Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evidence from the literature strongly supports that high doses of TMP, as used in the treatment of PCP in AIDS patients, have the propensity to cause hyperkalemia by inhibiting sodium channels in the distal nephron, thereby impairing potassium secretion. The mechanism of TMP-induced hyperkalemia is believed to be similar to that of triamterene and amiloride because of the structural similarity of these agents. It is also possible that declining renal function, which is a natural progression of HIV disease, may contribute to the hyperkalemia seen in this patient population. In addition, patients with AIDS also may exhibit a defect in adrenal function, potentiating the hyperkalemic effect of TMP therapy. Therefore, it is crucial for clinicians to monitor closely the serum potassium concentration in this patient population, especially during therapy with high doses of TMP.
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PMID:Hyperkalemia and high-dose trimethoprim/sulfamethoxazole. 763 23

Trimethoprim-sulfamethoxazole (TMP-SMX) is a fixed-dose antimicrobial agent used in a variety of infections. Adverse reactions are more common in patients with AIDS, but occasionally occur in immunocompetent patients. Renal toxicity is usually a hypersensitivity reaction to the sulfa component, and manifests as interstitial nephritis or sulfa crystallization in the renal tubules. Reversible hyperkalemia is a rarely reported side effect of TMP-SMX therapy attributed to TMP inhibition of potassium secretion in the distal renal tubule in a manner similar to the potassium sparing diuretic, amiloride. In this article, the author reports a case of hyperkalemia associated with TMP-SMK occurring in an elderly man with no other risk factors for hyperkalemia, which resolved upon discontinuation of the drug.
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PMID:Case report: reversible hyperkalemia associated with trimethoprim- sulfamethoxazole. 766 7

Pneumocystis carinii pneumonia remains one of the most common opportunistic infections in patients with acquired immune deficiency syndrome (AIDS). Treatment with either intravenous pentamidine or trimethoprim-sulfamethoxazole (TMP-SMX) is frequently complicated by serious adverse reactions. This study was a prospective, blinded comparison of 600 mg/d of pentamidine as an aerosol versus 15 mg/kg/d of trimethoprim plus 75 mg/kg/d of sulfamethoxazole for patients with mild or moderately severe P. carinii pneumonia (alveolar arterial oxygen difference of less than 55 mm Hg). Of 367 participants who were randomized to receive study therapies, 287 had proven and 16 had presumed Pneumocystis pneumonia. There were 29 deaths within 35 d of study initiation: 12 in the aerosolized pentamidine group and 17 in the TMP-SMX groups (log rank p = 0.28). The difference in mortality was 3.4% (95% CI = -3.5, 10.8%). Ninety-four patients treated with aerosolized pentamidine had to have their study therapy changed because of lack of efficacy, compared with 22 patients treated with TMP-SMX (p = 0.002). In addition PaO2 improved faster in patients treated with TMP-SMX. However, aerosolized pentamidine was discontinued less often than TMP-SMX because of toxicity (9.4 versus 40% p < 0.001). Rash (0.6 versus 14.9%), nausea and vomiting (1.7 versus 12.2%), and abnormalities of liver function tests (1.7 versus 12.2%) were the most common adverse effects necessitating treatment discontinuation. During 6-mo. follow-up there was no difference in mortality.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pentamidine aerosol versus trimethoprim-sulfamethoxazole for Pneumocystis carinii in acquired immune deficiency syndrome. 769 33

Atovaquone was compared to trimethoprim-sulfamethoxazole (TMP-SMZ) for the relationship of time receiving therapy, plasma drug concentrations, and incidence of adverse reactions in patients with AIDS-associated Pneumocystis carinii pneumonia. Treatment-limiting adverse events occurred in 9% of atovaquone-treated patients and 24% of TMP-SMZ-treated patients. Adverse events usually did not occur before day 7 for either treatment. Only the incidence of rash increased with increasing plasma concentrations of atovaquone. The incidence of anemia, neutropenia, and azotemia increased with increasing trimethoprim plasma concentration, while other adverse events (gastrointestinal disorders, rash, fever, and liver function abnormalities) were independent of plasma drug concentration.
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PMID:Adverse events associated with trimethoprim-sulfamethoxazole and atovaquone during the treatment of AIDS-related Pneumocystis carinii pneumonia. 775 6

