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| {{drugbox |
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| |image = Trimethoprim.jpg
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| |width = 200px
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| |IUPAC_name = 5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4-diamine
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| |CAS_number = 738-70-5
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| | ATC_prefix=J01
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| | ATC_suffix=EA01
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| | PubChem=5578
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| | DrugBank=APRD00103
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| | C = 14 | H = 18 | N = 4 | O = 3
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| |molecular_weight = 290.32 g/mol
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| |bioavailability = 90–100%
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| |metabolism = [[hepatic]]
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| |elimination_half-life = 8–10 hours
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| |excretion = [[renal]] 50–60%
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| | pregnancy_AU = B3
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| | pregnancy_US = C
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| |legal_AU = S4
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| |legal_UK = POM
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| |routes_of_administration = Oral
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| }}
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| {{SI}}
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| {{CMG}}
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| __NOTOC__ | | __NOTOC__ |
| | {{Trimethoprim}} |
| | '''''For patient information, click <u>[[Trimethoprim (patient information)|here]]</u>'''''. |
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| | {{CMG}} |
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| ==Overview== | | ==Overview== |
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| '''Trimethoprim''' ([[International Nonproprietary Name|INN]]) ([[International Phonetic Alphabet|IPA]]: {{IPA|[traɪˈmɛθəprɪm]}}) is a bacteriostatic [[antibiotic]] mainly used in the [[prophylaxis]] and treatment of [[urinary tract infection]]s. It belongs to the class of [[chemotherapy|chemotherapeutic]] agents known as [[dihydrofolate reductase]] inhibitors. Trimethoprim was formerly marketed by [[GlaxoSmithKline|GlaxoWellcome]] under trade names including '''Proloprim''', '''Monotrim''' and '''Triprim'''; but these trade names have been licensed to various [[generic drug|generic pharmaceutical]] manufacturers. In clinical use it is often abbreviated '''TRI''' or '''TMP'''; its common laboratory abbreviation is '''W'''.
| | ==Category== |
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| ==Mechanism of action== | |
| [[Image:THFsynthesispathway.jpg|frame|left|Tetrahydrofolate synthesis pathway]]
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| Trimethoprim acts by interfering with the action of bacterial [[dihydrofolate reductase]], inhibiting synthesis of [[folic acid|tetrahydrofolic acid]]. Tetrahydrofolic acid is an essential precursor in the [[de novo synthesis|''de novo'' synthesis]] of the DNA nucleotide [[thymine]]. Bacteria are unable to take up folic acid from the environment (i.e. the infection host) and are thus dependent on their own ''de novo'' synthesis. Inhibition of the enzyme starves the bacteria of bases necessary for [[DNA replication]].
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| ==Co-trimoxazole==
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| Trimethoprim was commonly used in combination with [[sulfamethoxazole]], a [[Sulfonamide (medicine)|sulfonamide]] antibiotic, which inhibits an earlier step in the folate synthesis pathway (see diagram above). This combination, also known as [[co-trimoxazole]], TMP-sulfa, or TMP-SMX, results in an in vitro [[synergistic]] antibacterial effect by inhibiting successive steps in folate synthesis, this claimed benefit was not seen in general clinical use.<ref>{{cite journal |author=Brumfitt W, Hamilton-Miller JM |title=Reassessment of the rationale for the combinations of sulphonamides with diaminopyrimidines | journal=J Chemother |year=1993 |month=Dec |volume=5 |issue=6 |pages=465-9 |pmid=8195839}}</ref>
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| <ref>{{cite journal |author=Brumfitt W, Hamilton-Miller JM |title=Limitations of and indications for the use of co-trimoxazole | journal=J Chemother |year=1994 |month=Feb |volume=6 |issue=1 |pages=3-11 |pmid=8071675}}</ref>
