Trimethoprin

Trimethoprin is an antibiotic belonging to sulfonamides class.

Trimethoprin is sulfonamides antibiotic used in the treatment of number of infections, including those of the urinary tract, respiratory tract, and gastrointestinal tract

Trimethoprin is Rapidly and well absorbed from the gastrointestinal tract. Bioavailability: .56% It gets Penetrates into the lung tissue and respiratory mucus. Volume of distribution: Approx 67 L and get Metabolised via acetylation, decarboxylation, and sulfoxidation. It get excreted Via urine (as unchanged drug and metabolites). Elimination half-life: 1-4 hours

The Tmax of Trimethoprin was found within Approx 2 hour.

Trimethoprin shows common side effects like itching or a mild rash.feeling or being sick (nausea or vomiting),diarrhoea and headaches.

Trimethoprin is available in the form of tablets and oral solutions.

Trimethoprin is available in India, Germany, Canada, Italy.

Trimethoprim is a reversible inhibitor of dihydrofolate reductase, one of the principal enzymes catalyzing the formation of tetrahydrofolic acid (THF) from dihydrofolic acid (DHF).Tetrahydrofolic acid is necessary for the biosynthesis of bacterial nucleic acids and proteins and ultimately for continued bacterial survival – inhibiting its synthesis, then, results in bactericidal activity. Trimethoprim binds with a much stronger affinity to bacterial dihydrofolate reductase as compared to its mammalian counterpart, allowing trimethoprim to selectively interfere with bacterial biosynthetic processes.

Trimethoprin is available in the form of tablets and solutions.

Trimethoprin is a antibacterial agent used in the relief of Acute otitis media, Urinary tract infections.

Trimethoprim is an antifolate antibacterial agent that inhibits bacterial dihydrofolate reductase (DHFR), a critical enzyme that catalyzes the formation of tetrahydrofolic acid (THF) in doing so, it prevents the synthesis of bacterial DNA and ultimately continued bacterial survival.

Trimethoprin is approved for use in the following clinical indications

• Acute otitis media
• Susceptible infections, Urinary tract infections
• Prophylaxis of recurrent urinary tract infections

Oral

As a antibacterial

Adult: Acute infection: 100 mg or 200 mg bid. Alternatively, 200 mg or 300 mg once daily as a single dose. Treatment duration is based on the nature and severity of the infection. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).

Child: Acute infection: 6 weeks to 5 months 25 mg bid; 6 months to 5 years 50 mg bid; 6-12 years 100 mg bid; >12 years Same as adult dose. Treatment and dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).

Elderly: Dose reduction may be required.

Trimethoprin is available in various strengths as

• Tablets 100mg, 200mg
• Solution 50mg/5ml

Trimethoprin is available in the form of , syrup, tablet.

Hypersensitivity. Megaloblastic anaemia due to folate deficiency and other blood dyscrasias.

Patient at risk of developing hyperkalaemia (e.g. poorly controlled diabetes mellitus, hypoaldosteronism; concomitant use K-sparing diuretics, K supplements, K-containing salt substitutes, renin-angiotensin system inhibitors, heparin); acute porphyria; with potential folate deficiency (e.g. malnourished, chronic anticonvulsant therapy).

Not indicated for prophylactic or prolonged administration at any age (when used in otitis media).

Renal and hepatic impairment. Children and elderly. Pregnancy and lactation.

• Common Adverse effects

Depression of haemopoiesis, hyperkalaemia; Clostridium difficile-associated diarrhoea.

• Less Common Adverse effects

Anaphylactic reactions, fixed drug eruption.

• Rare Adverse effects

Hypersensitivity reaction.

Blood and lymphatic system disorders: Thrombocytopenia, leucopenia, neutropenia, megaloblastic anaemia, methemoglobinaemia.

Gastrointestinal disorders: Diarrhoea, nausea, vomiting.

Infections and infestations: Monilial overgrowth.

Metabolism and nutrition disorders: Hyponatraemia.

Nervous system disorders: Headache.

Skin and subcutaneous tissue disorders: Rash, urticaria, pruritus, exfoliative dermatitis.

Increased risk of hyperkalaemia with K-sparing diuretics, K supplements, K-containing salt substitutes, renin angiotensin system inhibitors (e.g. ACE inhibitors, renin-angiotensin receptor blockers), other drugs associated with increase in serum K (e.g. heparin). May induce folate deficiency with folate antagonists or anticonvulsants. Increased serum concentration with dapsone. Increased risk of haematologic toxicity with cytotoxic drugs (e.g. azathioprine, mercaptopurine, methotrexate). Increased incidence of thrombocytopenia with purpura with diuretics (particularly thiazides). Increased risk of nephrotoxicity with ciclosporin. Increased antifolate effect with pyrimethamine. May enhance hypoglycaemic effects of repaglinide. May potentiate anticoagulant effect of warfarin and other coumarins. May increase serum concentration of lamivudine, phenytoin, procainamide, digoxin, dapsone, zidovudine. May decrease serum concentration with rifampicin.

The common side effects of Trimethoprin include the following Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis.

Symptoms: Acute: Nausea, vomiting, headache, dizziness, mental depression, confusion, bone marrow depression. Chronic: Bone marrow depression manifested as thrombocytopenia, leucopenia, megaloblastic anaemia. Management: Symptomatic and supportive treatment. Acute: Perform gastric lavage and forced diuresis. May give IM calcium folinate for depression of haematopoiesis. Enhance elimination through urine acidification. Chronic: May administer leucovorin.

Pharmacodynamic

Trimethoprim exerts its antimicrobial effects by inhibiting an essential step in the synthesis of bacterial nucleic acids and proteins. It has shown activity against several species of gram-negative bacteria, as well as coagulase-negative Staphylococcus species. Resistance to trimethoprim may arise via a variety of mechanisms, including alterations to the bacterial cell wall, overproduction of dihydrofolate reductase, or production of resistant dihydrofolate reductase.Rarely, trimethoprim can precipitate the development of blood disorders (e.g. thrombocytopenia, leukopenia, etc.) which may be preceded by symptoms such as sore throat, fever, pallor, and or purpura – patients should be monitored closely for the development of these symptoms throught the course of therapy.

Pharmacokinetics

• Absorption: Rapidly and almost completely absorbed from the gastrointestinal tract. Time to peak plasma concentration: Approx 1-4 hours.
• Distribution: Widely distributed to various tissue and fluids (e.g. kidneys, liver, lung, bronchial secretions, aqueous humour, saliva, prostatic tissue and fluid, vaginal secretions); present in CSF. Crosses the placenta and enters breast milk. Volume of distribution: Approx 1.3 L/kg. Plasma protein binding: Approx 45%.
• Metabolism: Partially metabolised (10-20%) in the liver via demethylation, oxidation, hydroxylation.
• Excretion: Primarily via urine (50-60%; 80% as unchanged drug); faeces. Elimination half-life: Approx 8-10 hours.

• https://go.drugbank.com/drugs/DB00440
• https://www.uptodate.com/contents/trimethoprim-sulfamethoxazole-an-overview#H461130956
• https://www.mims.com/malaysia/drug/info/trimethoprim?mtype=generic