PKPD

Question 1

What might cause a delay in onset of effect of drugs (analgesics, hypnotics) in older patients?

Answer 1

Delayed rate of absorption

Question 2

Older patients have (increased/decreased) acid production

Answer 2

Decreased

Question 3

Decreased gastric acid secretion may be normal in older patients, but what might we be still worried is causing it?

Answer 3

Atrophic gastritis (H. Pylori)

Question 4

What comorbidity might cause decreased gastric blood flow?

Answer 4

HF

Question 5

Which drugs are high-extraction drugs?

Answer 5

• Propranolol
• MSO4
• Lidocaine
• Verapamil
• Labetalol

Question 6

We need (higher/lower) doses of high-extraction drugs in older patients

Answer 6

LOWER

Reduce 1st pass effect leads to higher concentrations

Question 7

T/F: Evidence shows a reduced bowel CYP3A4 and Pg-P activity

Answer 7

FALSE
no proven effect

Question 8

T/F: There is not a significant effect on rate or extent of oral drug absorption in older patients due to aging

Answer 8

TRUE

Question 9

Why do older patients have decreased absorption of topical lipophilic compounds?

Answer 9

Their skin is dryer, less perfused, and more fatty

Question 10

What is the condition to be concerned with when using fentanyl patches?

Answer 10

Cachexia (decreased effect)

Question 11

What ointments/creams can have decreased absorption in older patients?

Answer 11

Steroids, hormones

Question 12

T/F: Drugs taken via the sublingual, buccal, and rectal routes will have impaired absorption in older patients

Answer 12

FALSE
mostly the same

Question 13

What effect does decreased body mass have on digoxin?

Answer 13

Higher concentrations
Less mass (Vd) to distribute into causes higher concentrations

Question 14

What effect does increased fat percentage have on benzodiazepines?

Answer 14

Longer t1/2
Higher Vd of lipophilic drugs

Question 15

What effect does lower body water have on hydrophilic drugs?

Answer 15

Higher concentrations
Lower Vd

Question 16

T/F: Albumin levels are generally the same between older and younger patients

Answer 16

TRUE
albumin drops might alert us to severe, chronic, or underlying illnesses

Question 17

When is a1-acid glycoprotein (AAG) elevated?

Answer 17

Acute illness, infection, CA, inflammation

Question 18

What considerations with AAG do we have for drugs?

Answer 18

High affinity for basic drugs (decreased concentrations with high AAG levels)

Question 19

How does hepatic CYP3A4 activity change with aging?

Answer 19

Decreases

Question 20

How does hepatic CYP2D6 activity change with aging?

Answer 20

Not affected by aging

Question 21

T/F: Phase II metabolism (glucuronidation/acetylation) is generally unchanged with aging

Answer 21

TRUE

Question 22

What phase II process might be reduced in patients >80 years?

Answer 22

Glucuronidation

Question 23

T/F: There is an independent decrease in hepatic blood flow with age

Answer 23

FALSE: no clear evidence, may be due to lowered cardiac output

Question 24

What classes of drugs may not be metabolized well in older patients?

Answer 24

• Benzodiazepines
• CCBs
• NSAIDs

Question 25

What types of metabolizers might be at higher risk of ADEs with aging?

Answer 25

Slow metabolizers

Question 26

Inhibition of metabolism generally (increases/decreases/stays the same) with age

Answer 26

Stays the same

Question 27

How does kidney mass change with age?

Answer 27

Reduces up to 25% from ages 40-90

Question 28

How does renal blood flow change with age?

Answer 28

Reduces 10% per decade Exceeds reduction in cardiac output

Question 29

How does glomerular function change with age?

Answer 29

Biphasic decline Gradual until age 40, rapid afterwards

Question 30

Should you round or adjust for low SCr when calculating CrCl?

Answer 30

NO!!!

Question 31

Which drugs should we be worried about with impaired renal function?

Answer 31

- Hydrophilic beta blockers (atenolol, bisoprolol) - ACEi - Fluoroquinolones - Vancomycin, aminoglycosides

Question 32

T/F: There are no real generalizations for pharmacodynamics in aging

Answer 32

TRUE