Pharmacodynamics, Pharmacovigilance & Pharmacogenetics Flashcards
Why are protein binding interactions important?
Important for:
- IV drugs
- Short half lives (rapidly cleared)
- Narrow therapeutic index
What are the CYP450 inducers?
PCBRAS
P - Phenytoin C - Carbamazepine B - Barbituates R - Rifampicin A - Alcohol (chronic use) S - Sulphonylureas & St. John's wort
What are the CYP450 inhibitors?
ODEVICES
O - Omeprazole D - Disulfiram E - Erythromycin V - Valproate I - Isoniazid C - Cimetidine & Ciprofloxacin E - Ethanol (acutely) S - Sulphonamides
What is pharmacovigilance?
The process of identifying & then responding to safety issues about marketed drugs
What are Type A ADRs?
Predictable Dose dependent Exaggerated pharmacological response Common - 80% ADRs High morbidity, low mortality
What are Type B ADRs?
Unpredictable Independent of dose Not expected from known pharmacology Rare - 20% ADRs High mortality
Describe pre-marketing clinical studies (vs routine clinical experience
Relatively small no. of patients Type of patients restricted Limited duration of treatment Specialist doctors High level of patient monitoring
Describe routine clinical experience (vs pre-marketing clinical studies
Large no. of patients Patients - guided by indication Duration of treatment - guided by indication Usually any doctor Low level of patient monitoring
What limitations of pre-marketing clinical studies are there in identifying drug safety issues?
Relatively small no. of patients treated Frequent exclusion of pts who may be at risk of greater ADRs Structured nature of clinical trials - limited duration of treatment - restricted dodses - experienced specialist investigations
How can we identify ADRs?
Spontaneous reporting
Cohort studies
Case control studies
What are the advantages & disadvantages of spontaneous reporting?
Good at generating new ADR signals (hypotheses) Doesn't usually confirm hypotheses Can characterise the ADR May identify risk factors Cannot calculate incidence
Why does under reporting of ADRs occur?
F - Failure of pts to report ADR to their doctor
A - ADR is too trivial (e.g. minor rash)
I - Ignorance of reporting (and its procedures)
L - Lack of time
U - Uncertainty of relationship of drug to presentation
R - Relating to duration of marketed drug
E - Experience & familiarity with the ADR
What is pharmacogenetics?
The science of understanding how different individual genotypes relate to different drugs & thus know which drugs are safe & effective for each individual
What is pharmacogenomics?
Pharmacogenetics applied to the entire genome
What potential risk factors are there for drug inefficacy or toxicity?
Drug-drug interactions Age Renal & liver function Concurrent illness Lifestyle variables - smoking/alcohol Genetic variation
