Adverse Drug Reactions

Question 1

Define Type A ADR.

Answer 1

Extension of pharmacological effect
This is usually predictable and dose-dependent
This is the most common type of ADR – 2/3
Example: atenolol can slow down heart rate but if you give too much you could cause heart block

Question 2

Define Type B ADR.

Answer 2

‘Bizarre’ type of ADR
Idiosynchratic or immunologic reactions – includes allergy or pseudoallergy
This is very rare and unpredictable
Example: chloramphenicol and aplastic anaemia

Question 3

Define Type C ADR.

Answer 3

Associated with long-term use
Involves drug accumulation
E.g. methotrexate and liver toxicity

Question 4

Define Type D ADR.

Answer 4

Delayed effects – sometimes dose independent

E.g. carcinogenicity and teratogenicity

Question 5

Define Type E ADR.

Answer 5

Withdrawal reactions
Rebound reactions
Adaptive reactions

Question 6

What is the ABCDE classification of adverse drug reactions?

Answer 6

A – augmented pharmacological action   
B – bizarre 
C – chronic  
D – delayed  
E – end of treatment

Question 7

Describe the classification of allergies.

Answer 7

Type 1 – immediate, anaphylaxis (IgE)
Type 2 – cytotoxic antibody (IgG + IgM) ]
Type 3 – serum sickness (IgG + IgM)
Type 4 – delayed hypersensitivity (T cell)

Question 8

What are the most common causes of ADRs

Answer 8

Antineoplastics
Cardiovascular drugs
NSAIDs/analgesics
CNS drugs

Question 9

Why is it difficult to determine the incidence of drug-drug interactions?

Answer 9

There is a lack of availability of comprehensive databases
Difficulty in assessing OTC and herbal drug therapy use
Difficulty in determining contribution of drug interaction in complicated patients

Question 10

What are the three types of pharmacodynamic drug interaction?

Answer 10

Additive effects- have same effect on similar receptors
Synergistic effects- potentiates effects of another
Antagonistic effects- decreases effects of another

Question 11

What are the different types of pharmacokinetic drug interaction?

Answer 11

Alteration in drug absorption
Protein binding effects
Changes in drug metabolism
Alteration in elimination

Question 12

What is an example of alteration of absorption?

Answer 12

Chelation- irreversible binding of drugs in GI tract

Question 13

Explain what is meant by protein binding effects.

Answer 13

Competition between drugs for protein or tissue binding sites
It can increase free unbound concentration of a drug thus leading to enhanced pharmacological effects (e.g. warfarin)

Question 14

Which cytochrome P450 enzymes are responsible for over half ofdrug metabolism?

Answer 14

CYP2D6

CYP3A4

Question 15

Give a few examples of CYP450 inhibitors.

Answer 15

Cimetidine  
Erythromycin  
Ketoconazole  
Ciprofloxacin  
Ritonavir  
Fluoxetine  
Grapefruit juice

Question 16

Give a few examples of CYP450 inducers.

Answer 16

Rifampicin  
Phenytoin 
Carbamazepine  
St. John’s Wort (hypericin) 
Phenobarbitone

Question 17

Describe the difference in the speed of inhibition and the speed of induction of CYP450 enzymes.

Answer 17

Inhibition is RAPID

Induction takes hours/days

Question 18

Give an example of a deliberate drug interaction.

Answer 18

ACE inhibitors and thiazides

Question 19

3 ways to classify ADRs

Answer 19

Onset
Severity
Type

Question 20

Onset classification

Answer 20

Acute <1 hour
Sub-acute 1-24 hours
Latent> 2 days

Question 21

Severity classification

Answer 21

Mild- no therapy needed
Moderate- requires change in therapy or further treatment
Severe- disabling

Question 22

What can happen in severe ADR

Answer 22

Congenital abnormalities
Prolonged treatment
Life threatening

Question 23

What are pseudoallergies

Answer 23

Reactions to drugs that have no immune involvement

Question 24

Examples of pseudoallergies

Answer 24

ACE inhibitors- cough/ angioedema

Aspirin- bronchospasm

Question 25

What is the yellow card scheme

Answer 25

Came post thalidomide scandal
For drugs that are established you have to only report a serious ADR but for drugs that are “black triangle” which have only been on the market for less than 2 years you have to report any suspected ADR

Question 26

3 types of drug interactions

Answer 26

Pharmacodynamic- drugs effect in body
Pharmacokinetic- bodys effects in body
Pharmaceutical- drug interaction outside body in IV infusions