Antimetabolites: Sulfonamides and

Trimethoprim

Dr. P. Mekala, Ph.D., PGDEVP

Assistant Professor
Department of Veterinary Pharmacology and Toxicology
Veterinary College and Research Institute
Namakkal - 02
 Content
 Sulfonamides
Introduction
Classification
Mechanism of action & Resistance
PK & Drug Interaction
Adverse effects
Clinical use
 Diaminopyrimidines
 Potentiated Sulfonamides
Sulphonamides
Source

Metabolism

In vivo
 Chemistry

Organic acid

PABA Sulphanilamide
Sulfonamides
Sulfonamide derivatives

https://madhavuniversity.edu.in
 Classification
 Based on duration of action
Short acting (4-8 hrs)
Sulfadiazine, Sulfamerazine
Intermediate acting (12-24 hrs)
Sulfadimidine, Sulfamethoxazole
Long acting (24-48 hrs)
Sulfadimethoxine,
Sulfamethoxypyridiazine
Ultra long acting (> 48 hrs)
Profit: Rs. 120 Profit: Rs. 130
Sulfadoxine
 Classification
 Based on the site of action
 General purpose / Systemic sulfonamide
Sulfadiazine, Sulfadimidine, Sulfadoxine
 Gut acting / Enteric sulfonamide
Sulfaguanidine, Sulfasalazine
 Highly soluble sulfonamide for UTI
Sulfisoxazole, Sulfasomidine
 Topical
Sulfacetamide, Silver Sulfadiazine,
Mafenide
 Spectrum
 Broad spectrum
Susceptible
Bacteria – G +ve and G-ve aerobes and
some anaerobes
Protozoa – Toxoplasma, Coccidia
Chlamydia
Resistant – Mycobacteria, Mycoplasma,
Rickettsia
 Bacteriostatic
 Mechanism of action

Dihydrofolate synthase
Dihydrofolic acid
Dihydrofolate reductase
Tetrahydrofolic acid

Purine Thymidine Methionine, Glycine

(Nucleic acid) (Protein)

 Resistance
 Plasmid mediated resistance
sometimes MDR – Trimethoprim,
Streptomycin
 Chromosomal mutation – slow to develop
 Complete cross resistance among sulfa
Mechanism:
 Overproduction of PABA
 Resistant DHFS
 Altered permeability, altered metabolic pathway
 Utilize preformed folic acid
 Pharmacokinetics
 Absorption - well absorbed except gut acting
 Distribution - variable PPB, widely distributed
(CSF)
 Metabolism - Acetylation – Crystalluria
Slow acetylators & Dogs – Aromatic hydroxylation
Sulfadehydroxylamine in dogs
(hepatic necrosis in Dobermann)
 Excretion – Renal (alkalinize)
& faeces (enteric)
 Drug Interaction
 Antagonistic
 Pus and tissue debris
 Procaine, Benzocaine, Folic acid
 Antacids and Calcium
 Phenytoin and Warfarin
 Synergistic / Potentiation
 Trimethoprim
 Pyrimethamine - Toxoplasmosis, EPM
 Minocycline - Pneumocystis, Nocardia, Chlamydia
 Oral sulphonylureas, thiazides, uricosuric agents
 Adverse Effect
 Renal – Crystalluria, haematuria

Triple Sulfa
Sulfadiazine + Sulfamerazine + Sulfapyridine
“Law of independent solubility”
 Haemopoeitic system
Thrombocytopenia, anemia, leukopenia
Inhibit Vit K epoxide reductase
Haemolysis in G-6-PD deficiency
 Adverse Effect
 Hypersensitivity reaction
Rashes to Stevens - Johnson syndrome
Dobermann – Type III reaction
 GI system
Destroy ruminal flora
– Vit B and K deficiency
 Poultry: Thin shelled egg (Inhibits CA)
Adverse Effect
 Clinical Use
 Enteric infection
 Enterotoxemia – with CTC
 Pyoderma
 Feed lot pneumonia
 Burn wounds
 Eye infections
 Urinary tract infection
 Meningitis
 Clinical Use
 Chronic colitis in dogs
Sulfasalazine Sulfapyridine + 5-ASA
(Prodrug) (AB) (AI)

 Toxoplasmosis, Coccidiosis

 Poultry – Coccidiosis, Early chick mortality,

Enteric infections
 Your Reflection
 Which one is not the common adverse
effect of sulfonamide therapy in dogs?
a) Crystalluria
b) Hepatitis
c) Arthritis
d) KCS
Justify
Diaminopyrimidines
Mechanism of action

Dihydrofolate reductase
Diaminopyrimidines
 Clinical Use
 Prostatitis by Gram negative organism
 UTI, GIT, Respiratory infection - Mainly
used in combination with sulfa
 Polymicrobial infection in poultry
Sulfaquinoxaline + Trimethoprim /
Diaveridine
Sulfamethoxazole + Ormetoprim
 Brucellosis – with Rifampin / Doxycycline
 Anerobes - Sulfa trimethoprim + Ampicillin
 Clinical Use
 Toxoplasmosis
Sulfadiazine + Pyrimethamine
 EPM - Sulfadoxine + Pyrimethamine
 Pneumocystis jirovecii pneumonia – with
sulfa / Sulfone (Dapsone)
 Dapsone – Leprosy in human
Dermatitis herpetiformis in dog
Pneumocystis in foals
 Potentiated Sulfonamide
Sequential blockade
Potentiated sulfonamide
 Principles of Sulfonamide therapy
 Start therapy at early stage
 Maintain adequate tissue concentration
 Treatment should not exceed 7 days
 Discontinue treatment if not responding within 5 d
 Remove pus and tissue debris before treatment
 Provide adequate drinking water
 Alkalinize the urine with sodium bicarbonate to
avoid crystalluria
 Follow WDP – Milk 3-7days;
Meat 5 (PO) / 28 (Inj) days
 Current status

 Sulphonamide – 1935
 Trimethoprim – 1965
 Enteritis, Pyoderma, Coccidiosis
 Preferred drugs
Fluoroquinolones
Macrolides
Cephalosporins
 Brain Out
 A 24 Kg goat is presented with
haemorrhagic enteritis and your drug
of choice is potentiated sulfonamide @
30mg/kg
Each ml in the vial contains
Sulfadiazine 200mg
Trimethoprim 40mg
How will you calculate the dose?
How many ml you will administer?
9442092237