Trimethoprim pharmacology

Basic and Clinical Pharmacology > Chapter 46. Sulfonamides, Trimethoprim, Quinolones >... 

See Chapters 34 and 40 in Lippincott s Illustrated Reviews Pharmacology (3rd Ed.) and Chapters 29 and 38 (2nd Ed) for a discussion of sulfonamides, trimethoprim, and methotrexate... 

Petri WA. Sulfonamides, trimethoprim-sulfamethoxazole, quinolones, and agents for urinary tract infections. In Brunton LL, et al, eds. The Pharmacological... 

Pyrimethamine is a fohc acid antagonist (antifol) with pharmacological actions similar to chlorguanide, methotrexate, and trimethoprim. Pyrimethamine may be used in combination with sulfadoxine for suppression and sulfadiazine for treatment of chloroquine-resistant Plasmodium falciparum. 

A drug receptor is a specialized target macromolecule, present on the cell surface or intracellularly, that binds a drug and mediates its pharmacologic actions. Drugs may interact with enzymes (for example, inhibition of dihydrofolate reductase by trimethoprim, p. 294),... 

Mandell, G.L. Sande, M.A. Antimicrobial agents sulfonamides, trimethoprim, sulfamethoxazole, quinolones, and agents for urinary tract infections. In Pharmacological Basis of Therapeutics, 8th Ed. Gilman, A.G., Rail, T.W., Nies, A.S., Taylor, P., Eds. Pergamon Press New York, 1991 1047-1064. 

Nouws, J.F.M., van Ginneken, V.J.T., Grondel, J.L. Degen, M. (1993) Pharmacokinetics of sulphadiazine and trimethoprim in carp (Cyprinus carpio L.) acclimated at two different temperatures. Journal of Veterinary Pharmacology and Therapeutics, 16, 110-113. 

Ladefoged, O. (1979) Pharmacokinetics of antipyrine and trimethoprim in pigs with endotoxin-induced fever. Journal of Veterinary Pharmacology and Therapeutics, 2, 209-214. 

Mengelers, M.J.B., van Gogh, E.R., Kuiper, H.A. et al. (1995) Pharmacokinetics of sul-fadimethoxine and sulfamethoxazole in combination with trimethoprim after intravenous administration to healthy and pneumonic pigs. Journal of Veterinary Pharmacology and Therapeutics, 18, 243-253. 

The Physiological Basis of Veterinary Clinical Pharmacology Table 6.3 Half-life and urinary excretion of trimethoprim. 

Dihydrofolate reductase (DHFR, EC 1.5.1.3) is an essential enzyme required for normal folate metabolism in prokaryotes and eukaryotes. Its role is to maintain necessary levels of tetrahydrofolate to support the biosynthesis of purines, pyrimidines and amino acids. Many compounds of pharmacological value, notably methotrexate and trimethoprim, vork by inhibition of DHFR. Their clinical importance justified the study of DHFR in the rapidly evolving field of enzymology. Today, there is a vast amount of published literature (ca. 1000 original research articles) on the broad subject of dihydrofolate reductase contributed by scientists from diverse disciplines. We have selected kinetic, structural, and computational studies that have advanced our understanding of the DHFR catalytic mechanism with special emphasis on the role of the enzyme-substrate complexes and protein motion in the catalytic efficiency achieved by this enzyme. 

Nakatani-Freshwater, T., Babayeva, M., Dontabhaktuni, A., Taft, D. R. (2006). Effects of trimethoprim on the clearance of apricita-bine, a deoxycytidine analog reverse transcriptase inhibitor, and Lamivudine in the isolated perfused rat kidney. The Journal of Pharmacology and Experimental Therapeutics, 319, 941—947. 

Figure 46-1. Inhibitory effects of sulfonamides and trimethoprim on folic acid synthesis. Inhibition of two successive steps in the formation of tetrahydrofolic acid constitutes sequential blockade and results in antibacterial synergy. (Modified and reproduced, with permission, from Katzung BG [editor] Basic Clinical Pharmacology, 8th ed. McGraw-Hill, 2001.)...

I. Pharmacology. Folic acid is a B-complex vitamin that is essential for protein synthesis and erythropoiesis. In addition, the administration of folate to patients with methanol poisoning may enhance the elimination of the toxic metabolite formic acid, based on studies in folate-deficient primates. Note Folic acid requires metabolic activation and is not effective for treatment of poisoning by dihydrofolate reductase inhibitors (eg, methotrexate and trimethoprim). Leucovorin (see p 460) is the proper agent in these situations. 

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