grandmother, and two of her great aunts. Although the pathophysiologic events leading to this type of reaction are unknown, these cases of familial occurrence suggest that genetic predisposition might be an important causal factor.

Drug-triggered pemphigus in a predisposed woman.

A 31-year-old woman with three pemphigus-prone antigens in her HLA haplotype (B7, DR4, DQw7) developed the disease soon after taking a pyrazolone derivative, viz. feprazone. The pemphigus lesions persisted despite withdrawal of the drug and worsened appreciably when she used ceftriaxone (a new cephalosporin with three sulphur atoms) for a bout of acute pharyngitis. Thiol groups formed from the metabolic breakdown of ceftriaxone are thought to have promoted acantholysis via a biochemical route. Genetic predisposition alone ('the soil') may be essential, though not per se sufficient for outbreak of pemphigus; the intervention of exogenous, heterogeneous factors ('the seed') often seems decisive in triggering full-blown disease.

The pharmacokinetics of single oral doses of feprazone in healthy volunteers and elderly patients.

1. The pharmacokinetics of feprazone were studied in nine healthy volunteers and 10 elderly patients. 2. The mean elimination half-life of feprazone after a single oral dose in the healthy volunteers was 22.3 h, the mean apparent clearance 0.0051 1/h per kg and the mean volume of distribution 0.1681/kg. Corresponding values for the elderly patients were 22.6 h, 0.00561/h per kg and 0.1651/kg, which are not different from those for the volunteers. Thus, we were unable to detect any changes in feprazone pharmacokinetics which are related to age, or to the concurrent use of chronic medications, such as digoxin, diuretics, or hormones.

Feprazone in osteoarthritis: comparison of twice and 3-times daily dosage regimens.

In a double-blind crossover trial, 200 mg feprazone 3-times a day was compared with 200 mg twice a day in the treatment of osteoarthritis. There was no difference in clinical efficacy or in adverse effects between the two dosage schedules. Because of its long elimination half-life (approximately 24 hours) it is suggested that feprazone should be given in twice daily dosage and is a simple and effective treatment for osteoarthritis.

Feprazone: absence of hemolytic effects in glucose-6-phosphate dehydrogenase-deficient subjects.

Some drugs, including nonsteroidal antiinflammatory compounds, can be hemolytic in glucose-6-phosphate dehydrogenase-deficient patients. We have studied the potential hemolytic activity of feprazone, a nonsteroidal antiinflammatory compound in vitro and in vivo. Agents that may be hemolytic for glucose-6-phosphate dehydrogenase-deficient erythrocytes will stimulate the hexose monophosphate shunt in normal erythrocytes. Eleven normal subjects were treated with feprazone and their erythrocytes were incubated in their own sera (containing active feprazone metabolites) and [1-14C]-glucose. Because no statistically significant increase in 14CO2 evolution was observed, 15 pediatric male patients with glucose-6-phosphate dehydrogenase deficiency who required antiinflammatory treatment were treated with feprazone. No hemolytic crises and no statistically significant changes of hematologic tests were observed.

[Results of an open study and a controlled comparative study of feprazone and naproxen in patients with rheumatoid arthritis or osteoarthrosis (author's transl)]. / Ergebnisse einer einfach offenen sowie einer kontrollierten Vergleichesstudie mit Feprazon und Naproxen bei Polyarthritis- und Osteoarthrose-Patienten.

The so-called non-steroid antirheumatics have considerable significance in medical armamentarium for controlling polyetiological complexes of diseases. The numerous new developments are designed to reduce the side effects, some of which seem inevitable with increased efficacy. In this two-part study the authors deal with the new Feprazone. Prior to a double-blind randomized comparative study against Naproxen, an open study on effect and tolerance was performed in ten rheumatic patients over three months. In the second part a controlled study was carried out in 30 patients for four weeks following this treatment. The patients half of whom were each given 600 mg Feprazone or 750 mg Naproxen showed a definite improvement in the rheumatic symptoms as compared with their initial situation. A difference in therapeutic efficacy and tolerance was only noticeable in a slight trend in favour of Feprazone.

Hepatic injury following feprazone therapy.

Two cases of feprazone-induced hepatic injury are reported. Both patients developed jaundice within one month of commencing therapy. Histological investigation showed a granulomatous reaction in one case and hepatitic changes in the other. The changes were similar to those seen as a complication of phenylbutazone therapy. When the administration of feprazone was discontinued both the clinical and biochemical changes were resolved.

Safety and efficacy of feprazone for long-term treatment of rheumatoid arthritis and osteoarthritis.

Long-term safety and efficacy of feprazone (4-prenyl-1,2-diphenyl-3,5-pyrazolidinedione), an antirheumatic drug that is well tolerated in the gastrointestinal tract, were assessed in a noncontrolled multicenter trial. Administered at a daily dosage of 600 mg for a mean duration of 114.1 days, feprazone was well tolerated by 43 (77%) of 56 treated subjects. Thirteen patients reported side effects, but only five discontinued treatment. The side effects were generally mild and occurred in the first weeks of therapy. Feprazone was found effective after one month on both considered indices of disease activity: Ritchie index (articular index for assessment of joint tenderness) and corticosteroid consumption.

Miscellaneous rheumatological conditions treated in monitored-release studies with feprazone.

In two monitored-release studies of feprazone (Methrazone), one in hospital and the other in general practice and involving a total of about 4,000 patients, there were 343 patients with a variety of sero-negative rheumatological conditions or soft tissue lesions. The diagnoses included spondylosis, ankylosing spondylitis, psoriatic arthritis, capsulitis, frozen shoulder, polymyalgia rheumatica and gout. Most of the patients were classified as moderately or severely affected. Feprazone in a dose of 200 mg thrice daily appeared to benefit about 60% of patients during a course of 8 weeks of therapy. No serious adverse reactions directly attributable to the drug were recorded. About 20% of patients stopped treatment because of side-effects, usually gastro-intestinal disturbance or rash. Two patients experienced a marked fall in platelet count which might have been due to the drug, but neither developed any signs of thrombocytopenic purpura.

A monitored-release study of methrazone in general practice.

Methrazone, a non-steroidal anti-inflammatory drug, was used on a monitored release study in general practice to treat 2,693 patients with rheumatoid or osteoarthritis. In a dose of 200 mg three times daily, it appeared to produce clear benefit in between 50% and 60% of patients. Adverse reactions such as dyspepsia and skin rash led to the drug being withdrawn in 11% of patients. There were three major adverse reactions possibly due to the drug (haematemesis, rectal bleeding and acute purpura), but no cases of severe leucopenia or thrombocytopenia. Methrazone is a useful anti-inflammatory agent. In particular, it is unlikely to cause interactions with other drugs, including cardiac glycosides such as digoxin.

A trial of feprazone in ankylosing spondylitis.

Feprazone, a non-steroidal anti-inflammatory drug, was compared with indomethacin in a double-blind cross-over trial in 24 patients with ankylosing spondylitis, over eight weeks. Both regimes caused significant reduction in pain. There were fewer side-effects and more patient preferences with feprazone but these differences did not reach statistical significance.