medication use in elderly

8/2/2019 Medication Use in Elderly

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Dr. DOHA RASHEEDY ALYLecturer of Geriatric MedicineDepartment of Geriatric and GerontologyAin Shams University


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Scope of the issue

Pharmacokinetics

Pharmacodynamics

Adverse drug reactions and adherence

Underuse of drugs

Nonprescription and alternative therapies

Common sense solutions


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Elderly account for 1/3 of prescription drug use, whileonly 13% of the population.

One survey: Average of 5.7 prescription medicines perpatient.

Average nursing home patient on 7 medicines.


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Surveys indicate that elders take average of2-4 nonprescription drugs daily.

Laxatives used in about 1/3-1/2 of elders -

many who are not constipated. Non-steroidal anti-inflammatory medicines,

sedating antihistamines, sedatives, and H2blockers are all available without aprescription, and all may cause major sideeffects.


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PharmacokineticChanges

ABSORPTION DISTRIBUTION

ELIMINATION (METABOLISM& EXCRETION)

Pharmacodynamics Changes


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There is little evidence of any major alteration in drugabsorption with age.

However, conditions associated with age may alter therate at which some drugs are absorbed. Such conditionsinclude:

greater consumption of nonprescription drugs (eg, antacidsand laxatives)

changes in gastric emptying, which is often slower in older

persons, especially in older diabetics.


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Decrease in total body water (due todecrease in muscle mass) and increase intotal body fat affects volume of distribution.

Water soluble drugs: lithium,aminoglycosides, alcohol, digoxin

Serum levels may go up due to decreased volume

of distribution Fat soluble: diazepam, thiopental,

trazadone

Half life increased with increase in body fat


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Albumin concentration: Drugs such as phenytoin,salicylates, and disopyramide are extensively bound toplasma albumin. Albumin levels are low in many diseasestates, resulting in lower total drug concentrations.

2. Alpha1-acid glycoprotein concentration: 1-Acidglycoprotein is an important binding protein with bindingsites for drugs such as quinidine, lidocaine, andpropranolol. It is increased in acute inflammatory

disorders and causes major changes in total plasmaconcentration of these drugs even though drugelimination is unchanged.


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decrease in serum albumin(which binds many drugs,especially weak acids)

There may be a concurrent increase in serumorosomucoid ( -acid glycoprotein), a protein that binds

many basic drugs.

Thus, the ratio of bound to free drug may be significantlyaltered.


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The capacity of the liver to metabolize drugs does not appear todecline consistently with age for all drugs.

The greatest changes are in phase I reactions, ie, those carriedout by microsomal P450 systems. There are much smallerchanges in the ability of the liver to carry out conjugation (phase

II) reactions1. Some of these changes may be caused by decreased liver blood,2. there is a decline with age of the liver's ability to recover from injury, eg,

that caused by alcohol or viral hepatitis. Therefore, a history of recentliver disease in an older person should lead to caution in dosing withdrugs that are cleared primarily by the liver, even after apparentlycomplete recovery from the hepatic insult.

3. Finally, malnutrition and diseases that affect hepatic functioneg, heartfailureare more common in the elderly. Heart failure may dramaticallyalter the ability of the liver to metabolize drugs by reducing hepaticblood flow.

4. Similarly, severe nutritional deficiencies, which occur more often in oldage, may impair hepatic function.


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Variable changes in first pass metabolism due to variabledecline in hepatic blood flow (elders may have less firstpass effect than younger people, but extremely difficult topredict).

Acetylation and conjugation do not change appreciablywith age

Oxidative metabolism through cytochrome P450 systemdoes decrease with aging, resulting in a decresed

clearance of drugs

Hepatic blood flow extremely variable


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GFR generally declines with aging, but is extremelyvariable

30% have little change

30% have moderate decrease

30% have severe decrease Serum creatinine is an unreliable marker.

If accuracy needed, do Cr Cl.

The Cockroft and Gault Equation

Cr Cl = 140-age(yrs) X wt (kg) X .85 for women

Cr (mg/100ml)X72

May overestimate Cr Cl, especially in frail elders


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Some effects are increased

Alcohol causes increase is drowsiness andlateral sway in older people than youngerpeople at same serum levels

Fentanyl, diazepam, morphine, theophylline

Some effects are decreased

Diminished HR response to isoproterenoland beta -blockers


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Unnecessary drug Not prescribing new needed Rx Contraindicated drug

Dose too low or too high Adverse drug event/ drug interaction Nonadherence Prescribing cascade


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Recent studies reported that under-prescribing of medications forthe elderly lead to negative health outcomes. Specifically, thisrefers to the use of b-blockers and thrombolytics in the treatmentof a myocardial infarction (MI) and warfarin to prevent stroke inpatients with atrial fibrillation

CAD Beta blockers only 21% of eligible patients received b-blocker therapy .

