Transcript Absorption, Metabolism& Excretion

SULFONAMIDES
Sulfonamides introduced in 1930s.
They are bacteriostatic.
Their usefulness is limited by:
Bacterial resistance
Formation of crystaluria
Development of effective antibiotics
A sulfonamide alone is not the drug of first choice for any
bacterial pathogen.
They act by interfering with bacterial synthesis of folic acid.
Sulfamethoxazole- Trimethoprim
(SMX)
(TMP)
Co-trimoxazole ( Bactrim, Septra )
Introduced in mid 1970s
Alone, each agent is bacteriostatic
Together they are bactericidals
The ratio of TMP to SMX in vivo is 1:20
Currently, sulfonamides are used most frequently
in this combination
TMP-SMX act on 2 sequential steps of the
enzymatic pathway for the synthesis of folic acid
by the bacteria.
MECHANISM OF ACTION
P-Aminobenzoic Acid
Dihydropteroate
synthetase
Dihydrofolate
Dihydrofolate
reductase
Tetrahydrofolate
Sulfonamides
Trimethoprim
Nucleic acid synthesis
Absorption, Metabolism&
Excretion
Sulfonamides
Mainly given orally
Rapidly absorbed from stomach and small
intestine.
Widely distributed to tissues and body fluids (
including CNS, CSF ), placenta and fetus.
Absorbed sulfonamides bind to serum protein
( approx. 70% ).
Metabolized in the liver by the process of
acetylation.
Eliminated in the urine, partly as such and
partly as acetylated derivative and in the
feces.
Trimehoprim ( TMP )
Usually given orally, alone or in combination with SMX
Well absorbed from the gut
Widely distributed in body fluids & tissues ( including
CSF )
More lipid soluble than SMX
Protein bound ( approx.40 % )
60% of TMP or its metabolite is excreted in the urine
TMP concentrates in the prostatic fluid.
CLINICAL USES
A.TOPICAL
1. Opthalmology- ocular infections
Sulfacetamide 10- 30%
2. Ulcerative colitis
Sulfasalazine ( sulfapyridine+ 5amino salicylate )-( orally, not absorbed )
3. Infected burns
Mafenide acetate ( sulfamylon cream )
Silver sulfadiazine
Effective against p.aeruginosa
Less effective against staphyllococci
CLINICAL USES ( CONT. )
B. ORAL
1. Pneumocystis carinii pneumonia **
2. Nocardiosis**
3. Toxoplasmosis**
4. UTIs – limited cases
5. RTIs ( H. influenza; S. pneumonia )
6. Acute otitis media in children- L. cases
7. Prostatitis
8. Shigellosis
9. Falciparum malaria
Fansidar ( sulfadoxine+ pyrimehamine )
ADVERSE EFFECTS
1.Gastrointestinal- Nausea, vomiting
2. Allergy
Skin rash, urticaria,erythema multiform
3. Hematologic
Acute hemolytic anemia
a) hypersensitvity b) G6PD deficiency
Megaloblastic anemia, leukopenia or
thrombocytopenia
4. HIV patients
Drug- induced fever, rashes & diarrhea
5. Drug interactions
Displace bilirubin- if severe – kernicterus
Potentiate warfarin, oral hypoglycemics, methotrexate
CONTRAINDICATIONS
1. Pregnancy
2. Nursing mother
3. Infants under 6 weeks
4. Renal or hepatic failure
5. Blood disorders