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sulfonamides, Cotrimoxazole , trimethoprim, Selective toxicity to bacteria…
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Cotrimoxazole
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This is a fixed dose combination of sulfamethoxazole and trimethoprim in a ratio of 5:1.
both the drugs have similar half life and combination is bactericidal to most pathogens
Due to different bioavailability more for sulfamethoxazole, plasma concentration of these two drugs attained is 20:1.
Bactericidal activity is due to sequential blockade at two steps in the DNA synthesis.
Sulfamethoxazole inhibits the folate synthase and trimethoprim inhibits DHFRase.
trimethoprim
It is a bacteriostatic antimetabolite that inhibits dihydrofolate reductase.
It attains high concentrations in the prostate and vaginal fluids.
For most of the indications, it is combined with sulphonamides,
however it can be used in prostatitis and UTI.
It can cause megaloblastic anemia (can be ameliorated by folinic acid), leucopenia and pancytopenia.
Also results in hyperkalemia due to amiloride like action i.e inhibition of epithelial Na+ channels in CD.
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For topical use:
For topical use: silver sulfadiazine, sulfacetamide and mafenide
Other sulfonamides:
Sulfacetamide is used for ocular infections whereas mafenide and silver sulfadiazine are used in burns patient as topical agents.
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Toxicity:
Toxicity: skin rash due to hypersensitivity is the most common adverse effect.
These can also cause granulocytopenia, thrombocytopenia and aplastic anemia more common in HIV infected patients.
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Kernicterus
These can displace bilirubin from plasma protein binding sites and may result in kernicterus in the newborn if given in third trimester.
Uses of Cotrimoxazole
Cotrimoxazole is effective in UTI, respiratory tract infections, MRSA, middle ear and sinus infections caused by hemophilus and Moraxella.
It is the DOC for pneumocystosis and nocardiosis.
Adverse effects are similar to sulphonamides and trimethoprim.