Adverse drug reactions Flashcards
Define adverse drug reactions (ADRs).
Any undesirable effect of a drug beyond its anticipated
therapeutic effects occurring during clinical use.
– Including physical and mental harm, as well as loss of
function
… response to a medicinal product which is
noxious and unintended.
… may be new and previously unrecognised.
How many of all adult admissions to hospital are due to ADRs?
How many of these are avoidable?
1-in-16
3-in-4 of these ADRs were avoidable
Why are ADRs so important?
1 in 16 of all adult hospital admissions, median bed stay is 8 days so 4% of NHS bed capacity and a cost of >£500 million per year.
How many of all adult admissions to hospital experience an ADR whilst in hospital?
How many of these are avoidable?
Why is this important?
1-in-7
1 in 2
It increases mean bed stay by 0.25 days
How many of all paediatric admissions to hospital are due to ADRs?
How many of these are avoidable?
Why is this so important?
1-in-30
1-in-4
Projected cost of >£100 million annually
How many of all paediatric admissions to hospital experience an ADR whilst in hospital?
How many of these caused serious harm?
1-in-6
1-in-100
Why may ADRs in children be different? (3)
Altered FREQUENCY
– INCREASED frequency of hepatotoxicity to valproate
Altered SEVERITY
– REDUCED susceptibility to hepatotoxicity from paracetamol in infants
UNIQUE to childhood population
– GROWTH SUPPRESSION from corticosteroids
Give 4 examples of ADRs in children.
Aspirin –> Reye’s syndrome
Systemic chloramphenicol (abx) –> Gray baby syndrome
High dose pancreatic enzyme replacement –> bowel stenosis
SSRIs –> increased suicidal ideation in teenagers
Explain WHY ADRs may be different in children.
This is to do with changes in metabolic capacity. Using the following enzymes as examples:
CYP3A4 - the % of adult activity increases gradually, and doesn’t reach 100% until 1-10 years.
CYP1A2 - even at 1-10 years, this is only at 40%.
CYP2D6 - 25% at 8-28 days.
UGT2B7 - almost 170% at 1-10 years.
Describe the A-E classification of ADRs.
Type A (augmented) Type B (bizarre) Type C (continuing) Type D (delayed) Type E (end-of-use) (Type F (failure), G (genetic) and I (idiosyncratic))
Describe the DoTS classification of ADRs.
Dose
Timing
Susceptibility
What is a type A (augmented) reaction?
Exaggeration of a drugs normal pharmacological
actions when given at usual therapeutic doses.
It is normally dose-dependent and usually identified in clinical trials.
Most common drugs to cause type A ADRs. (4)
– Anti-platelets
– Diuretics
– NSAIDs
– Anticoagulants
Explain primary and secondary pharmacology in relation to type A reactions, using the examples of aspirin, bisoprolol and salbutamol.
Primary pharmacology = augmentation of desired actions
Secondary = often different organ systems
Aspirin - bleeding vs gastric irritation
Bisoprolol - bradycardia vs bronchospasm
Salbutamol - bronchodilation vs lactic acidosis
Pharmacologically Predictable ADRs - what are the 4 types (and give examples)?
Pharmaceutical e.g. phenytoin
Pharmacokinetic e.g. digoxin
Pharmacogenomic e.g. warfarin
Pharmacodynamic e.g. unfractionated heparin
Phenytoin - describe the toxicity and the mechanism.
Ataxia, nystagmus, etc
Increased bioavailability due to change in formulation
Digoxin - describe the toxicity and the mechanism.
Visual aura, nausea, arrhythmias, etc
Decreased elimination in renal failure
Warfarin - describe the toxicity and the mechanism.
Bleeding
CYP2C9 polymorphism
Unfractionated heparin - describe the toxicity and the mechanism.
Bleeding
Potentiates action of antithrombin III
