L.13 Adverse medicine reactions

Question 1

Define adverse drug reaction

Answer 1

A noxious or unintended response to a drug which occurs at doses normally used in humans for medical therapy.

Question 2

What are the 6 classifications of adverse drug reactions

- based on drug mechanisms

Answer 2

• Type A (augmented pharmacological effect),
• Type B (bizarre),
• Type C: chronic effects,
• Type D: delayed effects,
• Type E: end of treatment effect,
• Type F: failure of treatment

Question 3

What is the mechanism of Type A: Augmented adverse drug reaction and give example.

Answer 3

Related to main pharmacological action of the drug or the cytotoxic action of the drug or its metabolites.
- its predictable and proportional to dose

Eg. hypoglycaemia with too much insulin/ glipizide, paracetamol hepatotoxicity

Question 4

What does cytotoxicity mean and what are the two main types

Answer 4

Drugs or reactive metabolites may directly damage cells by forming covalent bonds or alter target molecules by noncovalent interaction.

Hepatotoxicity: high levels of metabolites in liver damage it.
Nephrotoxicity: high levels of polar drugs/metabolites within the nephron which damage it.

Question 5

What is the mechanism of Type B: Bizarre drug reaction and give example.

Answer 5

Not related to the main pharmacological action of the drug.

• Not predictable or dose related.
• Occur by mechanisms of allergic reactions or pharmacogenetic variability
  eg. Benzylpenicillin allergy

Question 6

What are the features of Allergic reaction as an adverse drug reaction

Answer 6

After initial exposure and sensitisation, then on repeated exposure an allergic reaction.
This has acute hypersensitivity, skin rash, haematological reaction.

More commonly to antibiotics, NSAIDS, radio contrast and anaesthetic agents.

Question 7

What is the mechanism of Type C: Chronic effects of longterm therapy drug reaction and give example.

Answer 7

Adverse reaction where long term treatment may alter receptor expression/ and or tissue sensitivity to drugs. This can occur during therapy or after withdrawal of the drug.
eg. Haloperidol induced dyskinesia

Question 8

What is the mechanism of Type E: End of treatment effect drug reaction and give example.

Answer 8

Abrupt cessation of treatment can cause symptoms because of unopposed change in receptor expression or tissue sensitivity- withdrawal reaction
eg. Dexamethasone induced adrenocorticoid insufficiency

Question 9

What is the mechanism of Type D: delayed drug reaction and give example.

Answer 9

1. Reaction is carcinogenesis because the drug causes mutations by covalently modifying DNA in growth regulatory proto-oncogenes or tum-sup-genes. Or by promoting cell proliferation
   eg. Doxorubicin topoisomerase inhibitor used in child survivors of cancer increase 2nd cancer risk
2. Reaction is fetal malformations at birth (teratogenecity) due to drugs prescribed in pregnancy
   eg. Doxycycline induced tooth discolouration and malformation

Question 10

How are adverse drug reactions prevented

Answer 10

Know the different classifications, know when ppl have increased risk for

• fetus, elderly, patients with previous drug reaction, liver or kidney disease and the higher number drugs given due to statistics, renal/hepatic function, drug-drug interactions etc
• Post market monitoring aims to detect serious or unexpected adverse drug reactions

Question 11

Where do you source information for prescriber about adverse drug reactions

Answer 11

Information about drug safety pre trial is in the DATA sheet on the NZformulary drug label: legal document

Post market info is found through Intensive medicines monitoring programme, and also voluntarily reported