PK and PD of aging Flashcards
What are the CV related changes in aging?
Decrease in myocytes w/in myocardium Hypertrophy of remaining myocytes Stiffening of ventricles Reduced number of pacemaker cells in sinoatrial node Valvular dilation and calcifications Stiffening of arterial wall
What are the results of CV changes in aging?
Reduced ability to relax heart - diastolic dysfunction
Loss of filling from atrial contraction
Isolated systolic HTN (vessels can no longer absorb high pressures from systolic contraction)
What are the changes seen in the CNS d/t aging?
Decreased brain mass, cerebral blood flow, and cerebral autoregulation
Decreased dopaminergic, muscarinic, and serotonergic receptors
Mental speed and novel problem solving decrease
More time spent in stage 1 and 2 non-REM sleep, less in stages 3, 4 and REM
What are the changes seen in the kidneys d/t aging?
Kidney mass and wt decrease
Glomeruli decrease
SCr is less dependable
What are the results of changes seen in the kidneys d/t aging?
Decrease in glomerular filtration
Impaired ability to regulate electrolyte and fluid balance when restrictions and overloads occur
What are the changes seen in women’s genitourinary system d/t aging?
Loss of estrogen occurs with menopause - atrophic urethritis
Childbirth weakens pelvic floor muscles
Result = predisposed to stress and urge incontinence
What are the changes seen in men’s genitourinary system d/t aging?
Potential urinary obstruction and overflow incontinence
What are the effects of aging on the endocrine system?
NE and Epi levels increase, but response to stress is maintained
Insulin concentrations increase, though this may be d/t increase % body fat which predisposes to insulin resistance
Estrogen and testosterone decrease
What are the effects of aging on the GI system?
Peristalsis may be slowed resulting in increased satiety and slowed gastric emptying (constipation)
Size of liver is reduced, pancreas may be reduced but function os mostly sustained
What are the effects of aging on the Musculoskeletal system?
Decrease in muscle mass - 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
What are the effects of aging on the immune/hematologic system?
Hgb 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
What are the 4 pieces of absorption that are affected in elderly?
Intestinal permeability
Gastric acid secretion
GI motility
Transdermal/intramuscular
How is intestinal permeability affected by aging?
Passive diffusion or permeability is probably unchaged
Active transport may be impaired (glucose, calcium, vit B12)
How is gastric acid secretion affected by aging?
Declines with age thereby increasing the gut pH and drug absorption, this only affect small portion of older adults
Clinician can expect potential decreased effect of some drugs which are reliant upon acidic environments for absorption
How is GI motility affected by aging?
Could affect Tmax and C max but not AUC
How is transdermal/intramuscular dosing affected by aging?
Atrophy of the epidermis and dermis is balanced by reduced perfusion of tissues
What factors affect volume of distribution d/t aging?
Protein binding
Body fat and body water
How is protein binding affected by aging?
10% reduction in blood albumin and possible increase in alpha-1-acid glycoprotein in older adults - associated with an increased in the unbound fraction of many medications
How is body fat and body water affected by aging?
Body fat increases
Body water decreases
How is the liver affect by aging?
Reduction in blood flow to the liver and reduction in mass
No significant change in hepatic microsomal protein content or activities
Phase II metabolism is unchanged
Phase I reduced
Can influence susceptibility to toxins and ADR since the liver acts as a gatekeeper and protects from toxic xenobiotics
How are the kidneys affected by aging and how does that affect drug elimination?
After age 30 GFR decreases 1ml/min per year
Decline in GFR is often considered the most important PK change in old age
How does the kidney change with age?
Decreased mass
Increased fibrosis, tubular atrophy, and arteriosclerosis
Decreased glomeruli
How does the kidneys ability to manage concentrations change with aging?
Decreased ability to maximally concentrate or dilute urine
Decreased response to inadequate dietary salt
Impaired handling of potassium
How does Cockroft-Gault equation change with age?
Overestimates GFR in patients with low creatinine/low muscle mass
Underestimates GFR in patients based solely on age and gender
What are PD changes in elderly?
Changes in receptor concentration, number and affinity, post-receptor alterations, and impairment of homeostatic mechanisms
How is homeostasis affected by age?
Less effective because of decreased counter-regulatory measures. This causes reactions to medications to be stronger/incidence of ADRs to be higher
What happens to baroreceptor response in aging?
Blunted = increased susceptibility to orthostasis
How do diuretics affect the elderly population?
D/t decreased body water, diuretic effects are more severe (more concentrated)
What cardiovascular PD changes are there in aging?
Beta-adrenergic receptors are down regulated
CCBs have increased risk of hypotesnion/bradycardia
Warfarin has increased risk of bleeding
What CNS PD changes are there in aging?
Decreased DA receptors and neurons = increased sensitivity to EPS
Decrease in cholinergic neurons and receptors = importance for cognition
Decrease in brain mass
Change in BDZ-GABA receptor complex = increased sensitivity to BDZ
Increased sensitivity to opioid analgesics, anesthetic agents and lithium
