2. 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.

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 Now largely superceded by antibiotics and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

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

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

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

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

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

15. 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.

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

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

18. CONTRAINDICATIONS

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

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

23. COTRIMOXAZOLE
 Optimal ratio of the two drugs is 5:1 sulfa
:trimethoprim.

24. Synergism

25. ADVANTAGES
 Expanded number of organisms inhibited.
 Bactericidal .
 Decreased resistance.
 Decreased toxicity.

26. THERAPEUTIC USES

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

29. PNEUMOCYSTIS PNEUMONIA
(PCP)


30. PNEUMOCYSTIS PNEUMONIA
(PCP)
www.learningradiology.com/

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. other sulphonamides
 Sulphonylureas (anti-diabetic agents)
 Carbutamide
 Acetohexamide
 Chlorpropamide
 Tolbutamide
 Tolazamide
 Glipizide
 Gliclazide
 Glibenclamide (glyburide)
 Glibornuride
 Gliquidone
 Glisoxepide
 Glyclopyramide
 Glimepiride


38.  Anticonvulsants
 Acetazolamide
 Ethoxzolamide
 Sultiame
 Zonisamide
 Dermatologicals
 Mafenide

39.  Other
 Celecoxib (COX-2 inhibitor)
 Darunavir (Protease Inhibitor)
 Fosamprenavir (Protease Inhibitor)
 Tipranavir (Protease Inhibitor)
 Probenecid (PBN)
 Sotalol (Beta-blocker)
 Sulfasalazine (SSZ)
 Sumatriptan (SMT)

40.  Diuretics
 Acetazolamide
 Bumetanide
 Chlorthalidone
 Clopamide
 Dorzolamide
 Furosemide
 Hydrochlorothiazide (HCT, HCTZ, HZT)
 Indapamide
 Mefruside
 Metolazone
 Xipamide

41. Viable organisms
6
control
4 sulfonamide
2
0
1 2 3 4 5 6 7 8 9
Time of incubation (hrs)

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

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

46. ADVERSE EFFECTS
 Hypersensitivity reactions -common
 allergic rashes
 photosensitivity
 drug fever
 Stevens-Johnson syndrome

47.  hypersensitivity reaction to sulfa drugs are
rash and hives. However, there are several
life-threatening manifestations of
hypersensitivity to sulfa drugs, including
Stevens–Johnson syndrome, toxic epidermal
necrolysis, agranulocytosis, hemolytic
anemia, thrombocytopenia, and fulminant
hepatic necrosis, among others.

48. 

57. CRYSTALLINE
AGGREGATES,
HEMATURIA,
OBSTRUCTION

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

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