Module 9

Question 1

The variation in individual response to medication is due to what factors?

Answer 1

Environment, genetics and disease state

Question 2

_______ ______ are an important first step in determining interpatient variability to drug response.

Answer 2

Clinical trials

Question 3

Phase 1 CT:

• __-____ _______ volunteers
• Evaluation of _________ and ___________
• ________ studies guide dosing

Answer 3

20-100 healthy volunteers
Evaluation of pharmacokinetics and pharmacodynamics
Animal studies guide dosing

Question 4

Phase 2 CT:

• ____-______ patients with the _______
• ____-term trial to determine ______ and _____-_______
• ____-response is determined

Answer 4

300-500 patients with the disorder
Short term trial to determine efficacy and side effects
Dose-response is determined

Question 5

Phase 3 CT:

• ____-_____ patients with the target disorder
• ______ verified and ___-term _____-______ evaluated

Answer 5

500-5000 patients with the target disorder

Efficacy verified and long-term side effects evaluated

Question 6

Phase 4 CT - most important part.

Answer 6

PMS - post-market surveillance

Question 7

Dose required to produce a response in 50% of the population

Answer 7

ED50

Question 8

The ______ is often used as the initial dose for therapy.

Answer 8

ED50

Question 9

How do we dose drugs that have a narrow therapeutic range?

Answer 9

Dose should initially be titrated - i.e. start low and increase slowly until the desired response is achievved

Question 10

When is it okay to use the ED50 as a starting dose?

Answer 10

When the drug has a wide therapeutic range

Question 11

Tests for toxic or lethal doses are carried out on who?

Answer 11

Animals

Question 12

Dose in which 50% of animals experience drug toxicity.

Answer 12

TD50 - average toxic dose

Question 13

Dose in which 50% of animals die

Answer 13

LD50 - average lethal dose

Question 14

Indicator of a drug’s safety. How is it calculated?

Answer 14

Therapeutic index
LD50/ED50 = TI
or
TD50/ED50

Question 15

What are the 7 factors that affect interpatient variation in response to drugs?

Answer 15

Body weight and composition
Genetics
Gender
Race
Kidney disease
Liver disease
Environment

Question 16

Clinicians often adjust the dose of drugs by ______ because this partially accounts for body composition.

Answer 16

BSA - body surface area

Question 17

What is the normal BSA?

Answer 17

1.73m2

Question 18

Study of the effect of DNA sequence variation to the clinical response of drugs

Answer 18

Pharmacogenomics

Question 19

Single nucleotide changes in DNA

Answer 19

SNPs

Question 20

Up until recently, the majority of drug research was conducted in ____.

Answer 20

men

Question 21

In what year did Health Canada and the FDA put pressure on drug companies to include women in trials of new drugs?

Answer 21

1997

Question 22

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

Answer 22

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

Question 23

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?

Answer 23

Rosuvastatin concentrations tend to be 2-3x higher in Asians vs. caucasians and thus dosing should be lowered for Asians

Question 24

Decreased renal function affects drug pharmacokinetics in what way?

Answer 24

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

Question 25

Dosage is changed how in patients with kidney disease?

Answer 25

Dosage is decreased

Question 26

How does liver disease affect drug pharmacokinetics?

Answer 26

Metabolism is impaired, thus drug half-life increases greatly

Question 27

Describe the effects of each of the following environmental factors on pharmacology.
Cigarette smoking
Alcohol
Exercise
Pesticides

Answer 27

Cigarette smoking induces certain drug metabolizing enzymes

Alcohol exacerbates the toxicity of some drugs

Exercise improves insulin activity

Some common pesticides induce CYPs