Sulfonamides and cotrimoxazole are antibacterial drugs that work by inhibiting folic acid synthesis. Sulfonamides are classified based on half-life as short, intermediate, or long acting. Cotrimoxazole is a combination of sulfamethoxazole and trimethoprim that has synergistic antibacterial effects. These drugs are used to treat infections like toxoplasmosis, UTIs, nocardiosis, and pneumocystis pneumonia. Common adverse effects include nausea, crystalluria, rashes, and hemolytic anemia in G6PD deficiency.

1. Dr.Shaila Banu
PG
SULFONAMIDES &
COTRIMOXAZOLE

2. Learning Outcome
At the end of the session student
should be able to:
•Classify the Sulfonamides.
•Explain the mechanism of action,
therapeutic uses, adverse effects* of
clinically useful Sulfonamides
•Explain the rationale of combination of
sulfamethoxazole and Trimethoprim in
Cotrimoxazole
Sulfonamides/ SSRMC/2020
2

3.  First antimicrobial agent effective
against pyogenic bacterial
infection
 Scientist-DOMAGK
 PRONTOSIL RED
DYE 3

4.  Structural analogue of Para
amino benzoic acid(PABA)
Sulfonamides/ SSRMC/2020 4

5. (1)Oral absorbable – Three types on the
basis of half life:
(a) Short acting(4-8hr) –Sulfadiazine
(b) Intermediate acting(8-12hr) -
Sulfamethoxazole*,Sulfamoxole
(c) Long acting (~7days) – Sulfadoxine ,
Sulfamethopyrazine
Sulfonamides/ SSRMC/2020 5

6. Special purposeSulfonamides
(2) Oral non absorbable – Sulfasalazine*
Sulfonamides/ SSRMC/2020 6
(3) Topical – Mafenide,
Sulfacetamide, Silver
sulfadiazine**

7. Pteridine + PABA
Sulfonamides/ SSRMC/2020 7
Dihydropteroate synthase(- Sulphonamides )
Dihydrofolic acid
Dihydrofolate reductase (-Trimethoprim)
Tetrahydrofolic acid

Purine

DNA


Bacteriostatic in nature

8. SPECTRUM
Both gram positive and gram negative
Bacteriostatic.
Eg.s.pyogenes,s.pneumonia,H.influenza,H.ducreyi,
nocardia,actinomyces.
MIC(minimum inhibitory conc) range from
0.1microg/ml (C.trachomatosis ) to 4-64 micg/ml for
E.coli.

9. PHARMACOKINETICS
Abs:70-100% orally absorbed
sulfonamides can be found in urine within 30 mins
peak plasma levels 2-6hrs
major site:SI>Stomach
bound to albumin
Dis:throughout all the tissues and body fluids
crosses placenta and cause both antibacterial
and troxic effects.

10. Cont..
Metabolism:Liver
Acetylation
metabolic derivative(N4 acetylated sulfonamide)
Excretion:excreted in urine
t1/2 (depends on renal function)
In acid urine,the older sulfonamides are insoluble
and may ppt ,forming crystalline deposits tat can
cause urinary obs.
Small amounts-feces,bile,milk and other secretion.

11.  Toxoplasmosis – Combination of
sulfadiazine
& Pyrimethamine is DOC .
 Urinary tract infection – Due to appearance
of resistant organism , no longer therapy of
first choice.
- Co-trimoxazole ,Fluoroquinolones are
preferred drugs.
 Nocardiasis- Sulfadiazine may be given 6-8
gm daily.
 P. falciparum malaria- 3 tab stat of
Sulfadoxine (500mg ) + Pyrimethamine
(25mg) Sulfonamides/ SSRMC/2020 1

12.  To prevent burn infection – Silver
sulfadiazine 1% cream
 In Ulcerative colitis – Sulfasalazine in dose
of 3-4 gm /day induces remission for few
weeks. Maintance therapy 1.5-2 gm is
required.
 Trachoma- Sulfacetamide Sod. as eye drops
& eye ointment. Systemic therapy with
tetracycline is preferred.
 Preventing of Streptococcal infection &
recurrence of Rheumatic fever- Used in
who are sensitive to Penicillin.Sulfonamides/ SSRMC/2020 1

13.  1.Nausea , vomiting , epigastric pain
 2.Crystalluria is dose related
 Advice- Alkalization of urine increases
pHsolubility of sulfonamide
increased.
 Plenty of fluid – daily urine volume in
adult at least 1200 ml.
 3. Hypersensitivity reactions
 Rashes , urticaria,& drug fever
Sulfonamides/ SSRMC/2020 10

14.  Characterized by distinctive iris or target
lesions ,acrally distributed & associated
with sore throat.
 Target lesions include three zones: an erythematous
or dusky small central papule that may form blister, a
raised edematous middle ring, and an erythematous
outer ring.
Sulfonamides/ SSRMC/2020 14

15.  More severe than Erythema Multiforme
characterized by Dusky or Purpuric
Macules, erosion of mucous membrane
& blister in <10% of total body surface
area
Dusky or Purpuric
MaculeTypical of
Stevens-Johnson Syndrome.
Macules may
coalesce to form
blisters.
Sulfonamides/ SSRMC/2020 15
Ulceration & erytherma
of
Oral mucous membrane
& lips

16. Or Lyells syndrome > 30 % of body
surface area.
7. Hemolysis in dose dependent
in G- 6-PD deficiency patients.
8.Kernicterus may precipitate in
premature neonate , by displacement
of bilirubin from plasma protein
binding site.
9. Hepatitis
Sulfonamides/ SSRMC/2020 16

17. DRUG INTERACTION:
Oral anticoagulants,
sulfonylureas,hypoglycaemic agents and
hydantoin anticonvulsants
In each case sulfonamides can potentiate the
effects of each other drug.

