A sound structure—activity relationship between the antibacterial arylpyrimidine In summary, the sulfonamides and the arylpyrimidine antifolates are potent. Well discussed classification, mechanism of action, structures- authorSTREAM Presentation. Structure activity relationship General 1. This is followed by a study of structure – activity relationship methods; The practical work (synthesis and antibacterial structure activity relationship of sulfonamides) of the practical component is provided in the laboratory manual and on the The final exam (/50%) will be 3 hours in length with 10 minutes reading time.
Poorly absorbed sulphonamides 3.
Sulfonamides: Chemistry, Classification and Adverse Reactions | Animals
Topically used sulphonamides 10 Structure activity relationship: Structure activity relationship General 1. Sulphonamide skeleton is the minimum structural requirement for antibacterial activity. The active form of sulphonamide is the ionized form.
Maximum activity is observed bretween the pk a value 6. Sulphonamides competes for binding site on plasma albumin with causes increased action of drugs like Aspirin, Phenylbutazonemethotrexate etc.
Adverse effects Hypersensitivity reactions Crystalluria,hematuria,renal obstruction. Allergic nephritis Haemolytic anaemia, aplastic anaemia, thrombocytopenia. Kernicterus in new born 14 Trimethoprim - Sulfamethoxazole combination Co-trimoxazole: Trimethoprim - Sulfamethoxazole combination Co- trimoxazole 15 Mechanism of action:: Sequential blocking of purine synthesis synergism.
Trimethoprim inhibits dihydrofolate reductase enzyme so inhibits tetrahydrofolic acid synthesis The combination is bactericidal 16 Slide Clinical uses Acute or Complicated or recurrent urinary tract infections especially in females Upper respiratory tract infections Pneumocystis jiroveci pneumonia Toxoplasmosis Shigellosis Nocardiosis 18 Slide Emergence of drug resistant bacteria is frequent.
Resistance may develop due to enzyme adaptation, alternate enzyme pathway, chromosomal mutation or plasmid mediation R-factor.
Cross resistance is commonly observed. While evaluating the potency of the drug, poor correlation is recorded between in vitro and in vivo tests. Higher concentration is required for successful therapy as compared to in vitro results.
Emergence of resistant strain of bacteria can be prevented by: Course of Sulfonamide Therapy: Too short sulfonamide therapy is generally avoided due to failure of cure.
In no case, sulfonamide therapy should be discontinued before 3 days. Initial doses of sulfonamides are higher for establishing the therapeutic blood concentration and subsequent doses are smaller. This action of sulfonamide is selective over bacteria without interfering animal cells. Bacterial growth is inhibited by bacteriostatic action. Inhibited bacteria can be eliminated by host defence system preferably by phagocytosis. Sulfonamides should not be given with procaine penicillin as this combination is antagonistic.
Sulfonamides combined with pyrimethamine are the regimen of choice for toxoplasmosis.
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Urine acidification enhances the risk of crystal Luria. Combination of sulfa drug with trimethoprim has synergistic effect. Sulfonamides exist in non-ionized form in biological fluids. They are rapidly absorbed from GI tract and distributed to all tissues and fluids.
Medicinal Chemistry Sulfonamides |authorSTREAM
Distribution of the drug, however, depends upon ionization of drug and barriers to diffusion vascularity of tissues. Drug distribution occurs by passive diffusion. Metabolism of drug affects its antibacterial toxic activity. Sulfonamides are metabolized in the body by acetylation, oxidation, conjugation with sulphate or glucuronic acid and cleavage of heterocyclic ring.
Acetylated, hydroxylated and conjugated sulfonamides have less antibacterial activity. Acetylated drugs cause renal damage because of their insolubility. Acetylation does not take place in dogs.
However, toxicity in dog is less because the drug is metabolised by glucuronide conjugation and glucuronide conjugates are soluble. But in cow the high toxicity is due to acetylation. Sulfonamides having longer plasma disappearance half-lives are generally preferred to those having shorter half-lives. Sulfonamides are excreted as such or as metabolic products.
They are eliminated in urine, faeces, bile, milk and sweat. Urine is the main source of their excretion. The mammary gland epithelium is permeable to the non-ionized form of sulfonamides Rasmussen, Routes of Administration: Oral route-is common route. The drug is available as tablet, bolus, solution and water soluble powder. In ruminants cattle, sheep sulfonamides administered orally has depressing and adverse effect on rumen microorganisms.
It is generally used for treatment of acute infection. IV administration is followed by oral dose for maintenance therapy. Drug is given slowly by this route. Intramuscular IM or subcutaneous SC route: Specific preparations buffered to a neutral pH may be administered. It is not common route. Alkaline preparations should not be injected IP. Drug combined with urea is prescribed for uterine infections.
This route is not suitable for wound treatment due to tissue debris interference with drug. Solution and ointment of sulfacetamide are generally indicated in eye for conjunctival infections. A wide variety of side effects are produced. This may be allergic or toxic.
Nephrotoxicity is common side effect. Renal damage is characterised by crystalluria, haematuria and obstruction of renal tubules. During therapy water should be readily available to animals to maintain adequate hydration to avoid occurrence of crystalluria.
Aciduria increases the risk of crystalluria hence, sodium bicarbonate is given to make the urine alkaline. In alkaline urine sulfonamides are dissolved and chances of crystal urea reduced. Use of triple sulfonamides sulfonamide mixture decreases concentration of each sulfonamide in urine and thus, minimizes the chance of crystal formation. Anorexia, depression, haematuria, renal colic, frequent urination and rise in BUN level are signs of crystalluria.
In case of such symptoms observed, drug is discontinued and fluid therapy is indicated. Neuritis and Jaundice are observed in cattle. Cyanosis develops in dogs.Sulphonamides
Decreased egg production, weight reduction, production of rough thin shelled eggs, liver and kidney lesions, agranulocytosis and anaemia are observed in poultry. It is given orally or iv. It is pyrimidine sulfonamide generally prescribed orally and parenterally. It is available in oral bolus, IV solution and powder form.
It has long half-life and readily absorbed from G. It has limited use in veterinary practice. It is also pyrimidine sulfonamide available in combination with trimethoprim for use in dogs. It is brominated sulfamethazine. In advanced pregnancy drug is contraindicated. It is administered orally or IV. It is used in form of tablets, bolus or IV injection in companion animals.
Its powder form is meant for medication of drinking water. It is indicated in dog and cats. Mafenide Sulfamylon is indicated in burn wounds as cream daily for two times. Succinyl sulfathiazole, phthalyl sulfathiazole and sulfa-guanidine are gut active sulfa drugs. They are prescribed in enteric infections of domestic animals.