- MOA: Interferes with cellular metabolism.
- Drugs: Sulfonamides, trimethoprim, pyrimethamine, proguanil & methotrexate.
Important drug details:
- Bacteriostatic agents.
- Acts by inhibiting folate synthase competitively.
- Ineffective in presence of pus –
- Due to excessive PABA levels.
Metabolism: Hepatic by acetylation.
- For systemic use as oral agents:
- Short acting: Sulfisoxazole, sulfamethiazole, sulfacytine.
- Intermediate acting: Sulfamethoxazole, sulfadiazine.
- Long acting: Sulfadoxine
- For use in GIT:
- Sulfasalazine, olsalazine
- For topical use:
- Sulfacetamide, silver sulfadiazine, mafenide
- For ocular infections – Sulfacetamide.
- In burn patients as topical agents – Mafenide & silver sulfadiazine
- In nocardiosis – Sulfadiazine.
- For urinary tract infections – Sulfisoxazole.
- For ulcerative colitis treatment – Sulfasalazine & olsalazine.
- For malaria, toxoplasmosis treatment & Pneumocystis jiroveci pneumonia prophylaxis in AIDS patients – Sulfadoxine & pyrimethamine.
- Skin rash (most common) – Due to hypersensitivity.
- Cause granulocytopenia, thrombocytopenia & aplastic anemia (more common in HIV infected patients).
- Cause acute hemolysis in patients with G-6 PD deficiency.
- Crystalluria & Hematuria:
- Solubility of sulfonamides decreases in acidic urine resulting in drug precipitation.
- Minimum risk with soluble drugs like sulfisoxazole.
- Selective bacterial toxicity:
- Due to lack of ability of mammalian cells to synthesize folic acid & utilize preformed folic acid in diet.
- Kernicterus in new born (if given in third trimester of pregnancy):
- Due to bilirubin displacement from plasma protein binding sites.
- Bacteriostatic antimetabolite inhibiting dihydrofolate reductase.
- High concentrations in prostate & vaginal fluids.
- Mostly combined with sulfonamides.
- Given alone in prostatitis & UTI.
- Cause megaloblastic anemia (can be ameliorated by folinic acid), leucopenia & pancytopenia.
- Result in hyperkalemia – Due to amiloride like action & inhibition of epithelial Na+ channels in collecting ducts.
- Fixed dose combination of sulfamethoxazole & trimethoprim in ratio of 5:1.
- Plasma concentration of two drugs attained – 20:1.
- Due to sequential blockade at two steps in DNA synthesis
- Sulfamethoxazole inhibits folate synthase; Trimethoprim inhibits DHFRase.
- DOC for pneumocystosis & nocardiosis.
- Effective in UTI, respiratory tract infections, MRSA, middle ear & sinus infections.
- Caused by Hemophilus & Moraxella.
- Short-acting sulfonamides include Sulfisoxazole, sulfamethizole, sulfacytine.
- Sulfadoxine is a long-acting sulfonamides.
- Skin rash is the most common adverse effect of sulfonamide due to hypersensitivity.
- Solubility of sulfonamides decreases in acidic urine resulting in drug precipitation causing Crystalluria & Hematuria.
- Crystalluria risk is minimum with soluble drugs like sulfisoxazole.
- Sulfonamides if given in third trimester of pregnancy result in kernicterus in new-born, due to bilirubin displacement from plasma protein binding sites.
- Trimethoprim is a bacteriostatic antimetabolite inhibiting dihydrofolate reductase
- Trimethoprim is highest concentration in prostate & vaginal fluids.
- Trimethoprim due to amiloride like action results in megaloblastic anemia (ameliorated by folinic acid), hyperkalemia (inhibition of epithelial Na+ channels in collecting ducts).
- Cotrimoxazole is bactericidal with fixed dose combination of sulfamethoxazole & trimethoprim in ratio of 5:1.
- Sulfamethoxazole inhibits folate synthase.
- Trimethoprim inhibits DHFRase.
- Cotrimoxazole is DOC for pneumocystosis & nocardiosis.
Don’t Forget to Solve all the previous Year Question asked on ANTI-METABOLITES