useful for MBBS Students

1. SULFONAMIDES
AND
COTRIMAXIZOLE
DR V R PATKAR

2. SULFONAMIDES
 THEY WERE THE FIRST ANTIMIROBIALS EFFECTIVE
AGAINST PYOGENIC MENINGITIS.
 CHEMISTRY- ALL SULFONAMIDES ARE CONSIDERED TO BE
DERIVATIVES OF SULFINILAMIDE (PARA – AMINO BENZENE
SULFONAMIDE)

3. CLASSIFICATION
 SHORT ACTING(4-8 HRS) – SULFADIAZINE
 INTERMIDIATE ACTING(8-12 HRS)- SULFAMETHAXOLE
 LONG ACTING(7 DAYS)- SULFADOXINE,
SULFAMETHOPYRAZINE
 SPECIAL PURPOSE SULFONAMIDES- SULFACEMIDE SOD. ,
MAFENIDE, SILVER SULFADIAZINE, SULFASALAZINE.

4. ANTIBACTERIAL SPECTRUM
 PRIMARILY BACTERIOSTATIC AGAINST GM POSITIVE AND
GM NEGATIVE BACTERIA.
 SENSITIVITY PATTERNS CHANGE FROM TIME TO TIME AND
PLACE TO PLACE.
 STREPTO. PYOGENS, HAEMOPHILUS INFLUENZE, H.
DUCREYI, VIBRO CHOLERA ARE SENSITIVE.
 ANAEROBIC BACTERIA ARE NOT SENSITIVE.

5. MECHANISM OF ACTION
 PARA AMINO BENZOIC ACID IS A PRECURSOR OF FOLIC
ACID WHICH IS ESSENTIAL FOR GROWTH AND
MULTIPLICATION OF BACTERIA.
 SULFANAMIDES BEING STRUCTRALLY SIMILAR TO PABA ,
COMPETITIVELY INHIBITS, FOLATE SYNTHASE ENZYME
AND PREVENT FORMATION OF FOLIC ACID. THEREBY
PRODUCING BACTERIOSTATIC EFFFECT.
 MAMMALIAN CELLS ARE UNAFFECTED BY SULFONAMIDES.

6. RESISTANCE TO
SULFONAMIDES
MAY BE DUE TO –
 DECREASED AFFINITY OF FOLATE SYNTHETASE FOR THE
DRUG.
 EFFLUX OF DRUG BY BACTERA.
 DEVELOPMENT OF ALTERNATE METABOLIC PATHWAY FOR
FOLATE SYNTHESIS.

7. PHARMACOKINETICS
ALL SYSTEMIC ACTING SULFONAMIDES ARE WELL ABSORBED
FROM THE GUT. THEY ARE BOUND TO PLASMA PROTIENS,
PARTICULARLY ALBUMIN. SULFONAMIDES ARE DISTRIBUTED
IN ALMOST ALL TISSUES OF BODY INCLUDING CSF. THEY
CROSS PLACENTAL BARRIER AND REACH FETAL CIRCULATION.
THEY ARE METABOLISED IN LIVER MAINLY BY
ACETYLATON.EXCRETED PARTLY UNCHANGED AND PARTLY AS
METABOLIC PRODUCTS.

8. ADVERSE EFFECTS
 THE ACETYATED PRODUCTS OF SULFONAMIDES ARE
POORLY SOLUBLE IN ACIDIC URINE AND MAY CAUSE
CRYSTALLURIA, HAEMATURIA OR EVEN OBSTRUCTION TO
URINARY TRACT.
 HYPERSENSITIVITY REACTIONS INCLUDE SKIN RASHES,
ITICHING, DRUG FEVER AMD EXOFFOLIATIVE DERMATITIS.
 ACUTE HEMOLYTIC ANAEMIA IN G6PD DEFICIENT PATIENT.
 RARELY CAUSE HEPATITS AND SUPPRESSION OF BONE
MARROW.
 MAY CAUSE KERNICTERUS IN NEW BORNS.

9. THERAPEUTIC USES
 SYSTEMIC USE OF SULFONAMIDES ALONE IS RARE NOW.
THOUGH THEY CAN BE USED FOR SUPPRESSIVE
THERAPYOF CHRONIC URINARY TRACT INFECTION, FOR
STREPTOCOCCAL INFECTIONS AND GUM INFECTIONS
SUCH USES ARE OUTMODED.
 OCULAR SULFACETAMIDE SOD. IS A CHEAP ALTERNATIVE
IN TRACHOMA INCLUSION CONJUNVTIVITIS.
 TOPICAL SILVER SULFADIAZINE OR MEFANIDE ARE USED
FOR PREVETING INFECTIONS ON BURN SURFACES.

