Session 4 Pharmacovigilance and Pharmacogenetics Flashcards
What is Pharmacovigilance?
Identification, assessment and subsequent prevention of ADR’s whilst optimising benefits
The responsibility lies with prescribers, patients and carers
What is the most common clinical adverse event?
A drug reaction
What were the lessons learnt when thalidomide was found to produce non-lethal but significant effects?
- adequate testing needed
- government regulation
- reporting systems
- implications of unfounded claims
- most medicines cross the placenta
- avoidance of unnecessary use during pregnancy
What would class ADR’s as being ‘serious’?
- if reactions are fatal
- if reactions are life-threatening
- if reaction causes prolonged hospitalisation
- if reaction causes long term disability
- if reaction causes congenital abnormalities
Take all these things into account along with medical judgement
Outline the difference between Type A (augmented) and Type B (bizarre) adverse drug reactions.
Type A vs Type B
Dose related / not dose related Predictable (PK/PD) / unpredictable Common / uncommon Reversible / serious or irreversible Dose adjustment / need to STOP treatment
Examples of Type A (augmented) reactions
Bleeding = Warfarin Hypoglycaemia = diabetes medication
Examples of Type B (bizarre) reactions
Anaphylaxis = Penicillin Agranulocytosis = clozapine
What do ADR type’s C, D and E stand for?
C = Chronic D = Delayed E = End of use
Mechanisms of Action of ADR’s
What are they? (4)
They usually mimic disease or syndrome that occur naturally (may have non-therapeutic causes)
Four broad MoA
1. Exaggerated response
2. Desired pharmacological effect at alternative / additional site (GTN can cause a headache)
3. Additional or Secondary pharmacological effect
(QT length)
4. Triggering an immunological response
(Anaphylaxis)
What are the limitations of pre marketing clinical studies and ADR’s?
We need to firstly, evaluate the safety and secondly, the efficacy of a new drug so pre marketing clinical trials often have:
- small number off patients
- limited by age and possibly gender
- selected following precise diagnoses
- short, well defined duration
- specialist doctors and continuous follow-up
- concomitant therapeutics usually excluded
What does detection of an ADR depend on?
Number of patients required to be 95% (p<0.05) sure of detecting an ADR depends on predicted incidence
What do we use for spontaneous reporting of ADR’s and why would we perform this type of report?
If there is a signal produced that creates further questions
Also if there are increased cases of false positives and negatives
If there is increased ADR reporting to the MHRA
There is a yellow card scheme in place to report:
- recently introduced products - all suspected ADR’s including the minor ones and all reactions to any vaccines
- established products - serious or unusual suspected reactions (life threatening, disabling or prolonged hospitalisation)
UPSIDE DOWN TRIANGLE
Outline the advantages and disadvantages of the reporting of ADR’s
Advantages
- simplicity
- timely and inexpensive to administer
- detects both COMMON and RARE reactions
- accessible by all health care professionals (patients and carers too)
Disadvantages
- inevitable and unquantifiable under-reporting
- positive bias - serious, unrecognised or new drugs (good)
- duplication
- effect of publicity
- incomplete poor quality data
What is pharmacogenetics?
How individual gene may affect response to drug or drug response on body
Person-person variability contributes to 7% of serious ADRs and 3/1000 fatal reactions
What is genetic polymorphism?
The inheritance of a trait controlled by a single genetic locus with two alleles in which the least common allele has a frequency of about 1% or greater.