Age greater than 75 years was associated with underuse of b-blockers.The mortality rate was 43% less among b-blocker recipients than nonrecipients.

ASA

Anticoagulation in AF:more than 20% of patients with risk factors forstroke and no contraindications to anticoagulation were not receivingantithrombotic therapy. Of this group, 34% were prescribed aspirin, eventhough they did not have contraindication to anticoagulation

HTN, especially systolic HTN Pain

Particular fear of narcotics in the elderly


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A case control study has reported that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is correlated with initiation ofantihypertensive therapy in the elderly population.

a recent clinical trial demonstrates that the addition of ibuprofen

to antihypertensive therapy with hydrochlorothiazide reducedblood pressure control.

The OTC use of NSAIDs has also been recognized as animportant cause of upper GI hemorrhage .

The use of these medications is frequently self-directed, and whilethey are generally very safe, patients may not recognize thatibuprofen, naproxen, and fenoprofen or famotidine, ranitidine,cimetidine, and nizatidine are from the same pharmacologicclasses. Patients may use multiple products from within the same

pharmacologic class unless they are specifically advised always toconsult the harmacist or h sician.


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Natural products may have benefits, side effects, anddrug interactions

Very commonly used in the elderly

Some common herbs and alternative therapies:

Anti-aging DHEA, growth hormone

Dementia Gingko biloba

BPH Saw palmetto

OA Chondroiton sulfate,glucosamine

Depression St. Johns wort


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Ginkgo may increase anticoagulant effects of ASA, warfarin,NSAIAs, ticlopidine.

Kava: is used to treat anxiety. It's also used to relieveinsomnia and nervousness. Do not take Kava if you have ahistory of liver problems. Also do not mix with antidepressants,

sedatives, and do not mix Kava with alcohol. Licorice: used to treat coughs, colds and peptic ulcers. Highdoses can lead to increased blood pressure, water retentionand potassium loss. Do not use with diuretics or digoxinbecause it could lead to further loss of potassium, essential forheart function.

St. John's wort: a natural anti-depressant for mild tomoderate depression. Do not take with other anti-depressants,HIV medications, oral contraceptives, Tamoxifen (a cancerdrug).

Valerian: a mild sedative with hypnotic effects, used to

promote sleep, Should not be taken with alcohol or Valium.


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About 15% of hospitalizations in the elderly arerelated to adverse drug reactions.

The more medications a person is on, the higher therisk of drug-drug interactions or adverse drug

reactions. The more medications a person is on, the higher the

risk of non-adherence.

Most clinical trials published today focus on adultsless than 70 years old. As geriatric health careproviders, we often put our patients at risk by tryingmedications that have shown benefit in youngerpatients in hopes of similar results in our olderpatients


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Many drugs commonly prescribed for older patients result inpotentially life-threatening or disabling adverse reactions.

Cardiovascular and psychotropic drugs are the agents most

commonly associated with serious adverse reactions in theelderly.

This fact results from a combination of their narrow therapeutic-toxicwindow, age-related changes such as reduced renal excretion, and aprolonged duration of action, which predisposes the older patient to

adverse reactions. Adverse drug reactions are often not recognized because the

symptoms are nonspecific or mimic the symptoms of otherillnesses. Often another drug is prescribed to treat thesesymptoms, resulting in polypharmacy and further increasing

the likelihood of an adverse drug reaction. An overstatement that is of great clinical use and forms a

good starting point for clinical evaluation can be stated as

follows: Any symptom in an elderly patient may be

a drug side effect until proved otherwise.


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Common cause of ADEs in elderly Almost countless good role for pharmacist and

computer or on-line programs

Some common examples

Statins and erythromycin and other antibiotics TCAs and clonidine or type 1Anti-arrythmics

Warfarin and multiple drugs

ACE inhibitors increase hypoglycemic effect of

sulfonylureas


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Patient with PD have increased risk of druginduced confusion.

NSAID (and COX-2s) s can exacerbate CHF.

Urinary retention in BPH patients ondecongestants or anticholinergics. Constipation worsened by calcium,

ahticholinergics, calcium channel blockers.

Neuroleptics and quinolones lower seizurethresholds


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1. Complete drug history, including herbs and nonprescriptiondrugs

2. Avoid medications if benefit is marginal or if non-pharmacologic alternatives exist

3. Consider the cost

4. Start low, go slow, but get there!5. Keep regimen as simple as possible6. Write instructions out clearly7. Have patient bring in medications at each visit.

