Pharmacotherapeutic group: Antibacterials for systemic use - oxytetracycline, combinations
ATCvet Code: QJ01AA56
Pharmacodynamic properties
The veterinary medicinal product provides initial anti-inflammatory activity for 24-36 hours and sustained anti-bacterial activity for 5-6 days following a single intramuscular injection.
The tetracyclines are a family of broad-spectrum bacteriostatic antibiotics which inhibit protein synthesis in susceptible microorganisms. Oxytetracycline is active against Mannheimia (Pasteurella) haemolytica associated with acute respiratory disease in cattle.
After oxytetracycline diffuses through the outer bacterial cell membrane, an active carrier mediated process transports the drugs through the inner cytoplasmic membrane. Inside the cell, oxytetracycline binds irreversibly to receptors on the 30S sub-unit of the bacterial ribosome where it interferes with the binding of the aminoacyl-transfer RNA to the acceptor site on the messenger RNA ribosome complex. This effectively prevents the addition of amino acids to the elongating peptide chain, inhibiting protein synthesis. Acquired resistance to oxytetracycline has been noted. Such resistance is usually plasmid mediated. Cross-resistance to other tetracyclines occurs. Continuous treatment with low doses of oxytetracycline can also result in increased resistance to other antibiotics.
Flunixin meglumine is a relatively potent non-narcotic, non-steroidal analgesic with anti-inflammatory, anti-endotoxic and anti-pyretic properties.
Flunixin meglumine acts as a reversible inhibitor of cyclo-oxygenase, an important enzyme in the arachidonic acid cascade pathway which is responsible for converting arachidonic acid to cyclic endoperoxides. Consequently, synthesis of eicosanoids, important mediators of the inflammatory process involved in pyrexia, pain perception and tissue inflammation, are inhibited. Through its effects on the arachidonic acid cascade, flunixin also inhibits the production of thromboxane, a potent platelet pro-aggregator and vasoconstrictor which is released during blood clotting. Flunixin exerts its antipyretic effect by inhibiting prostaglandin E2 synthesis in the hypothalamus. By inhibiting the arachidonic acid cascade pathway, flunixin also produces an anti-endotoxic effect by suppressing eicosanoid formation and therefore preventing their involvement in endotoxin associated disease states.
Pharmacokinetic properties
Once absorbed, tetracyclines are well distributed throughout the body, with highest concentrations found in liver, spleen, kidney and lung. Tetracyclines are slowly excreted in urine, explaining their long persistence in blood.
Flunixin is characterised by a very high degree of plasma protein binding and hence volumes of distribution are generally low. The unbound fraction is distributed throughout the body fluid, including the CNS. It tends to accumulate in inflamed tissue. Renal excretion contributes extensively to the elimination of flunixin from the body.
Environmental properties
Flunixin is toxic to avian scavengers although foreseen low exposure leads to low risk.