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| Its use has been declining due to reports of sulfamethoxazole [[bone marrow]] toxicity, resistance and lack greater efficacy in treating common urine and chest infections,<ref>{{cite journal |author=Bean DC, Livermore DM, Papa I, Hall LM |title=Resistance among Escherichia coli to sulphonamides and other antimicrobials now little used in man |journal=J Antimicrob Chemother |year=2005 |month=Nov | volume=56 |issue=5 |pages=962-4 |pmid=16150859 |url=http://jac.oxfordjournals.org/cgi/content/full/56/5/962}}</ref><ref>{{cite journal |author=Felmingham D, Reinert RR, Hirakata Y, Rodloff A |title=Increasing prevalence of antimicrobial resistance among isolates of Streptococcus pneumoniae from the PROTEKT surveillance study, and compatative in vitro activity of the ketolide, telithromycin |journal=J Antimicrob Chemother |year=2002 |month=Sep | volume=50 |issue=Suppl S1 |pages=25-37 |pmid=12239226 |url=http://jac.oxfordjournals.org/cgi/reprint/50/suppl_2/25}}</ref><ref>{{cite journal |author=Johnson JR, Manges AR, O'Bryan TT, Riley LW |title=A disseminated multidrug-resistant clonal group of uropathogenic Escherichia coli in pyelonephritis |journal=Lancet |year=2002 |month=Jun 29 | volume=359 |issue=9325 |pages=2249-51 |pmid=12103291 |url=}}</ref><ref>{{cite journal |author=Lawrenson RA, Logie JW |title=Antibiotic failure in the treatment of urinary tract infections in young women |journal=J Antimicrob Chemother |year=2001 |month=Dec | volume=48 |issue=6 |pages=895-901 |pmid=11733475 |url=}} - suggest some small advantage in UTIs</ref> and [[Sulfonamide (medicine)#Side effects|side effects of antibacterial sulfonamides]]. As a consequence, the use of co-trimoxazole was restricted in 1995.<ref>{{cite journal |author= |title=Co-trimoxazole use restricted |journal=Drug Ther Bull |year=1995 |month=Dec | volume=33 |issue=12 |pages=92-3 |pmid=8777892 |url=}}</ref>
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| ==Clinical indications==
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| Trimethoprim, used as [[monotherapy]], is indicated for the [[prophylaxis]] and treatment of [[urinary tract infection]]s ([[cystitis]]). [[Co-trimoxazole]], with its greater efficacy against a limited number of bacteria, remains indicated for some infections; for example, it is used as prophylaxis in patients at risk for [[Pneumocystis pneumonia|''Pneumocystis jirovecii'' pneumonia]] (e.g. [[AIDS]] patients and those with some [[hematological malignancy|hematological malignancies]]) and as therapy in [[Whipple's disease]].
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| == Footnotes==
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| <div class="references-small"><references/></div>
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| ==External links==
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| * [http://www.med.sc.edu:96/Biopharm/PDFs/NucleicAcidInhibitors.pdf Nucleic acid inhibitors] (PDF file).
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| {{Acne Agents}}
| | ==US Brand Names== |
| {{Sulfonamides and trimethoprim}}
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| [[Category:Antibiotics]]
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| [[Category:Dihydrofolate reductase inhibitors]]
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| | ==FDA Package Insert== |
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| | ''' [[Trimethoprim description|Description]]''' |
| | '''| [[Trimethoprim clinical pharmacology|Clinical Pharmacology]]''' |
| | '''| [[Trimethoprim microbiology|Microbiology]]''' |
| | '''| [[Trimethoprim indications and usage|Indications and Usage]]''' |
| | '''| [[Trimethoprim contraindications|Contraindications]]''' |
| | '''| [[Trimethoprim warnings and precautions|Warnings and Precautions]]''' |
| | '''| [[Trimethoprim adverse reactions|Adverse Reactions]]''' |
| | '''| [[Trimethoprim drug interactions|Drug Interactions]]''' |
| | '''| [[Trimethoprim overdosage|Overdosage]]''' |
| | '''| [[Trimethoprim clinical studies|Clinical Studies]]''' |
| | '''| [[Trimethoprim dosage and administration|Dosage and Administration]]''' |
| | '''| [[Trimethoprim how supplied|How Supplied]]''' |
| | '''| [[Trimethoprim labels and packages|Labels and Packages]]''' |
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| [[de:Trimethoprim]]
| | ==Mechanism of Action== |
| [[hu:Trimetoprim]]
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| [[pl:Trimetoprim]]
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| [[pt:Trimetoprim]]
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| [[sk:Trimetoprim]]
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| [[sv:Trimetoprim]]
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| [[th:ไตรเมโทพริม]]
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| | ==References== |
| | {{Reflist|2}} |
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| | [[Category:Folate antagonist]] |
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| | [[Category:Wikinfect]] |