Involvement of imidazoline and opioid receptors in the enhancement of clonidine-induced analgesia by sulfisoxazole.

Clonidine, an alpha2-adrenergic agonist, has been demonstrated to produce significant analgesia and potentiate morphine analgesia. Endothelin (ETA) receptor antagonists have also been found to potentiate the antinociceptive response to morphine. Clonidine and ET have been reported to have cardiovascular interactions involving the sympathetic nervous system, but it is not known whether ETA receptor antagonist affects clonidine analgesia. This study examined the influence of sulfisoxazole (ETA receptor antagonist) on clonidine analgesia. Male Swiss Webster mice were used to determine antinociceptive response of drugs by measuring tail-flick latency. The effect of clonidine (0.3, 1.0, and 3.0 mg/kg, i.p.) alone or in combination with sulfisoxazole (25, 75, and 225 mg/kg, p.o.) on analgesia and body temperature was determined. Clonidine produced a dose-dependent analgesia and hypothermia. Sulfisoxazole (25, 75, and 225 mg/kg), when administered with clonidine (0.3 mg/kg), significantly potentiated (31% increase in area under the curve (AUC)) the analgesic effect of clonidine. Yohimbine (alpha2-adrenergic receptor antagonist) did not affect analgesic effect of clonidine plus sulfisoxazole. Idazoxan (I1-imidazoline and alpha2-adrenergic receptor antagonist) reduced (47% decrease in AUC) the analgesic effect of clonidine plus sulfisoxazole. Treatment with naloxone reduced (46% decrease in AUC) the analgesic effect of clonidine plus sulfisoxazole. The effect of another ETA receptor antagonist, BMS-182874 (2, 10, and 50 microg, i.c.v.) was studied, and it was found that the dose of 10 microg significantly potentiated (26% increase in AUC) the analgesic effect of clonidine. These results indicate that sulfisoxazole, an ETA receptor antagonist, potentiates the analgesic effect of clonidine, which could be mediated through I1-imidazoline receptors and opioid receptors.

Trimethoprim and sulfonamide-associated meningoencephalitis with MRI correlates.

Early recognition of trimethoprim and sulfonamide-induced aseptic meningitis is important because drug cessation leads to rapid clinical improvement. We present clinical and laboratory findings in two typical cases. In both cases, MRI revealed previously undescribed diffuse white matter abnormalities that resolved within a few months. These MRI findings are important because they may aid in early diagnosis of this condition in the appropriate clinical setting. In addition, the white matter abnormalities suggest an encephalitic component in addition to the meningitis.

Urolithiasis as a hazard of sulfonamide therapy.

We identified 40 patients (25 men and 15 women) who developed calculi composed totally or partially of sulfonamides (acetylsulfamethoxazole, sulfadiazine, and acetylsulfisoxazole) between 1980 and 1987. The incidence of sulfonamide stones is less than 1% of stones. Patient characteristics were determined from questionnaires sent to the patients and attending physicians. The majority of patients developed symptoms 1 to 4 weeks after beginning sulfonamide therapy. The bladder was the most common stone location. Obstruction of the urinary system by the acetyl derivatives of the drug is the most serious consequence of sulfonamide therapy. Early recognition of drug-related stones is essential to protect patients from recurrences, reduce the risk of renal complications, and avoid continuing ineffective therapeutic regimens.

Sulfonamide-reactive lymphocytes detected at very low frequency in the peripheral blood of patients with drug-induced eruptions.

BACKGROUND: The role of T lymphocytes in mediating drug eruptions is uncertain. METHODS: Twenty-four patients with eruptions induced by sulfonamide-related drugs were studied to detect lymphocyte reactivity to drugs. Both the lymphocyte transformation test and limiting dilution analysis were used as assays for drug-reactive lymphocytes. Peripheral blood lymphocytes were expanded in interleukin-2 and tested for reactivity to sulfamethoxazole and furosemide. RESULTS: The lymphocyte transformation test results to sulfamethoxazole, sulfisoxazole, and furosemide were found to be generally unreliable with a high rate of false-negative and false-positive results. However, as determined by limiting dilution analysis, sulfamethoxazole-reactive lymphocytes were detected in the peripheral blood of one patient at a frequency of 1/172,000. This is within the lower range of frequencies of urushiol-reactive T cells in the peripheral blood of patients with allergic contact dermatitis to urushiol (poison ivy). Two sulfonamide-reactive lymphocyte lines were cultured from two patients. Both lines proliferated in response to sulfamethoxazole but not in response to furosemide, suggesting that furosemide does not cross-react with the sulfonamides. CONCLUSIONS: Lymphocytes reactive to sulfamethoxazole were detected at low frequencies in the peripheral blood of three patients with drug eruptions secondary to administration of sulfamethoxazole.

Antibodies in sulfonamide-induced immune thrombocytopenia recognize calcium-dependent epitopes on the glycoprotein IIb/IIIa complex.

