SULFONAMIDE S&COTRIMOXAZOLE

Dr. R. MirunaliniAsst. Professor

Dept. of Pharmacology

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].

Sulfonamides Trimethoprim/ Iclaprim Pyrimethamine

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: Sulfacetamide,Silver sulfadiazine,,Mafenide,Sulfasalazine

ANTIBACTERIAL SPECTRUMSENSITIVE 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.

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.

MECHANISM OF ACTION

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

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.

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.

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)

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 .

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.

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.

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

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

Uses:1.Urinary tract infection/ prostatitis2.Respiratory tract infection.3.In case of typhoid 4.bacterial diarrhoeas and dysentery5.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

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

Summary Sulfanomides Trimethoprim Pyrimethamine