Trimethoprim-sulfamethoxazole (TMP-SMZ) is the drug of choice as prophylaxis for Pneumocystis carinii pneumonia in patients with AIDS. However, adverse reactions ascribed to TMP-SMZ are common in such patients. We previously described a rapid method of oral TMP-SMZ desensitization in patients with AIDS and varying degrees of intolerance to the drug. To assess the feasibility, safety, and long-term clinical utility of our desensitization protocol, we retrospectively studied 22 consecutive patients who underwent desensitization. Prior to the procedure each of the study subjects had exhibited moderate to severe reactions to TMP-SMZ. Desensitization was successfully completed in 19 (86%) of the patients. The three patients for whom desensitization failed experienced chills and/or vomiting that resolved promptly with symptomatic therapy. One of the 19 patients was unavailable for long-term follow-up. Of the remaining 18 patients, three discontinued taking TMP-SMZ within 2 weeks of desensitization because of macular rash and fever. The other 15 (71%) of the evaluable patients tolerated both desensitization and subsequent prophylaxis and took TMP-SMZ for a mean of 14 months (in some cases, for as long as 41 months). None had P. carinii pneumonia while receiving TMP-SMZ. These results indicate that most patients who are presumed to be TMP-SMZ-intolerant can be rapidly desensitized with oral TMP-SMZ and subsequently receive the drug for protracted periods as effective prophylaxis for P. carinii pneumonia.
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PMID:Rapid oral desensitization to trimethoprim-sulfamethoxazole (TMP-SMZ): use in prophylaxis for Pneumocystis carinii pneumonia in patients with AIDS who were previously intolerant to TMP-SMZ. 779 84

At the start of the AIDS epidemic, the only agents licensed for treatment of Pneumocystis carinii pneumonia (PCP) were trimethoprim-sulfamethoxazole (TMP-SMX) and pentamidine. Both are effective against PCP, but their use has been compromised by adverse reactions that necessitate discontinuing therapy in < or = 54% of patients. As a result of the limitations in the use of these therapies, research efforts have been directed toward the development of effective agents with an improved safety profile. Of these agents, one of the best studied is atovaquone, a hydroxynaphthoquinone that has been licensed by the U.S. Food and Drug Administration for use in the treatment of mild to moderate PCP in patients intolerant to TMP-SMX. Clinical studies have shown that atovaquone is associated with overall therapeutic success rates equivalent to those of intravenous pentamidine and TMP-SMX, although its therapeutic efficacy rates are somewhat lower. However, atovaquone is associated with fewer treatment-limiting side effects than the other drugs. The literature concerning the efficacy and safety of atovaquone for the treatment of PCP will be reviewed.
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PMID:The role of atovaquone tablets in treating Pneumocystis carinii pneumonia. 785 36

We retrospectively studied all courses of treatment with trimethoprim-sulfamethoxazole (TMP-SMZ) alone and with adjuvant corticosteroids for AIDS-associated Pneumocystis carinii pneumonia. The corticosteroids were administered for 8-21 days (mean, 14 days) because of hypoxemia. We evaluated the influence of corticosteroids on the incidence of cutaneous adverse reactions to TMP-SMZ and on the course of AIDS during 3 months of follow-up. Of 38 patients treated with TMP-SMZ alone, 18 (47%) developed cutaneous side effects, whereas three (13%) of the 23 patients who received adjuvant corticosteroid therapy experienced such effects (P = .014). Of the 21 reactive patients, 14 were treated throughout the duration of hypersensitivity. Therapy was interrupted for seven patients (18%) treated with TMP-SMZ alone and for none of those who were given adjuvant corticosteroid therapy (P = .23). During follow-up, the incidence of mucocutaneous herpes simplex virus infection was higher among patients who received adjuvant corticosteroids than among those treated with TMP-SMZ alone (P = .005). Adjuvant corticosteroids thus reduce the incidence of adverse cutaneous reactions to TMP-SMZ in patients with AIDS who are treated for hypoxemic P. carinii pneumonia.
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PMID:Effect of corticosteroids on the incidence of adverse cutaneous reactions to trimethoprim-sulfamethoxazole during treatment of AIDS-associated Pneumocystis carinii pneumonia. 801 11

