Sulfonamides

SULFONAMIDES

Chemistry:-
Structural analog of PABA.
Sulfonamide with diff. chemical physical
pharmacological and anti bacterial properties
are produced by substitutions at amido gp (-
SO2 – NH – R )or the amino gp. (-NH2) of
sulfanilamide nucleus.
102.
/102.
 CLASSIFICATION

I. Well absorbed by Mouth and Rapidly

eliminated (short Acting)
a. General Purpose
– Sulfadiazine
– Sulfamethoxazlole
b. Mainly for UTI
– Sulfisoxazole
– Sulphamethizole
II. Well absorbed by GIT and Slowly
eliminated (Long Acting)
– Sulphadoxine

III. Poorly absorbed by GIT

– Sulphasalazine
IV. For Topical Application
– Sulphacetamide
– Silversulfadiazine

v. Sulfonamide Combination
– Cotrimoxazole (Sulfamethoxazole &
trimethoprim)
– Fansidar (Sulfadoxine & Pyrimethamine
PHARMACOKINETICS
Mostly well absorbed after oral adm. Divided
into three major groups.
1. Oral absorbable
2. Oral non absorbable
3. Topical

Oral absorbable on the basis of their half lives

divided into
1. Short
2. Medium
3. Long acting
 Absorption – stomach and intestine
 Distribution – Widely distributed
 PPB parts per billion20 – 90 % to serum
albumin
 Plasma half life 2 – 6 hrs
 Metabolism – Liver
 Excretion – Urine
ANTIBACTERIAL SPECTRUM

 G +ve , G-ve bact, some enterobacteria

like
E. Coli, Shigella, Salmonella, Klebsiella
Nocardia, Chlamydia trachomatis and
Some protozoa.
 MOA
They are bacterio static

Dihydropteroate Synthetase
PABA naturally substance
X Sulfonamides
As a catalyst or enzyme act
Dihydrofolic Acid (Folate)
Dihydrofolate Reductase X Trimethoprim
Tetrahydrofolic Acid

Purines

DNA
 THERAPEUTIC USES

I. As Topical Agents in
– Adjunctive therapy for Trachoma(eye infection)
– (Na -Sulfacetamide)
– Bacterial Conjunctivitis Na - Sulfacetamide)
– Prevention of infection of burn wounds (Mafenide,
Silver sulfadiazine)

II. UTI
III. Ulcerative Colitis, enteritis(inflammation of small
intestine), other inflammation. Bowel diseases
IV. Rheumatoid arthritis (Sulphasalazine)
V. Dermatitis herpetiformis (Sulfapyridine)
VI. Used in combination in
• Pneumocystis Carinii (fungal infection of lung)–
sulfamethoxazole combined with trimethoprim (Co-
trimoxazole)
• Resistant Malaria (Sulfadoxine + Pyrimethamine –
Fansidar)
• Acute toxoplasmosis – (Sulfadiazine +
Pyrimethamine)
 ADVERSE EFFECTS

A Urinary Tract Disturbances:- Crystalluria, Hematuria

or even obstruction.

B 1. Fever, Skin rashes, exfoliative dermatitis,

photosensitivity, urticaria, N, V, D, Angioedema &
Steven – Johnson syndrome

2. Hematopoietic Disturbances :- Hemolytic or

Aplastic anemia, Granulocytopenia,thrombocytopenia
 CONTRAINDICATIONS

 Newborns & infants less than 2 months

 Pregnant woman at term – Kernicterus
 (Cefadroxil)
 TRIMETHOPRIM

Chemistry:
Chemically Related to anti malarial drug pyrimethamine both are
folate antagonist.
Pharmacokinetics:
Given orally fully absorbed from GIT.
Distributions:- Widely distributed, in body fluids and tissues,
including CSF concentrates in acidic media of prostatic and
vaginal fluid.
PPB: 65 – 70 %
Excretion : in urine within 24 hrs.
 MOA

PABA
Dihydropteroate Synthetase X
Sulfonamides
Dihydrofolic Acid (Folate)
Dihydrofolate Reductase X Trimethoprim
Tetrahydrofolic Acid

Purines

DNA
Clinical Uses
 Acute UTI: 100 mg – B.d.
 Bacterial Prostatitis (Fluroquinolones are
preferred )
Co-Trimoxazole (TMP/SMX)
 Combination gives synergistic antibacterial
action
 CO-TRIMOXAZOLE

Mixture of trimethoprim with sulfamethoxazole.

Sulfamethoxazole – 400 mg. Ratio 1:5
Trimethoprim – 80 mg.
Advantages of Using Co-Trimoxazole
1.Bactericidal. (Individual drugs are bacterio static)
2.Wide antibacterial spectrum.
3.More efficacy.
4.Less dose of each drug.
5.Less incidence of toxicity.
PHARMACOKINETICS

Can be given orally or I/V

 MOA

PABA
Dihydropteroate Synthetase X Sulfonamides
Dihydrofolic Acid (Folate)
Dihydrofolate Reductase XTrimethoprim
Tetrahydrofolic Acid

Purines

DNA
 CLINICAL USES

1. Respiratory infections:
– Pneumocystis Carinii Pneumonia
– Hemophilis influenzae
– Streptococcus Pneumoniae
– Moraxella Catarrhalis
– Klebsiella Pneumoniae
2.GIT Infections:
Shigellosis
Systemic Salmonella infection (Typhoid Fever)
3. UTI, Chronic & Recurrent UTI
4. Prostatitis
5.Acute Gonococcal Urethritis
6. Non tuberculous mycobacterial infections
 Adverse Effects

1. Hematological
 Trimethoprim – Megaloblastic Anemia, Leukopenia,
Granulocytopenia
 Prevented by simultaneous administrations of folinic acid 6 – 8
mg/D which does not enter bacteria.
2. Rashes, Fever, Vasculitis
3. GIT dist. – N,V, Glosstitis & stomatitis.
4. HIV patients with pneumocystis pneumonia shows fever, rashes,
leukopenia, diarrhea, elevation of hepatic aminotransferases,
hyperkalemia, hyponatremia.