CONSIDERATIONS GERONTOLOGICAL PHARMACOLOGY UPDATE Handout Samples/Full Handouts... · GERONTOLOGICAL PHARMACOLOGY UPDATE Thomas W. Barkley, Jr., DSN, ACNP-BC, FAANP Professor of Nursing

GERONTOLOGICAL PHARMACOLOGY UPDATE

Thomas W. Barkley, Jr., DSN, ACNP-BC, FAANP

Professor of Nursing

Director of Nurse Practitioner Programs

California State University, Los Angeles

and

President

Barkley & Associates

CONSIDERATIONS

Drug use in the older population Polypharmacy and inappropriate prescribing Senior health considerations Drugs for common indications Drug dosing in the older patient◦ Drugs most prone to cause adverse drug reactions◦ Dosage reduction of commonly prescribed drugs

Drug of abuse

Pharmacotherapeutics in the Geriatric Patient Older adults (age>65) are the fastest growing

segment of the population. Most Americans will suffer from at least 3

chronic illnesses. Adults over 65 consume over 30% of all

prescription meds; 86% have a chronic health problem requiring meds.

Elderly also consume the greatest number of over-the-counter meds.

Pharmacotherapeutics in the Older Patient Male Medicare patients are prescribed over 13

medications/year. Female Medicare patients are prescribed over

16 medications/year.

Pharmacotherapeutics in the Older Patient

Over 20% of hospitalizations in adults over 65 are due to effects of prescription drugs.

Polypharmacy and inappropriate prescribing are major contributors to these hospitalizations. WHAT PREDISPOSES

THE OLDER PATIENT TO ADVERSE DRUG REACTIONS?

Facts About Adverse Drug Effects in the Elderly Elderly have more ADEs than any other group

due to greater number of medications and concurrent disease states.

ADEs rank 5th after congestive heart failure, breast cancer, hypertension, and pneumonia among leading preventable threats to health of older Americans.

Increased number and potency of drugs contributes.

Elderly population is increasing.

Predisposing Factors for Drug Toxicity in the Older Patient Increased prevalence of chronic disease(s). Adverse drug effects may go unnoticed or

unreported. Decreased drug absorption with increasing age.

ENVIRONMENTAL FACTORS COMPLICATING THE PROBLEM Gastrointestinal tract: Altered gastric pH

(more alkaline) and altered GI transit time due to the use of stimulant laxatives.

Dietary factors: Such as grapefruit juice, vitamins, alcohol use.

Smoking: Affects the metabolism of tricyclic antidepressants, propranolol, neuroleptics, theophylline and warfarin.

Predisposing Factors for Drug Toxicity in the Older Patient Physiological changes which affect drug

metabolism and excretion◦ Decreased hepatic blood flow ◦ Decreased liver enzyme activity and synthesis◦ Decreased renal blood flow Use creatinine clearance, not serum creatinine, as a

measure.

◦ Decreased renal excretion of drugs ALL OF THESE TEND TO INCREASE THE DURATION OF

THE DRUG IN THE BODY.

Metabolism and Polypharmacy

Use of medications that interfere with drug metabolism at the same cytochrome P450 enzyme also elevates risk of cognitive adverse effects (e.g. CYP3A inhibitor, fluoxetine with alprazolam can increase risk of oversedation).

Consider pharmacogenetics as well.

Gerontological Pharmacology:Implications For All Prescribers

Effects of Aging on Pharmacokinetics

Absorption Distribution Elimination

Photo by rubberpaw

EFFECTS OF AGING ON PHARMACOKINETICS: DRUG ABSORPTION

Effects of Aging on Pharmacokinetics: Drug Absorption Elderly may have:◦ Decreased gastrointestinal motility◦ Decreased blood flow◦ Increased gastric pH

• These changes are expected to decrease gastrointestinal blood absorption, but decreased motility results in a longer drug absorption time.

• As a result, alternate administration routes for drugs should be considered.

