Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017160 (gastroenteritis)
 11,398 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The newer fluoroquinolones are a major advance in antimicrobial chemotherapy. They inhibit the supercoiling activity of the DNA gyrase enzyme, thus exerting their antibacterial action on DNA and RNA synthesis, resulting in a biphasic response and killing of susceptible organisms. The newer fluoroquinolones have an extended antimicrobial spectrum compared to their older congeners, and are highly active against most Gram-negative pathogens including the Enterobacteriaceae and Pseudomonas aeruginosa. While Staphylococcus aureus and coagulase-negative staphylococci are usually susceptible to the fluoroquinolones, streptococci are generally more resistant and enterococci are resistant. All of the newer fluoroquinolones may be administered orally and most of them have been administered parenterally. They are widely distributed in the body, attaining therapeutic concentrations in most tissues. All of the fluoroquinolones have long half-lives and may be administered once or twice daily. The fluoroquinolones have proved effective in many infections, including uncomplicated or complicated urinary tract infections, respiratory tract infections, gonorrhoea, bacterial gastroenteritis, and soft tissue infections due to Gram-negative organisms. In general, success has been notable in the management of Gram-negative infections but less so with Gram-positive infections. Resistance has occurred and is proving a problem with P. aeruginosa in some cystic fibrosis patients, but as yet no plasmid-mediated resistance has developed. Cross-resistance occurs between the quinolones but only rarely with other classes of antibacterial drugs. The fluoroquinolones have an excellent safety record and their adverse effects, which include hypersensitivity reactions, dizziness, headache, gastrointestinal disturbance and minor haematological abnormalities are usually mild and transient. However, the fluoroquinolones have been found to damage juvenile weight-bearing joints in animals and are therefore only to be used with caution in children; transient arthralgia has been reported in a cystic fibrotic teenager on long term ciprofloxacin therapy. All of the fluoroquinolones except ofloxacin are associated with a variable increase in the serum concentration of theophylline, warfarin and caffeine. Thus, the fluoroquinolones are an attractive option in the management of many infections. Cost and possible resistance, however, should counsel caution in their use, and may limit them to situations where a cheaper antimicrobial of equivalent efficacy is not available.
 ...
PMID:Fluoroquinolone antibiotics. Microbiology, pharmacokinetics and clinical use. 305 26

A case is presented of a fatal drug interaction caused by ingestion of clozapine (Clozaril) and fluoxetine (Prozac). Clozapine is a tricyclic dibenzodiazepine derivative used as an "atypical antipsychotic" in the treatment of severe paranoid schizophrenia. Fluoxetine is a selective serotonin reuptake inhibitor used for the treatment of major depression. Clinical studies have proven that concomitant administration of fluoxetine and clozapine produces increased plasma concentrations of clozapine and enhances clozapine's pharmacological effects due to suspected inhibition of clozapine metabolism by fluoxetine. Blood, gastric, and urine specimens were analyzed for fluoxetine by gas chromatography/mass spectrometry (GC/MS) and for clozapine by gas-liquid chromatography (GLC). Clozapine concentrations were: plasma, 4.9 micrograms/mL; gastric contents, 265 mg; and urine, 51.5 micrograms/mL. Fluoxetine concentrations were: blood, 0.7 microgram/mL; gastric contents, 3.7 mg; and urine 1.6 micrograms/mL. Norfluoxetine concentrations were: blood, 0.6 microgram/mL, and none detected in the gastric contents or urine. Analysis of the biological specimens for other drugs revealed the presence of ethanol (blood, 35 mg/dL; vitreous, 56 mg/dL; and urine 153 mg/dL) and caffeine (present in all specimens). The combination of these drugs produced lethal concentrations of clozapine and high therapeutic to toxic concentrations of fluoxetine. The deceased had pulmonary edema, visceral vascular congestion, paralytic ileus, gastroenteritis and eosinophilia. These conditions are associated with clozapine toxicity. The combined central nervous system, respiratory and cardiovascular depression of these drugs was sufficient to cause death. The death was determined to be a clozapine overdose due to a fatal drug interaction.
 ...
PMID:A fatal drug interaction between clozapine and fluoxetine. 972 31