Geriatric PK-PD Flashcards
With age related biological changes, what are the 6 cardiovascular changes you may see?
- decrease in myocytes
- hypertrophy of remaining myocytes
- stiffening of ventricles
- reduced number of pacemaker cells in sinoatrial node
- valvular dilation and calcifications
- stiffening of arterial walls
With the cardiovascular changes, what are some results of the changes ?
- reduced ability to relax heart- diastolic dysfunction
- loss of filling from atrial contraction
- Isolated systolic hypertension (vessels can longer absorb high pressures from systolic contraction)
- desensitization of beta-adrenergic receptors
T/F memory loss/cognitive dysfunction is part of normal aging
False, it is NOT
With age related biological changes, what are the 4 CNS changes you may see?
- decreased brain mass, cerebral blood flow, and cerebral autoregulation
- decreased dopaminergic, muscarinic, and serotonergic receptors
- mental speed and novel problem-solving decrease
- more time is spent in stage 1 and 2 non-REM sleep, less in stages 3 and REM
With age related biological changes, what are the 3 renal changes you may see?
- kidney mass and weight decrease
- glomeruli decrease
- serum creatinine is typically less dependable as a renal marker as muscle mass declines
With the renal changes, what are some results of the changes?
- decrease in glomerular filtration
2. impaired ability to regulate electrolyte and fluid balance when restrictions and overloads occur
With age related biological changes, what changes may you see with genitourinary in women
- loss of estrogen occurs with menopause-atrophic urethritis
- childbirth weakens pelvic floor muscles
- result = predisposed to stress and urge incontinence
With age related biological changes, what changes may you see with genitourinary in men
- Prostates may become enlarged
2. result = potential urinary obstruction and overflow incontinence
With age related biological changes, what are the 3 changes you may see with endocrine
- norepi and epi levels increase, but response to stress is maintained
- insulin concentration increased, though this may be due to increase % body fat which predisposes to insulin resistance
- estrogen & testosterone decrease
With age related biological changes, what are the 2 changes you may see in gastrointestinal
- peristalsis may be slowed, resulting in:
- increased satiety (decreased hunger)
- slowed gastric emptying (will cause, among other things, constipation) - Size of liver is reduced. Size of pancreas may be reduced. Function of both of these is mostly maintained despite size reduction
With age related biological changes, what 5 changes may you see in musculoskeletal?
- decrease in muscle mass by 30-40%; this is replaced with fat
- skin thins and loses elasticity. Depending on sun exposure over time, skin develops wrinkles, texture and color changing/disfiguration
- Sebum secretion changes, leading to dry, coarse skin
- Sweat glands diminish, leading to altered thermoregulation
- Gradual bone loss after age 30. More rapid loss when estrogen and testosterone decline in late life
With age related biological changes, what are the 3 changes you may see with immunology/hematology?
- Hemoglobin levels decline; anemia is not normal with aging, but is common
- Immunocompetence declines - older patients are unable to mount the same immune response compared with their younger counterparts
- 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
What are 3 ways absorption can affect intestinal permeability?
- Passive diffusion (how most drugs are absorbed) or permeability is probably unchanged
- Active transport may be impaired (glucose, calcium, Vit. B12)
- First pass metabolism is decreased, resulting in increased bioavailability for some drugs while decreasing bioavailability for some prodrugs
What are two ways absorption can affect gastric acid secretion?
- 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
- 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)
What are 2 ways absorption can affect GI motility
- As patients age, gastric emptying is delayed, peristalsis is reduced, and colonic transit slows (regional loss of neurons).
- Could affect Tmax and Cmax, but not AUC (the peak concentration and time of peak is affected but overall
What way can absorption affect transdermal/intramuscular?
Atrophy of the epidermis and dermis in older adults (increased absorption) balanced by reduced perfusion of tissues (decreased absorption)
What 2 ways does distribution affect aging
- Protein binding
2. Body fat and body water
What is protein binding important for in Vd and aging
- drugs that are highly protein bound
- drugs highly metabolized by the liver
- patients with poor renal function
What is protein binding not important for in Vd and aging?
patients with adequate renal function because when free drug increases, excretion increases to account for this change
How much body fat increases elimination half life of lipid soluble medications
20-40%
How much body water decreases to increase concentration of water soluble medications
10-15%
T/F both water and fat soluble medications have increased clinical effects
true
How does hepatic aging and drug affect metabolism
- 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
- Not significant change in hepatic microsomal protein content or activities
- Phase II metabolism is unchanged
- Phase I metabolism is reduced
- 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
How does renal aging and drug affect elimination
- generally accepted that after age of 30, GFR decrease 1 mL/min per year; however, wide variability exists among patients
- age related decline in glomerular filtration rate is often considered the most important pharmacokinetic change in olde age
- aging biology and the kidney
- Cockcroft-Gualt
T/F Kidney mass has been reported to be substantially reduced in old age
True
T/F Physiologic changes do not occur with aging
False, aging human kidney is characterized by increased fibrosis, tubular atrophy, and arteriosclerosis
T/F glomerulosclerosis in older humans leads to a loss of glomeruli in younger adults
True
What does an aged kidney have trouble with?
- decreased ability to maximally concentrate or dilute urine
- decreased response to inadequate dietary salt
- impaired handling of potassium
What does cockcroft gault overestimate
GFR in patients with low creatinine/low muscle mass
When should cockcroft gualt not be rounded
in elderly patients whose SCr is < 1 because rounding up may falsely reduce their CrCl estimate, resulting in under dosing
When should cockcroft gault be rounded
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
How can pharmacodynamics contribute to changes in the elderly
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
Does CCB increase or decrease PD with aging?
increase risk of hypotension/bradycardia
Does warfarin increase or decrease PD with aging
increase risk of bleeding
Does BDZ GABA receptor complex increase or decrease benzodiazepines
increases
Does beta adrenergic receptors increase or decrease BB in PD with aging
decreases
Does diuretics increase or decrease in PD with aging
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