18.  The resistant mutants either:
-Produced increase amount of PABA.
-Dihydropteroate synthase enzyme
has low affinity for sulfonamide.
Sulfonamides/ SSRMC/2020 18

19.  Combination of sulfamethoxazole(400mg) with
Trimethoprim (80 mg) – 5:1 Ratio
Combination preferred due to
 MOA- Individual compounds are
bacteriostatic
- combination become bactericidal due to
sequential blockade of folate metabolism.
- STUDENTS +TEACHER
15

20.  To achieve optimum synergism
-absorption &Excretion characteristics are
similar
-Half life sulfamethaoxazole – 10 hrs
Trimethoprim – 11 hrs
-Trimethoprim more widely distributed in
tissue than sulfamethaoxazole
 To reduce bacterial resistance.
Sulfonamides/ SSRMC/2020 20

21.  Trimethoprim 80 mg
Sulfonamides/ SSRMC/2020 21
+ 0ral or Inj/5ml
 Sulfamethoxazole 400 mg
= Co-trimoxazole
 Dose – 2 tab or double strength (DS) of
single tab given twice daily for 10 –14
days for management of most
infection

22.  Megaloblastic anemia occur in
patient with marginal folate level
 Hemolytic anemia may develop
individual with G6PD deficiency
 Stevens –Johnson syndrome & Lyell’s
syndrome can occur.
Sulfonamides/ SSRMC/2020 22

23.  Nausea, vomiting, stomatitis,
headache, rashes
 Patient with renal disease may develop
uremia
 Fever, bone marrow hypoplasia in AIDS
patients with Pneumocystis jiroveci
 Diuretics along with cotrimoxazole-
thrombocytopenia
Sulfonamides/ SSRMC/2020 23

24.  Urinary tract infection (UTI)
single dose of 4 tab of Co – trimoxazole
Sulfonamides/ SSRMC/2020 20
T/t for acute cystitis or Uncomplicated UTI
 Prostatitis has good value - 4-6
weeks T/t
 Bacterial respiratory tract infection
 Effective in acute otitis media in children
& acute maxillary sinusitis caused by H.
influenza
 Streptococcal pharyngitis– does not
eradicatestreptococcus

25.  Typhoid fever – Now DOC
Ciprofloxacin/ Cephalosporins
Used as alternative in patients not
tolerating Fluroquinolones
Bacterial diarrhoea & dysentry
Fluoroquinolone is better drugs
Chancroid – Co-trimoxazole 2 tabs
BD for 5-7 days is DOC.
Pneumocystis joroveci- severe
pneumoniaSulfonamides/ SSRMC/2020 21

26. Sulfonamides/ SSRMC/2020
Sulfo
namides
Mechanism of
Action Uses Adverse
effects
1.Orally
absorbable:
Sulfadiazine,
Sulfamethoxazole
,Sulfamoxole,
Sulfadoxine,
Sulfamethopyrazi
ne
2.Oral non
absorbable –
Sulfasalazine
3.Topical
Mafenide,
Sulfacetamide,
Silver sulfadiazine
Special Purpose
Sulfonamides
Group 2 & 3
• Bacteriostatic
in nature
• Toxoplasmosis
• Urinary tract
infection
• Nocardiasis
• P. falciparum
malaria
• To prevent burn
infection – Silver
sulfadiazine*
1% cream
• In Ulcerative
colitis –
Sulfasalazine
• Trachoma
• Preventing of
Streptococcal
infection &
recurrence of
Rheumatic fever
• Nausea, vomiting,
epigastric pain
•Crystalluria
•Hypersensitivity
reaction-
Rashes, urticaria,
drug fever
•Erythema
multiforme
•Steven Johnson
syndrome
•Toxic epidermal
necrolysis
•Hemolysis in
G6PD deficiency
patient
•Kernicterus

27. Cotrimoxazole
Sulfonamides/ SSRMC/2020
Mechanism
ofAction
Uses Adverse
effects
Combination of
sulfamethoxaz
ole (400 mg) +
Trimethoprim
(80 mg) – 5:1
Ratio
Individual
compounds-
bacteriostatic
combination
becomes
bactericidal
due to
sequential
blockade of
folate
metabolism
( Show with a
flow chart)
• Urinary tract infection
(UTI)
• Bacterial respiratory
tract infection
• Typhoid fever
• Bacterial diarrhoea &
dysentry
• Chancroid
• Megaloblastic
anemia
• Hemolytic
anemia may
develop
individual with
G6PD deficiency
• Stevens –
Johnson syndrome
& Lyell’s
syndrome

28. Sulfonamides/ SSRMC/2020