Adverse Drug Reactions

Question 1

What is an adverse drug reaction (ADR)?

Answer 1

Any undesirable reaction to a drug that results in harm to a patient in any way, regardless of whether the reaction is detectable or not

Question 2

What is the difference between an adverse drug reaction and a side effect?

Answer 2

A side effect is a reaction seen alongside the desired effect of the drug and can be harmful (adverse drug reaction), beneficial or neutral

An adverse drug reaction is always undesirable

Question 3

Adverse drug reactions are most common in what 3 patient groups?

Answer 3

• Elderly/frail
• Multimorbid (due to renal/hepatic clearance)
• Polypharmacy

(these risk factors are often all seen in one patient)

Question 4

What is meant by therapeutic index?

Answer 4

It is a measurement of the safety of a drug, taking into account the dose of drug required to have a toxic vs a therapeutic effect

Question 5

The higher the therapeutic index, the safer/more dangerous the drug

Answer 5

Safer

The smaller the therapeutic index, the more quickly a drug will move from therapeutic to toxic levels

Question 6

How is therapeutic index (TI) calculated?

Answer 6

TI = TD50 / ED50 where…

TD50 = median toxic dose
ED50 = median therapeutic dose

Question 7

A drug has a ‘narrow therapeutic index’ when the TI is…?

Answer 7

< 2

Question 8

List some drugs with a narrow therapeutic index

Answer 8

Theophylline
Warfarin 
Lithium
Digoxin
Gentamicin
Vancomycin 
Cyclosporin
Levothyroxine

Question 9

What are the 3 stages of ADR detection?

Answer 9

Drug development phase (pre-clinical)
Clinical trials (phases I-III)
Post-marketing surveillance (phase IV and beyond)

Question 10

Why aren’t all ADRs picked up at the clinical trial stages?

Answer 10

Most new drugs get ~3000 short-term patient exposures in trials before they are licensed

Rare ADR’s are only seen post-licensing when a larger number of patients take them

Question 11

ADRs are often related to drug metabolism. What are the 2 phases of drug metabolism?

Answer 11

Phase 1: Cytochrome P450 subsystems take the drug through oxidation, reduction, and hydrolysis

Phase 2: Drug is conjugated in the liver so it is able to be excreted in the urine/bile

Question 12

ADRs are almost always due to phase 2 drug metabolism. T/F?

Answer 12

False

ADRs are almost always due to Phase 1 interactions

Question 13

What are the 6 types of adverse drug reactions?

Answer 13

Type A: Augmented pharmacological effects
Type B: Bizarre effects
Type C: Chronic effects
Type D: Delayed effects
Type E: End-of-treatment effects
Type F: Failure of therapy

Question 14

Describe Type A (Augmented) ADRs

Give an example

Answer 14

They are predictable, dose-related reactions which are related to the pharmacological action of the drug

Acute tubular necrosis in a patient taking gentamicin

Question 15

Describe Type B (Bizarre) ADRs

Give an example

Answer 15

They are unpredictable, non-dose-related reactions which cannot be explained by the pharmacological action of the drug. They have a high mortality

Aplastic anaemia in a patient taking chloramphenicol antibiotics

Question 16

Describe Type C (Chronic) ADRs

Give an example

Answer 16

They are predictable, dose-related reactions which are expected when exposed to an accumulative dose of a drug overtime

Osteoporosis in a patient on long-term steroids for Cushing’s disease

Question 17

Describe Type D (Delayed) ADRs

Give an example

Answer 17

They are time-related effects that occur some time after the use of the drug

Secondary malignancies seen many years post-chemotherapy

Question 18

Describe Type E (End-of-treatment) ADRs

Give an example

Answer 18

They are effects seen soon after withdrawal of a drug therapy

Addisonian crisis in a patient stopping steroid therapy in adrenal insufficiency

Question 19

Drugs can have a type A reaction with…? (3)

Answer 19

Other drugs
Disease
Foods

Question 20

Give an example of a drug-drug Type A ADR

Answer 20

Macrolide antibiotics inhibit the cytochrome P450 that metabolises Theophylline

Question 21

Give an example of a drug-disease Type A ADR

Answer 21

Beta blockers (e.g., prescribed for AF) can exacerbate asthma by binding to beta-2 receptors in the lungs, causing bronchoconstriction

Question 22

Give an example of a drug-food Type A ADR

Answer 22

ADR in a patient who eats grapefruit, apple, orange or cranberry while on a statin or antihistamine
(due to inhibition of their cytochrome P450 metabolism)

Question 23

In the BNF, new medicines that contain a new active ingredient which may cause an ADR are marked with a…?

Answer 23

An upside-down, black triangle

Question 24

How can prescribers and patients report an ADR for a drug marked with the black triangle?

Answer 24

Using the Yellow Card Scheme

via the app (most popular), website, or filling in a paper form

Question 25

When is the black triangle removed from a drug?

Answer 25

It’s status is reviewed every 2 years and the triangle is removed when safety has been established