Geriatric Pharmacology

Question 1

How do the changes associated with aging seen with lean body mass and body fat affect the volume of distribution of hydrophilic and lipophilic medications?

Answer 1

Decreased lean body mass and total body water. Reduction of the half-lives of hydrophilic drugs since their volume of distribution is reduced. Increased body fat. Lipophilic medications exhibit an increase in volume of distribution and half-life.

Question 2

What would be the pharmacokinetic characteristics of the ideal drug for use with
older patients?

Answer 2

Rapid onset and relatively brief duration.
If possible use drugs that undergo Phase II metabolism. See below for further
explanation.

Question 3

What changes occur in Phase I metabolism as compared to Phase II metabolism
in elderly patients?

Answer 3

Decreased elimination rate of drugs that undergo oxidative Phase I metabolism.
Age does not have an effect on Phase II hepatic metabolism.

Question 4

Why are the changes in pharmacodynamics important to consider when choosing and dosing a medication for an elderly patient?

Answer 4

In the elderly, there is an increased sensitivity to the effects of many drugs. As an example, geriatric patients exhibit a greater sensitivity to the effects of drugs that gain access to the CNS (e.g., benzodiazepines (BZ; anxiolytic, sedative/hypnotic), cimetidine (histamine H2 antagonist)). In most cases, lower doses are required for adequate response, and patients have a higher incidence of adverse effects. For example, lower doses of opioids provide sufficient pain relief for older patients, whereas conventional doses can cause over-sedation and respiratory depression.

Similarly, elderly patients appear of be more sensitive to the sedating effects of BZ. Sedation is induced by diazepam at lower doses and lower plasma concentrations in elderly patients. The sensitivity of the elderly to BZ and their effects last longer than in the young. It is common clinical experience that BZ given to the elderly at hypnotic doses used for the young can produce prolonged daytime confusion even after single doses.

Similarly, the incidence of confusion associated with cimetidine is increased in the elderly. Among the more serious complications, falls that lead to hip fracture have been associated with increasing dosages and prolonged half-lives of psychotropic drugs, including antidepressants and BZ.

Therefore, these drugs should be initiated at lower doses than those used for younger patients and titrated slowly for safe and appropriate sedation. Also, agents with a favorable pharmacokinetic profile (e.g., rapid onset and relatively brief duration) should be chosen. For example, start with very low doses of BZ and titrate slowly, longer interval between doses, and closely monitoring the patient for any adverse response. Furthermore, choose lorazepam or oxazepam due to their hydrophilic properties and Phase II metabolism.

Question 5

What proportion of adverse drug events are considered preventable?

Answer 5

50% of ADEs are considered preventable.

Question 6

Why are elderly patients more or less vulnerable to hospitalization due to ADEs relative to younger patients?

Answer 6

The elderly often take many more drugs than their younger counterparts.
Consequently, this polypharmacy adds to risk.

Question 7

What risk factor for ADEs is most consistently described in the literature?

Answer 7

Polypharmacy

Question 8

In which category (prescribing, monitoring, dispensing, or administration) do the
majority of adverse drug events occur?

Answer 8

Inappropriate prescribing

Question 9

How is absorption affected?

Answer 9

Not significantly affect orally.
- Vitamin B12, Ca, Iron, and thiamine is reduced

Unpredictable transdermal, subcutaneous, and intramuscular drug absorption

GI disease may interfere with absorption

Question 10

Young old, old, old old

Answer 10

young old: 65-75
old: 75-85
old old: >85

Question 11

Lipid vs water soluble distribution

Answer 11

Greater lipid soluble distribution

Decreased volume of distribution for water-soluble drugs

Question 12

How much is liver mass reduced with advancing age?

Answer 12

20-30%

Question 13

What enzymes are affected by aging and lead to decreased elimination rates?

Answer 13

CYP450

Question 14

Does age affect Phase II hepatic metabolism?

Answer 14

No

Question 15

What happens to renal clearance between 25 to 85?

Answer 15

Renal blood flow, renal mass, glomerular filtration rate (GFR), and tubular secretion decrease with aging. From age 25 to 85 years, average renal clearance decline by as much as 50% and is independent of the effects of disease.

Question 16

Why does serum creatinine remain unchanged with age?

Answer 16

It is important to note that despite a dramatic decrease in renal function (creatinine clearance, CrCl) with aging, serum creatinine (Scr) may remain fairly unchanged and remain within normal limits. This is because elderly patients have decreased muscle mass resulting in less creatinine production for input into circulation.

Question 17

Polypharmacy definition:

How many community-dwelling elderly?

Answer 17

Polypharmacy is defined as taking multiple medications concurrently (at least five) or the use of unnecessary medications.

An estimated 50% of the community-dwelling elderly take 5 or more medications,
and 12% of them take 10 or more.

Question 18

Beers criteria: (3 categories)

Answer 18

The new Beers criteria are divided into three categories: (a) medications that should
be avoided regardless of disease/condition, (b) medications to avoid in certain
diseases/conditions, and (c) medications to use with caution.

Question 19

% ADEs considered predictable? preventable?

Answer 19

More than 95% of ADEs that occur in the elderly are considered predictable, and
50% are considered preventable. In the United States over two million serious ADEs
occur annually and account for over 100,000 deaths.

Question 20

What drugs increase falls?

Answer 20

Diuretics and nitrates
ACE inhibitors, β-blockers and diuretics
Psychoactive drugs
Antipsychotics
TCA's and SSRI's
benzodiazepines (not clear which type: fast or slow)
Anticonvulsives

Question 21

Double incontinence:
definition
% of people >75

Answer 21

Double incontinence is the inability to perceive, retain and evacuate stool and urine at the
time and place of choice. At least 15% of men and women above 75 years of age suffer from
double incontinence.

Question 22

Prescribing cascade definition:

Examples: (Don’t memorize, just skim)

Answer 22

A “prescribing cascade” occurs when the side effect of a drug is misinterpreted as a sign or
symptom of a new disorder, leading to a new drug being prescribed to treat that effect.

NSAIDs > HTN&raquo_space; anti-hypertensive therapy initiated

NSAIDs > Blood in stool&raquo_space; H2 blocker&raquo_space;> delirium&raquo_space;» Haldol initiated

Metoclopramide > Parkinsonism&raquo_space; carbidopa/levodopa initiated&raquo_space;>
fludrocortisone for hypotension

HCTZ > gout&raquo_space; NSAIDs&raquo_space;> antihypertensive initiated

SSRIs > hyponatremia&raquo_space; declomycin

OTC pseudoephedrine > urinary retention&raquo_space; alpha blocker

Antipsychotic > extra pyramidal side-effects > primidone

Cholinesterases > urinary incontinence&raquo_space; oxybutynin

Question 23

Nonadherence

Answer 23

Nonadherence is the failure to take or administer the medication as prescribed and can be a
problem of either under-use or over-use.