Sulfonamides were the first effective antibacterial agents discovered in the 1930s and were widely used before the development of penicillin. While now largely replaced by other antibiotics, they continue to have therapeutic uses. Key points include: sulfonamides work by inhibiting folic acid biosynthesis; they are excreted renally so dosage should be adjusted for renal impairment; and trimethoprim-sulfamethoxazole is a commonly used combination that is synergistic and has expanded antimicrobial activity. Adverse effects can include allergic reactions and hematological effects like anemia.

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 Now largely superceded by antibiotics and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).