1. SULFONAMIDES Recognized since 1932. In clinical usage since 1935.
First compounds found to be effective antibacterial agents in safe dose ranges.
Mainstay of therapy before penicillins.

2. SULFONAMIDES
Now largely superceded by antibiotics and trimethoprim-sulfamethoxazole.
They continue to occupy a small place in therapy.

4. Wheel of Bugs Gram-negative Neissseria spp H. influenzae E. Coli
(coliforms)
Bacteroides spp
P. aeruginosa
Anaerobic
Clostridium spp
Considerable resistance has emerged
S. aureus
Streptococcus spp
Enterococcus spp
Gram-positive

5. ANTIBACTERIAL ACTIVITY
Bacteriostatic.
Broad spectrum antibacterials

6. FOLIC ACID BIOSYNTHESIS
DIHYDROPTERIDINE
2 ATP
PYROPHOSPHATE DERIVATIVE
Dihydropteroate
Synthetase
2HN
COOH
2HN
SO2NH2
DIHYDROPTEROIC ACID
Glutamic Acid
DIHYDROFOLIC ACID

7. BLOOD Oral X Topical Parenteral CSF Protein Bound Kidney Metabolites
Free
Kidney
Other-Sweat,
Saliva,
Prostatic fluid,
Stool
Oral
X Topical Parenteral
Body Fluids & Tissues
CSF

8. KERNICTERUS IN THE NEWBORN
Results from displacement of bilirubin from plasma protein binding sites.
Free bilirubin goes into the CNS.
High concentrations in the brain cause kernicterus in the newborn.

9. KERNICTERUS IN THE NEWBORN
Displacement of bilirubin from plasma protein binding sites.

11. METABOLISM Acetylated sulfonamides-inactive, toxic, and less soluble N
3HC O H
SO2N R
Acetylated sulfonamides-inactive, toxic,
and less soluble

12. EXCRETION
They are excreted in the urine partly as the parent and partly as the metabolite.
Some sulfonamides are very insoluble in the acid urine.

13. EXCRETION Half life of the sulfonamides depends on renal function.
Dosage should be modified or the sulfonamides should not be used in renal failure.

14. SULFONAMIDE PREPARATIONS
Rapidly absorbed and rapidly eliminated (prototype- sulfisoxazole).
Poorly absorbed sulfonamides (sulfasalazine).
Topical sulfonamides (sulfacetamide, silver sulfadiazine).
Long-acting sulfonamides (sulfadoxine)

15. THERAPEUTIC USES
Parasitic diseases (combined with other antimicrobials)- malaria, toxoplasmosis, PCP.

16. CONTRAINDICATIONS

19. DRUG-DRUG INTERACTIONS
Inhibit metabolism of some drugs.
Displace certain drugs from plasma albumin.

20. TRIMETHOPRIM-SULFAMETHOXAZOLE
2HN CH 2
OCH3
80 mg TRIMETHOPRIM O
2HN
SO2NH N
CH3
400 mg SULFAMETHOXAZOLE

21. SULFONAMIDE TRIMETHOPRIM PABA DIHYDROPTEROIC ACID DIHYROFOLIC ACID
+ Pteridine
SULFONAMIDE
Dihydropteroate Synthetase
DIHYDROPTEROIC ACID
Dihydrofolate Synthetase
DIHYROFOLIC ACID
TRIMETHOPRIM
Dihydrofolate Reductase
TETRAHYDROFOLIC ACID

22. COTRIMOXAZOLE
Optimal ratio of the two drugs is 5:1 sulfa :trimethoprim.
Trimethoprim is X as potent as the sulfonamide.

23. Synergism

24. ADVANTAGES Expanded number of organisms inhibited. Bactericidal .
Decreased resistance.
Decreased toxicity.

25. THERAPEUTIC USES Urinary tract infections.
Bacterial respiratory tract infections.
Pneumocystis jirovicii (carinii) pneumonia (PCP)

26. THERAPEUTIC USES

27. hcd2.bupa.co.uk/.../ html

29. PNEUMOCYSTIS PNEUMONIA (PCP)

30. PNEUMOCYSTIS PNEUMONIA (PCP)

31. PNEUMOCYSTIS PNEUMONIA (PCP)
The most common opportunistic infection in advanced AIDS (80% of AIDS patients have at least one episode).
Now considered a fungus (P.jurovecii).
Multiple infections are often present simultaneously with the PCP.

32. PROPHYLAXIS
Routine prophylaxis has been successful in improving survival.
PCP prophylaxis is indicated if the patient has a CD4 T lymphocyte count lower than 200 cells/mm3, or has oral candidiasis regardless of the CD4 count.

33. TREATMENT OF PCP
Early therapy is essential as success of therapy is related to severity of the disease at the time of initiation of therapy.

34. TMP-SMX Treatment of choice.
Oral form used for mild-moderate cases or after initial response to IV therapy and for prophylaxis.

35. TMP-SMX Excellent tissue penetration.
Produces a rapid clinical response.

36. DRUG INTERACTIONS
Same as with sulfonamides

37. SULFONAMIDE SUMMARY
SULFONAMIDE
THERAPEUTIC USE
ADVERSE REACTIONS
Sulfisoxazole
Sulf-acetamide
Silver sulfadiazine
UTI’s
Opthalmic Infs.
Burn therapy
GI, Hypersensitivity reactions, crystalluria
TMP+SMX
PCP, Respiratory Infs., UTI’s
Hypersensitivity reactions, Hematologic effects

40. RESISTANCE Altered dihydropteroate synthetase.
Decreased transport into the bacteria.
Increased PABA synthesis.
Cross-resistance among all sulfonamides.

41. RESISTANCE Results from multiple mechansims.
Altered dihydropteroate synthetase.
Cross-resistance among all sulfonamides.

42. SULFONAMIDE TRIMETHOPRIM PABA DIHYDROPTEROIC ACID DIHYROFOLIC ACID
+ Pteridine
SULFONAMIDE
Dihydropteroate Synthetase
DIHYDROPTEROIC ACID
Dihydrofolate Synthetase
DIHYROFOLIC ACID
TRIMETHOPRIM
Dihydrofolate Reductase
TETRAHYDROFOLIC ACID

45. ADVERSE EFFECTS Hypersensitivity reactions -common allergic rashes
photosensitivity
drug fever
Stevens-Johnson syndrome

53. ADVERSE EFFECTS DRINK ADEQUATE FLUIDS. Urinary tract disturbances
-formation of crystalline aggregates in urinary tract, hematuria and obstruction.
DRINK ADEQUATE FLUIDS.
Less likely with the newer more soluble sulfonamides.

54. CRYSTALLINE
AGGREGATES,
HEMATURIA,
OBSTRUCTION

55. ADVERSE EFFECTS Headache, nausea, vomiting and diarrhea.
Hematological effects -anemia, agranulocytosis.

57. ADVERSE REACTIONS Dermatological reactions including skin rashes.
GI (nausea and vomiting).

58. HEMATOLOGICAL EFFECTS
Leukopenia, thrombocytopenia and megaloblastosis.
Most likely in patients with preexisting folate deficiency or in patients taking prolonged therapy.
Unlikely in normal patients in recommended doses.