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Drug Categories of Concern in the Elderly
source: Merck Manual
Some drug categories (eg, analgesics, anticoagulants, antihypertensives,
antiparkinsonian drugs, diuretics, hypoglycemic drugs, psychoactive drugs) pose
special risks for elderly patients.
Analgesics: NSAIDs are widely used; several are available without prescription.
Serious adverse effects include peptic ulceration and upper GI bleeding; risk is
increased when an NSAID is begun and when dose is increased. Risk of upper GI
bleeding increases when NSAIDs are given with warfarin COUMADIN
or aspirin BUFFERIN ECOTRIN GENACOTE or other antiplatelet drugs (eg, clopidogrel
PLAVIX). NSAIDs may increase risk of cardiovascular events and can cause fluid
retention and, rarely, nephropathy.
NSAIDs can also increase BP
NSAIDs may increase risk of cardiovascular events and can cause fluid retention.
Selective COX-2 inhibitors (coxibs) cause less GI irritation and platelet inhibition than
other NSAIDs. Nonetheless, coxibs have a risk of GI bleeding, especially in patients
taking warfarin COUMADIN or aspirin BUFFERIN ECOTRIN GENACOTE
(even at low dose) and in those who have had GI events. Coxibs, as a class, appear to
increase risk of cardiovascular events, but that risk may vary by drug; their use should
be approached cautiously. Coxibs have renal effects comparable to those of other
NSAIDs. Monitoring serum creatinine is necessary, especially in patients with other risk
factors (eg, heart failure, renal impairment, cirrhosis with ascites, volume depletion,
diuretic use).
Anticoagulants: Aging does not alter the pharmacokinetics of warfarin COUMADIN
but may increase sensitivity to its anticoagulant effect. Careful dosing and scrupulous
monitoring can largely overcome the increased risk of bleeding in elderly patients taking
warfarin COUMADIN.
Antihypertensives: In many elderly patients, lower starting doses of antihypertensives
may be necessary to reduce risk of adverse effects; however, for most elderly patients
with hypertension, achieving BP goals requires standard doses and multidrug therapy.
Initially, a thiazide-type diuretic is usually given alone or with one of the other classes
(ACE inhibitors, angiotensin II receptor blockers, β-blockers, Ca channel blockers)
shown to be beneficial. Short-acting dihydropyridines (eg, nifedipine ADALAT,
PROCARDIA) may increase mortality risk and should not be used.
Antiparkinsonian drugs: Levodopa clearance is reduced in elderly patients, who are
also more susceptible to orthostatic hypotension and confusion. Therefore, elderly
patients should be given a lower starting dose of levodopa and carefully monitored for
adverse effects . Patients who become confused while taking levodopa may also not
tolerate newer dopamine INTROPIN agonists (eg, bromocriptine PARLODEL, pergolide
PERMAX, pramipexole MIRAPEX, ropinirole REQUIP. Because elderly patients with
parkinsonism may be cognitively impaired, anticholinergic drugs should be avoided.
Digoxin: Digoxin DIGITEK, LANOXIN
clearance decreases an average of 50% in elderly patients with normal serum
creatinine levels. Therefore, maintenance doses should be started low (0.125 mg/day)
and adjusted according to response and serum digoxin levels. Digoxin DIGITEK
LANOXIN must be used with caution in patients with heart failure. In men with heart
failure and a left ventricular ejection fraction of ≤ 45%, serum digoxin levels > 0.8 ng/mL
are associated with increased mortality risk. Among women with heart failure and
depressed left ventricular function, digoxin regardless of serum level, is associated with
increased mortality risk.
Diuretics: Lower doses of thiazide diuretics (eg, hydrochlorothiazide ESIDRIX
HYDRODIURIL or chlorthalidone HYGROTON
12.5 to 25 mg) can effectively control hypertension in many elderly patients and have
less risk of hypokalemia and hyperglycemia.Thus, K supplements may be required less
often. K-sparing diuretics should be used with caution in the elderly; the K level must be
carefully monitored, particularly when these diuretics are given with ACE inhibitors.
Antihyperglycemics: Doses of antihyperglycemics should be titrated carefully in
patients with diabetes mellitus. Risk of hypoglycemia due to sulfonylureas may increase
with aging. Chlorpropamide DIABINESE is not recommended because elderly patients
are at increased risk of hyponatremia due to syndrome of inappropriate antidiuretic
hormone secretion (SIADH) and because the drug's long duration of action is
dangerous if adverse effects or hypoglycemia occurs. Risk of hypoglycemia is greater
with glyburide GLYNASE, MICRONASE than with other oral antihyperglycemics.
