SULPHONAMIDES O Classification: 1. Oral absorbable (Based on half life) — 2. Short acting (Half fe 6-9 hours) Sulfeorazle Sulfmethizole, Sucytine b. Intermediate acting (al Iie 10-17 hours) ~ Sulfadatine,Sufamethoxarole Long aetng (al ie 7-9 days) — Solfadoxne 2. Oral nonabsorbable ~ Suifasaarine, saline 3. Topical — 2. Nasulacetamide (eye drop) 1b. Mefenide acetate, 1% ser sultacazine bur ointment) 4. Combination with other drugs ~ 41 Sulfamethoraole + Timethoorim (Cotrimoxazole) 2. Salfadoxin+ Pyrimethamine (Fansdar) 2. Sfadasine + Pyrmethamine O Pharmacokinetics C1 Resistance C1 Antimicrobial spectrum & clinical uses: + Bacteriostatic (Cotrimoxazole is bactericidal) + Now a days sulfonamide use (alone) are no longer recommended except in few cases because of ~ 4, Increase bacterial resistance, 2. Allergic property. 3. Better drug available + Sulfonamide inhibit both Gram positive, Gram negative bacteria, Nocardia, Chlamydia trachomatis, some protozoa, some enteric bacteria such as E. coli, Shigella, Salmonella, Klebsiella, Enterobacter. + Bacteriostatic. * Antifolate. + Now used in combination. + Most allergenic. chemistry: = Synthetic + Structural analogue of PABA. Hae coos PABA, \, — so,NH-R Sulphonamide Ha — CiMechanism of action: PABA LDihydropteroate synthase «"") suifonamides: Dihydrofolic acid Diysototeacid reductase {°° Trimethoprim Tetrahydrofolic acid v Purine v DNA Steps of folic acid synthesis in microorganism A. Asa single agent therapy — 1. Sulfisoxazole, Sulfamethoxazole — a. Acute uncomplicated UT 2. Sulfasalazine (salicylazo sulfapyridine) — 2. Widely used in inflammatory bowel disease (160), ulcerative b. Enteritis 3. Sodium sulfacetamide (eye drop) — a, Bacterial conjunctivitis b. Adjuvant therapy for trachoma, 4. Mefenide acetate (Sulfamylon cream) - a. To prevent bacterial colonization and infection of burn, wound, 5. 1% silver sulfadiazine — a Butn (Preferred drug and less toxic than Mefenide acetate)B. Asa combination therapy — 1. Sulphamethoxazole (400 mg) + Trimethoprim (80 mg) > Cotrimoxazole (480 mg) — Most widely used 2, Sulfadoxine (500 mg) + Pyrimethamine (25 mg) > Fansidar (525 mg) ~ , Malaria~2™ line therapy (3 tab together) 3. Sulfadiazine + Pyrimethamine — a. Acute toxoplasmosis (drug of choice) b. Leishmaniasis 2. Nephrotoxicity ~ Conjugated acetylated form of sulphonamide Insoluble in acidie and neutral urine v Precipitation of drugs v Crystaluria v Haematuria v Oliguria v ‘Anuria Treatment — = Adequate Fu intake = NaHCO,~To alkaline rine C2 Drug interaction: + Bilirubin f serum concentration by displacing from binding ste + Oral hypoglycaemic agents, Coumarine derivatives Serum concentration by displacing from binding site ‘© Warfarin - serum clearance. So T prothrombin time. + Phenytoin- J metabolism, 7 serum concentration. * Carbonic anhydrase inhibitor, Thiazides, Frusemide, Bumetanide, Diazoxide, Sulfonylurea ~ Cross allergenic due to structural similarity Q Contraindication: 1. Newborn, 2. Pregnant women (3 trimester) O Adverse effects: Partly due to allergy and partly due to toxicity of active drugs and its metabolites 1. Allergic reaction — * Most common + Allsulfonamides are cross allergenic * Possibly cross allergenic with sulfonylurea hypoglycaemics * Skin rashes, Urticaria, Fever, Photosensitivity, Steven Johnson syndrome, Exfoliative dermatitis, Erythema multiforme, Stomatitis, Conjunctivitis, Arthritis, 3. Haematological disturbance — * Granulocytopenia, Thrombocytopenia, Leukaemoid reaction, Megaloblastic anaemia ‘+ Haemolytic anaemia ~in patient with G6PD deficiency 4, Neurological disturbances — ‘+ Headache, Confusion, Neuropathy, Insomnia, Seizure, Kernicterus {toxic encephalopathy) 5. GIT & Hepatotoxicity — Anorexia, Nausea, Vomit 6. Polyarteritis 7. Drug interaction i, Diarrhea, Hepatitis nodosa and Psychosis ~ rare. CO-TRIMOXAZOLE * Bactericidal * Combination of sulphamethoxazole and trimethoprim (Chemotherapeutic potentiation) composition: Sulphamethoxazole ~5 parts ~ 400 mg + Trimethoprim ~ 1 part —80 mg -> 1 tab (480 mg)Q Clinical use: 1 Pneumonia caused by P. carinii (P, jroveci) in AIDS patient effective Shigelloss - effective ‘systemic Salmonella infection (typhoid and paratyphoid) where chloramphenicol or ampicilin is resistant Complicated UTI ~ effective Prostatitis ~ effective Some nontuberculous Mycobacterial infection Upper respiratory tract infection and community acquired pneumonia caused by Pneumococcas, Haemophyllus, M. catarrhalis. Klebsiella pneumoniae Antimetabolites Q Def: A substance inhibiting cell growth by yew np competing with or substituting for, a natural substrate in an enzymatic process. Sulphonamide Trimethoprim Cotrimoxazole Antiviral drugs Anticancer drugs