Trimetrexate is a powerful inhibitor of the dihydrofolate reductase of Pneumocystis carinii. AIDS patients (n = 215) with moderate to severe P. carinii pneumonia were enrolled in a double-blind study of trimetrexate plus leucovorin versus trimethoprim-sulfamethoxazole (TMP-SMZ) for 21 days. By study day 10, study therapy failed because of lack of efficacy in 16% of patients assigned to TMP-SMZ and 27% assigned to trimetrexate (P = .064), and the PAO2-PaO2 improved significantly faster with TMP-SMZ. By study day 21, failure rates were 20% with TMP-SMZ and 38% with trimetrexate (P = .008), with respective mortality rates of 12% and 20% (P = .088). By study day 49, the difference in mortality (16% vs. 31%) was significant (P = .028). The cumulative incidence of serious and treatment-terminating adverse events including hematologic toxicities was less with trimetrexate (P < .001). Thus, trimetrexate plus leucovorin was effective, albeit inferior to TMP-SMZ, for moderately severe P. carinii pneumonia but was better tolerated than TMP-SMZ.
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PMID:Trimetrexate with leucovorin versus trimethoprim-sulfamethoxazole for moderate to severe episodes of Pneumocystis carinii pneumonia in patients with AIDS: a prospective, controlled multicenter investigation of the AIDS Clinical Trials Group Protocol 029/031. 801 93

In a patient with the acquired immunodeficiency syndrome, a progressive increase in the serum potassium concentration occurred with high-dose trimethoprim-sulfamethoxazole (TMP-SMX) therapy for Pneumocystis carinii pneumonia. In this patient, factors known to alter transcellular potassium shifts to induce hyperkalemia were not present. There was no evidence of glucocorticoid or mineralocorticoid insufficiency at the time of hyperkalemia, while the transtubular potassium gradient decreased. The hyperkalemia resolved spontaneously on discontinuation of TMP-SMX therapy, suggesting that this electrolyte abnormality is related to altered renal tubular secretion of potassium as a consequence of the high-dose TMP-SMX therapy.
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PMID:Hyperkalemia with high-dose trimethoprim-sulfamethoxazole therapy. 821 4

Concern has been arisen about the recently reported increasing incidence of PCP in patients with cancer and the potential transmissibility of this infection. Whether or not there is an increase in the incidence of P. carinii infections, PCP should be considered in the differential diagnosis of pulmonary infiltrates in bone marrow transplant recipients, in patients with hematologic neoplasms and in patients with primary or metastatic brain neoplasms. Intensity of immunosuppression plays a crucial role, especially long-term (> 2 months) corticosteroid treatment. PCP is usually manifested clinically during augmentation or during tapering of corticosteroid dose. Thus, if the chest radiograph of a high-risk patient shows diffuse infiltrates, bronchoscopy and bronchoalveolar lavage should be done immediately. Treatment options are the same as for the AIDS population, except that TMP-SMX is tolerated better in non-AIDS patients. The role of supportive care, including mechanical ventilation in such patients should not be underestimated. Oral therapy with dapsone-trimethoprim or with atovaquone, can be as effective as conventional therapy in mild disease, permitting treatment on an outpatient basis. PCP is often preventable and our understanding has improved about when prophylaxis should be initiated. In the future, the emergence of new technologies for diagnosis and of new agents for treatment and prophylaxis, will bring us closer to the goal of controlling this serious infection.
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PMID:Pneumocystis carinii pneumonia in cancer patients. 822 11


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