DRUG PRESCRIBING

FOR THE ELDERLY

Aly A. Misha’l MD, FACP

Senior consultant in Medicine

and Endocrinology

Amman-Jordan

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الرحمن الله بسمالرحيم

Senility and frailty was described in the Glorious Qur’an in a sense of physical weakness and decline in capabilities, implying significant needs for care, sympathy and mercy.

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“ .... ” عتيًا الكبر من بلغت وقد

“…. And I have grown quite decrepit from old age”

The Glorious Qur’an, Chapter19: Verse 8

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العظم ” وهن إني ربي قًال“.....مني

“ O my lord! Infirm (Brittle) indeed are my bones …”

The Glorious Qur’an, Chapter 19: Verse 4.

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ال ” لكي العمل أرذل إلى يرُّد' من ومنكم شيئًا علم بعد “يعلم

“Some of you are sent back to feeble age, so that they know nothing after what they have known”

The Glorious Qur’an, Chapter 16: Verse 70

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Caring for sick elderly subjects, as part of medical practice, is an act of worship, human and religious duty, that the whole society (Ummah) will be held sinful if it fails to induce and support some of its members to become caring medical professionals (Fardh Kifayah).

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Optimizing medical care is a cornerstone in both Itqan (perfection) and Ihsan (excellence)

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Optimizing drug therapy is a cornerstone of proper caring for older individuals.

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Basic parameters:1.Deciding whether a drug is

indicated. 2.Choosing the most appropriate

drug. 3.Determining dose schedules.

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4. Monitoring for effectiveness and toxicity.

5. Educating the patient (and family) about expected side effects.

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6.Educating the patient (and family) about indications for seeking consultation.

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7. Always inquire about the use of over the counter drugs, herbal preparations and dietary supplements.

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8. The possibility of an adverse drug event should always be borne in mind when evaluating an elderly individual.

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Any new symptom should be considered drug-related until proven otherwise.

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Geriatric Clinical pharmacology: Addresses: Pharmacokinetics:

i.e, absorption, distribution, metabolism and excretion.

Pharmacodynamics: i.e, the physiologic affects of the drug.

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Adverse drug reactions. Drug interactions. Rational drug therapy for older

persons.

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OLD AGE AND

PHARMACOKINETICS

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Age related increase in the proportion of body fat: causes increase in volume of distribution for lipid-soluble drugs: e.g: benzodiazepines.

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Age-related decrease in lean body mass: causes 10-15% decrease in total body water:

The volume of distribution declines for hydrophilic drugs e.g, alcohol.

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Plasma albumen concentration decreases in elderly malnorished subjects, especially those with advanced cancer.

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The plasma-binding of some drugs decreases and the unbound fraction may exceed 50% increase free drug concentrations and toxicity. e.g, Salicylate, Naproxen, Acetazolamide, Valproate.

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Age-related decrease in liver mass: 20-50%: during the age span up to 80 years.

Decreased amount of drug-metabolizing enzymes.

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Associated with that, there is gradual decrease of hepatic blood flow.

Decrease in clearance of drugs.

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Decrease in elimination by conjugation of some drugs by up to 25%. e.g. Theophylline.

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Decreased first-pass metabolism of some drugs that are highly extracted by the liver. e.g. Labetalol, Propranolol, Verapamil and Morphine: This results in decreased systemic bioavailability and decreased concentration.

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Older smokers: Decreased hepatic metabolizing enzymes: increased mortality in older smokers.

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Malnutrition: e.g. in cancer patients with anorexia. Impairment of drug metabolism. Adjusting of dosage (esp. cancer drugs) is important.

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Old frail subjects and decreased clearance of acctominophen: Up to 42% in one study.

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Warfarin: Age-related decline in liver volume. decrease in warfarin dose requirement: may start at age of 50 years.

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Renal function: Renal mass decreases by 25-30% across the age span.

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Renal blood flow decreases by 1% per year after age of 50 years.

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GFR decreases by 35% in healthy individuals between ages 20 and 90 years.

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In some individuals: this decline does not occur!

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This GFR decrease affects the clearance of drugs that are secreted or filtered by the kidney.

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PHARMACODYNAMICS

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High affinity receptors are diminished. Decline in receptor- effectar coupling. e.g: I.V isoproterenol to increase heart

rate in older patients: Compromised More doses are needed.

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Sensitivity to psychoactive drugs is greater in older persons: e.g anxiolic drugs and hypnotics.

