Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, several class-related adverse events have been recognized with antiretroviral drugs. For nucleoside analogue reverse transcriptase inhibitors. (NRTI), lactic acidosis with hepatomegaly and hepatic steatosis have been reported. These appear to occur at a low frequency, but with a high fatality rate. We report a case of fatal lactic acidosis in a patient with acquired immunodeficiency syndrome (AIDS) treated with stavudine (d4T), lamivudine (3TC) and indinavir (IDV). A 48-year-old male AIDS patient was admitted with complaints of general fatigue and dyspnea. His medications at presentation included d4T, 3TC and IDV. Physical examination demonstrated icteric sclerae and abdominal tenderness with hepatomegaly. Laboratory data demonstrated a severe metabolic acidosis with an anion gap due to lactate accumulation. Despite intensive treatment, cardiorespiratory arrest occurred and this could not be resuscitated.
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PMID:[Fatal lactic acidosis in a patient with acquired immunodeficiency syndrome treated with stavudine, lamivudine and indinavir]. 1065 86

The aim of the present investigation was to reduce the hepatic toxicity, enhance the cellular uptake and alter the pharmacokinetics of stavudine using galactosylated liposomes. beta-D-1-Thiogalactopyranoside residues were covalently coupled with dimyristoyl phosphatidylethanolamine, which was then used to form liposomes. The galactosylated liposomal system was assessed for in vitro ligand-specific activity. The drug release from liposomes was studied by dialysis method. Ex vivo cellular uptake study was performed using liver parenchymal cells harvested from male albino rats. Changes in hematological parameters, hepatic enzymes, hepatomegaly, plasma and tissue distribution of the formulations (free stavudine solution, uncoated liposomal and galactosylated liposomes) were determined using albino rats. Percent cumulative drug release in 24h was low (34.8+/-2.6%). Enhanced hepatic cellular d4T uptake (27.96+/-2.41pg d4T/million cells) was seen in case of galactosylated liposomal d4T. Galactosylated liposomes maintained a significant level of d4T in tissues rich in galactose specific receptors and had a prolonged residence (11.44+/-1.25h) in the body resulting in enhanced half-life of d4T (23.07+/-1.25h). This formulation did not show either hematological or hepatic toxicity. Galactosylation of liposomes alter the biodistribution of encapsulated drug thereby delivering the drug to cells bearing galactose specific receptors.
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PMID:Reduced hepatic toxicity, enhanced cellular uptake and altered pharmacokinetics of stavudine loaded galactosylated liposomes. 1730 96

Nucleoside analogue reverse-transcriptase inhibitors (NRTIs) especially stavudine, used for the treatment of HIV infection have been rarely associated with lactic acidosis syndrome (LAS) and severe neuromuscular weakness mimicking Guillain Barre syndrome. A 36-year-old man presented with a one-week history of nausea, vomiting, epigastric pain, dyspnea associated with progressive muscle weakness and numbness in glove and stocking pattern. He had symptomatic HIV infection, diagnosed 2 years before the admission and was treated with GPOvir (lamivudine, stavudine and nevirapine). Physical examination revealed afebrile dyspnic drowsy man with crepitation in both lungs and hepatomegaly. Neurological examination showed areflexic symmetrical weakness of both extremities and decreased pin-prick sensation in glove and stocking pattern as well as loss of vibration and touch sensation in both hands and feet. He developed cardiopulmonary arrest and was intubated. Investigations revealed severe lactic acidosis (lactic acid = 21.1 mg/dl). Electrophysiological studies revealed severe sensorimotor axonopathy predominantly involved the lower extremities. Stavudine was discontinued. Severe LAS dramatically improved and polyneuropathy gradually recovered with symptomatic as well as supportive interventions. Monitoring of LAS and neuromuscular weakness is advocated in HIV patient who receive stavudine therapy. Immediate discontinuation of the medication after detection of these complications may prevent this fatal complications.
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PMID:Lactic acidosis associated with severe neuromuscular weakness and stavudine therapy. 2159 38