Adverse Drug Interactions

Question 1

What is the difference between side effect and Adverse Drug Reaction?

Answer 1

=> Side effect:
- Any effect other than the therapeutic effect, whether beneficial, neutral or harmful

=> Adverse drug interaction:
- Narrow definition specifically concerning the unwanted or harmful effect of a drug

Question 2

Why are ACEi good to take in CKD, but not advised for AKI?

Answer 2

ACEi cause dilation of the efferent arteriole, reducing the pressure difference across the glomerulus. In CKD, this is what you want as it decreases hyper-perfusion (something that can exacerbates kidney damage long term). However, in AKI, hyper-perfusion is necessary as the problem is more acute, meaning giving ACEi and stopping this process exacerbates the persons condition

Question 3

What is the pathophysiology of ADRs?

Answer 3

• ADRs usually occur as a result of primary, secondary or unrelated effects of the drug

=> Primary effects:

• Usually predictable
• Eg. B blockers given in cases of tachycardia can induce bradycardia

=> Secondary effects:

• Sometimes predictable
• B blocks inducing bronchospasm

=> Unpredictable

• Not predictable
• Hypersensitivity reactions

Question 4

What are the different hypersensitivity reactions, mechanisms and characteristics?

Answer 4

=> Type 1 hypersensitivity:

• IgE medicated
• Rapid onset, Urticaria, Angioedema

=> Type 2 Hypersensitivity:

• Antibody-mediated cell destruction
• Cell line is lost: anaemia, thrombocytopenia or neutropenia

=> Type 3 Hypersensitivity reaction:

• Circulating immune complexes
• Fever, lymphadenopathy, purpura, arthralgia

=> Type 4 Hypersensitivity reaction:

• T cell mediated
• Typically delayed onset, dermatitis, severe skin reactions

=> Main difference between type 2 and 3 is that in type 2, the antigen-antibody complexes is bound to a cell surface where as in type 3 the immune complex is free floating and the clinical feature depends on where this complex is deposited

Question 5

How are ADRs classified?

=> Mnemonic - DoTS

Answer 5

=> Do - Dose relatedness

=> T - Time course

=> S - Susceptibility factors

Question 6

What are some examples of drugs that cause ADRs depending on dose?

Answer 6

=> Excessive doses

• Cause Toxic ADRs
• Gentamicin can cause Nephrotoxicity

=> Therapeutic doses

• Collateral ADRs
• Antibiotics causing C-diff associated diarrhoea

=> Sub-therapeutic doses:

• Hyper susceptibility ADRs
• Anaphylaxis

Question 7

What are some examples of drugs that cause ADRs depending on time?

Answer 7

=> Rapid immediate ADRs:
- Drugs that cause type 1 hypersensitivity

=> ADRs only at the first dose:
- ACEi or alpha blocker cause hypotension on first dose

=> ADRs only in early courses then diminish later on:

• Metformin may cause nausea at first
• Gabapentin may cause drowsiness or GI upset at first

=> ADRs that occur during the intermediate course:

• Can cause Erythema multiforme which can develop into the ore severe Steven Johnson Syndrome
• Steven Johnson Syndrome can progress to Toxic necrotising fascitis
• Stop drug immediately
• Carbamazapine, Allopurinol

=> ADRs that occur late, due to cumulative effect:
- Exposure to a carcinogenic compound where the cancer does not develop until several years after