adverse drug rxns

Question 1

Formula and definition for therapeutic index

Answer 1

Td50/Ed50, a ratio that expresses the relationship between the dose expected to elicit some adverse effect and the dose needed to elicit therapeutic effects

Question 2

adverse drug reaction definition

Answer 2

Unintended noxious effect of a pharmacological substance at regular therapeutic doses. Causally related to drug’s MOA. Occurs despite proper dosing and administration

Question 3

What is contraindication?

Answer 3

Context in which some drug should NOT be used because there is a high risk of harmful effects

Question 4

adverse drug event definition

Answer 4

Untoward medical occurrence which does not necessarily have a causal relationship with the MOA of the drug, but there is correlation between the occurrence and drug administration (e.g. overdosing, drug-drug interactions)

Question 5

type A (augmented) ADR

Answer 5

Accounts for 80% of ADRs, dose-dependent predictable/expected due to augmentation of the drug’s known pharmacological effects. Management = modification of the dose (e.g. hypotension from treatment with anti-hypertensive agent)

Question 6

type B (bizarre) ADR

Answer 6

dose-independent, unpredictable, unrelated to the pharmacology of the drug, but still causally related to the drug itself, e.g. hypersensitivity (immune-mediated)/idiosyncratic (immune-independent) drug allergies. High mortality relative to type A. Managed by ceasing administration.

Question 7

type I hypersensitivity

Answer 7

IgE-mediated, drug-IgE complex binds to mast cells triggering degranulation, histamine release

Question 8

type II hypersensitivity

Answer 8

cytotoxic, IgG/IgM directed to drug-hapten coated cells, results in haemolytic anaemia

Question 9

type III hypersensitivity

Answer 9

Drug-antibody complex causes complement activation, causes fever/rash over 1-3 weeks

Question 10

type IV hypersensitivity

Answer 10

cell-mediated, drug is presented to T cells causing cytokine/mediator release

Question 11

name of the receptor that has been implicated in idiosyncratic type B ADRs (causes mast cell activation without allergen-IgE interaction)

Answer 11

Mas-related GPCR X2 (MRGPRX2)

Question 12

type C ADR

Answer 12

chronic, long-term cumulative effect due to combination of dose and duration, can result in nephrotoxicity

Question 13

type D ADR

Answer 13

delayed, ADR is seen after drug administration is ceased, e.g. in the case of carcinogens, where cancer may only manifest years after exposure

Question 14

type E ADR

Answer 14

end-of-dose, withdrawal syndrome due to physiological dependency, e.g. adrenal insufficiency crisis due to shutdown of HPA axis from corticosteroid treatment, so patients need to be weaned off

Question 15

what is pharmacovigilance?

Answer 15

Study of drug-related injuries: Encompass detection, assessment, understanding, reporting, and prevention of ADRs