Adverse drug reactions

Question 1

What are the different types of ADRs?

Answer 1

A - extension of pharmacological effect
B - idiosynchratic/immunological reactions (allergy, pseudoallergy)
C - chronic, involves dose accumulation
D - delayed effects
E - withdrawal, rebound and adaptive reactions

Question 2

How can genetic differences influence individual responses to drugs?

Answer 2

Genetic polymorphisms in genes coding for specific enzymes that metabolise specific drugs can lead to drug toxicity

Question 3

How can polypharmacy affect drug reaction?

Answer 3

Pharmacodynamic drug interactions:

1. Additive effects - 2 drugs add together
2. Synergistic effects - 2 drugs potentiate each other’s actions –> greater effect than expected
3. Antagonist effects - drugs can antagonise each other’s action

Also drug metabolism could be inhibited/enhanced by coadministration of other drugs

Question 4

How can age affect drug reaction?

Answer 4

Elderly patients w/multiple medical problems taking multiple drugs, those who have a history of ADRs, and those w/reduced capacity to eliminate drugs (poor renal function) are at high risk for ADRs

Infants and young children at high risk of ADRs bc capacity to metabolize the drug is not fully evaluated

Neonates have immature renal tubular function, low body fat (affected by lipid soluble drugs), immature BBB (increased anaesthetic effects)

Question 5

How can diet affect drug reaction?

Answer 5

• Can alter drug absorption
• Chelation - irreversible binding of drugs in GIT makes it difficult to absorb
• E.g. tetracyclines + ferrous sulphate, antacids, dairy products (Ca2+) interferes w/absorption

Question 6

How can renal function affect drug reaction?

Answer 6

Poor renal function prevents drug elimination

Drug can accumulate to toxic dose

Question 7

List the drugs known to be CYP450 inducers

Answer 7

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

Question 8

List the drugs known to be CYP450 inhibitors

Answer 8

• Cimetidine (H2 antagonist)
• Erythromycin + related ABs
• Ketoconazole
• Ciprofloxacin + related ABs
• Ritonavir + other HIV drugs
• Fluoxetine + other SSRIs
• Grapefruit juice

Question 9

How may enzyme inducers and inhibitors cause ADRs?

Answer 9

If specific enzyme inhibitor is coadministered w/drug metabolised by that single isozyme of CYP450, drug will not be eliminated
Inhibition is rapid and induction takes hours/days, drug accumulates and can become toxic

Question 10

What is an ADR?

Answer 10

Preventable or unpredicted medication event with harm to patient

Question 11

How can ADRs be classified by onset?

Answer 11

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

Question 12

How can ADRs be classified by severity of reaction?

Answer 12

Mild - requires no change in therapy
Moderate - requires change in therapy, additional treatment, hospitalisation
Severe - disabling or life-threatening - results in death, requires/prolongs hospitalisation, causes disability, causes congenital abnormalities, requires intervention to prevent permanent injury

Question 13

How can ADRs be classified?

Answer 13

1. By onset
2. By severity
3. By type