- Antibacterial activity
- Bacteriostatic at all concentrations.
- Bactericidal in combination with potentiators IF concentrations and organism susceptibility align.
- Broad spectrum aerobes and anaerobes.
- Bacterial resistance
- Resistance limits usefulness of sulfonamides alone.
- Resistance to TMP/Sulfa combinations is moderate and even high among organism groups resistant to multiple classes. (e.g. Salmonella, Pseudomonas)
- Concentrations and doses
- Bactericidal action only occurs if organisms are adequately susceptible and optimum concentrations of each agent are produced.
- Toxicity Profile
- Life threatening adverse effects are extremely rare.
- Typical adverse effects (idiosyncratic and immune) occur often enough to limit clinical utility.
- sulfadimethoxine, trimethoprim / sulfadiazine, trimethoprim / sulfamethazine, ormetoprim, pyrimethamine, sulfaquinoxaline
Beneficial actions and effects
Antibacterial activity (sulfonamides)
- bacteriostatic at all concentrations
- Bacteria that cannot acquire or utilize exogenous tetrahydrofolic acid or manufacture their own
- Sulfonamides and potentiators inhibit sequential steps in the synthesis of tetrahydrofolic acid (Figure 1).
- Resistance is relatively high
- Coccidia remain susceptible
- sulfonamides are combined to avoid urinary crystal formation (independent solubility)
Antibacterial activity (potentiators)
- bacteriostatic for bacteria that CAN acquire adequate dihydrofolic acid (they would be resistant to sulfonamide alone)
- bacteriocidal when combined with sulfonamides for bacteria that CANNOT acquire DHF
- the inhibitor pyrimethamine less active against bacteria, more active against protozoa
Resistance (by bacteria)
- plasmid encoded SECOND DHP synthetase with low affinity for sulfonamides
- synthesis of sulfa resistant DHP synthetase
- increased synthesis of PABA
- increased synthesis of pteridine
- Trimethoprim, ormetoprim, pyrimethamine
- Increased production of normal dhf reductase
- Plasmid mediated dhf reductase that does not bind TMP
- Crystalluria. very rare with sulfonamides currently marketed
- Relatively rare idiosyncratic allergic and immune disorders. Cross-reactive with sulfonamide diuretics.
- cutaneous drug eruption
- blood dyscrasias (anemia, leukopenia, thrombocytopenia)
- drug fever
- non-septic polyarthritis
- associated with carcinogenic effects in laboratory animals. ELDU is banned in dairy cattle.
Sulfonamide pharmacokinetics follow some general patterns
- widely distributed in the body though available veterinary sulfonamides do not cross blood-brain or blood-prostate barriers
- Metabolised by the liver (multiple metabolites)
- (pattern and rate) varies with species and between specific sulfonamide drugs.
- Less than half eliminated kidneys, still produce meaningful (antibacterial) urine concentrations
- Oral absorption is generally good except for sulfonamides that are not absorbed at all (e.g. sulfaquinoxaline,usually referred to as an "enteric" sulfa).
- Important pharmacokinetic differences between individual sulfonamides.
Trimethoprim, ormetoprim and pyrimethamine share similar pharmacokinetic patterns.
- Extensively metabolised by the liver. Very little drug is excreted unchanged. Urinary concentrations CAN still be adequate for therapy. (Animal must be able to concentrate urine.)
- Oral absorption is good in monogastric animals. Oral absorption is VERY poor in ruminants.
- Protein binding is relatively high but does not rise to levels associated with drug interactions.
- Distributed widely including reserved spaces.
Veterinary Sulfonamide products
There are a limited number of sulfonamides approved for veterinary use and even fewer are currently being marketed.
||Long-half life allows once-daily administration. Good oral absorption. Injectable product for IV use.
||Likely the most commonly used single un-potentiated sulfonamide in use (excepting medicated water applications).
||Pharmacokinetics of sulfadiazine and trimethoprim are not well matched. Sulfadiazine should be dosed BID and trimethoprim QD. Tissue distribution of trimethoprim, especially CNS and prostate, is much better than that of sulfadiazine.
||Injectable forms do not perform particularly well (toxicity), especially IV.
||Almost identical to sulfadiazine/trimethoprim.
||Generally less expensive human generic often substituted for sulfadiazine/trimethoprim
||Pharmacokinetics of the two drugs are much better matched. Sulfadimethoxine does not cross blood-brain and blood-prostate barriers particularly well.
||Little to no oral absorption
||CSF concentrations of sulfadiazine ~50% of serum (inflammed meningies). Role of sulfadiazine in therapy during recovery phase is questionable.
||Equine product for treatment of protozoal encephalopathy.
|"triple sulfa" (sulfathiazole + sulfamethazine + sulfamerazine)
||independent solubilities of these three allow higher doses than would otherwise be tolerated (crystalluria is avoided)
||Only ornamental fish products marketed