Sulphonamides

• Were the 1st effective AMAs used in the t/t of

bacterial infection, compound containing a
sulphonamide(SO2NH2)
• They are derivatives of sulphanilamide (para-
aminobenzene sulphonamide) & are synthetic
compound
• Are white crystalline powder, mildly acidic and
relatively insoluble in water. They form salts with
bases and their sodium salts are water soluble.
BCZ of the marked alkalinity IM injection causes
damage to the tissue
Classifications
MOA
 Pharmacokinetics
• All systemic acting sulphonamides are well absorbed
from the gut. They are bound to plasma proteins,
• particularly albumin. Sulphonamides are distributed in
almost all the tissues of the body including CSF. They
cross placental barrier and reach foetal circulation;
they are metabolized in liver mainly by acetylation. The
acetylated products have no antibacterial activity, but
retain the toxic potential of the parent compound.
Sulphonamides are excreted partly unchanged and
partly as metabolic products.
• Topical not used due to contact sensitization
• Ocular used is permitted
 Adverse effects
• The acetylated products of sulphonamides are poorly soluble in acidic urine
and may cause crystalluria, haematuria or even obstruction to urinary tract.
This may be avoided by taking plenty of water and alkalinizing the urine.
• Hypersensitivity reactions include skin rashes, itching, drug fever
• In patients with G6PD defi ciency, sulphonamides may cause acute
haemolytic anaemia.
• Rarely cause hepatitis and suppression of bone marrow.
• Use of sulphonamides in neonates, especially in premature babies, may
cause displacement of bilirubin from plasma proteins. The free bilirubin can
cross the blood–brain barrier and get deposited in the basal ganglia resulting
in kernicterus
• Hemopoitic toxicity includes agranocytosis,thrombocytopenia, hematuria and
epitaxis
• In man sulfonamide toxicity causes endrocrinal disturbances such as goiter
and hypothyroidism
 Indications
• Sulphonamides alone are rarely used now for systemic
infections. They are used in combination with other
antimicrobial agents.
• 1. Sulphadoxine and pyrimethamine can be used in
combination with artesunate in the treatment of mefl
oquine-resistant Plasmodium falciparum malaria.
• 2. Sodium salt of sulphacetamide is used topically for
the treatment of ophthalmic infections.
• 3. Silver sulphadiazine and mafenide are used topically
for preventing infection of burn wound.
• Silver sulphadiazine is not effective in the presence of
pus and tissue fluid
 Trimethoprim
• Is a pyrimidine derivatives and chemically
related to the pyrimethamine(antimalarial)
• Is a bacteriostatic, active against all common
pathogenic bacteria except mycobacteria and
pseudomonas .
MOA:
 Pharmacokinetics
• Orally absorbes
• Widely distributed
• Plasma half life : 6-12 hrs
• Metabolized in liver
• Excreated via urine
Adverse effects
Vomiting, skin rashes
Contraindicated in pregnancy due to teratogenecity
 Cotrimoxazole
• Cotrimoxazole is a World Health Organization (WHO)-
approved–fi xed-dose combination of sulphamethoxazole
and trimethoprim in the ratio of 5:1.
• Cotrimoxazole (sulphamethoxazole and trimethoprim)
produces sequential blockade, i.e. two drugs interfere with
two successive steps in the same metabolic pathway;
hence, their combination produces supra-additive effect.
Sulphamethoxazole inhibits folate synthetase whereas
trimethoprim inhibits folate reductase enzyme. The
pharmacokinetic properties of these two drugs match each
other almost closely
The advantages of this combination are:
1. Individually, both are bacteriostatic but the combination
has a cidal effect.
2. Chances of development of bacterial resistance are also
greatly reduced.
MOA
 Pharmacokinetics
• Cotrimoxazole is well absorbed after oral
administration and is also available for
parenteral use;
• widely distributed to various tissues including
the CSF
• metabolized in liver and excreted mainly in
urine; hence dose reduction is needed in
patients with renal insufficiency
 Adverse effects
• Cotrimoxazole is well tolerated in most patients. Most of
the adverse effects are same as that of sulphonamides.
• The common adverse effects are skin rashes and
gastrointestinal (GI) disturbances.
• Exfoliative dermatitis, Stevens–Johnson syndrome are rare.
• The GI symptoms
• include nausea, vomiting, glossitis and stomatitis.
Megaloblastic anaemia due to folate deficiency may occur
rarely, especially in alcoholics and malnourished persons.
Bone marrow suppression with leukopaenia,
• neutropaenia and thrombocytopaenia occurs rarely.
• Cotrimoxazole is contraindicated in pregnancy.
 Indications
• 1. Urinary tract infection
• 2. Bacterial respiratory tract infections
• 3. Bacterial diarrhoeas
• 4. Typhoid fever
• 5. P. jiroveci infections
• 6. Nocardiosis
• 7. Chancroid (STD caused by Haemophilus ducreyi)
• Note : in veterinary medicine trimethoprim is
sometimes combined with sulfadoxine(7-55mg/kg)
and trimethoprim (3-6 mg/kg) given to cows and both
drugs are bond in blood plasma and milk.