4.1 Pharmacovigilance and pharmacogenetics Flashcards
what is pharmacovigilence?
Monitor safety of all medicines throughout usage, pro-active risk
management
who collects data on pharmacovigilence?
European Medicines agency MRHA
why is thalidomide no longer prescribed as a sedative?
as although one enantiomer does have sedative effects, another causes phocomelia and limb malformation
what is phocomelia?
congenital absence of the proximal portion of a limb or limbs, the hands or feet being attached to the trunk by a small, irregularly shaped bone. adj., adj phocome´lic.
what is done to ensure pharmacovigilence?
adequate testing, government regulation,
reporting systems, implications of unfounded claims, most medicines
cross the placenta, avoidance of unnecessary use during pregnancy
what is a serious ADR?
Fatal Life-threatening Prolonged hospitalisation Long term disability Congenital abnormalities - along with medical judgement
what is the difference between an adverse drug event and an adverse drug reaction?
an adverse drug event is an injury that occurs during treatment, and is
not necessarily caused by the drug itself. Where as an adverse drug reaction is in response to a drug that is noxious and unintended.
there are 5 major classes of ADRs, what are they?
A = augmented (dose dependent, frequent and predictable B = bizarre (not dose related/ dose independent and unpredictable) C = chronic (rare response due to long term exposure) D = delayed (time dependent, very rare) E = end of treatment ( withdrawal effects)
what are the 4 broad mechanisms of action of adverse drug reactions?
Exaggerated response
Desired pharmacological effect at alternative/additional site (GTN – headache)
Additional/secondary pharmacological effect (QT length)
Triggering an immunological response (anaphylaxis)
what are the limitations in evaluating the safety and the efficacy of a new drug in pre-marketing clinical studies?
- Small number of 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 system is currently in place to report ADRs?
Yellow card scheme
recently introduced products – all suspected ADRs inc. minor ones, all reactions to vaccines
Established products – serious or unusual suspected reactions (life threatening, disabling or prolonging hospitalisation)
what is pharmacogenomics?
The study of genetically determined variations in responses to drugs in humans or in laboratory organisms.
what factors contribute to intervariability in drug response?
- Age
- Race/ethnicity
- Weight
- Gender
- Concomitant Diseases
- Concomitant Drugs
- Compliance
- Social factors
- Biomarkers
- GENETICS
what is meant by personalised medicine?
uses new approaches to better manage patients health and target therapies to achieve the best outcome in the management of a patients disease or predisposition to disease
what are the 4 P’s of personalised medicine?
prediction and prevention
precise
personalised
participatory
what are HLA alleles?
HLA alleles, also known as human leucocyte antigens are located on the short arm of chromosome 6, the most polymorphic region of the human genome.
why is there genomic testing before prescribing abacavir?
as patients with specific HLA antigens are predisposed to developing serious hypersensitivity reactions with multiorgan involvement when taking abacavir
why is there genomic testing before prescribing carbamazepine?
as patients with specific HLA antigens (increased frequency in south east asians) are predisposed to developing toxic epidermal necrolysis and steven-johnson syndrome
why do codeine painkillers not work for many people?
As codeine (along with antidepressants, antipsychotics and beta blockers) are broken down by CYP 2D6 enzyme. Many caucasians lack this enzyme and therefore cannot metabolise these drugs.
