adverse drug reactions Flashcards
define side effect
any effect of a drug other than its intended therapeutic effect. Side effects may be beneficial, neutral or harmful,
example of a neutral side effect
• Digoxin causes a ‘reverse-tick’ (upwardly concave) pattern of ST-segment depression on the ECG. This is a ‘neutral’ marker of digoxin effect; it is neither beneficial nor harmful (although other ECG changes, such as premature beats, may indicate digoxin toxicity).
define adverse drug reaction
An adverse drug reaction (sometimes used synonymously with adverse effect) is by definition an unwanted or harmful reaction to a drug.
example of ADR related to the primary therapeutic effect of the drug
These are where the intended effect of the drug is intensified to the point that it is no longer desirable. An example is when beta-blockers induce heart block. This is related to the intended effect of beta-blockade on the heart, which is to reduce the rate and force of contraction, thus improving myocardial perfusion and oxygen demand. However, in inducing heart block (that is, impaired conduction between the atria and the ventricles) it has been taken to an undesirable level where it may cause harm. These effects are usually predictable, and can often be managed by reducing the dosage
ADR related to the known pharmacology or biochemistry of the drug, but not its primary therapeutic effects
For example, beta-blockers are known to cause bronchospasm in susceptible people, due to blockade of beta2 receptors in the airways. These are sometimes, but not always, predictable. Often, they are related to susceptibility factors (discussed later) in the person receiving the drug - e.g. bronchospasm due to beta-blockade is more likely in people who have asthma. Or they may be due to toxicity - e.g. in paracetamol-induced hepatotoxicity, the high concentrations of paracetamol lead to saturation of the main metabolic pathways, and the generation of a toxic metabolite through a different pathway.
characteristics of an IgE mediated immune reaction
Type 1
rapid onset, urticaria, angioedema
e.g. anaphylaxis
characteristics of an antibody-mediated cell destruction immune reaction
type 2
often haematological- haemolytic anaemia, thrombocytopenia, neutropenia
e.g. clozapine
characteristics of circulating immune complex mediated immune reaction
type 3
vasculitis type reactions, fever, lymphadenopathy, purpura, arthralgia
e.g. vasculitis due to furosemide
characteristics of a T cell mediated immune response
type 4
delayed onset, maculopapular rashes, contact dermatitis, severe skin reactions
e.g. SJS
classification of adverse drug reactions
DoTS:
dose relatedness
time relatedness
susceptibility factors
describe dose related ADRs
- Toxic reactions e.g. beta blocker induced heart block
- Collateral reactions: happen within the therapeutic dose range
- Maximal throughout the clinical therapeutic range: hyper-susceptibility reactions
describe time related ADRs
- Time independent
- Only on first dose, don’t recur on subsequent doses e.g. ACEi and alpha-blockers.
- Early: maximal when tx is started but diminish in intensity as treatment progresses, e.g. metformin. Can be mitigated by starting on low dose and patient education on what to expect.
- Intermediate: usually about 4 week mark, cell-mediate hypersensitivity reactions, toxic epidermal necrolysis and Steven-Johnson syndrome
- Late: build up progressively over time e.g. long term steroid therapy and Cushinoid syndrome
- Withdrawal: cold turkey- cold clammy skin with goosebumps
- Delayed: thocomelia and thalidomide
describe susceptibility factors in ADRs
- Genetics- malignant hyperthermia and inhaled anaesthetics
- Age- neonates and older people affect pharmacogenetics and pharmacodynamics
- Sex- reproductive system effects e.g. spironolactone is poorly tolerated by men because it is commonly associated with gynaecomastia
- Special circumstances- pregnancy
- Co-morbidity- renal or hepatic impairment
- Interactions- pharmacokinetic and pharmacodynamics
what are prescribers asked to report in the yellow card scheme
- All suspected ADRs for drugs marked with a black triangle in the BNF (this denotes drugs subject to additional monitoring—including all new drugs)
- All suspected ADRs in children
- All serious suspected ADRs in other circumstances
