Clinical PK Exam 3 (tran)

is the aging population increasing or decreasing?

increasing

are older americans living longer or shorter?

longer

describe the epidemiology of prescription drug use in adults ≥ 65 years old

~89% report taking any prescription medicine

~54% report taking ≥ 4 prescription drugs

describe drug reaction related hospitalizations in adults ≥ 65 years old

more common and more likely to be preventable

what are the three age brackets geriatrics are broken into?

65 to < 75 years

75 to < 85 years

≥ 85 years

describe tissue perfusion in geriatric patients

decreased

describe the GI tract in geriatric patients

decreased intestinal blood flow

decreased gut motility

decreased gastric acid production

describe muscle mass in geriatric patients

decreased

describe the liver in geriatric patients

decreased liver mass

decreased liver blood flow

describe the kidney in geriatric patients

decreased kidney size

decreased renal blood flow

describe absorption of medications in geriatric patients

generally unalterred or clinical significance is minimal or unknown despite physiological changes

describe the onset or time to reach maximal concentrations for oral medications in geriatric patients

decreased

describe the absorption of oral medications requiring acidic environments

decreased

describe the absorption of medications via transdermal, subcutaneous, or intramuscular routes

decreased or increased

what are the impacts of decreased lean body mass and decreased total body water in geriatric patients?

decreased Vd of hydrophilic drugs

increased concentration of hydrophilic drugs

decreased half-life of hydrophilic drugs

what are the impacts of increased body fat in geriatric patients?

increased Vd of hydrophilic drugs

decreased concentration of hydrophilic drugs

increased half-life of hydrophilic drugs

albumin is decreased in geriatric patients. what effect does this have?

increased concentration of unbound (free or active) form of drugs

alpha1-acid glycoprotein is increased in geriatric patients. what effect does this have?

decreased concentration of unbound (free or active) form of drugs

describe first pass metabolism in geriatric patients

decreased

increased bioavailability of medications with high extraction ratios

describe phase I (cytochrome P450) metabolism in geriatric patients

the same or decreased but be sure to consider if it is a prodrug or if it has active metabolism, as this may change things

describe phase II (conjugation reactions) metabolism in geriatric patients

the same

describe renal drug clearance in geriatric patients

decreased

how much does CrCl decline by for every decade of age over 20 to 30 years old?

~10 mL/min

what is the alternative method of "estimating" renal function?

CrCl (mL/min) = 120 mL/min - [(age - 20 or 30 years)]

what is the "optimal" renal function in a healthy 20 to 30 year old?

~120 mL/min

summary of the effect on aging on:

intestinal blood flow and gut motility

overall effect

decreased

ADME effect(s)

absorption is delayed, decreased onset

examples

medications for acute illnesses or symptoms

summary of the effect on aging on:

gastric acid production

overall effect

decreased

ADME effect(s)

absorption is decreased for medications reliant on an acidic environment

examples

calcium

iron

vitamin B12

summary of the effect on aging on:

total body water and lean body mass

overall effect

decreased

ADME effect(s)

decreased Vd for hydrophilic medications

examples

aminoglycosides

digoxin

summary of the effect on aging on:

body fat

overall effect

increased

ADME effect(s)

increased Vd for lipophilic medications

examples

benzodiazepines

antipsychotics

summary of the effect on aging on:

albumin

overall effect

decreased

ADME effect(s)

increased unbound (free or active) drug

examples

phenytoin

valproic acid

warfarin

summary of the effect on aging on:

alpha1-acid glycoprotein

overall effect

increased

ADME effect(s)

decreased unbound (free or active) drug

examples

lidocaine

valproic acid

warfarin

summary of the effect on aging on:

liver mass and liver blood flow

overall effect

decreased

ADME effect(s)

decreased first pass metabolism

examples

morphine

propranolol

verapamil

summary of the effect on aging on:

kidney size and renal blood flow

overall effect

decreased

ADME effect(s)

decreased renal excretion

examples

several!

what are some challenges regarding the clinical application of ADME priniciples in geriatric patients?

-there is limited evidence

-comorbid conditions

-polypharmacy

what are some things to consider regarding the clinical application of ADME priniciples in geriatric patients?

-comorbid conditions

-severity of illness

-narrow therapeutic window?

-availability of therapeutic drug monitoring?

-literature to support dosing recommendations

Drug B is a new intravenous drug for seizure disorder. A total (free + bound) Drug B level obtained resulted at 15 mg/L (therapeutic range 10 to 20 mg/L) and a free Drug B level resulted at 5 mg/L (therapeutic range 1 to 2 mg/L). Pertinent pharmacokinetic data include: bioavailability of 100%; Vd of 0.1 L/kg (hydrophilic); 95% protein bound, primarily albumin.

Which of the following physiologic changes seen in geriatric patients explains the results above?

a. Decreased albumin levels

b. Increased body fat

c. Decreased gastric acid production

d. Increased alpha1-acid glycoprotein levels

a

Drug Z is a prodrug that undergoes significant first-pass metabolism and has an extraction ratio of 0.9 (high > 0.7, intermediate 0.3 to 0.7, low < 0.3).

Based on how Drug Z is metabolized what dose change for Drug Z would you recommend in an elderly patient that will account for physiologic and pharmacokinetic changes commonly seen in geriatric patients?

a. Increase dose

b. Decrease dose

c. No dose change is recommended

a