Population Variability in Drug Response

Question 1

5 factors affecting drug response

Answer 1

Compliance
Drug interactions
Disease
Genetics
Age (young and old)

Question 2

Primary vs secondary compliance

Answer 2

Primary: was the prescription filled
Secondary: was the drug taken

Question 3

Ways to improve compliance

Answer 3

Extended release or depot formulations (decrease number of doses)
Generic alternatives (cost)
Pill organizers/blister packing
Involve family/caregivers
Clear written instructions
Avoid an excess of meds

Question 4

Pharmacogenetics vs pharmacogeneomics

Answer 4

Genetics: single genes
Genomics: entire genome

Question 5

Most genetic variation is due to//

Answer 5

Single nucleotide polymorphisms (SNPs)

Question 6

Range of CYP450 metabolizers

Answer 6

Ultrarapid metabolizers (up regulation of the enzymes - need higher doses_
Extensive metabolizers (normal)
Intermediate metabolizers
Poor metabolizers (requires a lot less drug)

Question 7

What is the most significant contributer to drug activity

Answer 7

Age

Question 8

How is absorption different in pediatrics

Answer 8

They have a higher gastric pH
Acid labile drugs will have a higher relative concentration
The absorption of weak acid drugs decreases, while weak base drugs increase
Thinner stratum corneum (skin) so there is potential for systemic effects and toxicity

Question 9

Do adults or neonates have more

1. Total body water
2. Plasma proteins
3. Fat

Answer 9

1. Neonates (80 vs 60)
2. Adults (20 vs 10)
3. Adults (20 vs 10 (term) or 1-2 (premies))

Question 10

Metabolism in pediatrics

Answer 10

Elimination of drugs that undergo significant hepatic metabolism is decreased due to immaturity of some phase 1 and 2 enzymes
Require smaller doses or longer dosing intervals

Question 11

Excretion in pediatrics

Answer 11

Elimination of renally excreted drugs is decreased in infants due to reduced GFR and renal tubular secretion
Need to decrease dose or increase dosing interval
Preterm infants have even less renal function

Question 12

Young old vs old old

Answer 12

Young: 65-84
Old: 85+

Question 13

Absorption in geriatrics

Answer 13

Increased gastric pH
Same as peds
The absorption of weak acid drugs decreases, while weak base drugs increase

Question 14

Distribution in geriatrics

Answer 14

Increased adipose tissue (lipophilic drugs have a lower plasma concentration)
Decreased TBW (hydrophilic drugs have a higher plasma concentration)
Decreased plasma albumin (free fraction of drugs that bind plasma proteins will be increased)

Question 15

Metabolism in geriatrics

Answer 15

Decreased liver mass, decreased hepatic blood flow, decreased phase 1 enzyme activity
Drug half life will increase
Need to decrease dose or increase dosing interval
Phase 2 reactions are largely unchanged, so when possible use drugs that are metabolized by phase 2 system

Question 16

Excretion in geriatrics

Answer 16

Overall decrease in kidney function (reduced size, fever glomeruli, fewer nephrons, reduced blood flow)
Drug half life will increase
Need to decrease dose or increase dosing interval