Geriatric Pharmacology Flashcards
What is the Beers list (Beers Criteria)? What categories does it have?
List of medications likely to cause adverse effects in elderly
Categories:
- high risk (problematic to most older patients)
- moderate risk (problematic for certain disease conditions)
- some risk (use with caution)
Name age-related changes in body composition
Decrease total body water
Decrease lean body mass
Increased body fat
Name age-related changes in liver function
Decreased hepatic size
Decreased hepatic blood flow
Name age-related changes in cardiac function
Decreased myocardial sensitivity to beta-adrenergic stimulation (beta-blockers may have less effect)
Decreased baroreceptor activity
Decreased cardiac output
Increased total peripheral resistance
Name age-related changes in kidney function
GFR tends to decrease
Decrease in RBF
Decrease in filtration fraction
Decrease in tubular secretory function
Decrease in renal mass
Name age-related changes in pharmacokinetics. (absorption, distribution, metabolism, clearance/elimination)
Absorption: least affected, can change secondary to reduced stomach acidity
First-pass metabolism: reduced
Distribution: affected because of different body composition (less body water, lower lean body mass %)
Metabolism/clearance: decreased d/t changes to kidney and liver function and blood flow
How does aging affect the Vd of lipophilic and hydrophilic drugs?
Aging increases Vd for lipophilic drugs
Decreases Vd for hydrophilic drugs
How does aging affect the loading dose of highly water soluble drugs?
Aging leads to decreased loading dose for highly water soluble drugs
Given constant clearance, which will have a longer half-life in an elderly patient: a lipophilic drug or a hydrophilic drug?
Lipophilic drug
What is the effect of aging on 1/2 life and maintenance dose of flow-limited phase I drugs (metabolized by liver)? flow-limited Phase II drugs?
increased half life for both, thus maintenance dose should be decreased.
What is the effect of aging on 1/2 life and maintenance dose of capacity limited liver metabolized phase 1 drugs? Phase 2 drugs?
increased half life for phase I drugs; no change for phase II
increased maintenance dose for phase I capacity-limited drugs.
Why would you use creatinine clearance estimates to guide dosing?
Creatinine clearance gives estimate of GFR. Serum creatinine used to estimate
(Rate of creatinine clearance used because creatinine is filtered, not actively absorbed or secreted)
What is the Cockcroft-Gault equation? Why do we use it?
Accounts for decreased muscle mass (thus decreased serum creatinine) in elderly patients
What are the adverse effects of NSAIDS? How are they changed in the elderly
Renal damage (blocked formation of prostaglandins which maintain renal blood flow), GI bleeding and irritation (protective mucus secretion/negative acid secretion feedback is blocked)
Both effects worsened in the elderly d/t decreased renal clearance
Which classes of drugs have high anti-cholinergic activity?
Anticonvulsants
Antidepressants TCAs > SSRI (Paroxetine > other SSRIs)
Antihistamines (use second generation antihistamines to avoid)
Muscle relaxants
Parkinson disease
Urinary antispasmodics Vertigo
Anti-psychotics
Cardiovascular
GI antispasmodics
H2 antagonists not specifically discussed in class, but on chart
What are the adverse effects of anticholinergic drugs? Which effects are more pronounced in the elderly?
Dry mouth, decreased GI motility, urinary retention, orthostatic hypotension, blurry vision
Increased fall risk in elderly!
How many drugs/wk is considered polypharmacy? What do you need to watch out for?
> or = 5 drugs/wk
Concern for drug-drug interactions
Ex. impaired excretion due to competition for tubular drug transporters
(Not in objectives)
How can you prevent a “prescribing cascade”?
- start with low dose and titrate
- avoid prescribing before confirming diagnosis
- don’t change multiple drugs at once
- reach therapeutic dose before switching or adding agents.
(Not in objectives)
What is the risk with inadequate monitoring the elderly?
Pts may not associate adverse effect with drug. Set up follow-up appointment beforehand.
Why is overdosage of specific concern in the elderly?
Decreased clearance of drugs leads to increased circulating concentrations.
What is STOPP
Screening Tool of Older Persons’ potentially inappropriate prescriptions
- assess use of drug with specific patient conditions
What is START?
Screening Tool to Alert doctors to Right Treatment
- identify underuse of beneficial medications in older adults
What is bio-availability (F)?
Fraction of drug reaching systemic circulation (is 1 for IV dose)
Change in first-pass metabolism in elderly patients?
Reduced first pass metabolism; can lead to decreased INACTIVATION of drug, or decreased ACTIVATION of prodrug
What drugs might need a higher dose d/t decreased first-pass metabolism in the elderly?
Codeine, propanolol, enalapril, perindopril, simvastatin
What is volume of distribution?
Volume of fluid in which drug must be dissolved to Achieve desired plasma concentration
amt of drug in body/plasma drug concentration
Does a lipophilic drug have a high volume of distribution or low volume of distribution?
High Vd
Would a muscle binding drug (eg Digoxin) have increased Vd or decreased Vd in elderly?
Decreased Vd in elderly
Less bound to muscle, more bound to systemic circulation
Would a highly water soluble drug (eg Gentamicin) have increased or decreased Vd in elderly?
Decreased Vd in elderly d/t decreased body water
What is the effect of increased Vd on half-life?
Depends on clearance.
t(1/2) = 0.693*Vd/CL
Lipid soluble drug would have increased Vd. Increased half-life???
Water soluble drug would have decreased Vd. However, clearance is also reduced, so there would be less of an increase than with lipid solubles.
What is the effect of decreased Vd on loading dose?
If Vd is decreased, loading dose will be smaller (assuming bio availability is constant!
What is clearance?
Rate of elimination of drug from body relative to drug concentration
CL=Q (flow rate to organ) x E (extraction ratio)
What factors affect hepatic drug clearance?
Q: hepatic blood flow (via portal vein, hepatic artery)
E: liver metabolism
Phase I enzymes = cytochrome p450s
Phase II enzymes = polar group conjugation (eg. glucoronidation) to facilitate excretion
How does aging affect hepatic drug clearance?
Q: hepatic blood flow decreases
E: Phase I enzyme activity reduced
Phase II enzymes activities UNCHANGED
Capacity limited drugs have a clearance rate limited by:
a) hepatic blood flow
or
b) liver enzyme function?
Rate-limiting step is b) liver enzyme function
True or False?
A capacity limited drug will have decreased clearance in the elderly if metabolized by phase I enzymes
True!
If phase II enzymes, clearance is unchanged
How is clearance of flow-limited drugs changed in the elderly?
Hepatic clearance is decreased secondary to decreased hepatic blood flow
What maintenance rate is required to maintain a steady state drug concentration?
Maintenance rate must be equal to clearance.
Reduction of hepatic clearance requires more or less frequent maintenance doses?
Less frequent or lower doses.
Change in maintenance dose in elderly for capacity limited phase II enzyme metabolized drugs?
No change in maintenance dose, d/t no change in clearance
Change in maintenance dose in elderly for capacity limited phase I enzyme metabolized drugs?
Decreased maintenance dose
Change in maintenance dose in elderly for flow-rate limited drugs?
Decreased maintenance dose
In elderly patients, will GFR estimated from serum creatinine be an overestimate or underestimate?
Less muscle mass, means lower serum creatinine means falsely OVERestimated GFR
Responsiveness of elderly to hypotensive beta-blocking effects is increased or decreased?
Decreased
BP response to calcium channel blockers in elder is increased or decreased?
Increased (exaggerated acute response d/t reduced baroreflex activation)
Sensitivity to anesthetic agents increases or decreases with age?
Increased sensitivity