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Pain management for cancer patients: e.g Morphine and pentazocine. Duration of pain relief is prolonged with increasing age. Probably due to decreased volume of distribution.

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Anesthesia: Increased brain sensitivity to I.V fentanyl and altentanil.

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ISSUES IN DRUG PRESCRIBING

FOR THE ELDERLY

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Quality of Drug Prescribing: Several dimensions: Avoidance of inappropriate

medications. Appropriate utilization of

indicated drugs.

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Monitoring for side effects, and drug levels.

Avoidance of drug-drug interactions.

Involvement of the patient and integration of his/her values.

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Indicator title Description Rationale

Monitoring warfarin therapy

When warfarin is prescribed, international normalized ratio (INR) should be monitored using standard protocols.

Older adults are at high risk for drug toxicity that can be identified earlier if there is close monitoring for agents with a narrow therapeutic range.

Monitoring loop diuretic therapy

When loop diuretic therapy is prescribed, electrolytes should be checked within one week after initiation and at least annually

Risk of hypokalemia due to diuretic therapy

Quality indicators for appropriate medication use in older adults:

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Indicator title Description Rationale

hypoglycemic agent

When prescribing an oral hypoglycemic agent, chlorpropamide should not be used.

This therapy has a prolonged half- life that can result in serious hypoglycemia and is more likely than other agents to cause the syndrome of inappropriate secretion of antidiuretic hormone.

Avoid drugs with strong anticholinergic properties

Do not prescribe drug therapies with a strong anticholinergic effect, if alternative therapies are available.

These therapies are associated with adverse events such as confusion, urinary retention, constipation, and hypotension.

Cont.

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Indicator title Description Rationale

Avoid barbituates

If an older adult does require the therapy for control of seizures, do not use barbiturates.

These therapies are potent central nervous system depressants, have a low therapeutic index, are highly addictive, cause drug interactions, and are associated with an increased risk for falls and hip fracture.

Avoid meperidine as an opioid analgesic

When analgesia is required, avoid use of meperidine.

This therapy is associated with an increased risk for delirium and may be associated with the development of seizures.

Monitor renal function and potassium in patients prescribed angiotensin- converting enzyme inhibitors

If ACE inhibitor therapy is initiated, potassium and creatinine levels should be closely monitored.

Monitoring may prevent the development of renal insufficiency and hyperkalemia.

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Knight, El, Avorn, Ann Intern Med 2001; 135:703.

In evaluating subjects on multiple medications, always consider:

Over-the-counter drugs. Herbal preparations. Supplements.

POLYPHARMACY

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Around 50% of older patients use 5 or more medications.

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Older individuals are at greater risk for adverse drug events (ADE), due to changes in pharmacokinatics and pharmacodynamics.

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Polypharmacy increases the potential of drug-drug interactions.

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Polypharmacy is a risk factor for falls and hip fractures.

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Polypharmacy increases the risk of “Prescribing Cascades”: When an ADE is misinterpreted as a new medical condition.

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Initial drug therapy Adverse drug event Subsequent drug therapy

Antipsychotics Extrapyramidal signs and symptoms Antiparkinsonian therapy

Cholinesterase inhibitors Urinary incontinence Incontinence treatment

Thiazide diuretics Hyperuricemia Gout treatment

NSAIDs Increased blood pressure Antihypertensive therapy

EXAMPLES OF PRESCRIBING CASCADES:

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Rochon, PA, Gurwitz, JH. BMJ 1997; 315:1096Gill, SS, Mamdani, M, Naglie, G, et al. Arch Intern Med 2005;165-808

Associated with multiple adverse effects in older individuals:

Memory impairment. Confusion, hallucinations. Dry mouth. Blurred vision.

ANTICHOLINERGIC MEDICATIONS

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Constipation, nausea. Urinary retention. Impaired sweating. Tachycardia. Can precipitate acute glaucoma.