Drug-dependent IgG antibodies (DDAb) induced by sulfamethoxazole (SMX) and sulfisoxazole (SIX) were identified by flow cytometry in 15 patients who developed thrombocytopenia while taking one of these medications. Fourteen of the 15 DDAb were specific solely for the glycoprotein (GP)IIb/IIIa complex, and 13 of these reacted wholly or in part with epitopes present only on the intact GPIIb/IIIa heterodimer. None of 12 SMX-induced DDAb cross-reacted with SIX, but one of three SIX-induced antibodies reacted with SMX. Each of 10 SMX-induced DDAb tested reacted with the N1-acetyl metabolite of SMX, but only one reacted fully with the N4-acetyl derivative. Detection of the SMX- and SIX-dependent antibodies was facilitated by using bovine serum albumin (BSA) to achieve suspension of these weakly soluble drugs in an aqueous medium. Our findings indicate that DDAb induced by SMX and SIX, in contrast to those induced by quinidine and quinine, are mainly specific for GPIIb/IIIa and react preferentially with calcium-dependent epitopes present only on the intact GPIIb/IIIa heterodimer.

Pneumonia caused by Nocardia nova and Aspergillus fumigatus after cardiac transplantation.

Nocardia nova, a newly established species of the Nocardia asteroides complex, has recently been characterized as a human pathogen. This report of a case of pneumonia caused by Nocardia nova and Aspergillus fumigatus in a patient after cardiac transplantation is the first reported infection caused by Nocardia nova following its detailed description. Accurate identification and susceptibility testing of the Nocardia nova isolate allowed successful oral therapy with clarithromycin when therapy with sulfisoxazole was not tolerated.

Malaria prophylaxis with proguanil and sulfisoxazole in children living in a malaria endemic area.

The effects of three separate antimalarial prophylactic regimens (proguanil, sulfisoxazole, and proguanil plus sulfisoxazole) and of vitamins in a control group were compared in a study population of 380 children living in a malaria endemic area along the Thai-Burmese border. The subjects, aged 5-16 years, were matched for age, weight, and presence of splenomegaly, then randomly assigned to one of the four groups. All medications were administered daily by the investigators and malaria smears were performed on a weekly basis. Among 99 subjects taking proguanil plus sulfisoxazole for a total of 1464 man-weeks, there was only one case of falciparum and no vivax malaria. Statistically, this regimen proved superior to each of the other groups against both Plasmodium falciparum and P. vivax. The data show that proguanil alone, as a causal or suppressive prophylatic, has poor efficacy against P. falciparum. Side-effects were infrequent and generally mild, except for two subjects whose sulfisoxazole prophylaxis was discontinued because of urticarial rash.

Trimethoprim in the treatment of acute urinary tract infections in children.

In the first study to assess the effect of trimethoprim in the treatment of acute urinary tract infections in children, we compared it with sulphisoxazole. Eighteen girls, mean age 5.3 years, were treated with trimethoprim 6 mg/kg/day. Seventeen girls, mean age 5.0 years, treated with sulphisoxazole 150-200 mg/kg/day for 10 days served as controls. All infections were cured. Three patients in each group had reinfections during the 6 months of follow-up. In each group, one of the reinfections occurred within 2 weeks after the end of the treatment. One patient developed a rash from sulphisoxazole and so required drug change. No other adverse effects were observed. We conclude that trimethoprim is as effective as sulphisoxazole in the treatment of simple acute urinary tract infections of children and recommend it, in the dosage used, as an alternative first-choice drug, especially for patients who have had side effects from sulphonamides or nitrofurantoin.

Sulfadiazine versus sulfafurazole excretion in urine and risk of crystallization in children with conventional dosage regimen.

The excretion of sulfadiazine (Adiazin) (n = 8) and sulfafurazole (n = 8) in urine and the risk of crystallization were compared in children, 3-14 years of age. They suffered from acute urinary tract infection and were treated with conventional dosage regimen of either of the sulfonamides. Sulfadiazine (4 mg/kg twice daily, the initial dose 8 mg/kg) produced active serum drug levels which in relation to antimicrobial activity of sulphonamides corresponded to 25-30% of those obtained with sulfafurazole (50 mg/kg four times a day). In urine the corresponding sulfadiazine levels were 21-61% of those of sulfafurazole. In none of the urine fractions sulfadiazine concentrations exceeded the theoretical drug solubility but sulfafurazole exceeded this risk limit altogether in 4 urine fractions (2 patients). Urine sediment showed, however, sulfonamide crystals in only one urine fraction of the sulfafurazole group. The results suggest that with conventional dosage regimen sulfafurazole produces higher effective serum and urine drug concentrations in children than sulfadiazine but shows a higher risk to crystallize in urine.

Treatment of urinary tract infections with varying regimens of sulfisoxazole.

Four therapeutic regimens of sulfisoxazole were compared and contrasted with the antibody-coated bacteria test in patients with acute urinary tract infections. Of 158 college coeds who entered the study 146 completed the randomly assigned regimen. All 146 patients received 2 gm. sulfisoxazole initially and 1 gm. 4 times daily for 3 days in 44 patients (group 1), 7 days in 51 (group 2), 14 days in 29 (group 3) and 21 days in 22 (group 4). The presumptive sites of infection by the antibody-coated bacteria test were kidney (positive test) in 43 per cent of the patients and bladder (negative test) in 51.3 per cent. There was no correlation between the results of the antibody-coated bacteria test with either the presenting symptoms or the therapeutic responses. The bacteriologic cure rates at 2 days after therapy were 100 per cent in all groups and at 4 weeks after therapy they were 88.6 per cent in group 1, 86.3 per cent in group 2, 86.2 per cent in group 3 and 91 per cent in group 4. A 3-day course of sulfisoxazole was as effective as the longer regimens.