Principles of Drug Toxicity Flashcards
Therapeutic index =
Effective dose (50%)/ Toxic dose (50%) Risk Benefit Analysis done before drug is authorized
Why do we see drug toxicity in veterinary patients?
use of drugs in untested species
mistakes in dose calculation
multiple drugs in use
adverse drug reactions (ADR) - Type A reactions
Predictable from knowledge of mechanism of action of the drug
Beta blockers causing bradycardia
ACE inhibitors causing acute renal failure
Sulphonylurea drugs causing hypoglycaemia
adverse drug reactions (ADR) - Type B reactions
Not related to the mechanism of action of the drug therapeutically – non/predictable
Factors that enhance ADR
Physiological Factors - Age, breed, gender
Disease status - Hepatic, renal and cardiovascular
Concomitant use of other drugs
differences in physiology in neonates
decr gut motility, underdeveloped mucosa + flora
incr total body water
Immature liver enzymes
Decr GFR
drug in neonates - Empirical guidelines
Avoid if possible
drugs with wide therapeutic indices if possible
formulation that allows accurate dosing
Weigh the animal accurately
Examples of toxicities specific to neonates
Fluoroquinolones – damage to articular cartilage
Tetracyclines – discolouration of teeth
Increased risk of ADRs in geriatrics because
Smaller body size Poor nutritional status Presence of multiple disease processes Altered compliance Age related changes in organ function (e.g. renal function)
why does decr renal function incr chance of ADR
decr clearance of drugs via the kidneys
Monensin toxicity in horses
Clinical signs - neuronal, skeletal and cardiac muscle effects of ionophores
susceptibility d/t low first pass metabolism in horses -systemic bioavailability of this drug much higher than in sheep.
Pyrethrum insecticide treatment of cats
more sensitive to the toxic effects flea products for dogs
d/t ineffective metabolism
hyper-excitability leading to convulsions
incidence of accidental toxicity is high, despite clear labels saying toxic to cats
Type A examples - Beta blockers
bradycardia
Type A examples - ACE inhibitors
acute renal failure
Type A examples - Sulphonylurea drugs
hypoglycaemia