8. Consider medication box or mediset

9. If things dont make sense, consider a home visit

10. Discontinue drugs when possible if benefit unclear or sideeffects could be due to drug

11. Be cautious with newer drugs


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Interactions between drugs and food

warfarin and Vitamin K containing foods (remembergreen tea, as well)

Phenytoin & vitamin D metabolism

Methotrexate and folate metabolism

Drug impact on appetite

Digoxin may cause anorexia ACE inhibitors may alter taste


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Try non-pharmacological approaches such as walking orregular activity or exercise, getting adequate sleep,quitting smoking, consuming alcohol in moderation and

dietary changes toward a healthier lifestyle.


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Drug 1

ADE interpreted as newmedical condition

Drug 2

ADE interpreted as new

medical condition

Drug 3

Rochon PA, Gurwitz JH. Optimizing drug treatment in elderly people: the prescribing cascase. BMJ 1997;315:1097.


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Common cause of polypharmacy in elderly

Some common examples

NSAID->HTN->antihypertensive therapy

Metoclopromide ->Parkinsonism ->Sinemet

Dihydropyridine -> edema ->furosemide

NSAID ->H2 blocker ->delirium ->haldol

HCTZ ->gout->NSAID ->2nd antihypertensive


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Multiple chronic disorders

Multiple prescribers

Multiple prescriptions

Multiple doses

Change in daily drug regime

Cognitive or physical impairment

Living alone

Recent Hospital discharge

Inability to pay for drugs

Presence of side effects


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1. Making drug regimens and instructions as simple aspossible. a. Use the same dosage schedule whenever feasible (e.g., once or

twice per day) b. Time the doses in conjunction with a daily routine.

2. Instruct relatives and caregivers on the drug regimen. 3. Enlist others (e.g., home health aides, pharmacists) to helpensure compliance.

4. Make sure the older patient can get to a pharmacist (or viceversa), can afford the prescriptions, and can open thecontainer.

5. Use aids (such as special pillboxes and drug calendars)whenever appropriate.

6. Keep updated medication records 7. Review knowledge of and compliance with drug regimens

regularly.


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Is there a specific indication for the drug, and isit effective?Every drug should be matched to a well-documented diagnosis. The use of drugs unpaired to adiagnosis should be carefully reevaluated and their use

discontinued whenever possible.

Is the dosage appropriate, given renal andhepatic function?

Are the instructions for use practical and

appropriate to the person?In the hospital, complicateddosing regimens for drugs such as warfarin permit the carefultitration of therapy to the person. At home, dosing regimensshould be as simple as possible. Whenever possible, doses

should be linked to specific daily events such as bedtime tominimize problems.


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- Definition: The process of comparing a patientsmedication orders to all medications that the patienthas been taking.

Medication Reconciliation will avoid:1. omissions,

2. duplications

3. dosaging errors

4. drug interactions


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Polypharmacy means "many drugs.

The use of more medication than is clinicallyindicated or warranted.

5 or more drugs

7 or more drugs


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The elderly use more drugs because illness is morecommon in older persons.

Cardiovascular disease

Arthritis Gastrointestinal disorders

Bladder dysfunction


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Polypharmacy leads to: More adverse drug reactions

Decreased adherence to drug regimens

Patient outcomes Poor quality of life

High rate of symptomatology

(Unnecessary) drug expense


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The most consistent risk factor for adverse drug reactionsis:

number of drugs being taken

Risk rises exponentially as the number of drugs increases.


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Annual Brown Bag

At least yearly, and more often if indicated, askelderly patients to bring in all medications theyhave at home. Prescription

Over-the-counter

Vitamins supplements

Herbal preparations


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I dont knowthe doctor told me to

Digoxin

Allopurinol

Antidepressants

Anticonvulsants Anxiolytics


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Discontinuing unnecessary medications is one of themost important aspects of decreasing polypharmacy

Drugs without indications should be stopped!


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Acetaminophen as effective as NSAIDs in mild OA NSAIDs side effects

GI hemorrhage (less with COX-2)

Decline in GFR (COX-2 as well)

Can Worsen BP- removal of NSAID can affect mean blood

pressure controlFluid retention, Worsen CHF

Decreased effectiveness of diuretics, anti-hypertensive agents

Indication should justify the increased toxicity ofNSAIDs Newer Cox-2 agents, gastric sparring Less risk of Alzheimer's and cognitive decline


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Phenothiazine major tranquilizers (promethazine,thorazine, chlorpromazine, haloperidol)

Tricyclic anti-depressants (imipramine, amitriptyline,nortriptyline, desipramine)

Narcotics-demerol, codeine, morphine Anti-spasmotics-oxybutynin, diclomine, tolterodine,

probanthine, atropine, hyoscyamine, probanthine,belladonna alkaloids.

