[03.20] Drug Use in the Geriatric Age Group V2

The elderly

Which population segment uses more drugs than any other segment of society?

Pharmacokinetics and Pharmacodynamics

What two concepts are important to be aware of concerning physiologic changes in the aging process and their effect on drug absorption and use?

Multiple comorbid factors

Why is drug use in the elderly often complicated, especially since they are not often included in drug trials?

Expert consensus and extrapolation of data

What does drug use in the elderly primarily rely on?

90%

According to a 2015 JAMA survey, what percentage of older adults take at least 1 prescription drug?

80%

According to a 2015 JAMA survey, what percentage of older adults take at least 2 prescription drugs?

36%

According to a 2015 JAMA survey, what percentage of older adults take 5 prescription drugs a day?

Frail, Hospitalized, Nursing home elder

In which three specific groups is drug use greatest among the elderly?

Women

Which gender takes more drugs among the older adult population?

11% in 2010

What was the proportion of the global population over the age of 65 in 2010?

32% by 2100

What is the projected proportion of the global population over the age of 65 by the end of the century?

5.4%

According to the 2020 PSA data, what percentage of the total Philippine population was 65 years and over?

74.3 years

What is the life expectancy for females in the Philippines, according to 2020 PSA data?

Improved sanitation, potable water, improved quality and preservation of food, improved housing, better education, improved health awareness, and improvements in medical sciences

Name three contributory factors to global aging.

Non-communicable diseases (NCDs) and degenerative diseases (e.g., Alzheimer's disease)

What leading causes of death are emerging as the global population ages?

Increased risk of adverse drug reactions and drug interactions

Requiring multiple medications due to multiple comorbid factors in the elderly leads to what specific risks?

Reduced physiologic reserves

What key physiological state, which may be further reduced by acute or chronic illness/disorders, can be altered by aging, affecting the pharmacodynamics and pharmacokinetics of drugs?

Absorption, Distribution, Metabolism, Elimination

What are the four processes that constitute Pharmacokinetics?

Decrease in small-bowel surface area due to atrophy, slowed gastric emptying, and increase in gastric pH

Name three observed physiologic changes that may affect drug absorption in the elderly.

They are likely inconsequential/minimal

What is the clinical relevance of the documented changes in drug absorption in the elderly?

Sarcopenia

What is the term for the largely physiologic reduction of skeletal muscle mass in the elderly?

Increase in body fat mass

What occurs at the expense of skeletal muscle mass in sarcopenia, affecting drug distribution?

Wider VD and Longer half-life

What does the increase in fat mass mean for lipophilic drugs in the elderly?

Increased volume of distribution (VD)

What is the primary change in drug distribution for lipophilic (fat-binding or fat-soluble) drugs in the elderly?

Benzodiazepines such as diazepam (Valium)

Provide an example of a lipophilic drug that carries a higher risk for prolonged sedation and falls in the elderly.

Decrease volume of distribution (VD)

What is the primary change in drug distribution for hydrophilic (water-soluble) drugs in the elderly?

Higher serum levels

Decrease in VD for hydrophilic drugs leads to what outcome in the elderly?

Digoxin (Lanoxin)

Provide an example of a hydrophilic drug that can cause severe side effects in the elderly due to high serum concentrations relative to the administered dose.

Albumin and alpha-1 glycoprotein

What are the two most commonly involved proteins in pharmacokinetics that act as carriers and storage depots?

Rapid reductions in serum albumin and increase in alpha-1 glycoprotein

Acute illness in the elderly may lead to what two changes regarding protein binding?

Heightened action of drug but short-lived

What is the net effect of rapid drops in serum albumin resulting in increased free or unbound drug?

Increased side effects or adverse drug reactions

What is the clinical risk associated with higher levels of free or unbound drugs?

They metabolize more quickly

Why is the action of free or unbound drugs short-lived?

Diazepam, Phenytoin, Warfarin, Aspirin

Name two acidic drugs that bind to albumin.

Decreased effect of drug

What is the net effect of an increase in alpha-1 glycoprotein resulting in increased binding of drugs?

