Geriatric PK-PD

Question 1

With age related biological changes, what are the 6 cardiovascular changes you may see?

Answer 1

1. decrease in myocytes
2. hypertrophy of remaining myocytes
3. stiffening of ventricles
4. reduced number of pacemaker cells in sinoatrial node
5. valvular dilation and calcifications
6. stiffening of arterial walls

Question 2

With the cardiovascular changes, what are some results of the changes ?

Answer 2

1. reduced ability to relax heart- diastolic dysfunction
2. loss of filling from atrial contraction
3. Isolated systolic hypertension (vessels can longer absorb high pressures from systolic contraction)
4. desensitization of beta-adrenergic receptors

Question 3

T/F memory loss/cognitive dysfunction is part of normal aging

Answer 3

False, it is NOT

Question 4

With age related biological changes, what are the 4 CNS changes you may see?

Answer 4

1. decreased brain mass, cerebral blood flow, and cerebral autoregulation
2. decreased dopaminergic, muscarinic, and serotonergic receptors
3. mental speed and novel problem-solving decrease
4. more time is spent in stage 1 and 2 non-REM sleep, less in stages 3 and REM

Question 5

With age related biological changes, what are the 3 renal changes you may see?

Answer 5

1. kidney mass and weight decrease
2. glomeruli decrease
3. serum creatinine is typically less dependable as a renal marker as muscle mass declines

Question 6

With the renal changes, what are some results of the changes?

Answer 6

1. decrease in glomerular filtration

2. impaired ability to regulate electrolyte and fluid balance when restrictions and overloads occur

Question 7

With age related biological changes, what changes may you see with genitourinary in women

Answer 7

1. loss of estrogen occurs with menopause-atrophic urethritis
2. childbirth weakens pelvic floor muscles
3. result = predisposed to stress and urge incontinence

Question 8

With age related biological changes, what changes may you see with genitourinary in men

Answer 8

1. Prostates may become enlarged

2. result = potential urinary obstruction and overflow incontinence

Question 9

With age related biological changes, what are the 3 changes you may see with endocrine

Answer 9

1. norepi and epi levels increase, but response to stress is maintained
2. insulin concentration increased, though this may be due to increase % body fat which predisposes to insulin resistance
3. estrogen & testosterone decrease

Question 10

With age related biological changes, what are the 2 changes you may see in gastrointestinal

Answer 10

1. peristalsis may be slowed, resulting in:
   - increased satiety (decreased hunger)
   - slowed gastric emptying (will cause, among other things, constipation)
2. Size of liver is reduced. Size of pancreas may be reduced. Function of both of these is mostly maintained despite size reduction

Question 11

With age related biological changes, what 5 changes may you see in musculoskeletal?

Answer 11

1. decrease in muscle mass by 30-40%; this is replaced with fat
2. skin thins and loses elasticity. Depending on sun exposure over time, skin develops wrinkles, texture and color changing/disfiguration
3. Sebum secretion changes, leading to dry, coarse skin
4. Sweat glands diminish, leading to altered thermoregulation
5. Gradual bone loss after age 30. More rapid loss when estrogen and testosterone decline in late life

Question 12

With age related biological changes, what are the 3 changes you may see with immunology/hematology?

Answer 12

1. Hemoglobin levels decline; anemia is not normal with aging, but is common
2. Immunocompetence declines - older patients are unable to mount the same immune response compared with their younger counterparts
3. In the presence of an infection, older adults may not have a fever or leukocytosis, making diagnosis of infections difficult.
   - baseline temp. is about 1 degree F lower in adults, resulting in potential to miss or misdiagnose fevers when present

Question 13

What are 3 ways absorption can affect intestinal permeability?

Answer 13

1. Passive diffusion (how most drugs are absorbed) or permeability is probably unchanged
2. Active transport may be impaired (glucose, calcium, Vit. B12)
3. First pass metabolism is decreased, resulting in increased bioavailability for some drugs while decreasing bioavailability for some prodrugs

Question 14

What are two ways absorption can affect gastric acid secretion?

