Adverse Drug Reactions Flashcards
What is an adverse drug reaction (ADR)?
Any undesirable reaction to a drug that results in harm to a patient in any way, regardless of whether the reaction is detectable or not
What is the difference between an adverse drug reaction and a side effect?
A side effect is a reaction seen alongside the desired effect of the drug and can be harmful (adverse drug reaction), beneficial or neutral
An adverse drug reaction is always undesirable
Adverse drug reactions are most common in what 3 patient groups?
- Elderly/frail
- Multimorbid (due to renal/hepatic clearance)
- Polypharmacy
(these risk factors are often all seen in one patient)
What is meant by therapeutic index?
It is a measurement of the safety of a drug, taking into account the dose of drug required to have a toxic vs a therapeutic effect
The higher the therapeutic index, the safer/more dangerous the drug
Safer
The smaller the therapeutic index, the more quickly a drug will move from therapeutic to toxic levels
How is therapeutic index (TI) calculated?
TI = TD50 / ED50 where…
TD50 = median toxic dose ED50 = median therapeutic dose
A drug has a ‘narrow therapeutic index’ when the TI is…?
< 2
List some drugs with a narrow therapeutic index
Theophylline Warfarin Lithium Digoxin Gentamicin Vancomycin Cyclosporin Levothyroxine
What are the 3 stages of ADR detection?
Drug development phase (pre-clinical)
Clinical trials (phases I-III)
Post-marketing surveillance (phase IV and beyond)
Why aren’t all ADRs picked up at the clinical trial stages?
Most new drugs get ~3000 short-term patient exposures in trials before they are licensed
Rare ADR’s are only seen post-licensing when a larger number of patients take them
ADRs are often related to drug metabolism. What are the 2 phases of drug metabolism?
Phase 1: Cytochrome P450 subsystems take the drug through oxidation, reduction, and hydrolysis
Phase 2: Drug is conjugated in the liver so it is able to be excreted in the urine/bile
ADRs are almost always due to phase 2 drug metabolism. T/F?
False
ADRs are almost always due to Phase 1 interactions
What are the 6 types of adverse drug reactions?
Type A: Augmented pharmacological effects Type B: Bizarre effects Type C: Chronic effects Type D: Delayed effects Type E: End-of-treatment effects Type F: Failure of therapy
Describe Type A (Augmented) ADRs
Give an example
They are predictable, dose-related reactions which are related to the pharmacological action of the drug
Acute tubular necrosis in a patient taking gentamicin
Describe Type B (Bizarre) ADRs
Give an example
They are unpredictable, non-dose-related reactions which cannot be explained by the pharmacological action of the drug. They have a high mortality
Aplastic anaemia in a patient taking chloramphenicol antibiotics
Describe Type C (Chronic) ADRs
Give an example
They are predictable, dose-related reactions which are expected when exposed to an accumulative dose of a drug overtime
Osteoporosis in a patient on long-term steroids for Cushing’s disease
Describe Type D (Delayed) ADRs
Give an example
They are time-related effects that occur some time after the use of the drug
Secondary malignancies seen many years post-chemotherapy
Describe Type E (End-of-treatment) ADRs
Give an example
They are effects seen soon after withdrawal of a drug therapy
Addisonian crisis in a patient stopping steroid therapy in adrenal insufficiency
Drugs can have a type A reaction with…? (3)
Other drugs
Disease
Foods
Give an example of a drug-drug Type A ADR
Macrolide antibiotics inhibit the cytochrome P450 that metabolises Theophylline
Give an example of a drug-disease Type A ADR
Beta blockers (e.g., prescribed for AF) can exacerbate asthma by binding to beta-2 receptors in the lungs, causing bronchoconstriction
Give an example of a drug-food Type A ADR
ADR in a patient who eats grapefruit, apple, orange or cranberry while on a statin or antihistamine
(due to inhibition of their cytochrome P450 metabolism)
In the BNF, new medicines that contain a new active ingredient which may cause an ADR are marked with a…?
An upside-down, black triangle
How can prescribers and patients report an ADR for a drug marked with the black triangle?
Using the Yellow Card Scheme
via the app (most popular), website, or filling in a paper form
When is the black triangle removed from a drug?
It’s status is reviewed every 2 years and the triangle is removed when safety has been established
