Adverse drug reaction Flashcards
Define adverse drug reaction
Response to medicinal product, or combination of medicinal products, which is noxious and unintended
What do ABCDEFG stand for in ADR classification?
A - augmented
B - bizzare
C - chronic/ continuing
D - delayed
E - end of use/withdrawal
F - failure of treatment
G - genetic
Describe effects of Bizzare ADR, and give examples
Not related to pharmacology of drug
Not dose related
Can cause serious illness or mortality
Symptoms don’t always resolve on stopping drug
E.g. anaphylaxis w/penicillins, tendon rupture w/quinolone antiboitics, Steven Johnson Syndrome w/IV vancomycin
Describe effects of Chronic/continuing ADR, and give examples
ADRs continues after drug has been stopped
E.g. Osteonecrosis of jaw w/bisphosphates, heart failure w/pioglitazone
Describe effects of delayed ADRs and give an example
ADRs that become apparent some time after stopping drug
E.g. Leucopenia w/chemotherapy
Describe effects of End of use/Withdrawal ADRs, and give examples
ADR develops after drug has been stopped
E.g. insomnia post benzodiazepine, rebound tachycardia post beta-blocker, nasal congestion post xylometolazine nasal spray
Describe effects of Failure of Treatment ADRs, and give examples
- Unexpected treatment failure
- Could be due to drug-drug interaction/ drug-food interaction
- Poor compliance w/administration insutrctions
- E.g. failure of oral contraceptive pill due to St. John’s Wort, failure of DOAC due to enzyme inducer, failure of bisphosphonate due to taking with food
Describe effects of Genetic ADRs and give an example
Drug causes irreversible damage to genome
E.g. phacomelia in children of thalidomide
State what the DoTS classification of ADRs stands for
- Dose relatedness
- Timing
- Suseptibility
Describe factors relating to Dose-relatedness in ADRs, and give examples
- Hypersusceptibility - ADRs at subtherapuetic doses, e.g. anaphylaxis w/penicillins
- Collateral effects - ADRs at therapeutic doses, e. g. hypokalaemia w/loop diuretics
- Toxis effects - ADRs at subpratherapeutic doses, e.g. liver damage w/paracetamol
State four factors relating to Susceptibility in ADRs, and give examples
Age
gender
disease states
physiological states
How are ADRs identified?
- Preclinical testing, e.g. on animals
- Clinical trials data
- Post marketing surveillance
- Pharmacovigilance
Describe the steps of toxicity testing
- Testing in animals before given to humans
- Long term administration to diff species
- Toxic doses given to identify ‘targets’ of toxic effects
- Recovery studies aim to identify irriversible ADRs
- Acceptable level of toxicity depends on intended indication
- Findings can halt development of drug
State 3 stages of clinical trials for Pre marketing evaluation
- Administration of 1 dose to usually healthy volunteers, or patients
- Administration of drug to selected populations for which drug is intended - to find dose
- RTCs, any ADRs identified are included in SPC
State some limitations of Pre marketing evaluation
- Low patient numbers
- Exclusion of patient groups who may be at high risk of ADRs
- ADRs of type A more likely to be identified
- Less common ADRs, e.g. type B, less likely identified
