Adverse Drug Reactions Flashcards
What is the cost benefit ratio?
Any drug has the potential to effect an individual patient adversely but we need to compare the ratio of anticipated benefits and potential risks
What isn’t included in adverse drug reactions (ADRs)?
Overdoses
ADRs only occur when drugs are given at correct doses
What are the different types of ADR?
Type A (augmented) Type B (bizarre) Type C (chronic) Type D (delayed) Type E (end of treatment) Type F (failure of treatment)
What is the incidence of ADRs in animals?
0.33% in one study
Why do we miss ADRs?
Almost always non-specific and rarely if ever pathognomonic for an ADR
Multiple medications
Underlying pathology
Assumption that active principle of a medication is responsible for ADR
How are ADRs detected?
Prior to registration in pre-marketing clinical trials
Post marketing surveillance in phase IV trials and through spontaneous reporting schemes
What are the reasons for low spontaneous reporting of ADRs?
Difference between types of practitioners (medical/surgical)
Belief that unusual/infrequent reactions were infrequent
Belief that common/trivial ADRs didn’t warrant reporting
Apathy
Too busy to fill in the paperwork
What are the factors that increase the reporting of ADRs?
Novelty of the reaction Severity of the reaction Limited time of suspected drug on market Media coverage Litigiousness of the owner
What are the limitations of spontaneous reporting of ADRs?
Suspected ADR reports are often incomplete and highly variable
Both under and over ascertainment occur
Not possible to calculate rates or incidences
Why are spontaneous ADR reports valuable?
Permit signal detection which permits hypotheses to be raised that can then be tested
What are type A ADRs?
Expected but exaggerated pharmacologic or toxic responses to a drug
Dose dependent
Avoidable if sufficient is known about the drug and patient
What factors influence type A ADRs?
Bioavailability
Distribution
Metabolism
Elimination
What factors influence drug disposition?
Species differences
Body size - dose reduciton in very large dogs
Body composistion - adjust dose if very fat/thin
Age
Pathology
Genetics
What effect does protein malnutrition have on drug metabolism?
CYP3A4 is reported to be decreased in 40-50% of control levels in rats with protein malnutrition
Reduced metabolism of clarithromycin and doxorubicin has been demonstrated
What effect does malnourishment have on drug metabolism?
Can have altered hepatic oxidative drug biotransformations and conjugates
What effect does starvation have on drug metabolism?
Significantly prolonged half-life and reduced hepatic clearance of phenazone in calves
What effect does fever have on drug metabolism?
Significant decreased in several hepatic enzymes demonstrated in febrile greyhounds
What genetic differences can alter drug metabolism?
CYP2D15 metabolises celecoxib (reduced in Beagles)
CYP2B11 metabolises propofol (14x difference in activity)
TMPT key for azathioprine (low in cats = myelosuppresion, high = poor antineoplastic activity)
P-gp or Mdr1 in Collies and collie like dogs
What are type B ADRs?
Unexpected or aberrant responses unrelated to the drug’s pharmacological effect
Not dose dependent, Unpredictable and idiosyncratic
Virtually impossible to avoid first time round
Should be considered a DDx in immune-mediated disease
What are pseudoallergic drug reactions?
Resemble drug allergies but don’t have an immunologic bases and often termed anaphylactoid
May be due to non-specific release of mediators of hypersensitivity
When do pseudoallergic drug reactions occur?
Rapid IV administration