Anti-histamines : Diphenhydramine, Cyproheptadine,OTC cold medications, OTC sleep agents,Trihexyphenidyl, Benztropine


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B-Blockers (propranolol)-side effects of: Precipitation of or exacerbation of CHF Masking of hypoglycemia Development of hypotension Masking of symptoms of endocrine disease

(hypothyroidism)

Exacerbation of chronic lung disease or bronchospasm Depression Memory loss

use selective ones: atenolol and metoprolol

Less side-effect profile Better compliance-once or twice daily Use associated with reduced cardiovascular morbidity

and mortality in high risk patients

.


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Alpha-methyl-dopa

Clonidine

Alpha-blocking agents: useful for combined hypertensionand prostatic hyperplasia

Reserpine


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Once daily dosing increases compliance Inexpensive First line agents effective in reducing risk of stroke and

CV disease Thiazides generally not effective in the presence of renal

insufficiency, May cause hypercalcemia Contribute to or cause incontinence

Adverse reactions Dehydration; postural hypotension; K loss (especially during the

summer and sweating)

Consider discontinuing in elderly when possible,especially advanced, demented, or depressed elderly(reduced thirst and appetite drive)


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Worsen dementia and delirium

Cause hip fractures and falls

Cause postural hypotension

Risk of tardive dyskinesia with phenothiazines


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Cause Hypoglycemia-- chlorpropamide

SIADH more frequent with aging (idiopathic 30%)


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(Few indications currently for use except for ratecontrol or congestive heart failure to improvefunction). Side-effects: Confusion

Anorexia

Nausea

Yellow Green Colors

Agitation

Depression


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May cause cognitive dysfunction

Have anti-cholinergic side effects

urinary retention

constipation dry mouth

sedation


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Anorexia Nausea

Arrhythmias

Hypotension

Drug-drug interactions-erythromycin, cimetidine,diazepam, phenytoin

Useful for acute wheezing or asthma, not for COPD


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Anticholinergic- Sedation

Cognitive dysfunction

Dry mouth

Blurred vision

Constipation

Urinary retention


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Sedation

Falls

Anti-cholinergic side-effects

Contraindicated in elderly


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Beta blocker preparations-can achieve significantsystemic absorption leading to heart block, CHF,bronchospasm.


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Common cause of potentially reversible cognitiveimpairment

Demented patients are particularly prone to delirium fromdrugs

Anticholinergic drugs are common offenders (TCAs,benadryl and other antihistamines, many others)

Other offenders cimetidine, steroids, NSAID


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Biggest risk drugs are long actingbenzodiazepines and other sedative-hypnotics

Both SSRIs and TCAs associated with increasedrisk of falling

Beta blockers NOT associated with increased riskof falling in published literature

Mild increase in fall risk from diuretics, type 1A

anti-arrythmics, and digoxin


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Reduced thirst and appetite with normal aging Reduced thirst and appetite is associated with

depression and/or dementia

DRUG induced ANOREXIA:

Theophylline Macrodantin

Pronestyl

Digoxin

Thyroxin

SSRIs


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Liver- cirrhosis, malnutrition, malignancy, hepatitis withresultant decreased albumin and total protein levels (ex:sodium warfarin and phenytoin

Kidney- chronic renal insufficiency, renal failure

Brain-dementia, delirium

Intestinal tract- malabsorption syndrome

stomach- gastritis


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Narcotics Begin lactulose or sorbitol and a stimulant laxative

Steroids

Think about osteoporosis prevention

Remember steroid induced diabetes


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Meperidine Diphenhydramine

The most anticholinergic tricyclics: amitryptiline,

doxepin, imipramine Long acting benzodiazepines such as diazepam

Long acting NSAIAs such as piroxicam

High dose thiazides (>25mg)

Iron: 325 mg once daily is enough.