Lidocaine, Propranolol

Name two basic drugs that bind to alpha-1 glycoprotein.

Decreased hepatic blood flow and decreased liver volume (up to 30%)

What are the two primary observed physiologic changes in the liver that affect drug metabolism in the elderly?

Clearance of drugs with high extraction ratios

What is specifically affected by decreased hepatic blood flow?

Phase I Reaction

Which phase of drug metabolism is non-synthetic, involves oxidation, reduction, and hydrolysis, and is most affected by aging?

Cytochrome P450 (CYP450) enzyme system

Which specific enzyme system's capacity for metabolism is reduced by 30% or more due to decreased hepatic volume and blood flow, leading to prolonged hepatic clearance?

Phase II Reaction

Which phase of drug metabolism is synthetic, involves conjugation and glucuronidation, and is less affected by age?

More polar

Metabolites formed in synthetic (Phase II) reactions are __, making them more readily excreted than those formed in non-synthetic reactions.

Before a drug reaches the systemic circulation

When does first-pass metabolism occur?

Decreases by about 1% per year after the age of 40

What is the age-related change observed in first-pass metabolism?

Higher concentrations of circulating drug

What is the result of a decrease in first-pass metabolism?

Nitrates, Propranolol, Nifedipine

Name two drugs that may cause significant toxicity or adverse reactions in high serum concentrations due to reduced first-pass metabolism.

Glomerular Filtration Rate (GFR)

What process is drug elimination largely dependent on?

Decreased GFR

What causes decreased renal elimination in the elderly?

Reduction in the number of functioning glomeruli

What specific change leads to decreased GFR and decreased creatinine clearance in the elderly?

8-10 mL/min/1.73m²/decade

At what rate does creatinine clearance typically decrease?

Sarcopenia and less physical activity

Why does serum creatinine often remain within normal limits in the elderly, even when kidney function is reduced?

Normal kidney function

Normal creatinine in the elderly may not necessarily reflect what?

Acute illness or dehydration

When must renal function be measured in the elderly due to its dynamic nature?

Cockcroft-Gault equation

What equation is used to estimate creatinine clearance (CrCl)?

Plasma cystatin C

What is an alternative to or used in addition to creatinine to estimate GFR?

Drugs with narrow therapeutic range or index

Which class of drugs is likely to have serious adverse effects or be lethal if they accumulate even marginally above intended levels?

Aminoglycosides

Which antibiotics are drugs of concern in the elderly due to nephrotoxicity (usually reversible) and ototoxicity (tends to be irreversible)?

Severe slowing of heart rate and Potassium accumulation in the blood

What are two key concerns when using the cardiac medication Digoxin in the elderly?

Bipolar mood disorder

Lithium, an old drug of concern in the elderly, is still the drug of choice for treating what condition?

Hemodialysis

What is the treatment for Lithium toxicity, since there is no antidote?

Drug’s effect on the body or the response of the body to the drug

What is the definition of pharmacodynamics?

Receptor binding, Post-receptor effects, Chemical interactions, Homeostatic regulation

Name two factors that affect pharmacodynamics in the elderly.

Increased sensitivity

Do the elderly generally have increased or decreased sensitivity to psychoactive drugs, anti-hypertensive drugs, and oral hypoglycemic agents?

Decreased sensitivity

Do the elderly generally have increased or decreased sensitivity to vasodilators, diuretics, and bronchodilators?

Sedative hypnotics and Benzodiazepines (e.g., Diazepam)

Name the class and one specific example of psychoactive drugs to which the elderly have increased sensitivity.

Calcium channel blockers (e.g., Nifedipine)

Name a specific class and example of antihypertensive drugs to which the elderly have increased sensitivity.

Metformin

Name an oral hypoglycemic agent to which the elderly have increased sensitivity.

Nitrates (e.g., Isosorbide)

Name a class and example of vasodilators to which the elderly have decreased sensitivity.

Loop diuretics (e.g., Furosemide)

Name a class and example of diuretics to which the elderly have decreased sensitivity.

