Adverse Drug Reactions

Question 1

What is an adverse drug reaction?

Answer 1

Preventable or unpredictable medication event with harm to patient

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

Question 4

Define Type A ADR and give an example

Answer 4

Extension of pharmacological effect
Predictable + dose-dependent
Most common type of ADR
E.g. Atenolol slows HR but excess can cause heart block

Question 5

Define Type B ADR and give an example

Answer 5

‘Bizarre’ type of ADR
Idiosynchratic or immunologic reactions– includes allergy or pseudoallergy
Rare + unpredictable
E.g. Chloramphenicol + aplastic anaemia

Question 6

Define Type C ADR and give an example

Answer 6

Associated with long-term use
Involves drug accumulation
E.g. Methotrexate + liver toxicity

Question 7

Define Type D ADR and give an example

Answer 7

Delayed effects: sometimes dose independent

E.g. immunosuppressants are associated with delayed carcinogenicity

Question 8

Define Type E ADR and give an example

Answer 8

Withdrawal reactions (sudden cessation) e.g. Opiates
Rebound reactions (Stop drug, pathophysiology worsens than pre-drug) e.g. B-blockers
Adaptive reactions e.g. Neuroleptics

Question 9

Describe and explain clonidine rebound.

Answer 9

Clonidine is an A-2 agonist so suppresses release of NA
Long-term use leads to upregulation in adrenergic receptors on the post-synaptic membrane
If dose is missed, it will cause an increase in NA release, which then acts on an increased number of receptors so has a greater effect
Causes a large increase in BP

Question 10

What is 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.

Answer 11

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

Question 12

Give 2 examples of pseudoallergies.

Answer 12

Aspirin/NSAIDs + bronchoconstriction
Occurs because aspirin + NSAIDs inhibit production of prostanoids (bronchodilators) + promote production of leukotrienes (bronchoconstrictors)
ACE inhibitors + cough/ angioedema
ACE inhibitors prevent breakdown of kinins
Kinins accumulate in sensory nerves in lungs + trigger cough

Question 13

What are the 4 most common causes of ADRs?

Answer 13

Antineoplastics
Cardiovascular drugs
NSAIDs/ analgesics
CNS drugs

Question 14

What is the yellow card scheme?

Answer 14

Voluntary scheme allowing prescribers to report serious adverse drug reactions

Question 15

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

Answer 15

Lack of availability of comprehensive databases
Difficulty in assessing OTC + 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: 2 drugs provide similar effects by different MOA
Synergistic: 1 drug potentiates the effect of another
Antagonistic: 1 drug cancels the action of another

Question 17

What are 4 different types of pharmacokinetic drug interaction?

Answer 17

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

Question 18

What is an example of alteration of absorption?

Answer 18

Chelation:

Irreversible binding of drugs in GI tract forming insoluble complex which is un-absorbable

Question 19

Explain what is meant by protein binding interactions. Give an example of a drug in which this is clinically significant

Answer 19

Competition between drugs for protein or tissue binding sites
Can increase free unbound concentration of a drug thus enhancing pharmacological effects (e.g. warfarin)

Question 20

Which cytochrome P450 enzymes are responsible for over half of drug metabolism?

Answer 20

CYP2D6

CYP3A4

Question 21

Give 7 examples of CYP450 inhibitors.

Answer 21

Cimetidine  
Erythromycin + related antibiotics
Ketoconazole  
Ciprofloxacin + related antibiotics
Ritonavir + other HIV drugs
Fluoxetine + other SSRIs
Grapefruit juice

Question 22

Give 5 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 + thiazides (antihypertensives working in different ways)
Levodopa + Carbidopa (increases efficacy of levodopa in CNS)

Question 25

What characterises a severe adverse drug reaction/ what are the consequences?

Answer 25

Requires intervention to prevent permanent injury
Life threatening
Hospitalisation
Disability 
Congenital abnormalities 
Death

Question 26

How can type A adverse reactions differ? Explain using the examples of Digoxin and Paracetemol

Answer 26

Digoxin has a linear relationship between adverse reaction + dose
Paracetamol is harmless up to a certain dose, where toxicity sharply increases

Question 27

Give an example of a serious type B adverse reaction that was totally unexpected

Answer 27

Herceptin in breast cancer treatment caused cardiac toxicity

Question 28

In which way are most drugs metabolised? What is the consequence of this?

Answer 28

By multiple isozymes

Thus if 1 isozyme is inhibited, others can “pick up slack”

Question 29

Give 2 drug elimination interactions, one being desired the other unwanted

Answer 29

Good: Probenecid stopped elimination of penicillin, maintained high plasma conc.
Bad: Thiazide diuretics causing increased excretion of Na+, + lithium retention (to toxic levels)

Question 30

How does number of medications effect frequency of adverse drug reactions?

Answer 30

The more medications, the more adverse reactions