Special Populations - Oldies

frail or institutionalized elderly

Drugs act as a provocative stressors to shift organ systems to clinical signs of…

loss of hepatic and renal function, evidence of increased end-organ sensitivity to drugs

What has the greatest effect on PK and PD in the elderly?

Longer gastric emptying time, decreased gastric acid production

How is absorption affected by aging?

ketoconzaole, itraconazole, atazanavir, kinase inhibitor (anything that is acid dependent)

Which drugs are affected by a decrease in acid production?

Drugs that increase gastric emptying or change the pH, drugs that change GI motility, Divalent cations, food, enteral feedings (phenytoin)

What can change the rate and levels of absorption when taken concurrently with medications?

oral (dysphagia), IV (old people have terrible veins bro)

Which administration routes may be difficult in the elderly?

failure to decrease dose will increase plasma drug concentration or duration and toxicity

Why is it important to think about distribution in the elderly?

Increase circulation and prolonged distribution, delay absorption, Tmax, and/or onset of effect, decreased perfusion to kidneys and liver (longer clearance time)

How does decrease perfusion and CO affect drug distribution in the elderly?

Decreased (PgP aren’t working as well → increased response of drugs that cross)

How does the efficiency of the BBB change in the elderly?

Decreased liver size and blood flow, decreased phase 1 enzymes, decreased ability to recover from liver injury

How is metabolism affected by aging?

try to pick a phase II, no active metabolites

When selecting drugs for the elderly, what should we think about in terms of the liver?

Decreased renal blood flow, decreased GFR, decreased number of functioning nephrons, decreased tubular secretion (decreases the efficiency of diuretics)

How is excretion affected by aging?

Depends on muscle mass (old people have less)

Why is Serum creatinine not a good measurement of kidney function in the elderly?

Low intravascular volume (shock), decreased perfusion secondary to renal artery stenosis

Compensatory mechanisms for GRF are important when?

NSAIDs (Mess with PGs), Any RAAS drugs (ACEI, ARB, ARNI)

Which classes of medications mess with the compensatory mechanisms of the kidney?

Decreased baroreceptor reflex

Why are elderly people more at risk for postural hypotension - can lead to syncope and falls?

Alpha-1 Antagonists (-zosins), TCAs, Vasodilators, diuretics

Medications with a concern for postural hypotension

Beta blockers (decreased response mediated by beta receptors)

When treating HTN in the elderly, what drugs may not be as effective?

Decreased cholinergic receptors, decreased levels of ACh, decreased cognitive reserve

How is the cholinergic system affected by aging?

TCAs, anti-emetics, urinary antispasmodics, muscle relaxants, antihistamine

Old people are more sensitive to antagonism of cholinergic receptors - which drugs have these effects?

increased frequency and severity of EPS, antipsychotic-induced delirium , could produce “drug-induced parkinsonism” if levels in the substantia nigra are low

What are the concerns with anti-dopaminergic agents (1G antipsychotics, metoclopramide) in the elderly?

Amnesia, agitation, delirium, sedation, psychomotor impairment, ataxia, imbalance (chronic)

Since the elderly has an increased sensitivity to drugs acting on the CNS and increased GABA receptor mediated effects - what side effects are we worried about for Benzos?

Drowsiness, sedation, respiratory depression, constipation

Since the elderly has an increased sensitivity to drugs acting on the CNS - what side effects are we worried about for CNS depressants (antihistamines, antipsychotics, antidepressants, and opioids)?

Antacids (acid base imbalance, constipation), Corticosteroids (sodium retention, osteoporosis), Hypoglycemics and insulin, Anti-asthmatic drugs (palpitations, tachy)

Problematic Drug Classes for the elderly

Opiates, NSAIDs (bleeding), benzos, antidopaminergics, ACEI/ARBs (increased SCr and K), digoxin (low TI)

What are some of the drugs that have altered sensitivity in the elderly?

2-3x

ADRs are _____ more common in the elderly

increased falls and fractures (anti-HTN), urinary retention (anticholinergics)

Examples of common ADRs in the elderly

Aging physiology, multiple concurrent diseases (polypharmacy), medication errors, non-adherence (intentional or nah)

Risk factors for increased ADRs in the elderly

Why/when/how to take them, potential issues with concurrent meds or EtOH, potential side effects, do not recognize specific medication, exacerbated by impaired cognitive functions and poor communications, motor problems, multi-drug regimens, cost-vs-incomes

Why might old people have problems with their medications?

bleeding risk

DDI for warfarin and NSAIDs (warfarin and anything really)

hyperkalemia

DDI for ACEI and K supplements

QT prolongation

DDI for digoxin and Amio

cimetidine, trimethoprim

Which drugs inhibit of tubular secretion of procainamide?

probenecid

Which drugs inhibit of tubular secretion of PCN?

piperacillin

Which drugs inhibit of tubular secretion of flucloxacillin?

Correct diagnosis (get a good med hx), start low and slow (achieve therapeutic effect first), decrease the number of meds if you can or use meds with different appearences, repeat instructions to caregivers

Guideline for Appropriate Drug Use

Proper name, dosage form (use liquid if possible), and strength; when and how to take the med, what to do for missing/double dosing, storage/dietary instructions if needed, expected outcomes and side effects, unexpected side effects and what to do

Guidelines for appropriate Rx instructions

AGS Beers Criteria (not for hospice or palliative)

What is a GREAT resource for geriatric medications?

CCBs, iron

Potential offenders of Constipation

alpha-blockers

Potential offenders of orthostatic hypotension

TCAs, antihistamines

Potential offenders of anticholinergic effects (DRY, FAST, ETC)

benzos

Potential offenders of falls, ataxia