Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0206061 (interstitial pneumonia)
 6,105 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pentamidine is an aromatic diamidino compound synthesized originally for the therapy of trypanosomiasis. The pharmacologic effects of pentamidine vary, depending on its route of administration. In animals, the dominant effects have been a precipitous, transitory drop in blood pressure after injection and renal toxicity following repeated administration. To avoid the possibility of immediate toxic reactions associated with iv administration, we now usually give the drug im to humans. Further interest in pentamidine has been stimulated by its usefulness in the treatment of interstitial pneumonia caused by Pneumocystis carinii. In some patients receiving antineoplastic or immunosuppressive therapy who have superimposed P. carinii pneumonia, pentamidine may cause serious renal toxicity. Distribution and excretion studies in animals indicate pentamidine is deposited in tissues, with the greatest concentration in the kidneys, and gradually eliminated over a prolonged period. The mechanism of action of pentamidine against P. carinii or the means whereby fixation in tissues and subsequent toxicity occur have not been elucidated. Recent investigations to help clarify these points indicate that pentamidine inhibits dihydrofolate reductase in all tissues studied both in vitro and in vivo. In addition, pentamidine interacts and forms water-insoluble products with specific nucleotides and nucleic acids.
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PMID:Pharmacologic aspects of pentamidine. 101 18

Pneumocystis (Pc) jirovecii causes severe interstitial pneumonia in patients with immunodeficiency, in whom this fungus adheres with type-I alveolar epithelial cells. Therefore, it is important to perform quick diagnosis and treatment for Pc pneumonia (PcP). In general, a combination of two antifolate agents, sulfamethoxazole (inhibition of dihydropteroate synthase (DHPS)) and trimethoprim (inhibition of dihydrofolate reductase), is the first choice for PcP treatment, and pentamidine or atovaquone (inhibition of cytochrome b) are the alternative reagents for the therapy. Amino acid substitutions of drug-binding sites in DHPS shown in genotypic analysis have been reported to be associated with failures of prophylaxis / treatment or severe mortality for PcP, while there is another article showing a negative relationship between the DHPS mutations and poor prognosis. Drug sensitivity tests using the phenotypes as well as genotypes are necessary, although it is difficult to culture Pc. This review focuses on the relationship between mutations of drug-targeting molecules and treatment failure based on original data and other reports. In addition, trials of phenotypic analyses for Pc are described as promising investigations.
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PMID:[Mutations of drug target molecules in Pneumocystis jirovecii isolates and future investigations]. 1943 Jan 80