Adverse drug reactions Flashcards
what is an Adverse drug reaction (ADR)
World Health Organisation (WHO) definition (1):
A response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis or therapy of disease
How do we learn about ADRs?
common ADR found in pre marketing trials
Trials can be short and low patient number’s compared to population- old , young, pregnant, co morbidities and other drug interaction often not included
some ADR missed
Then found when drug enters market place
How does an Adverse Drug Reaction differ to an Adverse Event?
ADR –unwanted/harmful reaction experienced following the administration of a drug
ADE – more broad term and implies that the event may be coincidental
E.g patient having a road traffic accident while on a specific medication
Easy way to remember is ADE is seen from the point of view of the patient and ADR is seen from the point of view of the drug
what is an unexpected ADR?
An adverse reaction is “unexpected” if its nature and severity are not consistent with the information about the medicinal product
what is a serious ADR /
Results in death
Is life-threatening,
Requires hospitalisation or prolonged or existing hospitalisation,
Results in persistent or significant disability or incapacity,
Consists of a congenital anomaly or birth defect, or
Anything deemed to be of clinical significance
Describe the mnemonic A-E for classifying ADRs?
Type A - Augmented
Type B - Bizarre
Type C - Chronic
Type D - Delayed
Type E – End of dose
What key factors associated with ADRs?
The Drug- Narrow therapeutic window, components of the formulation have a tendency to cause allergy
The Patient- Age, genetic constitution, disease
The Prescriber- Drug given for inappropriately long time (deprescribing?), drug withdrawn too rapidly, drug given with other drugs leading to interaction
what is a type A ADR?
Augmented
Dose- Related
Common, related to pharmacological action, predictable, low-mortality
E.g. Bradycardia with Beta-blockers, Constipation with opioid
what is a type B ADR?
Bizarre
Non Dose-Related
Uncommon, unrelated to pharmacological action, unpredictable, high mortality
EG: anaphylaxis due to penicillin
Anaphylaxis is the most common serious ADR
what is a type C ADR?
Chronic
Dose Related and time related
Uncommon, related to the cumulative dose
e.g. Osteoporosis with prolonged use of steroids
what is a type D ADR?
Delayed
Time-related
Uncommon, usually dose related, becomes apparent some time after the use of the drug
e.g. reports of skin cancer following use of topical tacrolimus
what is a type E ADR?
End of dose
Withdrawal
Uncommon, occurs soon after withdrawal of the drug
e.g. insomnia and anxiety with withdrawal of benzos; withdrawal seizures when anticonvulsants are stopped
what are the two mechanisms of ADRs ?
Pharmacokinetic ADRs
Pharmacodynamic ADRs
what is a Pharmacokinetic ADR
Pharmacokinetic = what the body does to the drug
Problems with the absorption, distribution, metabolism or excretion of a drug
Most common in patients with hepatic or renal impairment
E.g. Digoxin toxicity at normal doses in patients with reduced kidney function, N+V, blurred vision, bradycardia
what is a Pharmacodynamic ADR
Pharmacodynamic = what the drug does to the body
Drug causes harm by its effect on the body
E.g. Asthmatic patient given beta-blockers = airway constriction