Metformin GLUCOPHAGE, a biguanide excreted by the kidneys, increases peripheral
tissue sensitivity to insulin HUMULIN, NOVOLIN and can be effective given alone or
with sulfonylureas. Risk of lactic acidosis, a rare but serious complication, increases
with degree of renal impairment and with patient age. Heart failure is a contraindication.
Psychoactive drugs: In nonpsychotic, agitated patients, antipsychotics control
symptoms only marginally better than do placebos. Antipsychotics can reduce paranoia
but may worsen confusion. Elderly patients, especially women, are at increased risk of
tardive dyskinesia, which is often irreversible. The FDA has issued a warning regarding
the use of atypical antipsychotics in the treatment of behavioral disorders in elderly
patients with dementia. A review of placebo-controlled studies has shown a higher
death rate associated with their use. Sedation, orthostatic hypotension, anticholinergic
effects, and akathisia (subjective motor restlessness) can occur in up to 20% of elderly
patients taking an antipsychotic, and drug-induced parkinsonism can persist for up to 6
to 9 mo after stopping the drug. Antipsychotic drugs should be reserved for psychosis.
When an antipsychotic is used, the starting dose should be about ¼ the usual starting
adult dose and should be increased gradually. Extrapyramidal dysfunction can develop
when atypical antipsychotics (eg, olanzapine ZYPREXA, quetiapine
SEROQUEL, risperidone RISPERDAL) are used, especially at higher doses. Clinical
trial data relating to dosing, efficacy, and safety of these drugs in the elderly are limited;
thus, dose reduction is prudent.
Use of anxiolytics and hypnotics can be problematic. Treatable causes of insomnia
should be sought and managed before using hypnotics. Nonbenzodiazepine hypnotics
(eg, the imidazopyridines, alpidem and zolpidem AMBIEN) are options for treating
insomnia in the elderly if nonpharmacologic measures (eg, avoiding caffeinated
beverages, limiting daytime napping, modifying bedtime) are ineffective. These drugs
bind mainly to a benzodiazepine receptor subtype. Imidazopyridines disturb the sleep
pattern less than benzodiazepines and have a more rapid onset, fewer rebound effects,
and less potential for dependence.
Longer-acting benzodiazepines (eg, clonazepam KLONOPIN, diazepam VALIUM,
flurazepam DALMANE) should be avoided because they are likely to accumulate and
have adverse effects (eg, drowsiness, impaired memory, impaired balance leading to
falls and fractures). Duration of anxiolytic or hypnotic therapy should be limited if
possible because tolerance and dependence may develop; withdrawal may lead to
rebound anxiety and insomnia. Short- or intermediate-acting benzodiazepines with halflives < 24 h (eg, alprazolam XANAX, lorazepam ATIVAN, oxazepam SERAX,
temazepam RESTORIL) may be preferable to long-acting benzodiazepines, but these
drugs may also have adverse effects, including those that lead to falls and fractures.
Antihistamines (eg, diphenhydramine BENADRYL NYTOL, hydroxyzine ATARAX,
VISTARIL) are not recommended as anxiolytics or hypnotics because they have
anticholinergic effects.
Buspirone
BUSPAR, a partial serotonin agonist, can be effective for general anxiety disorder;
elderly patients tolerate doses up to 30 mg/day well. The slow onset of anxiolytic action
(up to 2 to 3 wk) can be a disadvantage in urgent cases.
Of antidepressants, SSRIs and mixed serotonin/ dopamine INTROPIN
reuptake inhibitors are generally preferred. These drugs appear to be as effective as
tricyclic antidepressants and cause less toxicity. A possible disadvantage of fluoxetine
PROZAC, SARAFEM is the long elimination half-life, especially of its active metabolite.
Paroxetine PAXIL is more sedating than other SSRIs, has anticholinergic effects, and,
like some other SSRIs, can inhibit hepatic cytochrome P-450 2D6 enzyme activity,
possibly impairing the metabolism of several drugs, including some antipsychotics,
antiarrhythmics, and tricyclic antidepressants. Sertraline ZOLOFT
is more activating; diarrhea is a common adverse effect. Doses of these drugs should
be reduced by up to 50%. Many SSRIs are available, but data on their use in the elderly
are sparse. Tricyclic antidepressants are effective but should rarely be used in the
elderly because safer alternatives exist.
Pharmacodynamics in the Elderly
Pharmacodynamics is defined as what the drug does to the body or the response
of the body to the drug; it is affected by receptor binding, postreceptor effects, and
chemical interactions. The effects of similar drug concentrations at the site of action
(sensitivity) may be greater or smaller than those in younger people . Differences may
be due to changes in drug-receptor interaction, in postreceptor events, or in adaptive
homeostatic responses and, among frail patients, are often due to organ pathology.
