Pharmacovigilance and Pharmacogenetics Flashcards
What is pharmacovigilance?
The identification, assessment and subsequent prevention of adverse drug reactions, whilst optimising the benefits of the drug
Who’s responsibility is it to report and identify ADR’s for pharmacovigilance?
- Prescribers
- Clinicians
- Patients
- Carers
- Pharmaceutical companies
- MHRA
How many cases of an ADR would need to be reported before anything was done about it today?
10 cases internationally
What ADR’s are classed as serious?
- Fatality
- Life threatening
- Prolonged hospitalisation
- Long term disability
- Congenital abnormalities
What are adverse drug reactions?
Unintended and noxious reactions that attributable to the therapeutic actions when given within normal therapeutic range
(any drug outside of TW can cause ADR)
What are the differences between Type A (augmented) and Type B (bizzare) adverse drug reactions?
What are some other classifications of ADRs that have been proposed?
- Chronic
- Delayed
- End of use
What is the ADR associated with the drug Diethylstilboestrol? (drug used to prevent premature labour)
An increase in vaginal cancer in those exposed to the drug in utero
What are the 4 broad mechanisms of action for ADRs?
- Exaggerated response of drug
- Desired pharmacological effect at an alternative/ additional site e.g. GTN spray for headache
- Additional/ secondary pharmacological effect
- Triggering an immunological response (anaphylaxis)
What are the limitations of pre-marketing clinical studies for identifying ADRs?
- Small number of patients
- Limited by age and/ or gender (typically male volunteers)
- Selected participants for precise diagnosis i.e. clinical trials use ‘ideal patients’ not always representative of the entire population
- Short, well defined duration of study
- Specialist doctors and continuous follow up
- Co-comitant therapeutics usually excluded
Why is relative risk of and ADR not always a good indicator of how common ADR’s are?
Depends on the baseline risk
A smaller relative risk in a population that has a high baseline risk gives more added cases!
What scheme is in place to report ADRs?
Yellow card reporting scheme
Used in both recently introduced (all suspected ADRs even minor ones reported) and well established products (serious and unexpected)
What is the black triangle on drug products?
Warning on new drugs or newly repurposed drugs that prompts extra vigillence when prescribing
What are the advantages and disadvantages of the yellow card reporting scheme?
Advantages:
- Simplicity
- Timely and theoretically inexpensive
- Detects both common and rare reactions
- Accessible by all HCPs, patients and carers
Disadvantages:
- inevitable under reporting
- Positive bias to serious reactions/ new drugs
- Duplication
- Incomplete poor quality data
What is pharmacogenetics?
How an individual gene may affect the response to a drug or the drugs effect on the body
What is pharmacogenomics?
The whole genome and the effects is has on drugs (epigenetics)
Why is it important to consider pharmacogenetics?
- person-person variability in drug response contributes to 7% of serious ADRs
- Drug reactions leading to hospital deaths may be related to pharmacogenetics
- Helps understand why a patient may not respond to therapeutics
Explain how patient care of patients prescibed Abacavir has changed following identification of pharmacogenetics
Abacavir associated with hypersensitivity in patients with HIV with identified split antigen
Screening for split antigen redueced hypersensitivty reactions by 75%
Explain how patient care has improved for patients taking carbamazepine based on pharmacogenetics?
Carbamazepine reaction causes Steven-Johnson syndrome in patients identified to have a certain split antigen predominantly found in Asian patients
Why are ACEi/ ARB not the primary choice of antihypertensives in African Caribbean populations?
Afro Caribbeans have low levels of RAAS
Angiodema more prevelent in Afro-Caribbeans (ADR to ACEi)
How can pharmacogenetic differences effect drug prescribing?
- May need a different drug
- May need higher doses of a drug for therapeutic effect
- May not respond at all
What is the effect of 6% of Caucasions carrying 2 null alleles to CYP2D6 at gene locus 19?
- decreased first pass metabolism - metoprolol → bradycardia can result as reduced metabolism
- Re-routing of metabolism - paracetamol can cause form toxic NAPQI intermediate