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3points 2 points 1 Point

Amitriptyline hydrochloride

Amantadine hydrochloride Carbidopa-levodopa

Atropine products Baclofen Entacapone

Benztropine mesylate Cetirizine hydrochloride Haloperidol

Carisoprodol Cimetidine Methocarbamol

Chlorpheniramine maleate Clozapine

Metoclopramide hydrochloride

Chlorpromazine hydrochloride

Cyclobenzaprine hydrochloride Mirtazapine

Cyproheptadine hydrochloride

Desipramine hydrochloride Paroxetine hydrochloride

ANTICHOLINERGIC RISK SCALE

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3points 2 points 1 Point

Dicyclomine hydrochloride

Loperamide hydrochloride

Pramipexole dihydrochloride

Diphenhydramine hydrochloride Loratadine Quetiapine fumarate

Fluphenazine hyrochloride

Nortriptyline hydrochloride Ranitidine hydrochloride

Hydroxyzine hydrochloride and hydroxyzine pamoate

Olanzapine Risperidone

Hyoscyamine products Prochlorperazine maleate Selegiline hydrochloride

Imipramine hydrochloride

Pseudoephedrine hyrochloride-triprolidine hydrochloride

Trazodone hydrochloride

Meclizine hydrochloride Tolterodine tartrate Ziprasidone hydroch

Cont.

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3points 2 points 1 Point

Oxybutynin chloride

   

Perphenazine

Promethazine hydrochloride

Thioridazine hydrochloride

Thiothixene

Tizanidine hydrochloride

Trifluoperazine hydrochloride

Cont.

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Rudolph, JL, Salow, MJ, Angelini, MC, McGlinchey. Arch Intern Med 2008; 168-508.

Commonly used in nursing homes: 20% individuals were found using at least one inappropriate drug.

SEDATIVE DRUGS FOR THE ELDERLY

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Therapy Therapy description Reason for concern

Always avoid

Barbiturates Hypnotic Highly addictive

Chlorpropamide Oral antihyperglycemicLong half-life, inappropriate ADH secretion

Meprobamate Hypnotic Highly addictive

Pethidine (Meperidine) Opioid Ineffective orally

BEERS CRITERIA DRUGS (ABBREVIATED)

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Therapy Therapy description Reason for concern

Rarely appropriate

Carisoprodol Skeletal muscle relaxantStrong anticholinergic properties, sedation and weakness

Diazepam Benzodiazepine Long half-life

Cont.

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Therapy Therapy description Reason for concern

Some indication (but often misused)

Amitriptyline AntidepressantStrong anticholinergic properties and sedation

Diphenhydramine AntihistamineStrong anticholinergic properties

Doxepin AntidepressantStrong anticholinergic properties and sedation

Indomethacin NSAIDMore CNS adverse effects than other NSAIDs

Methyldopa AntihypertensiveCan cause bradycardia and exacerbate depression

Oxybutynin Antimuscarinic Strong anticholinergic properties, sedation and weakness

Reserpine AntihypertensiveCan induce depression and sedation

Ticlopidine Platelet inhibitor Poor adverse effect profile

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Rochon, P, Lane, c, Bronskill, S, et al. Drugs aging 2004; 21:939

DRUG-DRUG INTERACTIONS:

ONE MAJOR PROBLEM OF POLYPHARMACY

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Older adults are particularly vulnerable: e.g: Increased risk of bleeding with warfarin therapy with co- administration of NSAIDs, SSRIs, Omeprazole, lipid-lowering agents, amiodarone and fluorouracil.

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Risk of hypoglycemia: Increased with concomitant use of glyburide and co-trimoxazole.

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Digoxin toxicity increases with concomitant use of clarithromycin

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Treating physicians should review all existing medications in every patient’s visit.

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Approach

Review current drug therapy

Discontinue potentially unnecessary therapy

Consider adverse drug events as a potential cause for any new symptom

Consider non-pharmacological approaches

Substitute with safer alternatives

Reduce the dose

Use beneficial therapies when indicated

STEPWISE APPROACH TO PRESCRIBING FOR OLDER ADULTS

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Rochon, P, JH, Gurwitz. The Lancet 1995;346:32.

SUMMARY AND

RECOMMENDATIONS

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The possibility of ADE should always be borne in mind. Any new symptoms should be considered drug-related until proven otherwise.

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Physicians must always review all medications used. Special attention to non-prescription drugs, herbs and supplements.

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Various criteria sets exist in the literature that identify medications to be avoided, or prescribed with caution.

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Physicians should avoid under-utilization, as much as over-utilization of drugs.

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ADEs result in 4 times as many hospitalizations in older compared with younger adults.

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Causes of PREVENTABLE ADEs include, among others:Prescribing cascades, Drug-drug interactions And inappropriate drug doses.

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Follow a step-wise approach to prescribing for older adults.

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والله نسأل أن يعلمنًا مًا ينفعنًا

وأن ينفعنًا بمًا علمنًا ...ويزيدنًا علمًا

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