8. Adverse Drug Reactions Flashcards
Why do dentists need to understand these?
- need to fully understand potential for interactions of drugs
- under-reported often as inability to recognise them or not seen
Define ‘adverse drug reaction’
- harmful or seriously unpleasant event
- occurring at a dose intended for therapeutic effect
- calls for reduction of dose or withdrawal of drug
Historical events and dates of major issues
- 1937 - sulphanilamide
- 1961 - thalidomide
- 1971 - diethylstilbestrol (uterine cancer in offspring)
- 2006 - TGN1412 (excess cytokine release)
How does the iceberg theory link to clinical trial?
- tip of the iceberg is what we know at the end of the clinical trial
- below the sea is what happens when drug is in normal practice
Are any drugs fully harmless?
- no
- any drug which is pharmacologically effective carries some hazard
Drug safety is a relative concept and takes into account …
- severity of adverse drug reaction
- disease
- therapeutic alternatives
- individual perception and acceptance of risk
What suggests a cause and effect relationship between drug administration and adverse drug reaction?
- time sequence between taking drug and adverse reaction
- reaction corresponds to known pharmacology of drug
- reaction stops on cessation of drug
- reaction returns on restarting drug
After what is a causal relationship highly probable?
- event has reasonable temporal association with drug
- de-challenge from drug
- observed event abated upon de-challenge
- re-challenge
- reaction reappeared upon re-challenge
What’s the yellow card?
- from Medicines and Healthcare products Regulatory Agency (MHRA)
- filled in after reactions and filed
Define ‘side effect’
- unavoidable consequence of drug administration
- arising as unwanted action is just as integral as therapeutic effect to pharmacology of drug
- can be of clinical benefit sometimes
Define ‘secondary adverse effect’
- indirect causation
- secondary to the drug
- e.g opportunistic infections due to glucocorticoid therapy
How is age a risk factor for ADR?
- 3 fold increase in ADR over 60 compared to under 30
- can be due to increased medications or pharmacokinetic factors
- neonates and children susceptible due to difference in pharmacokinetic factors
How is sex a risk factor for ADR?
- females more likley
- pharmacokinetics and hormone influence
How is medical history a risk factor for ADR?
- if ADR to one drug, more likely to experience it with another
How is disease a risk factor for ADR?
- pharmacokinetics
How is current medication a risk for ADR?
- drug interactions
How is ethnicity a risk factor for ADR?
- intrinsic ones (pharmacokinetics and pharmacodynamics)
- pharmacokinetics - metabolism 90% japanese are fast acetylators, 50% of caucasians
- pharmacodynamics - Ashkenazi Jews susceptible to agranulocytosis after clozapine (20% to 1% in normal pop), response to beta blockers (more in chinese than caucasian than african)
- extrinsic is alcohol, diet, smoking
Classifications of ADRs
- A to E
- augmented pharmacological effect, bizzare effect, chronic effect, delayed effect, end of treatment effect
Define ‘augmented pharmocological effect’
- adverse effect known to occur from primary pharmacology of drug
- usually dose dependent
Define ‘bizarre effects’
- adverse effects that are unpredictable from pharmacology of drug
