ADRs Flashcards
(31 cards)
ADR
Adverse Drug Reaction (ADR)
A response to a medicinal product, or combination of medicinal products, which is noxious and unintended.
What are the impacts of ADR for the patient?
Reduced Quality of life
Poor compliance
Reduced confidence in clinicians and the healthcare system
Unnecessary investigations or treatments
What are the impacts of ADR for the NHS?
Increased hospital admissions
Longer hospital stays
GP appointments
Inefficient use of medication
Classification of ADRs
A - Augmented
B - Bizarre
C - Chronic/continuing
D - Delayed
E - End of use/withdrawal
F - failure of treatment
G - Genetic
Type A - Augmented
Most common type of ADR (80%).
Exaggerated effect of drugs pharmacology at a therapeutic dose
Often not life threatening
Dose dependent and reversible upon withdrawing the drug
Examples:
AKI with ACE inhibitors
Bradycardia with betablockers
Hypoglycaemia with gliclazide, insulin
Respiratory depression with opiates
Bleeding with anticoagulants
Type B - Bizarre
Not related to pharmacology of drug.
Not dose related.
Can cause serious illness or mortality.
Symptoms do not always resolve upon stopping drug.
Examples:
Anaphylaxis with penicillins
Tendon rupture with quinolone antibiotics
Steven Johnson Syndrome with IV vancomycin
Type C - Chronic/continuing
ADRs that continue after the drug has been stopped.
Examples:
Osteonecrosis of the jaw with bisphosphonates
Heart failure with pioglitazone
Type D - Delayed
ADRs that become apparent some time after stopping the drug.
Examples:
Leucopenia with chemotherapy
Tyep E - End of use/withdrawal
ADR develops after the drug has been stopped
Examples:
Insomnia after stopping benzodiazepine
Rebound tachycardia after stopping beta-blocker
Nasal congestion after stopping xylometolazine nasal spray
Type F - Failure of treatment
Unexpected treatment failure.
Could be due to drug-drug interaction or drug-food interaction.
Poor compliance with administration instructions.
Examples:
Failure of oral contraceptive pill due to St John’s Wort
Failure of DOAC due to enzyme inducer (eg carbamazepine)
Failure of bisphosphonate due to taking with food
Type G - Genetic
Drug causes irreversible damage to genome.
Examples:
Phocomelia in children of women taking thalidomide.
DoTS
An alternative way to classify ADRs
Dose-relatedness
Timing
Susceptibility
Provides more details.
Dose-relatedness
Hypersusceptibility: ADRs at subtherapeutic doses (anaphylaxis with penicillins).
Collateral effects (side effects): ADRs at therapeutic doses (hypokalaemia with loop diuretic).
Toxic effects: ADR at supra therapeutic doses (liver damage with paracetamol).
Time independent ADRs
Develop during any time during treatment (often due to clinical changes in the patient).
Time dependent ADRs
Rapid - due to rapid administration, red man syndrome with IV vancomycin.
First dose - first dose only, hypotension with first dose of ACEi.
Early - occur during treatment but resolve as treatment progresses, headache with nitrates.
Intermediate - occur after some delay, interstitial nephritis with penicillins.
Late - risk increases with prolonged or repeated exposure, OA with prednisolone.
Delayed - occur some time after exposure or after drug withdrawal, drug related cancers.
DoTS - Susceptibility
Certain patient groups/populations may have a specific susceptibility to ADRs from a drug.
Age (anticholinergics in elderly patients)
Gender (metoclopramide in females)
Disease states (eg diclofenac in CVD)
Physiological states (eg phenytoin in pregnancy)
Susceptibility data may not be known
How are ADRs identified?
Pre-clinical testing (computer models, cells and toxicity testing in animals)
Clinical trial data (pre-marketing evaluation)
Post marketing surveillance
Pharmacovigilance
SPC form of drugs.
Toxicity testing
Testing in animals before being given to humans.
Long term administration in different species.
Toxic doses given to identify likely ‘targets’ of toxic effects.
Recovery studies aim to identify irreversible ADRs (e.g. carcinogenesis and neurodegeneration).
Acceptable level of toxicity depends on intended indication.
Findings may halt development of drug or provide focus for future trials
What are the three stages of clinical trials?
1- administration of 1 dose usually to healthy volunteers (sometimes in patients).
2 - administration of drug to selected populations for which the drug will eventually be indicated. Dose finding.
3 - Randomised controlled trials (RCTs). Any ADRs identified have to be included in the SPC.
What are the limitations of pre-marketing evaluation?
Low patient numbers
Exclusion of specific patient groups (many at high risk of ADRs):
Elderly, frail
Polypharmacy, multimorbid
Severe organ dysfunction
Neonatal and paediatric population
ADRs with incidence over 1% will generally be identified (most likely Type A).
Less common ADRs (including Type B) are less likely to be identified.
Post marketing surveillance
Full ADR profile is unlikely to be understood once the drug is in widespread clinical use.
ADR frequency (including rare ADRs)
Identify groups who may be especially susceptible:
- Drug dose ranges
- Gender
- Age
- Disease state
After product licence is granted by MHRA medicines are subject to post marketing surveillance (usually at least 5 years).
Additional monitoring to inform risk-benefit profile when used in everyday practice.
Established medicines may be placed back under post marketing surveillance if the manufacturer wants to amend licence (eg use for a new indication).
Black triangle medications
Medicines subject to post marketing surveillance are indicated by a black triangle:
BNF (under Medicinal Forms section)
SPC
Patient information leaflet (see below)
All ADRs should be reported for Black triangle medicines!
What are the steps of pharmacovigilance?
Collect reports of ADRs in everyday use for licensed medicines, unlicensed medicines, herbal medicines, biological products and vaccines.
Monitor known ADRs and identifies previously unknown ADRs.
Assess risk/benefits of the medicine and decide on safest course of action.
Provide information and guidance on identified safety issues to healthcare professionals and public.
What are the strengths of the yellow card system?
Confidential
No fear of litigation
Quick to submit
Accessible to all (HCPs and patients)