Salbutamol

Name an example of a bronchodilator to which the elderly have decreased sensitivity.

Increased effect

What is the age-related change in pharmacodynamic effect observed for Benzodiazepines and Morphine?

Decreased effect

What is the age-related change in pharmacodynamic effect observed for Beta-agonists, Beta-blockers (e.g., Metoprolol, Propranolol), and Furosemide?

Drugs that affect the CNS

Which general class of drugs tends to have an increased effect in the elderly?

Blockage of acetylcholine receptors

What causes anticholinergic effects?

Inhibition of parasympathetic nerve impulses

Blockage of acetylcholine receptors leads to what specific physiological inhibition?

Confusion, Drowsiness, Impaired concentration, Attention deficit, Memory impairment

Name three central anticholinergic effects.

Constipation, Urinary retention, Pupillary dilatation, Orthostatic hypotension, Dry mouth, Dry eyes, Blurred vision, Inhibition of diaphoresis, Decreased bronchial secretions, Tachycardia

Name four peripheral anticholinergic effects.

Urinary retention, especially in men with Benign Prostatic Hyperplasia (BPH)

Which specific peripheral anticholinergic effect is particularly concerning in men with BPH?

Orthostatic or postural hypotension

What specific anticholinergic effect causes dizziness and may lead to falls?

Falls and subsequent traumatic injuries

What potentially devastating outcome can anticholinergic effects lead to in older adults?

Tricyclic Antidepressants (TCAs), Sedating Antihistamines, Urinary Antimuscarinics for overactive bladder, Some Antipsychotic Drugs, Antiparkinsonian drugs

Name three classes of drugs with strong anticholinergic effects that should be avoided in the elderly.

Imipramine, Amitriptyline

Name two examples of TCAs with strong anticholinergic effects.

Diphenhydramine (Benadryl)

What is a common sedating antihistamine that should be avoided in the elderly due to strong anticholinergic effects?

Oxybutynin

Name an example of a Urinary Antimuscarinic with strong anticholinergic effects.

Haloperidol

Name an example of an Antipsychotic Drug with strong anticholinergic effects.

Levodopa and Carbidopa

Name two examples of Antiparkinsonian drugs with strong anticholinergic effects.

Unwanted, uncomfortable, or dangerous drug effects

What is the definition of Adverse Drug Reactions (ADRs)?

Oversedation, Confusion, Hallucinations, Falls, Bleeding

Name three examples of ADRs that are problematic because they are often unforeseen.

Exponentially

How does the risk of adverse drug reactions (ADRs) increase relative to the number of medications taken?

Type A

Which type of ADR is dose-related, predictable, and potentially avoidable?

Antibiotics, Anticoagulants, Digoxin, Diuretics, Hypoglycemic agents, Antineoplastic agents, NSAIDs

Name three examples of drugs commonly associated with Type A ADRs.

Type B

Which type of ADR is described as idiosyncratic, less common but potentially leading to serious toxicity (e.g., movement disorders, falls), and sometimes unforeseen?

Antipsychotics, Antiparkinsonian drugs, Benzodiazepines, Anticholinergic drugs

Name two examples of drugs commonly associated with Type B ADRs.

17%

What is the approximate hospitalization rate from ADRs in the elderly?

Warfarin, Antiplatelet agents (Clopidogrel and Aspirin), Hypoglycemic drugs (Metformin and Gliclazide), Insulin

Name the four drugs or drug classes linked to almost 17% of all ADRs in the elderly.

Less is more

What idiom particularly applies to drug use in the elderly because the risk of ADRs increases exponentially with the number of medications taken?

Type A

A 60-year-old man experiencing hypoglycemia after receiving insulin is classified as which type of adverse drug reaction?

Type B

Rashes and swellings due to benzodiazepine intake are considered which type of adverse drug reaction?

Exacerbation of a pre-existing condition

What occurs in a drug-disease interaction?

Prescribing cascade

What occurs when the adverse effect of a drug is misinterpreted as a symptom or sign of a new disorder and a new drug is prescribed to treat it?