Sulphonamides

• Sulphonamides are a group of synthetic organic chemicals with

chemotherapeutic agent.
• First chemotherapeutic agent used systematically for prevention and
treatment of various disease.
• Antibacterial activity of sulphonamide was first discovered by
Grehard Domagk in 1935, developed from the produrg Prontosil
dye.
• It is a bacteriostatic, broad spectrum drug that inhibit folic acid
synthesis.
 Source and chemistry:
• Sulphonamides posses a common chemical nucleus, which is closely
related to PABA ( essential member of vitamin-B complex).
• Sulphonamides are about twice or more soluble in alkaline PH as
compared with the acidic or neutral PH.
• In acidic urine, sulphonamides may form becoz of their decrease
solubility.
• A free amino group in N4 position is essential for antibacterial
activity.
• Therefore, combination of two or more sulphonamides is occasionally
used to increase solubility and efficacy (additive effect) and to
decrease toxicity (less crystallization in urine).
 Classification:
(1)Systemically acting sulphonamides:
(a) Short acting (duration < 12 hrs.)
sulphadiazine, sulphafurazole, sulphamirazine, sulphathiazole,
sulphachlorpyridine, sulphanilamide
(b) Intermediate acting (12-24 hrs.)
sulphadimidine, sulphamoxole, sulphamethoxazole,
sulphaphenazole
(c) Long acting sulphonamides (duration 24-48 hrs.)
sulphamethoxine, sulphaethoxypyridazine, sulphabromomethazine,
sulphamethoxypyridazine
(d) Ultra long acting (> 48 hrs.)
sulphadoxine, sulphamethopyrazine
(2) Locally acting sulphonamides:
(a) Gut acting sulphonamides (enteric poor soluble):
sulphaguanidine, sulphaquinoxaline, sulphasalazine,
succinyl sulphathiazole, phthalyl sulphacetamide,
phthalyl sulphathiazole
(b) Highly soluble (urinary):
sulphasoxazole, sulphasomidine
(c) Topically acting:
mefenide, sulphacetamide, silver sulphadiazine
 Mechanism of action:
• Folic acid essential for synthesis of nucleic acid.
• Bacteria synthesize their own folic acid from PABA with the help of
enzyme folic acid synthetase.
• Sulphonamides are structurally similar to PABA and competitively
inhibit the enzyme folic acid synthetase.
• Cause folic acid deficiency and thereby inhibition of bacterial growth
as well as injury to the bacterial cell.
• Mammalian cell are not affected becoz they required performed folic
acid supplied from diet and cannot synthesize folic acid themselves.
• Sulphonamides are more effective in acute stage of infection bacteria
multiply at a much faster rate utilizing larger amount of PABA and
host immune system is also active.
 Pharmacokinetic:
Absorption:
• Rapidly absorbed from GIT, except gut acting sulpha. Drug.
• In general dogs, cats and birds absorb sulphonamides rapidly, pigs
takes some time and cattle require much longer time.
Distribution:
• Diffuse well into body tissue and fluids.
Metabolism:
• Sulphonamides are primarily metabolized by acetylation at N4 by
non-microsomal enzyme in liver except sulphapyridine derivatives
( sulphadiazine, sulphamerazine and sulphadimidine).
• Acetylation of sulphonamide reduce their solubility in acidic urine
thus promoting crystallization.
• In cattle sulphonamides are more toxic due to extensive acetylation.
Excretion:
• Alkalinisation of urine favours ionisation of sulphonamide and its
rapid elimination.
• It also excrete in tears, faeces, bile and sweat, but gut acting are
poorly absorbed from the G.I tract and are primarily elimination in the
faeces.

 Triple sulpha: The combination (( sulphadiazine, sulphamerazine

and sulphadimidine) in form of triple sulpha has added antibacterial
action with minimized risk of crystalluria.
• The crystallization can be prevented by alkalizing the urine,
increasing water intake and reducing the dose rate or by using triple
sulpha.
• Sulphonamides and chlortetracycline act as growth promoter prevent
clostridial ET.
 Toxicity:
• Acute effect:
(a) Renal toxicity: Crystalluria, hematuria, obstruction of ureter and
bladder.
(b) Hypersensitivity reaction: Skin rashes due to anaphylactic shock.
(c) Other effects: Vomiting, nausea, anorexia and diarrrhoea.
• Chronic effect:
(a) Hematological alteration
(b) Hepatic degeneration
(c) Jaundice
(d) Drop in egg production in poultry.
 Clinical use: Colibacillosis, pasteurellosis, footrot and coccidiosis.
• In poultry prevention and treatment of coccidiosis, pullorum and fowl
typhoid disease.
 Potentiated Sulphonamides

• Sulphonamides in combination with trimethoprim, which potentiates

the antibacterial action of sulphonamides.
 Trimethoprim: Diaminopyrimidine derivatives.
• Bacteriostatic drug, selectively inhibit bacterial dihydrofolate
reductase enzyme.
• In combination with sulphonamide results in potentiation of
antibacterial action by sequential blockade.
• Readily absorbed after oral administration except in ruminants
trapped and undergo microbial degradation .
• Widely distributed, metabolized in liver and excretion by urine
glomerular filtration and tubular secretion.
• Common combinations:
Trimethoprim + sulphamethoxazole (cotrimoxazole)
Trimethoprim + sulphadiazine (cotriazine)
Trimethoprim + sulphadoxine

 Side effects:
• Swelling at the site of injection.
• Anemia
• Keratoconjuctivitis (reduced lacrimal secretion)

 Clinical uses:
• Urinary tract infection
• Salmonellosis and brucellosis
• Cattle – Salmonellosis, diarrhea and pneumonia
• Poultry – E.coli.