Answer 14

1. It was once believed that gastric acid secretion declines with age, thereby increasing the gut PH and drug absorption. However, this really only affects a small proportion of older adults
2. For this subset of patients (5-10% who have hypochlorhydria secondary to atrophic gastritis which is not “normal” aging), clinicians can expect potential decreased effect of some drugs which are reliant upon acidic environments for absorption (calcium, iron)

Question 15

What are 2 ways absorption can affect GI motility

Answer 15

1. As patients age, gastric emptying is delayed, peristalsis is reduced, and colonic transit slows (regional loss of neurons).
2. Could affect Tmax and Cmax, but not AUC (the peak concentration and time of peak is affected but overall

Question 16

What way can absorption affect transdermal/intramuscular?

Answer 16

Atrophy of the epidermis and dermis in older adults (increased absorption) balanced by reduced perfusion of tissues (decreased absorption)

Question 17

What 2 ways does distribution affect aging

Answer 17

1. Protein binding

2. Body fat and body water

Question 18

What is protein binding important for in Vd and aging

Answer 18

1. drugs that are highly protein bound
2. drugs highly metabolized by the liver
3. patients with poor renal function

Question 19

What is protein binding not important for in Vd and aging?

Answer 19

patients with adequate renal function because when free drug increases, excretion increases to account for this change

Question 20

How much body fat increases elimination half life of lipid soluble medications

Answer 20

20-40%

Question 21

How much body water decreases to increase concentration of water soluble medications

Answer 21

10-15%

Question 22

T/F both water and fat soluble medications have increased clinical effects

Answer 22

true

Question 23

How does hepatic aging and drug affect metabolism

Answer 23

1. aging is associated with roughly 40% reduction of blood flow to the liver and a comparable reduction in liver mass - these are the findings that led to the link between reduced hepatic clearance of medications and aging
2. Not significant change in hepatic microsomal protein content or activities
3. Phase II metabolism is unchanged
4. Phase I metabolism is reduced
5. changes that do occur in the liver with aging can influence susceptibility to toxins and adverse drug reactions since the liver acts as a gatekeeper and protects from toxic xenobiotics

Question 24

How does renal aging and drug affect elimination

Answer 24

1. generally accepted that after age of 30, GFR decrease 1 mL/min per year; however, wide variability exists among patients
2. age related decline in glomerular filtration rate is often considered the most important pharmacokinetic change in olde age
3. aging biology and the kidney
4. Cockcroft-Gualt

Question 25

T/F Kidney mass has been reported to be substantially reduced in old age

Answer 25

True

Question 26

T/F Physiologic changes do not occur with aging

Answer 26

False, aging human kidney is characterized by increased fibrosis, tubular atrophy, and arteriosclerosis

Question 27

T/F glomerulosclerosis in older humans leads to a loss of glomeruli in younger adults

Answer 27

True

Question 28

What does an aged kidney have trouble with?

Answer 28

1. decreased ability to maximally concentrate or dilute urine
2. decreased response to inadequate dietary salt
3. impaired handling of potassium

Question 29

What does cockcroft gault overestimate

Answer 29

GFR in patients with low creatinine/low muscle mass

Question 30

When should cockcroft gualt not be rounded

Answer 30

in elderly patients whose SCr is < 1 because rounding up may falsely reduce their CrCl estimate, resulting in under dosing

Question 31

When should cockcroft gault be rounded

Answer 31

in patients who have a condtion resulting in low muscle mass (general immobility, malnourshiment), their SCr may be falsely low and rounding up a bit may help to account for this

Question 32

How can pharmacodynamics contribute to changes in the elderly

Answer 32

Changes in…
1. concentration of a drug at receptor site
2. the numbers of receptors available
3. the affinity of the receptor for substrates
Post receptor alterations
Impaired homeostatic mechanisms in older adults

Question 33

Does CCB increase or decrease PD with aging?

Answer 33

increase risk of hypotension/bradycardia

Question 34

Does warfarin increase or decrease PD with aging

Answer 34

increase risk of bleeding

Question 35

Does BDZ GABA receptor complex increase or decrease benzodiazepines

Answer 35

increases

Question 36

Does beta adrenergic receptors increase or decrease BB in PD with aging

Answer 36

decreases

Question 37

Does diuretics increase or decrease in PD with aging

Answer 37

decreases due to decreased body water and decreased thirst/fluid intake by older adults, which reduces cardiovascular reflexes which can lead to severe dehydration when diuretics are used