Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acetazolamide is a carbonic anhydrase inhibitor commonly used to reduce intraocular pressure (IOP). We report the first pharmacokinetic study of acetazolamide in a patient undergoing continuous ambulatory peritoneal dialysis (CAPD). The patient was a Type I diabetic with end-stage renal disease (ESRD) undergoing CAPD who received acetazolamide for elevated IOP after surgery for a detached retina. Serum acetazolamide concentrations were measured prior to a 250 mg oral dose and 12 additional times during a 24-h dosing interval. All dialysate effluent was collected and assayed for acetazolamide. Serum concentrations at the beginning and end of the dosing interval were 18 and 17 mcg/mL, respectively, with a maximum concentration of 27 mcg/mL at 6.5 h (therapeutic range = 5-10 mcg/mL). The elimination half-life was prolonged, 28.5 h, compared to that seen in subjects with normal renal function (5-10 h). CAPD did not remove a clinically significant amount of drug (17.1 mg, or 6.8% of dose recovered in dialysate). The patient was very lethargic during therapy, a possible manifestation of acetazolamide toxicity. Marked reduction in acetazolamide dosage (in this case, 125 mg/day) would be required to prevent drug accumulation and toxicity.
Adv Perit Dial 1994
PMID:The pharmacokinetics of acetazolamide during CAPD. 799 62

Fatigue and lethargy, common symptoms in uraemia, have been attributed to many factors. To assess possible bioenergetic contributions to this, we examined the forearm muscle of five patients in end-stage renal failure using 31P-magnetic resonance spectroscopy. There was a small increase in the ratio of intracellular inorganic phosphate to ATP in resting muscle, suggesting an increased cytosolic phosphate concentration. During exercise, increased phosphocreatine breakdown was accompanied by rapid intracellular acidification and an increase in calculated lactic acid accumulation in the muscle of the uraemic subjects, suggesting glycolysis dominating over oxidative phosphorylation as a source of ATP. After exercise, the half-time of phosphocreatine (PCr) recovery was longer in the uraemic subjects, suggesting diminished mitochondrial function. The initial rate of PCr resynthesis was not significantly decreased, but when account was taken of the high cytosolic ADP concentration (which drives mitochondrial oxidative ATP synthesis) the calculated maximum oxidative capacity was significantly reduced in the uraemic subjects. Thus there was evidence of mitochondrial dysfunction in uraemia due either to limitation of oxygen supply, reduced mitochondrial content, or an intrinsic mitochondrial defect. This resulted in increased phosphocreatine depletion and increased glycolytic ATP production during exercise and there was partial compensation of the mitochondrial abnormality by increased ADP concentration. In three of these patients studied after elevation of haemoglobin with erythropoeitin (from 8 to 12 g/dl), initial phosphocreatine breakdown and lactic acid accumulation during exercise were normalized, while exercise duration and calculated maximum oxidative capacity remained significantly abnormal. This suggests that anaemia contributes to these metabolic abnormalities but does not fully explain them.
Nephrol Dial Transplant 1993
PMID:Effect of chronic uraemia on skeletal muscle metabolism in man. 838 87