module 9 Flashcards
what is interpatient variability response?
response to medications is variable between patients - because of this, pt response must be evaluated
what is phase 1 of clinical trials
20-100 healthy volunteers
evulation of pharmokinetics/dynamic
animaal studies guide dosing
what is included in phase 2 of clinical trials
300-500 pts with disorder
short term trial to determine efficacy/SI
dose response is determined
what is included in phase 3 clinical trials
500-5000 pts with disorder
efficacy verfied and long term SI evaluated
what is included in phase 4 clinical trials
post market surveillence
how do you determine a most appropriate dose for new medications?
frequency distrubution curve
average effective dose (ED50) to prodice a response in 50% of pop
how is TD50 & LD50 determined
acute and chronic (6months-2years) animal testing carried out
what is a therapeutic index
indicator of drug safety
how is therapeutic index calculated
TI = LD50/ED50
or
TI = TD50/ED50
what three things cause intersubject variability?
disease
genetic
environment
what environmental factors contribute to interpatient variability?
circadian rhythm
exercise
occupation
smoking
alcohol
diet
what genetic factors contribute to interpatient varibility?
altered drug transports
gender
race
altered drug targets
polymorphism
what diseases cause interpatient variability?
GI
hepatic
renal
CV
immune
how does body weight cause interpatient variability?
for drugs that are dosed by mg drug/kg of body weight
body composition changes drug distrubution so physicans use BSA for dosing
what is the normal BSA for an adult
1.73m 2
how do genetics affect interpatient variability
SNPs can exist in genes that regulate drug metabolism, drug transport or drug receptors
why are effects of gender unknown for interpatient variability?
majority of drug research conducted on men
1997 health canada put pressure on companies to include women
what are the known differences between gender & drugs
alcohol metabolism is slower in females
opioids more effective in women
drugs used to treat QT prlongation are more likely to cause a fatal cardiac dysrhytmia
what are known differnces between races and drugs?
statins - concentrations are 2-3x higher in Asian pts
how does kidney disease cause interpatient variability?
excretion is significantly decreased - causes an increase in half life
hepatic/intestinal metabolism is decreased in renal failure
how does liver disease cause intepatient variability
cirrhosis or hepatisis cause decreased drug metabolism - half life increased in patients with liver disease
how does the environment cause interpatient variability?
cigarettes induce drug metablosim makng drugs ineffective
alcohol can exacerbate toxicity of other drugs
exercise improves actions of insulin
commonly used pesticides can induce CYPs and decrease drug response
