Adverse Drug Reactions

Question 1

What is the cost benefit ratio?

Answer 1

Any drug has the potential to effect an individual patient adversely but we need to compare the ratio of anticipated benefits and potential risks

Question 2

What isn’t included in adverse drug reactions (ADRs)?

Answer 2

Overdoses

ADRs only occur when drugs are given at correct doses

Question 3

What are the different types of ADR?

Answer 3

Type A (augmented)
Type B (bizarre)
Type C (chronic)
Type D (delayed)
Type E (end of treatment)
Type F (failure of treatment)

Question 4

What is the incidence of ADRs in animals?

Answer 4

0.33% in one study

Question 5

Why do we miss ADRs?

Answer 5

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

Question 6

How are ADRs detected?

Answer 6

Prior to registration in pre-marketing clinical trials

Post marketing surveillance in phase IV trials and through spontaneous reporting schemes

Question 7

What are the reasons for low spontaneous reporting of ADRs?

Answer 7

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

Question 8

What are the factors that increase the reporting of ADRs?

Answer 8

Novelty of the reaction
Severity of the reaction
Limited time of suspected drug on market
Media coverage
Litigiousness of the owner

Question 9

What are the limitations of spontaneous reporting of ADRs?

Answer 9

Suspected ADR reports are often incomplete and highly variable
Both under and over ascertainment occur
Not possible to calculate rates or incidences

Question 10

Why are spontaneous ADR reports valuable?

Answer 10

Permit signal detection which permits hypotheses to be raised that can then be tested

Question 11

What are type A ADRs?

Answer 11

Expected but exaggerated pharmacologic or toxic responses to a drug
Dose dependent
Avoidable if sufficient is known about the drug and patient

Question 12

What factors influence type A ADRs?

Answer 12

Bioavailability
Distribution
Metabolism
Elimination

Question 13

What factors influence drug disposition?

Answer 13

Species differences
Body size - dose reduciton in very large dogs
Body composistion - adjust dose if very fat/thin
Age
Pathology
Genetics

Question 14

What effect does protein malnutrition have on drug metabolism?

Answer 14

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

Question 15

What effect does malnourishment have on drug metabolism?

Answer 15

Can have altered hepatic oxidative drug biotransformations and conjugates

Question 16

What effect does starvation have on drug metabolism?

Answer 16

Significantly prolonged half-life and reduced hepatic clearance of phenazone in calves

Question 17

What effect does fever have on drug metabolism?

Answer 17

Significant decreased in several hepatic enzymes demonstrated in febrile greyhounds

Question 18

What genetic differences can alter drug metabolism?

Answer 18

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

Question 19

What are type B ADRs?

Answer 19

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

Question 20

What are pseudoallergic drug reactions?

Answer 20

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

Question 21

When do pseudoallergic drug reactions occur?

Answer 21

Rapid IV administration