10. COTRIMAXIZOLE
 THE FIXED DOSE COMBINATION OF TRIMETHOPRIM AND
SULFAMETHOXAZOLE IS CALLED COTRIMAXIZOLE.
 TRIMETHOPRIM IS DIAMINOPYRIMIDINE RELATED TO THE
ANTIMALARIAL DRUG PYRIMETHAMINE WHICH
SEECTIVELY INHIBITS BACTRIAL DHFRase.
 TRIMETOPRIM IS 50000 TIME MORE ACTIVE AGAINST
BACTERIAL DHFRase THAN AGAINST MAMMALIAN
ENZYME. THUS HUMAN FOLATE IS NOT INTERFERED AT
ANTIBACTERIAL CONCENTRATION.

11. MECHANISM OF ACTION
 AS IN SULFONAMIDES , SULPHAMETHOXOLE INHIBIT
FOLATE SYTHETASE, AND AND DHYDROFOLIC ACID IS NOT
FORMED.
 ALSO, TRRIMETHOPRIM, INHIBITS DIHYDROFOLATE
REDUCTASE AND INHIBIT THE CONVERSION OF DHFA TO
TETRAHYDRO FOLIC ACID.

12. SPECTRUM
 INTIALLY BOTH OF THEM ARE BACTERIOSTATIC , BUT THE
COMBBINATION BECOMES CIDAL TO MANY ORGANISMS.
 ADDITIONAL ORGANISMS COVERED ARE-SALMONELLA
TYPHII, SERRATIA, KLEBSIELLA, ENTEROBACTER,
YERSINIA ENTEROCOLICA, PNEUMOCYSTITS JIROVECI AND
MANY SULFONAMIDE RESISTANT STRAINS ARE
SUSCEPTIBLE.

13. PHARMACOKINETICS
 COTRIMAXIZOLE IS WELL ABSORBED AFTER ORAL
ADMINISTRATION AND ALSO AVAILABLE FOR PARENTRAL
USE; WIDELY DISTRIBUTED TO VARIOUS TISSUES
INCLUDING CSF AND SPUTUM; METABOLISED IN LIVER AN
EXCRETED MAINLY IS URINE, HENCE DOSE REDUCED IN
RENAL PATIENTS WITH RENAL INSUFFICIENCY.

14. THERAPEUTIC USES
1. URINARY TRACT INFECTON- COTRIAXIZOLE IS
EFFECTIVE IN TREATMENT OF ACUTE UNCOMLICATED
OWER URINARY TRACT INFECTIION DUE TO GRAM
NEGATIVE ORGAINISMS SUCHH AS E. COLI, PROTEUS
AND ENTEROBACTOR SPP. THE USUAL DOSE IS 800 MG
SULPHAMETHAXOLE PLUS 160 MG OF TRIMETHOPRIM
BD FOR 3 DAYS.
2. BACTERIAL RESPIRATORY TRACT INFECTION-
COTRIMAXIZOLE IS EFFECTIVE FOR ACUTE AN CHRONIC
BRONCHITIS DUE TO S. PNEUMONIAE AND H.
INFLUENZE. IT I ALSO USEFUL FOR ACUTE MAXILLARY
SINUSITIS AND OTITIS MEDIA.

15. 3. BACTERIAL DIARRHOES- COTRIMAXIZOLE MAY BE USED FOR GI INFECTIONS
DUE TO SHHIGELLA , E.COLI, AND SALMONELLA SPP.
4. TYPHOID-COTRIMAXIZOLE MAY BE EFFECTIVE .FLOROQUINOLONES PLUS
3RD GENERATON CEPHALOSPORINS.
5. PNEUMOCYSTITS JEROVICI- HIGH DOSES OF COTRIMAXIZOLE ARE USED
FOR TREATMENT OF INFECTION DUE TO JEROVICI IN
IMMUNOCOMPROMISED PATIENTS.
6. NOCARDIOSIS
7. CHANCHROID- DRUG OF CHOICE IS AZITHROMYCIN BUT COTRIMAXIZOLE IS
ASLO EFFECTIVE.

16. ADVERSE EFFECTS
 COTRIMXIZOLE IS WELL ABSORBED IN PATIENTS. MOST
OF THEM ARE SAME AS THAT OF SULFONAMIDES.
 SKIN RASHES, GI DISTURBANCES, EXOFOLIATIIVE
DERMATITIS,ERYTHEMA MULTIFORUM.
 VOMITING, GLOSSITIS, AND STOMATITS. MEGALOBLASTIC
ANAEMIA DUE TO FOLATE DEFICIENCY MAY OCCUR
RARELY SPECIALLY IN ALCHOLICS, AND MALNOURISHED
PATIENTS.
 LEUKOPENIA, NEUTROPENIA ,AND THROMBOCYTOPENIA
OCCUR RARELY.

17. THANK YOU