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)

Two elderly patients, who were chronically receiving aspirin, developed lethargy, incontinence, and confusion after dosing with acetazolamide. Unbound plasma acetazolamide concentrations were elevated and plasma protein binding was reduced, suggesting an interaction with aspirin. In vitro studies demonstrated a concentration-dependent effect of salicylate on acetazolamide binding to serum proteins. At a therapeutic serum acetazolamide level of 8.0 micrograms/ml, the unbound percentage of acetazolamide in serum was 3.3% and increased to 11.0% and 30.0%, with serum salicylate levels of 200 and 386 micrograms/ml, respectively. Furthermore, the apparent association constant of acetazolamide for binding to serum proteins was decreased by 58% and 86% of its control value at these respective salicylate concentrations. The maximal binding capacity of serum for acetazolamide was not affected by salicylate. Pharmacokinetic studies in four volunteers showed that the plasma protein binding and renal clearance of acetazolamide were significantly reduced during chronic salicylate dosing. Salicylate appears to competitively inhibit the plasma protein binding of acetazolamide and simultaneously to inhibit acetazolamide renal tubular secretion. Caution is advised when acetazolamide and salicylate are used concurrently.
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PMID:Toxic interaction between acetazolamide and salicylate: case reports and a pharmacokinetic explanation. 376 83

We used exchange transfusion as an alternative to hemodialysis in an infant with severe salicylism. A 4-mo old, 5 kg male was presented to a local hospital with acute vomiting, tachypnea, hyperpnea and intermittent agitation and lethargy. Shortly after a generalized tonic-clonic seizure he passed several tablets in his stool. Salicylate (ASA) level was 85 mg/dL. He was transferred to our institution for further management: i.v. fluids, activated charcoal, whole bowel irrigation and supplementation with sodium bicarbonate, potassium and calcium. The patient's mental status and gas exchange deteriorated and he was intubated. Despite large amounts of sodium bicarbonate and potassium, severe hypokalemia, anion gap metabolic acidosis and aciduria persisted for 10 h. The small size of the infant precluded use of hemodialysis. An exchange transfusion using 180 mL/kg packed red blood cells reconstituted in fresh frozen plasma was performed. The pre-exchange transfusion ASA level was 70.1 mg/dL; the post-exchange transfusion ASA level was 34.4 mg/dL. There was rebound elevation of ASA to 35.2 mg/dL at 6 h post-exchange transfusion. The 18, 36 and 48 h post-exchange transfusion ASA levels were 20.2, 6.8 and < 2 mg/dL respectively. The ASA level dropped 17.6% before, 41.9% in 8.5 h during, and 40.5% by 48 h after the exchange transfusion. There were no complications. The patient recovered completely to his pre-morbid state. Double volume exchange transfusion was used safely as an effective alternative to hemodialysis in this case of severe infant salicylate poisoning.
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PMID:Exchange transfusion in severe infant salicylism. 1213 72