L5 pharmacovigilance Flashcards
Pharmacovigilance
Identification, assessment and prevention of adverse drug reactions while optimising benefits
Who is responsible for pharmacovigilance
Prescribers Patients Carers Health care workers - to report ADRs
Mechanism to manage pharmacovigilance
Yellow card reporting
What does thalidomide cause
Phocomelia- limited or no limb development
How many cases are needed to make a change?
10
What was changed due to the thalidomide cases?
- Adequate testing used
- Government regulations
- Reporting systems
- Most medicines cross the placenta
What is thalidomide used for currently?
Malignant myeloma in over 65 yr olds
Purposes of early phase trials
Identify serious ADRs
Limitations of trials
Low frequency of reporting Low publishing data Confounding variables Small number of patients Not representative Short duration Specialist doctors are needed with short follow up Concomitant therapeutics usually excluded
Classes of ADR
Type A - Augmented
Type B - Bizarre
Type A ADR
- Dose related
- Predictable - PK and PD
- common
- reversible
- Dose adjustment required
Examples of type A ADR
Warfarin causing bleeding
Insulin causing hypoglycaemia
Type B ADR
- not does related
- unpredictable
- uncommon
- serious or irreversible
- Stop treatment
Type B ADR example
Penicillin anaphylaxis
Clozapine (used to treat schizophrenia) - agranulocytosis
Mechanisms of ADR
- Exaggeration of response
- Desired pharmacological effect at alternative site/ additional site e.g. GTN spray causes headaches
- additional secondary pharmacological effect
- triggers immunological response - anaphylaxis
Relative risk
Relative risk in a rare condition doesn’t affect no. of cases that much
Advantages of reporting
Simple mechanism to report
Quick and inexpensive
Detects common and rare reactions
Accessible by all health care professionals and patients
Negatives of reporting
under reporting Positive bias Duplication Effect of publicity and media Poor quality data
Improving reporting
Implementing guidance
Medical reviews
Collecting data from under reported areas
Global approach - big data
Pharmacogenetics
How individual genes may affect response to drugs or side effects
Pharmacogenomics
Whole genome and epigenetic effect on drug interactions
Population and individual characteristics
Individual variability
CYP P450 expression
Split antigen reaction
Enzyme deficiency - aldehyde dehydrogenase
Abacavir example
Abacavir for HIV associated with hypersensitivity with patients that have the split antigen expressed
Therefore screening used - 75% reduction
Carbamazepine example
Stevens-Johnson syndrome or severe toxic epidermal necrolysis reaction to another split antigen found in Asian people therefore avoid giving to Asian patient group
Aldehyde dehydrogenase deficiency
Mutated ALDH2
Single point aa mutation
predominant in East Asian population
Warfarin
Racemix mixture of S and R anomers (S 3-5 x more more potent)
Metabolised by different CYPs
Genetic polymorphism is the expression of particular CYP can change potency of warfarin therefore no standard dose and based of INR
CYP 2D6
metabolises 25% of drugs but rate highly variable
6% of Caucasians have 2 null alleles therefore no CYP 2D6 activity
Use of genetic polymorphism information
Personalised drug therapy
Rapid screening of gene variants
Knowledge can be used to target specific receptors or enzymes
e.g. cancer
vaccines for allergies
statin side effect prediction
