Module 9 Therapeutic Index Flashcards
1
Q
Interpatient Response Variability
A
- Response to medication unique
- Evaluation ensure therapeutic response
2
Q
Medication Response Influences
A
- Genetics
- Disease state
- Environment
3
Q
Determining Interpatient Variability
A
- Clinical trails
- Setting an end point
4
Q
Phase 1
A
- 20 - 100 volunteers
- Animal studies guide dosing
- Evaluate pharmacokinetics & pharmacodynamics
5
Q
Phase 2
A
- 300-500 with disorder
- Determine dose-response over range of doses
- Short term trial
- Efficacy & side effects
6
Q
Phase 3
A
- 500-5000 with disorder
- Verify efficacy
- Evaluate long term side effects
7
Q
Phase 4
A
- Post-marketing surveillance
8
Q
Data Collection
A
- Plot on frequency distribution curve
- Average effective dose (ED50)
- Peak of curve
9
Q
ED50
A
- Required dose to produce response 50% of people
- Used as initial dose in therapy
10
Q
ED50 Wide Range
A
- Use ED50 measurement for initial dose
- Monitor patient response
11
Q
ED50 Narrow Range
A
- Titrate dose ED50 dose
- Start low & increase until response achieved
12
Q
Dosing Implications
A
- Dose adjustments from ED50 for effective therapy
- Patient response
13
Q
Toxic Doses TD50
A
- Animals used for testing
- Short term & chronic
- 50% of tested animals experience toxicity
- Drug/kg of body weight
14
Q
Lethal Doses LD50
A
- 50% of tested animals experience death
- Drug/kg of body weight
15
Q
Therapeutic Index
A
- Indicator of drug safety
- Ratio of LD50/TD50 to ED50 (division)
16
Q
High Index
A
- Safe drug
- Large space between therapeutic & toxic dose
17
Q
Low Index
A
- Unsafe drug
18
Q
Affecting Factors of Interpatient Response Variation
A
- Genetics
- Sex
- Race
- Kidney disease
- Liver disease
- Environment
19
Q
Body Weight/Composition
A
- Adjust dose for body weight
- Body fat % can alter distribution
- Adjust dose for body surface area (BSA)
- BSA accounts better for composition
20
Q
Genetics
A
- DNA sequence variation in drug response
- SNP change in DNA in regulating drugs
- Explain intrasubject variation
- Adjust dose for genotype
21
Q
Sex
A
- Slower alcohol metabolism in females
- Opioids more effective in women
- QT interval prolonged in women (cardiac dysrhythmia)
22
Q
Race
A
- Many races in each individual
- Unable to categorize in a single race
- Rosuvastatin high in Asians (decrease cholesterol)
23
Q
Kidney Disease
A
- Primary drug elimination
- Deceased drug excretion
- Increases half life of renally excreted drugs
- Decrease hepatic & intestinal metabolism
- Increases oral bioavailability
- Lower doses
24
Q
Liver Disease
A
- Primary drug metabolism
- Decreased hepatic metabolism
- Increased half life
25
Q
Environment
A
- Change response to drug
- Voluntary/involuntary
- Alcohol, smoke, exercise, pesticides
26
Q
Pesticide Exposure
A
- Induce CYPs
- Decrease drug response in CYP metabolizing enzymes
