Trimethoprim, Co-trimoxazole Flashcards
Trimethoprim and co-trimoxazole are Diaminopyrimidines , what are these drugs commonly indicated for?
1) Trimethoprim is a first-choice antibiotic for the treatment of: Acute lower UTI, Prophylaxis of recurrent UTI. (Alternatives include nitrofurantoin, amoxicillin and cefalexin)
2) acne, respiratory tract infections and prostatitis.
3) Co-trimoxazole is used for treatment and prevention of pneumocystis pneumonia in immunosuppression, e.g. HIV infection.
what is the spectrum of activity for Diaminopyrimidines?
1) G+ve & G-ve
2) Trimethoprim inhibits bacterial folate synthesis, slowing bacterial growth (bacteriostasis)
2) Its clinical utility is reduced by widespread bacterial resistance
what is co-trimoxazole a combination of and why are they formulated in a single agent?
Combination with a sulfonamide (e.g. sulfamethoxazole, as co-trimoxazole) extends the spectrum to include activity against the fungus Pneumocystis jirovecii
list some of the important side effects caused by Diaminopyrimidines
1) GI upset e.g. nausea, vomiting, fungal overgrowth
2) Blood disorders - especially in elderly (megaloblastic anaemia, leucopenia and thrombocytopenia)
3) hyperkalaemia
4) Steven-Johnson syndrome
what side effects are sulfonamides known to cause?
Severe hypersensitivity reactions, including anaphylaxis, drug fever and erythema multiforme, occur rarely with trimethoprim, but more commonly with sulfonamides, which limits their use
who should trimethoprim be used in caution with?
1) Avoid in First trimester of pregnancy as folate antagonist- risk of neural tube defects, cleft lip/palate
2) contraindicated in Blood dyscrasias
3) Excreted unchanged into urine, but less suitable in renal impairment, requires dose reduction
4) caution in neonates, elderly (due to folate deficiency)
5) Asthma, G6PD deficiency
outline some of the import side effects with regards to trimethoprim
1) hyperkalaemia if used with potassium-elevating drugs (e.g. aldosterone antagonists, ACEI, ARBs)
2) Use with other folate antagoncists (e.g. methotrexate) and drugs that increase folate metabolism (e.g. phenytoin) increases the risk of haematological effects.
3) enhance effects of warfarin by killing normal gut flora
what is the dose of trimethoprim for acute and prophylaxis of UTI?
1) acute UTI the usual dosage is 200 mg 12-hrly,
2) As prophylaxis for recurrent UTI, lower dose (100 mg) less often (once at night) for a prolonged period
what are the monitoring requirements for Diaminopyrimidines?
long-term treatment, full blood count monitoring may be useful for early detection and treatment of haematological disorders (e.g. by replacing folate and/or stopping the antibiotic)
outline the restrictions for use of Co-trimoxazole (Sulfamethoxazole and trimethoprim)
1) Co-trimoxazole is the drug of choice in the prophylaxis and treatment of Pneumocystis jirovecii pneumonia and toxoplasmosis.
2) only be considered in acute exacerbations of chronic bronchitis and UTI when there evidence of sensitivity
3) only be used in acute otitis media in children when there is good reason to prefer it.
what are the rare and serious side effects associated with the use of Co-trimoxazole?
Discontinue immediately if evidence of blood disorders or rash (including Stevens-Johnson syndrome or toxic epidermal necrolysis) develop.
