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Dr.Shaila Banu
PG
SULFONAMIDES &
COTRIMOXAZOLE

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

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

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

(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

Special purposeSulfonamides
(2) Oral non absorbable – Sulfasalazine*
(3) Topical – Mafenide,
Sulfacetamide, Silver
sulfadiazine**

Pteridine + PABA
Dihydropteroate synthase(- Sulphonamides )
Dihydrofolic acid
Dihydrofolate reductase (-Trimethoprim)
Tetrahydrofolic acid
?
Purine
?
DNA
?
?
Bacteriostatic in nature

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.

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.

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.

? 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

? 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

? 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

? 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.

? 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.
Ulceration & erytherma
of
Oral mucous membrane
& lips

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

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

? The resistant mutants either:
-Produced increase amount of PABA.
-Dihydropteroate synthase enzyme
has low affinity for sulfonamide.

? 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

? 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.

? Trimethoprim 80 mg
+ 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

? 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.

? 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

? Urinary tract infection (UTI)
?single dose of 4 tab of Co – trimoxazole
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

? 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

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

Cotrimoxazole
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

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Sulfonamidesssr2020 200528142847

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