Trimethoprim

Overview

Trimethoprim (TMP) is an antibiotic used mainly in the treatment of bladder infections. Other uses include for middle ear infections and travellers' diarrhoea. With sulfamethoxazole or dapsone it may be used for Pneumocystis pneumonia in people with HIV/AIDS. It is taken orally (swallowed by mouth).[1][2] WP

Common side effects include nausea, changes in taste, and rash. Rarely it may result in blood problems such as not enough platelets or white blood cells. Trimethoprim may cause sun sensitivity. There is evidence of potential harm during pregnancy in some animals but not humans. It works by blocking folate metabolism via dihydrofolate reductase in some bacteria, preventing creation of bacterial DNA and RNA and leading to bacterial cell death.[1][3] WP

Trimethoprim was first used in 1962. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication.[4][5][6] WP

Drug class

Diaminopyrimidines WP

From the Wikipedia article's infobox.

Uses, dosage and effects

Medical uses

It is primarily used in the treatment of urinary tract infections, although it may be used against any susceptible aerobic bacterial species. It may also be used to treat and prevent Pneumocystis jirovecii pneumonia. It is generally not recommended for the treatment of anaerobic infections such as Clostridioides difficile colitis (the leading cause of antibiotic-induced diarrhea). Trimethoprim has been used in trials to treat retinitis.[7][8] WP

Resistance to trimethoprim is increasing, but it is still a first-line antibiotic in many countries.[9] WP

Spectrum of susceptibility

Cultures and susceptibility tests should be done to make sure bacteria are treated by trimethoprim.[10][11] WP

• Escherichia coli[10][11] WP
• Proteus mirabilis[10][11] WP
• Klebsiella pneumoniae[10][11] WP
• Enterobacter species[10][11] WP
• Coagulase-negative Staphylococcus species, including S. saprophyticus[10][11] WP
• Streptococcus pneumoniae[10][11] WP
• Haemophilus influenzae[10][11] WP

Risks and side effects

Common

• Nauseas WP
• Change in taste WP
• Vomiting WP
• Diarrhoea WP
• Rashes WP
• Sun sensitivity WP
• Itchiness[12][13] WP

Rare

• Can cause thrombocytopenia (low levels of platelets) by lowering folic acid levels; this may also cause megaloblastic anemia.[14] WP
• Trimethoprim antagonizes the epithelial sodium channel in the distal tubule, thus acting like amiloride. This can cause increased potassium levels in the body (hyperkalemia).[15] WP
• Can compete with creatinine for secretion into the renal tubule. This can cause an artificial rise in the serum creatinine.[16] WP
• Use in EHEC infections may lead to an increase in expression of Shiga toxin.[17] WP

Contraindications

• Known hypersensitivity to trimethoprim WP
• History of megaloblastic anemia due to folate deficiency[10] WP

It may be involved in a reaction similar to disulfiram when alcohol is consumed after it is used, in particular when used in combination with sulfamethoxazole.[18][19] WP

Pregnancy

Based on the studies that show that trimethoprim crosses the placenta and can affect folate metabolism, there has been growing evidence of the risk of structural birth defects associated with trimethoprim, especially during the first trimester of pregnancy.[20] WP

The trophoblasts in the early fetus are sensitive to changes in the folate cycle. A 2013 study found a doubling in the risk of miscarriage in women exposed to trimethoprim in the early pregnancy.[21] WP

Pharmacology

Mechanism of action

Trimethoprim binds to dihydrofolate reductase and inhibits the reduction of dihydrofolic acid (DHF) to tetrahydrofolic acid (THF). THF is an essential precursor in the thymidine synthesis pathway and interference with this pathway inhibits bacterial DNA synthesis. Trimethoprim's inhibitory activity for bacterial dihydrofolate reductase is sixty thousand times greater than for human dihydrofolate reductase. Sulfamethoxazole inhibits dihydropteroate synthase, an enzyme involved further upstream in the same pathway. Trimethoprim and sulfamethoxazole are commonly used in combination due to possible synergistic effects, and reduced development of resistance. This benefit has been questioned.[22][23][24] WP

History

History

Trimethoprim was first used in 1962. In 1972, it was used as a prophylactic treatment for urinary tract infections in Finland.[4] WP

Its name is derived from trimethyloxy-pyrimidine. WP

Chemistry

Formula

C14H18N4O3 PC

CAS number

738-70-5 PC

Molar mass (g/mol)

290.32 PC

IUPAC name (computed by PubChem)

