Drug Toxicity Flashcards
How is drug toxicity assessed?
- idea of tox from lab animal studies
- once therapuetuc dose decided, target animal species safety studies undertaken in young animals
- if used in FPAs then lifetime safety studies in lab animals to assess chronic effects and placental transfer etc.
- field safety and efficacy studies done (sick animals), all adverse effects recorded (not placebo controlled so adverse effects not necesarily d/t drug, just looking for trends)
- periodic safety update reports filed for 2 years
Why is drug tox seen in vet?
- off label usege
- animals not clones of original animals used for testing
- mistakes in calculating,s toring and handling drugs
- animals with multiple dz -> drug interactions
What happens to tetracyclines if stored in subnlight?
Decay
Define adverse drug reactions
- unwanted effects when drugs administered for therapeutic purpose
- +- lack of efficacy in a pateitn where you would have expected the drug to wor k
Classifications of ADRs?
A: predictable from knowledge of drug actions (eg. B blockers -> bradycardia, ACE inhibitors -> acute renal failure, sulphonylurea drugs -> hypoglycaemia)
B: either
> predictable= not related to mechanism of action but predictable indirectly (eg. chronic use of doxorubicin -> muscle damage, aminoglycosides -> PCT necrosis, prednisolone -> hepatopathy)
> unpredictable/idiosyncratic (eg. chloramphenicol -> aplastic anaemia, phenylbutazone -> agranulocytosis, phenytoin -> hepatitis)
Why is PCT necrosis seen with chronic aminoglycoside usage?
transported actively into PCT cells and not transported out again
- also means residues stay for long time in FPA
Why is hepatopathy seen with chronic prednisolone administration?
- glycogen accumulation
How are idiosyncratic reactions detected?
- incidence
What factors may enhance ADR?
- age/breed/gender/pregnant?
- dz status (esp hepatic, renal, CV)
- concominant use of other drugs
How does drug use in neonates differ from adults? eg. of clinical implications of this?
- different and changing physiology
- v gut motility, under developed gut flora and mucosal enzymies (^ absorption)
- ^ total body water (^volume of distribution)
- immature liver enzymes
- v GFR ~3-6months becomes = adult
> eg. theophylline in puppies needs ^ dose (larger volume of distrubtion) but less frequently (delayed elimination)
Empirical advice for drug use in neonates
- avoid drugs in
give 2 specific examples of toxicity specific to neonates
> fluoroquinolones damage articular cartilage
> tetracyclines disclour teeth
How does drug use in geritrics differ?
^ risk ADR because..
- smaller body size
- poor nutritional status
- presence multiple diseases-
- altered complcance
- age related organ dysfunction eg. renal
Which drugs have ^ risk toxicity with subclinical renal impairment in humans?
- low TI eg. procainamide, digoxin, gentamicin
Which drugs are affected by decreased lean body mass?
cimetidine (for gastric ulcers) ^ plasma levels of polar drugs with v fat
