Sulfonamide & cotri

Sulfonamide & cotri

1. SULFONAMIDE s & cotrimoxazole Dr. R. Mirunalini Asst. Professor Dept. of Pharmacology

2. SULFONAMIDES - First antibacterial agents- prontosil - Effective against pyogenic bacterial infections . - Rapid emergence of bacterial resistance and the availability of many safer and more effective antibiotics ,their current utility is limited except in combination with trimethoprim[as cotrimoxazole ] or pyrimethamine [for malaria].

3. Sulfonamides Trimethoprim/ Iclaprim Pyrimethamine

4. SULFONAMIDES 1.SHORT ACTING(4-8 hrs) Sulfadiazine,sulfisoxazole 2. INTERMEDIATE ACTING(8-12 hrs): Sulfamethoxazole , sulfamoxole 3.LONG ACTING(7 days): Sulfadoxine,sulfamethopyrazine 4.SPECIAL PURPOSE SULFONAMIDES: S ulfacetamide , Silver sulfadiazine,, Mafenide , Sulfasalazine

5. ANTIBACTERIAL SPECTRUM SENSITIVE ORGANISMS ARE: Strepto pyogenes , Haemophilus influenzae , Vibrio cholerae . Staph.aureus , gonococci, meningococci , Pneumococci , Escherichia coli, and Shigella but majority resistant. Anaerobic bacteria are not susceptable .

6. MECHANISM OF ACTION Sulfonamide structural analogues of PABA, Inhibit bacterial folate synthase to form folic acid. Sulfonamide competitively inhibit union of PABA with PTERIDINE residue to form dihydropteroic acid which conjugate with glutamic acid to produce DIHYDROFOLIC ACID.

7. MECHANISM OF ACTION

8. PHARMACOKINETIC ASPECTS: Most sulfonamides are readily absorbed in the gastrointestinal tract and reach maximum concentration in the plasma in 4-6 hours. risk of sensitization and allergic reactions. The drug pass into inflammatory exudate and cross the placental and blood brain barriers. They are metabolized mainly in liver

9. CONT… SULFADIAZINE: Rapidly absorbed orally and rapidly excreted in urine. It is 50% plasma protein bound and 20-40% acetylated . Good penetrability in brain and CSF DOSE:0.5g QID to 2g TDS;SULFADIAZINE 0.5g tab. SULFAMETHOXAZOLE: Slower oral absorption and urinary excretion. t1/2 is 10 hrs. used in combination with trimethoprim( septran ) because of similar half life period. DOSE:1g BD for 2 days.then 0.5g BD.,GANTANOL 0.5g tab. SULFADOXINE,SULFAMETHOPYRAZINE: high plasma protein binding and slow renal excretion. used in combination with pyrimethamine ( laridox ) for malaria, Pneumocystis jiroveci pneumonia in AIDS and in toxoplasmosis .

10. CONT… SULFACETAMIDE SOD: highly soluble compound. mild irritation to eye in concentration upto 30%. used for occular infection by susceptable bacteria and chlamydia,Including opthalmia neonatorum MAFENIDE: It is employed for burn dressing to prevent infection, but not to treat already infected case. it cause burning sensation and severe pain. when applied in raw surface. cause acidosis ,hyperventilation, allergic reactions. SILVER SULFADIAZINE: used as 1% cream active against many bacteria and fungi.e.g Pseudomonas. to prevent infection of burns and chronic ulcers .

11. CLINICAL USES OF SULFONAMIDES: Combined with trimethoprim (co- trimoxazole ) for Pneumocystis carinii . Combined with pyrimethamine for drug resistant malaria and for toxoplasmosis . In inflammatory bowel disease and as an anti inflammatory drug- sulfasalazine ( sulfapyridine aminosalicylate combination) is used. For infected burns silver sulfadiazine given topically) For some sexually transmitted infection( trachoma,chlamydia,chancroid )

12. CONT… For respiratory infections ( e.g.infection with Nocardia ) For acute urinary tract infection . Ocular infection ; sulfacetamide sod.(10-30%) a cheap alternative in trachoma ,inclusion conjunctivitis though additional systemic azithromycin or tetracycline is required for eradication of disease. For streptococcal pharyngitis and gum infection .

13. ADVERSE EFFECTS Nausea ,vomiting, epigastric pain. Crystalluria -dose related. Hepatitis-unrelated to dose. Hypersensitivity-Stevens johnson syndrome and exfoliative dermatitis. Neutropenia and other blood dyscrasias are rare. Kernicterus -new born premature.

14. COTRIMOXAZOLE. The fixed dose combination of trimethoprim and sulfamethoxazole is called COTRIMOXAZOLE. same T1/2(~10hr) Concentation ratio of sulfmethoxazole 20: trimethoprim 1 Trimethoprim is metobolised in liver and excreted in urine.

15. SEQUENTIAL BLOCK IN BACTERIAL FOLATE METABOLISM: PABA Folate synthase SULFONAMIDE DHFA dihyrofolate reductase . TRIMETHOPRIM THFA

16. Trimethoprim adequately crosses blood brain barrier and placenta , while sulfamethoxazole has poor entry. Trimethoprim is more rapidly absorbed than sulfamethoxazole Maximum synergism is seen when both component is sensitive but even when it is moderately resistant to one component ,the action of other may be enhanced . Single & double strength(80/400; 160/800)

17. SPECTRUM OF ACTION. ORGANISM WHICH ARE SENSITIVE: Salmonella typhi , klebsiella , Staph aureus , Strep pyogenes shigella Pneumocytis jiroveci H.influenza E.coli

18. Uses: 1.Urinary tract infection/ prostatitis 2.Respiratory tract infection. 3.In case of typhoid 4.bacterial diarrhoeas and dysentery 5.Used in case of severe pneumonia in neutropenic and AIDS patients caused by Pneumocystis jiroveci . 6.chancroid. 7.It s an alternative to penicillin. 8.Used in septicaemias . 9.Nocardiosis- DOC

19. ADVERSE EFFECTS Nausea,vomiting Headache Stomatitis Rashes Blood dyscrasias Folate deficiency neonatal haemolysis .