Adverse Drug Reactions

Question 1

What is an adverse drug reaction?

What is the most basic form of ADR classification?

Answer 1

Preventable or unpredictable medication event with harm to the patient;

Onset
Severity
Type

Question 2

Describe the classification of ADRs based on onset.

Answer 2

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

Question 3

Describe the classification of ADRs based on severity of the reaction.

Answer 3

Mild – requires no change in therapy
Moderate – requires change in therapy
Severe – disabling or life-threatening, and requires or prolongs hospitalisation

Question 4

Describe Type A ADR. Give examples

Answer 4

• Extension of pharmacological effect
• This is usually predictable and dose-dependent
• This is the most common type of ADR

e.g. atenolol and heart block, anticholinergics and dry mouth, NSAIDS and peptic ulcer

Question 5

Describe Type B ADR.

Answer 5

‘Bizarre’ type of ADR

• Idiosynchratic or immunologic reactions
• Includes allergy or pseudoallergy
• Very rare and unpredictable

e.g. chloramphenicol and aplastic anemia, ACE inhibitors and angioedema

Question 6

Describe Type C ADR.

Answer 6

• Associated with long-term use
• Involves drug accumulation

e.g. methotrexate and liver toxicity

Question 7

Define Type D ADR.

Answer 7

Delayed effects – sometimes dose independent

E.g. carcinogenicity and teratogenicity

Question 8

What reactions come under Type E ADRs.

Answer 8

Withdrawal reactions
Rebound reactions
Adaptive reactions

Question 9

Describe and explain clonidine rebound reaction.

Answer 9

Clonidine is an alpha-2 agonist so it suppresses the release of noradrenaline
Long-term use of clonidine leads to an upregulation in adrenergic receptors on the post-synaptic membrane
If the dose of clonidine is missed once or twice, it will cause an increase in noradrenaline release, which then acts on an increased number of receptors so has a greater effect
This causes a large increase in blood pressure

Question 10

Recall the ABCDE classification of adverse drug reactions?

Answer 10

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

Question 11

Describe the classification of allergies (4 types)

Answer 11

Type I - immediate, anaphylactic (IgE)
e.g., anaphylaxis with penicillins
Type II - cytotoxic antibody (IgG, IgM)
e.g., methyldopa and hemolytic anemia
Type III - serum sickness (IgG, IgM)
antigen-antibody complex
e.g., procainamide-induced lupus
Type IV - delayed hypersensitivity (T cell)
e.g., contact dermatitis

Question 12

Give examples of pseudoallergies.

Answer 12

Aspirin/NSAIDs – bronchospasm

ACE inhibitors – cough/angioedema

Question 13

What are the most common types of drugs causing ADRs?

Answer 13

Antineoplastics
Cardiovascular drugs
NSAIDs/analgesics
CNS drugs

Question 14

What is the yellow card scheme?

Answer 14

A voluntary scheme allowing doctors, dentists, nurses, coroners and pharmacists (and members of the public) to report serious adverse drug reactions

Question 15

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

Answer 15

• Data for drug-related hospital admissions do not separate out drug interactions
• 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 16

What are the three types of pharmacodynamic drug interaction?

Answer 16

Additive effects
Synergistic effects
Antagonistic effects

Question 17

What are the different types of pharmacokinetic drug interaction?

Answer 17

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

Question 18

Describe an example of alteration of absorption?

Answer 18

Irreversible binding of drugs in the GI tract

Tetracyclines, quinolone antibiotics

Question 19

Explain what is meant by protein binding effects.

Answer 19

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

Question 20

How are most drugs metabolised?

Answer 20

Most drugs metabolized by more than one CYP450 isozyme.

If co-administered with CYP450 inhibitor, some isozymes may “pick up slack” for inhibited isozyme

Question 21

Give a few examples of CYP450 inhibitors.

Answer 21

Cimetidine
Erythromycin
Ketoconazole
Ciprofloxacin
Ritonavir
Fluoxetine
Grapefruit juice

Question 22

Give a few examples of CYP450 inducers.

Answer 22

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

Question 23

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

Answer 23

Inhibition is RAPID

Induction takes hours/days

Question 24

Give an example of a deliberate drug interaction.

Answer 24

ACE inhibitors and thiazides

Question 25

Which cytochrome P450 enzymes are responsible for over half of drug metabolism (i.e. the most prevalent)?

Answer 25

CYP2D6

CYP3A4

Question 26

Give examples of drug elimination interactions (one positive, one negative); Where do they almost always occur?

Answer 26

Drug elimination interactions almost always occur in the renal tubules:

GOOD = Probenecid + penicillin ; Probenecid reduced excretion of penicillin and penicillin used to be expensive.

BAD = Lithium and thiazides ; thiazides lead to toxic accumulations of lithium.