Sulfonamides, Cotrimoxazole and Quinolones

Thursday, June 1, 2023 20:23

Sulfonamides
Sulfonamides are primarily bacteriostatic against many gram-positive and gram-negative bacteria.

Mechanism of action
• being structural analogues of PABA, inhibit bacterial folate synthase, so that FA is not formed
• competitively inhibit the union of PABA with pteridine residue to form dihydropteroic acid which
conjugates with glutamic acid to produce dihydrofolic acid.
Uses
• Sulfametoxazole + trimethoprim used for many bacterial infections, P. jiroveci and nocardiosis
• Sulfonamides + Pyrimethamine used for malaria and toxoplasmosis
• Ocular sulfacetamide sod. (10–30% alternative in trachoma/inclusion conjunctivitis
• Topical silver sulfadiazine used for preventing infectionon burn surfaces
Resistance
Prominent among these are gonococci, pneumococci, S. aureus, meningococci, E. coli, Shigella, Strep. pyogenes
The resistant mutants either:
(a) produce increased amounts of PABA, or
(b) their folate synthase enzyme has low affinity for sulfonamides, or
(c) adopt an alternative pathway in folate metabolism.
because of rapid emergence of bacterial resistance, they are currently used only in combination with
trimethoprim (as cotrimoxazole) or with pyrimethamine (for malaria)
Pharmakokinetics
Absorbtion : rapidly and nearly completely absorbed from g.i.t
Distribution : widely distributed in the body, cross placenta freely
Metabolism : primarily in liver, acetylated derivative less soluble in acidic urine, may cause crystalluria
Excretion : mainly by the kidney through glomerular filtration
Sulfamethoxazole
slower oral absorption and urinary excretion, preferred compound for combining with trimethoprim because
the t½ of both is similar
Sulfadoxine, Sulfamethopyrazine
High plasma protein binding and slow renal excretion (t½ 5–9days), can caused serious cutaneous reactions
Silver sulfadiazine
Used topically as 1% cream against a large number of bacteria and fungi, even those resistant to other
sulfonamides, considered to be one of the most effective drugs for preventing infection of burnt surfaces
and chronic ulcers
Adverse Effect
• Hypersensitivity, mostly in the form of rashes, urticaria and drug fever, serious: SJS
• Nausea, vomiting and epigastric pain.
• Crystalluria, can be minimized by taking plenty of fluids and by alkalinizing the urine
Cotrimoxazole
The fixed dose combination of trimethoprim and sulfamethoxazole is called cotrimoxazole
both sulfonamide and trimethoprim are bacteriostatic, but the combination becomes cidal against many
organisms.
Cotrimoxazole should not be given during pregnancy, dose should be reduced in moderately severe renal
impairment, The elderly are also at greater risk of bone marrow toxicity
Dose : 80 mg T + 400 mg tab S: 2 BD for 2 days; 40 mg + 200 mg per 5 ml susp

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