Elderly patients are particularly sensitive to anticholinergic drug effects. Many drugs (eg,
tricyclic antidepressants, most nonselective antihistamines, some antipsychotic drugs,
many OTC hypnotics and cold preparations) are anticholinergic. The elderly, most
notably those with dementia, are particularly prone to CNS adverse effects of such
drugs and may develop confusion and somnolence. Anticholinergic drugs also
commonly cause constipation, urinary retention (especially in elderly men with benign
prostatic hyperplasia), blurred vision, orthostatic hypotension, and dry mouth.
Pharmacokinetics in the Elderly
Pharmacokinetics is best defined as what the body does to the drug; it includes
absorption, distribution across body compartments, metabolism, and excretion. With
aging, the metabolism and excretion of many drugs decrease, and the physiologic
changes of aging require dose adjustment for some drugs. Toxicity may accumulate
slowly because levels of chronically used drugs tend to increase for about 6 half-lives.
For example, certain benzodiazepines ( diazepam
VALIUM, flurazepam DALMANE, chlordiazepoxide LIBRIUM) have half-lives of up to 96
h in many elderly patients; signs of toxicity may not appear until days or weeks after
therapy is started.
Absorption: Despite an age-related decrease in small-bowel surface area and an
increase in gastric pH, changes in drug absorption tend to be trivial and clinically
inconsequential.
Distribution: With aging, the body's fat compartment increases, and the water
compartment decreases. Increased fat increases the volume of distribution for highly
lipophilic drugs (eg, diazepam VALIUM) and may increase their elimination half-lives.
Serum albumin decreases and reductions in serum albumin may enhance drug effects
because serum levels of unbound drug may increase.
Hepatic metabolism: Overall hepatic metabolism of many drugs through the
cytochrome P-450 enzyme system decreases with aging. For drugs with decreased
hepatic metabolism, clearance typically decreases 30 to 40%. Theoretically,
maintenance drug doses should be decreased by this percentage; however, rate of drug
metabolism varies greatly from person to person, and individual titration is required.
Nonpharmacologic Mgt of DM type 2:
 Exercise
 nutritional therapy - Charantia or Bitter Gourd contains Gurmarin, a polypeptide
similar to bovine insulin
 Patient education/ diet modification
 regular monitoring of glycemic status and associated complications
--------------------------------------------------------------------------------------------------------------------Adherence (compliance) is affected by many factors but not by age per se. However,
about 40% of elderly patients do not take drugs as directed, usually taking less than
prescribed (underadherence). Causes are the same as for younger adults. In addition,
financial and physical constraints may make purchasing drugs difficult, dementia may
make taking drugs difficult, and lack of information may lead to errors. Taking drugs can
be facilitated by easy-access containers, containers equipped with reminder alarms,
containers filled by daily drug needs, or reminder phone calls.
______________________________________________________________________
Common Adverse Effects Of Drugs In The Elderly
(source: IER NPTE Reviewer 2008, Chapter 8: GERIATRIC PHYSICAL THERAPY by Susan B. O'Sullivan)
(1) Confusion/dementia: e.g., tranquilizers, barbiturates, digitalis, antihypertensives,
anticholinergic drugs; analgesics, antiparkinsonians, diuretics, beta-blockers.
(2) Sedation/immobility: e.g., psychotropic drugs, narcotic analgesics.
(3) Weakness: e.g., antihypertensives, vasodilator, digitalis, diuretics, oral
hypoglycemics.
(4) Postural hypotension: e.g., antihypertensives, diuretics, tricyclic antidepressants,
tranquilizers, nitrates, narcotic analgesics.
(5) Depression: e.g., antihypertensives, antiinflammatory, antimycobacterial,
antiparkinsonians, diuretics, H2 receptor antagonists,
sedative-hypnotics, vasodilators.
(6) Drug induced movement disorders.
(a) Dyskinesias (involuntary, stereotypic and repetitive movements, i.e., lip
smacking, hand movements, etc.) associated
with long-term use of neuroleptic drugs and anticholinergic drugs, Levodopa.
(b) Akathisia (motor restlessness) associated with antipsychotic drugs.
(c) Essential tremor associated with tricyclic antidepressants, adrenergic drugs.
(d) Parkinsonism: associated with antipsychotics, sympatholytics.
(7) Incontinence: caused by or exacerbated by a variety of drugs, e.g., barbiturates,
benzodiazepines, antipsychotic drugs, anticholinergic drugs.
-----------------------------------------------------------------------------------------------------------------*Anticholinergic side effects include confusion, sedation, delirium, dry mouth, constipation,
urinary retention, blurred vision, and worsening of narrow angle glaucoma-- reasons why
patients are predisposed to falls and fractures.