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First article published August 2009 Consult Pharm 2009;24:601-10.

http://www.ascp.com/resources/clinical/upload/BeersCriteria.pdf

Focus on CNS medications Consensus panel of geriatricians, other providers
http://www.ascp.com/resources/clinical/upload/BeersCriteria.pdfhttp://www.ascp.com/resources/clinical/upload/BeersCriteria.pdfhttp://www.ascp.com/resources/clinical/upload/BeersCriteria.pdfhttp://www.ascp.com/resources/clinical/upload/BeersCriteria.pdf


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Mr. W. is a 86 year old man with pulmonary HTN, COPD,CRI (creatinine of 2.2), CHF with an ejection fraction of20%, mild dementia, depression, and severe anemia. Heis frequently admitted to the hospital because of severe

disease and poor adherence with his medical regimen.His discharge medications on last admission one monthago were aspirin 325mg, 02, enalapril 20mg QD,furosemide 80mg BID, combivent, and sertraline 50mg.The inpatient team decided that he was undertreated,and added metoprolol 12.5mg BID, aldactone, FeSo4325mg TID, and 3 inhalers. He was readmitted within aweek. How might you approach his regimen?

This man has already shown that he is not adherent, and addingmedications to his regimen has probably made his adherence worse.


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medications to his regimen has probably made his adherence worse.Asking him about adherence can be revealing. In this case, headmits that he is just taking too many medications and so randomlystopped a few. He also is complaining about urinating all day, soalmost always skips his PM furosemide.

Although beta blockers improve outcomes in severe CHF, in this manis who marginal with his medications, had lung disease, and limitedinsight, it may not be worth it. Keeping the regimen simple is morelikely to result in success. Likewise, his iron, if he needs it at all,would be adequate at a once daily dose. Probably combivent wouldbe a better choice to improve adherence.

RCTs have demonstrated decreased mortality with both betablockers and aldactone in CHF. However, applying those results tothis man with multiple severe diseases, mild dementia anddecreased adherence may not be wise.

So, in short we recommend: Changing furosemide to 120mg once daily D/c feSo4 or decrease it to once daily Drop metoprolol and aldactone

Change inhaler back to combivent

Mrs F is a 92 year old nursing home resident with a


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Mrs. F. is a 92 year old nursing home resident with ahistory of HTN, heart disease, osteoarthritis, and astroke. She has been declining recently, with a

decreased appetite. Her meds are HCTZ 12.5, ASA81, digoxin .125, and enalapril 10. She has been on thesame meds and dosages for years. On exam, shelooks frail BP 130/80 P60 R 16. Other than being thin,

her exam is fairly unremarkable. She has no signs ofCHF. She has mild left sided weakness and hyper-reflexia, and her MMSE is 27/30, she is not depressed.Her gait is slow with a walker. Labs: Hgb12, Cr 1.3,BUN 20, digoxin level 1.7, others normal. Her EKG is

normal except for borderline bradycardia andnonspecific ST changes, which are old.

What do you think is wrong?


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Digoxin can cause toxicity even with normal serumlevels. When you stopped her digoxin, her appetite wentback to normal. It is not uncommon for nursing homepatients may be on digoxin for unclear indications.


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An 83 y/o woman is brought to the ER because ofdizziness on standing, followed by brief LOC; the patientnow feels well

She has hypertension but is otherwise healthy

Daily medications: metoprolol 50mg/d, captopril 25 mg/d,and nitroglycerin 0.4mg SL prn

BP is 130/70 mmHg sitting and 100/60 standing; PE isotherwise normal; CBC, BUN, ECG, CMP are all normal


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Which of the following is the most likely cause of thissyncopal episode?

Sepsis

Drug-related event Hypovolemic hypotensive episode

Cardiogenic shock

Unidentifiable cause


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80 yr. widow who now lives with her daughter comes toyour office to establish care and complains of being anervous wreck and not being able to turn off her mind forthe past 2 yrs. She brings with her a bag of all her meds.

PMHx: CHF, irritable bowel syndrome, depression, HTN,recurrent UTIs, stress incontinence, anemia, occipitalheadaches, osteoarthritis, generalized weakness

Meds: sucralfate 1gm TID, cimetidine 300mg QID, enteric

asa 325mg, atenolol 100mg, digoxin 0.25, alprazolam0.5mg, naproxen 500mg TID, oxybutynin 5mg BID,dicyclomine 10mg TID, lasix 40mg , Tylenol #2 prn


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High risk drugs: alprazolam, oxybutynin, tylenol #2(narcotics), dicyclomine, NSAIDS

Digoxin at a higher then recommended dose (0.125mg)

naproxen and aspirin carry the potential drug related

adverse events of gastritis/GIB and sucralfate andcimetidine are being used to treat these side effects


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The elderly take more medications than anyother age group Pharmacokinetics and pharmacodynamics are

altered

Adverse drug reactions are common Risks go up with the number of drugs used Nonprescription and herbal therapies are

common

With care and common sense, we canprobably do a better job

medication use in elderly

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