Pharmacovigilance And Pharmacogenetics Flashcards
What is pharmacovigilace?
Identification, assessment and subsequent prevention of ADRs whilst optimising benefits.
The responsibility lies with the prescriber, patients and carers.
The most common clinical adverse event is a drug reaction.
Where does pharmacovigilace come from?
Thalidomide.
Used as sedative and for N&V.
But tetrogenic so, large amount of birth defects (phocomelia -arms and legs close to trunk)
Thalidomide then withdrawn from sale in 1961 (still used as chemotherapeutic)
What changes were made as a result of thalidomide?
Adequate testing Government regulations Reporting systems Implications of unfounded claims Most medicines DO cross the placenta Avoid unnecessary use during pregnancy
What is an adverse drug reaction?
Unintended and noxious.
Attributable to therapeutic given within the normal recommended human range.
Differs from an adverse event where causality has not been confirmed.
ADRs are easier to identify and confirm in RCT situation.
What is a Type A ADR?
Dose-related Predictable from pharmacology Common Reversible Manageable with dose adjustment Warfarin -bleeding, nitrates -headache, hypoglycaemia -oral anti diabetic agent.
What is a type B ADR?
Bizarre.
Not dose related Uncommmon Unpredictable Serious / irreversible Indication that drug bed to be stopped
e.g. Anaphylaxis with penicillin, agranulocytosis with clozapine, thrombocytopenia
How do you detect ADRs?
The number of patients required to be 95% sure of detected ADRs depends on the predicted incidence (now often the ADR occurs)
The relative risk is in context of the baseline risk.
What are DoTS?
Dose relatedness (toxic, collateral, hyper-susceptibility)
Time relatedness (independent, dependant, rapid admin, first dose, earlier / immediate /late, delayed, withdrawal)
Susceptibility (age, gender, ethnicity, genetic, disease)
What are the four main MOA for ADRs?
Exaggerated response (eg bleeding with warfarin)
Desired pharmacological effects at alternative sites / additional sites (eg GTN and headache)
Additional / secondary pharmacological effect (QT length)
Triggering an immunological response(anaphylaxis)
What are the limitations of pre marketing clinical studies and ADRs?
Small number of patients
Limited
Limited by age and possibly gender
Selected following precise diagnosis
Short, well differed duration
Specialist doctors ad continuous follow-up
Concomitant therapeutics usually excluded
How do you spontaneously report ADRs?
This system was developed in response to thalidomide.
Primarily producing a signal that creates further questions.
Yellow car system in place to report:
Recently invented 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 good about how to report ADRs?
Simple
Timely
Detect common and rare reactions
Accessible by all healthcare professions (patients and careers too)
What are the bad things about the way we report ADRs?
Inevitable and unquantifiable under-reporting Positive bias Duplication Effect of publicity Incomplete poor quality data.
How can we improve the reporting of and reduce ADRs?
Be aware and interested
Implement suggested guidance and monitor high risk situations
Use MDTs
MUR and CMR
Collect data
Global approach
What is pharmacogenetics?
How an individual gene may affect response to a drug or indeed the drug response to the body - PK and PD.
More broadly, it is how the whole genome affects on the drug (considering epigenetic)