5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidine-2,4-diamine PC

SMILES

COC1=CC(=CC(=C1OC)OC)CC2=CN=C(N=C2N)N PC

InChIKey

IEDVJHCEMCRBQM-UHFFFAOYSA-N PC

PubChem CID

5578

IUPAC name

5-(3,4,5-Trimethoxybenzyl)pyrimidine-2,4-diamine WP

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Other Trimethoprim
2. Journal / agency Masur H, Brooks JT, Benson CA, Holmes KK, Pau AK, Kaplan JE. Prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Updated Guidelines from the Centers for Disease Control and Prevention, National Institutes of Health, and HIV Medicine Association of the Infectious Diseases Society of America. Clinical Infectious Diseases. May 2014. doi:10.1093/cid/ciu094 · PMID 24585567 · PMC3982842
3. Other Prescribing medicines in pregnancy database. 3 March 2014
4. Journal / agency Huovinen P. Resistance to trimethoprim-sulfamethoxazole. Clinical Infectious Diseases. June 2001. doi:10.1086/320532 · PMID 11340533
5. Other World Health Organization model list of essential medicines: 22nd list (2021). 2021
6. Other Hamilton R. Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. 2015
7. Other Australian Medicines Handbook. 2013
8. Journal / agency Pradhan E, Bhandari S, Gilbert RE, Stanford M. Antibiotics versus no treatment for toxoplasma retinochoroiditis. The Cochrane Database of Systematic Reviews. May 2016. doi:10.1002/14651858.CD002218.pub2 · PMID 27198629 · PMC7100541
9. Other Three-day courses of antibiotics for uncomplicated urinary tract infection | Guidance and guidelines | NICE. 15 January 2015
10. Journal / agency TRIMETHOPRIM- trimethoprim tablet
11. Journal / agency PRIMSOL- trimethoprim hydrochloride solution
12. Journal / agency PROLOPRIM® (trimethoprim)100-mg and 200-mg Scored Tablets
13. Other Ellenhorn MJ, Schonwald S, Ordog G, Wasserberger J. American Hospital Formulary Service- Drug Information 2002
14. Other MICROMEDEX Thomson Health Care. USPDI. Drug Information for the Health Care Professional. 2002
15. Journal / agency Choi MJ, Fernandez PC, Patnaik A, Coupaye-Gerard B, D'Andrea D, Szerlip H, Kleyman TR. Brief report: trimethoprim-induced hyperkalemia in a patient with AIDS. The New England Journal of Medicine. March 1993. doi:10.1056/NEJM199303113281006 · PMID 8433730
16. Journal / agency Naderer O, Nafziger AN, Bertino JS. Effects of moderate-dose versus high-dose trimethoprim on serum creatinine and creatinine clearance and adverse reactions. Antimicrobial Agents and Chemotherapy. November 1997. doi:10.1128/AAC.41.11.2466 · PMID 9371351 · PMC164146
17. Journal / agency Kimmitt PT, Harwood CR, Barer MR. Toxin gene expression by shiga toxin-producing Escherichia coli: the role of antibiotics and the bacterial SOS response. Emerging Infectious Diseases. 2000. doi:10.3201/eid0605.000503 · PMID 10998375 · PMC2627954
18. Journal / agency Edwards DL, Fink PC, Van Dyke PO. Disulfiram-like reaction associated with intravenous trimethoprim-sulfamethoxazole and metronidazole. Clinical Pharmacy. December 1986. PMID 3492326
19. Journal / agency Heelon MW, White M. Disulfiram-cotrimoxazole reaction. Pharmacotherapy. 1998. doi:10.1002/j.1875-9114.1998.tb03913.x · PMID 9692665
20. Journal / agency Sivojelezova A, Einarson A, Shuhaiber S, Koren G. Trimethoprim-sulfonamide combination therapy in early pregnancy. Canadian Family Physician. September 2003. PMID 14526858 · PMC2214286
21. Journal / agency Andersen JT, Petersen M, Jimenez-Solem E, Broedbaek K, Andersen EW, Andersen NL, Afzal S, Torp-Pedersen C, Keiding N, Poulsen HE. Trimethoprim use in early pregnancy and the risk of miscarriage: a register-based nationwide cohort study. Epidemiology and Infection. August 2013. doi:10.1017/S0950268812002178 · PMID 23010291 · PMC9151599
22. Journal / agency Brogden RN, Carmine AA, Heel RC, Speight TM, Avery GS. Trimethoprim: a review of its antibacterial activity, pharmacokinetics and therapeutic use in urinary tract infections. Drugs. June 1982. doi:10.2165/00003495-198223060-00001 · PMID 7049657
23. Journal / agency Burchall JJ. Mechanism of action of trimethoprim-sulfamethoxazole. II. The Journal of Infectious Diseases. November 1973. doi:10.1093/infdis/128.Supplement_3.S437 · PMID 4585969
24. Journal / agency Brumfitt W, Hamilton-Miller JM. Reassessment of the rationale for the combinations of sulphonamides with diaminopyrimidines. Journal of Chemotherapy. December 1993. doi:10.1080/1120009X.1993.11741097 · PMID 8195839

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