Module 9 Flashcards
The variation in individual response to medication is due to what factors?
Environment, genetics and disease state
_______ ______ are an important first step in determining interpatient variability to drug response.
Clinical trials
Phase 1 CT:
- __-____ _______ volunteers
- Evaluation of _________ and ___________
- ________ studies guide dosing
20-100 healthy volunteers
Evaluation of pharmacokinetics and pharmacodynamics
Animal studies guide dosing
Phase 2 CT:
- ____-______ patients with the _______
- ____-term trial to determine ______ and _____-_______
- ____-response is determined
300-500 patients with the disorder
Short term trial to determine efficacy and side effects
Dose-response is determined
Phase 3 CT:
- ____-_____ patients with the target disorder
- ______ verified and ___-term _____-______ evaluated
500-5000 patients with the target disorder
Efficacy verified and long-term side effects evaluated
Phase 4 CT - most important part.
PMS - post-market surveillance
Dose required to produce a response in 50% of the population
ED50
The ______ is often used as the initial dose for therapy.
ED50
How do we dose drugs that have a narrow therapeutic range?
Dose should initially be titrated - i.e. start low and increase slowly until the desired response is achievved
When is it okay to use the ED50 as a starting dose?
When the drug has a wide therapeutic range
Tests for toxic or lethal doses are carried out on who?
Animals
Dose in which 50% of animals experience drug toxicity.
TD50 - average toxic dose
Dose in which 50% of animals die
LD50 - average lethal dose
Indicator of a drug’s safety. How is it calculated?
Therapeutic index
LD50/ED50 = TI
or
TD50/ED50
What are the 7 factors that affect interpatient variation in response to drugs?
Body weight and composition Genetics Gender Race Kidney disease Liver disease Environment
Clinicians often adjust the dose of drugs by ______ because this partially accounts for body composition.
BSA - body surface area
What is the normal BSA?
1.73m2
Study of the effect of DNA sequence variation to the clinical response of drugs
Pharmacogenomics
Single nucleotide changes in DNA
SNPs
Up until recently, the majority of drug research was conducted in ____.
men
In what year did Health Canada and the FDA put pressure on drug companies to include women in trials of new drugs?
1997
What are a few differences between women and men that we know of in terms of variation to drug response?
1 - Alcohol
2 - Opiods
3 - Drugs for heartbeat
Alcohol metabolism is slower in females
Certain opioids are more effective in women, requiring lower doses
Certain drugs used to treat irregular heartbeat cause prolongation of the QT interval - more likely to cause a fatal cardiac dysrhythmia
Although race is often hard to define, and even harder to generalize to drug effects, what are some instances where race plays a role in drug effects?
Rosuvastatin concentrations tend to be 2-3x higher in Asians vs. caucasians and thus dosing should be lowered for Asians
Decreased renal function affects drug pharmacokinetics in what way?
Decreased drug excretion and therefore an increase in excretion half-life
Decreased hepatic and intestinal drug metabolism
Net: increased oral bioavailability and decreased drug excretion
