Principles of Drug Toxicity Flashcards
How is the therapeutic index calculated?
Toxic dose (50%)/Effective dose (50%)
What is the therapeutic index?
Risk benefit analysis undertake before the drug is authorised balancing the harmful and beneficial effects
What can affect the ability to predict the toxic effects of a drug?
If a drug concentration is increased it might have effects unrelated to mechanism of action
Might have chronic toxic effects
If used in food producing animals might have side effects for humans
How is drug toxicity and margin of safety assessed?
Usually have an idea from lab animal studies
Therapeutic dose decided and target animal specific safety studies undertaken
If used in food-producing animals life-time safety studies required in lab animals
Field safety and efficacy studies done with all adverse effects recorded
Periodic safety update reports filed for 2 years
Why do we see drug toxicity in veterinary patients?
We use drugs off label
We use drugs authorised for human use but not animals
Animals aren’t clones of original animals involved in testing
Mistakes made in calculating doses, storing and handling the drugs
Animals have multiple diseases so multiple drugs used
Define adverse drug reactions (ADR)
Unwanted effects when drugs administered for therapeutic purpose
Could broaden to lack of efficacy in a patient where you would expect the drug to work
What are type A ADRs?
Predictable from knowledge of mechanism of action of the drug
What are type B ADRs?
Not related to the mechanism of action of the drug therapeutically - could be predictable but some are idiosyncratic
How are idiosyncratic drug reactions detected?
A post-licensing surveillance scheme
What factors enhance ADR?
Physiological factors such as age, breed, gender
Disease status such as hepatic, renal and CVS
Concomitant use of other drugs
How do neonates differ physiologically from adults?
Decreased gut motility, under-developed gut flora and mucosal enzymes
Increased total body water
Immature liver enzymes
Decreased GFR
What are the empirical guidelines for drug use in neonates?
Avoid using drugs in neonates if possible
Choose drugs with wide therapeutic indices if possible
Choose a formulation that allows accurate dosing
Weigh the animal accurately
What are two examples of toxicities specific to neonates?
Fluoroquinolones damage articular cartilage
Tetracyclines discolour teeth
Why do geriatrics have increased risk of ADRs?
Smaller body size Poor nutritional status Presence of multiple disease processes Altered compliance Age related changes in organ fucntion
Why are there breed/species differences in risk of ADRs?
Most can be explained by differences in pharmacokinetics
Idiosyncratic reactions can be due to genetic polymorphisms with low rate of occurence
