module 9

Question 1

what is interpatient variability response?

Answer 1

response to medications is variable between patients - because of this, pt response must be evaluated

Question 2

what is phase 1 of clinical trials

Answer 2

20-100 healthy volunteers
evulation of pharmokinetics/dynamic
animaal studies guide dosing

Question 3

what is included in phase 2 of clinical trials

Answer 3

300-500 pts with disorder
short term trial to determine efficacy/SI
dose response is determined

Question 4

what is included in phase 3 clinical trials

Answer 4

500-5000 pts with disorder
efficacy verfied and long term SI evaluated

Question 5

what is included in phase 4 clinical trials

Answer 5

post market surveillence

Question 6

how do you determine a most appropriate dose for new medications?

Answer 6

frequency distrubution curve
average effective dose (ED50) to prodice a response in 50% of pop

Question 7

how is TD50 & LD50 determined

Answer 7

acute and chronic (6months-2years) animal testing carried out

Question 8

what is a therapeutic index

Answer 8

indicator of drug safety

Question 9

how is therapeutic index calculated

Answer 9

TI = LD50/ED50

or

TI = TD50/ED50

Question 10

what three things cause intersubject variability?

Answer 10

disease
genetic
environment

Question 11

what environmental factors contribute to interpatient variability?

Answer 11

circadian rhythm
exercise
occupation
smoking
alcohol
diet

Question 12

what genetic factors contribute to interpatient varibility?

Answer 12

altered drug transports
gender
race
altered drug targets
polymorphism

Question 13

what diseases cause interpatient variability?

Answer 13

GI
hepatic
renal
CV
immune

Question 14

how does body weight cause interpatient variability?

Answer 14

for drugs that are dosed by mg drug/kg of body weight
body composition changes drug distrubution so physicans use BSA for dosing

Question 15

what is the normal BSA for an adult

Answer 15

1.73m 2

Question 16

how do genetics affect interpatient variability

Answer 16

SNPs can exist in genes that regulate drug metabolism, drug transport or drug receptors

Question 17

why are effects of gender unknown for interpatient variability?

Answer 17

majority of drug research conducted on men
1997 health canada put pressure on companies to include women

Question 18

what are the known differences between gender & drugs

Answer 18

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

Question 19

what are known differnces between races and drugs?

Answer 19

statins - concentrations are 2-3x higher in Asian pts

Question 20

how does kidney disease cause interpatient variability?

Answer 20

excretion is significantly decreased - causes an increase in half life

hepatic/intestinal metabolism is decreased in renal failure

Question 21

how does liver disease cause intepatient variability

Answer 21

cirrhosis or hepatisis cause decreased drug metabolism - half life increased in patients with liver disease

Question 22

how does the environment cause interpatient variability?

Answer 22

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