Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0000737 (abdominal pain)
 31,184 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We retrospectively investigated the clinical and histopathologic features of hospitalized patients infected with human immunodeficiency virus who had symptomatic lactic acidosis syndrome at a university teaching hospital during 1995-2000. Twelve patients were identified, 11 during 1998-2000; of these, 5 died with rapid progression to otherwise unexplained multiple-organ failure. All had extensive prior exposure to nucleoside analog reverse-transcriptase inhibitors (NRTIs). At presentation, the most commonly identified NRTI component of antiretroviral regimens was stavudine plus didanosine. Eleven patients presented with abdominal pain, nausea, and/or emesis. Eight patients had prior acute weight loss (mean [+/-SD], 12+/-5.3 kg). Median venous plasma lactate levels were > or =2-fold greater than the upper limit of normal (2.1 mmol/L). Serum transaminase levels were near normal limits at presentation. Histopathologic studies confirmed hepatic macrovesicular and microvesicular steatosis in 6 patients. Concurrent chemical pancreatitis was identified in 6 patients. The increasing number of cases identified during the study period suggests that physicians better recognize symptomatic lactic acidosis and/or that cumulative NRTI exposure may increase the risk for this syndrome.
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PMID:Symptomatic lactic acidosis in hospitalized antiretroviral-treated patients with human immunodeficiency virus infection: a report of 12 cases. 1169 4

Tipranavir (TPV) is a non-peptidic protease inhibitor belonging to the class of 4-hydroxy-5,6-dihydro-2-pyrones, which exhibits potent and specific activity against HIV type I (HIV-1) and 2 (HIV-2). Clinically effective plasma levels of TPV are achieved by concomitant administration of ritonavir (RTV). Therefore, TPV has been coadministered with RTV in clinical trials. TPV has demonstrated antiviral activity against HIV-1 isolates that are resistant to reverse-transcriptase and selected peptidic protease inhibitors. Therefore, TPV is emerging as one of the newer drugs in the armamentarium against HIV-1 in patients demonstrating multi-drug resistance. TPV administered orally to humans exhibits linear pharmacokinetics at doses of 100 - 2000 mg. Steady-state plasma levels are attained within 7 days of initiating multiple dosing. The half-life of the drug is approximately 6 h at steady-state. The plasma concentration is lower with repeated dosing than predicted from single-dose studies due to induction of the cytochrome p450 3A4 isoform of the liver microsomal enzyme system. Phase II clinical trials have shown that the administration of TPV and RTV in combination is safe and generally well-tolerated in HIV-1-infected adults. Phase III trials are underway to compare the efficacy of this drug versus other antiretroviral regimens. Gastrointestinal toxicity has been described with TPV, the most frequently reported side effects being diarrhoea, nausea, vomiting and abdominal pain. There is no known evidence of teratogenicity or effect on fertility. TPV dosed twice-daily, in the range of 500 - 1250 mg and combined with 100 - 200 mg of RTV has been shown to substantially and durably reduce viral load in HIV-1-infected drug-naive and experienced patients.
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PMID:Tipranavir: a novel non-peptidic protease inhibitor for the treatment of HIV infection. 1458 57

Nucleoside reverse-transcriptase inhibitors (NRTIs) have been associated with functional and structural mitochondrial abnormalities, leading to several adverse events, such as increased serum lactic acid levels and lactic acidosis. Mild-to-moderate, asymptomatic hyperlactataemia has been frequently reported in human immunodeficiency virus (HIV)-infected patients treated with NRTIs, with an estimated prevalence between 15% and 35%. On the contrary, symptomatic, severe hyperlactataemia and lactic acidosis are less common, with an incidence ranging from 1.7 to 25.2 cases per 1000 person-years of antiretroviral treatment, and are associated with a remarkable mortality rate, which varies from 30% to 60% in different studies. The clinical presentation of lactic acid syndrome is non-specific and includes asthenia, malaise, nausea, vomiting, abdominal pain, weight loss, tachypnoea, dyspnoea, liver steatosis and increased transaminase levels, and risk factors include previous or concurrent therapy with stavudine or didanosine. Management of symptomatic lactic acid alterations involves NRTI-therapy interruption and supportive care, while natural history of hyperlactataemia is still unknown, and it is uncertain whether asymptomatic patients with increased lactate concentrations are at increased risk of developing lactic acidosis.
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PMID:Hyperlactataemia and lactic acidosis in HIV-infected patients receiving antiretroviral therapy. 1568 Oct 97