adverse drug reactions

Question 1

what is an adverse drug reaction

Answer 1

• any unintended, harmful reaction/event to a drug

Question 2

when can adverse drug reactions occur

Answer 2

• at any time, either following treatment, after stopping, or after long term use

Question 3

Describe the thalidomide disaster and how it relates to ADR

Answer 3

In the 50s pregnant women would take a drug, thalidomide to help with nausea and vomiting, however the drugs had serious effects on newborn babies, causing limb malformations

Question 4

What is the intended use of vicodin?

Answer 4

it is an anti-inflammatory drug designed to help with pain

Question 5

what type of inhibitor is vioxx?

Answer 5

it is a Cox2 inhibitor

Question 6

What adverse reactions did vioxx have that caused it to be withdrawn from the market?

Answer 6

It increased heart attacks due to decreased blood flow to myocardium

Question 7

what is another anti-inflammatory drug that was pulled from the market?

Answer 7

valedcoxia was pulled due to severe skin reactions

Question 8

T/F. polypharmacy has no effect on the risk of ADRs

Answer 8

false.
polypharmacy can actively increase the risk of ADRs

Question 9

what are some risk factors for ADRs

Answer 9

age combined with other risk factors
gender
geriatric predispositions

Question 10

how is gender a risk factor when it comes to ADRs

Answer 10

females may be more susceptible to GI reactions

Question 11

what is type a classification of ADRs

Answer 11

dose-related

Question 12

give an example of a drug that can cause type A ADR

Answer 12

respiratory depression with opiods and bradycardia from propanolol

Question 13

what is the severity of type A ADR dependent on? How may we prevent this ADR

Answer 13

it is dose dependent and we can fix this by doing a dose adjustment

Question 14

what are drug effects mediated by?

Answer 14

same receptors in the same tissue
same receptors in different tissues

Question 15

Give an example of drug effects of the same receptors in the same tissue

Answer 15

warfarin toxicities result from extension of therapeutic actions

Question 16

example of drug effects from same receptors in different tissues

Answer 16

digoxin, which is used for the treatment of heart failure causes an increase in the force of contraction but it can disrupt electrolyte balance impairing renal function

Question 17

give an example of a drug where its effects are mediated by different receptor subtypes

Answer 17

beta adrenergic drugs have an affinity for different types of receptors

Question 18

what beta adrenergic drugs cause effects mediated by other receptors

Answer 18

dobutamide binds to beta 1 r found in cardiac myocyte more than beta 2 to force the rate contraction but adverse effects like hypotension due to other beta R’s found in periphery

terbutaline binds to beta R 2 more than beta 1 R to relax bronciole smooth muscle cells but adverse effects including increased chest pain

Question 19

What is type B ADR classification

Answer 19

dose-unrelated ADR, which is unpredictable and uncommon

Question 20

what causes non-drug related ADR

Answer 20

genetic predisposition

Question 21

Example of ADR caused by genetic predisposition

Answer 21

hypersensitivity to HIV-medication, abacavir

destruction of red blood cells by primaquine (malaria medication) in individuals with G-6PD deficiency

Question 22

What are the ADRs due to immunologic reactions

Answer 22

type 1: anaphylactic
type 2: cytotoxic and complement fixing
type 3: toxic immune complex
type 4: cell-mediated

Question 23

Type 1: anaphylactic

Answer 23

this is when the drug reacts with IqE antibody in mast cells and basophils releasing histamine leukotrienes

Question 24

type 2: cytotoxic complement fixing

Answer 24

antibody interaction with drug on cell surface causing reduction in blood cells

Question 25

methyldopa

Answer 25

used for treatment of hypertension that causes anemia

Question 26

toxic immune complex

Answer 26

antigen-antibody complex deposit on target tissue cells.

these attract neutrophils and initiates inflammatory response and release of lysosomal enzymes that cause tissue destruction

Question 27

what is the type 4 cell-mediated immunologic reactions

Answer 27

drug interactions with sensitized lymphocytes and releases cytokines

it will cause eczematous and dermatitis

Question 28

what kind of drugs cause type 4 immunologic reactions

Answer 28

aromatic convulsants like phenytoin, sulfonamides , NSAIDs

Question 29

what rare disease is caused by type 3 and 4 immunologic reactions

Answer 29

steven’s johnson’s syndrome caused by antibodies mixed with phenytoin

Question 30

what other types of ADRs are there

Answer 30

chronic effects
delayed effects
end of treatment
failure of treatment

Question 31

phase I clinical trials

Answer 31

small population with healthy pool of people
Purpose: safety/dose finding and PK

Question 32

phase II clinical trials

Answer 32

small group in the hundreds
length :2-3 years
purpose” controlled studies to assess safety and efficacy in actual patients

Question 33

phase III clinical trials

Answer 33

length: 2-5 years
bigger group around 100-100s
purpose: controlled trials to verify efficacy, monitor safety and optimal dose

Question 34

phase IV

Answer 34

big population to assess long-term safety indications

Question 35

what are some systems in place to monitor ADR

Answer 35

spontaneous reports: national drug monitoring centers
databases: compile information from post-marketing surveillance studies and spontaneous systems
cohort studies: following a group of people to determine risk of ADR
case control

Question 36

limitations of spontaneous reporting

Answer 36

system bias due to the low willingness to report and low awareness of ADR

Question 37

limitation of databases

Answer 37

does not compare drugs or assess incidence rates
does not confirm causal associations and doesn’t account for differences in patient populations

Question 38

limitation of cohort studies

Answer 38

section bias, expensive and difficult to perform as well as large sample sizes for rare events

Question 39

limitation of case control studies

Answer 39

difficult with high incidence of ADR and the confirmation of drug exposure history is difficult

Question 40

what 3 drugs were taken off the market due to adverse drug effects?

Answer 40

thalidomide, terfenadine, and diethylstibestrol