Effects of Aging on Pharmacokinetics: Drug Absorption

Gastrointestinal conditions may further complicate drug absorption

• Little information regarding absorption of:– Delayed release formulation– Transdermal administration

– Transbuccal administration– Transbronchial administration

Effects of Aging on Pharmacokinetics: Drug Distribution

Volume distribution◦ Not an actual physiological measurement but

important nonetheless◦ Volume of distribution (Vd) =

Amount of Drug in the Body

Concentration of Drug in the Blood or Plasma per Kilogram of Body Weight

Effects of Aging on Pharmacokinetics: Drug Distribution The volume of distribution determines the

loading dose of a drug◦ Loading dose (mg/kg) =

Desired Blood Concentration (mg/L)

Volume of distribution (L/kg)

Effects of Aging on Pharmacokinetics: Drug Distribution Aged have lean body mass and body water, thus

decreasing Vd◦ Decreased Vd will cause drugs that distribute into body

water or muscle will have higher initial plasma concentration following administration.◦ Water soluble drugs distributed less effectively in elderly

patients Cardiovascular (CV) disease can further complicate this

distribution

◦ Ethanol is thought to be affected by reduced Vd, causing a higher blood concentration for any quantity of ethanol consumed

Photo by Biggishben

Cw4

Effects of Aging on Pharmacokinetics: Drug Distribution More adipose tissue in elderly person increases

the Vd of lipophilic drugs because fat is a depot for these agents

The effect and duration of action of some drugs are increased as both liver size and hepatic blood flow decrease along with subsequent hepatic inactivation.

Renal function in the aged is also decreased, resulting in higher plasma levels of free drug.◦ More free drug concentration = more potent effect

Effects of Aging on Pharmacokinetics: Drug Distribution Orosomucoid or alpha-1 glycoprotein binding

is not altered with aging◦ Neutral pH, basic drugs not affected, as these

typically bind to orosomucoid However, most drugs are acidic and bound by

serum albumin◦ Serum albumin and, subsequently, the drug-binding

capacity of most drugs are decreased approximately 12% in the aged, thereby increasing free drug concentration.

Effects of Aging on Pharmacokinetics: Drug Distribution Drug-drug interactions can increase in free

drug concentration when one drug displaces another from albumin.

Notable drug-drug interaction occur only if:◦ Drug is highly bound to plasma albumin◦ The free drug has a narrow concentration range

between therapeutic and toxic concentration◦ Drug has small Vd

One such example of drug-drug interaction is between warfarin and acetylsalicylic acid.

Warfarin Acetylsalicylic acid

Effects of Aging on Pharmacokinetics: Drug Distribution Conditions in which drug-drug interactions can

occur include:◦ Inhibition of drug absorption◦ Decreased Hepatic blood flow◦ Inhibition of renal excretion◦ Inhibition or stimulation of drug metabolism◦ Displacement from albumin binding◦ Pharmacodynamic effects of drugs on tissue

Effects of Aging on Pharmacokinetics: Drug Distribution Narcotic analgesics also affected by decreased

protein binding◦ Meperidine study indicated a correlation between

aged patients and higher free drug fractions

Renal disease◦ Frequent acidosis also results and further decreases

binding

EFFECTS OF AGING ON PHARMACOKINETICS: DRUG ELIMINATION

Effects of Aging on Pharmacokinetics: Drug Elimination Where effect and duration of drug relate to

levels of the drug in the blood, the processes that eliminate the drug must also be considered.◦ Clearance◦ Half-life

Effects of Aging on Pharmacokinetics: Drug Elimination: Clearance Clearance is the amount of blood flow completely

extracted of the drug per unit of time◦ Not how much drug is removed but how much blood

must be cleared to eliminate the drug◦ Measured as milliliters per minute per kilogram

Total clearance is the sum of drug clearances of all organs◦ Liver and kidneys are two major sites

Studies indicate changes in drug clearance are primarily due to the combination of decreased blood flow and liver size.

Effects of Aging on Pharmacokinetics: Drug Elimination: Clearance Must maintaining plasma-drug concentration

steady state (Css) over time ◦ Use wide range of doses to maintain

The absolute rate of drug elimination is essentially a linear function of the plasma concentration of the drug. ◦ For most drugs, a constant fraction of the drug in

plasma is eliminated per unit time. Clearance determines what dose must be

administered per unit of time

Effects of Aging on Pharmacokinetics: Drug Elimination: Half-life Half life = time it takes for drug concentration

in plasma to decrease by ½ Clinical half‐life accounts for volume distribution and clearance

Half-life(t½) = 0.693 x Vd

Clearance

Effects of Aging on Pharmacokinetics: Drug Elimination: Half-life

Rule of thumb for obtaining over 90% Cssis that four doses of the drug are needed, administered at every half life; thus four half-lives are needed to remove over 90% of the drug from the body◦ Half-lives dictate dosing intervals◦ Half-lives dictate time necessary for

stabilization or reduction in effects of the drug in terms of drug concentration

Effects of Aging on Pharmacokinetics: Drug Elimination: Half-life

Half lives may increase in the aged; not all drugs are known, but some are.◦ Possibly due to decrease drug clearance or increase

in drug distribution

HEPATIC DRUG METABOLISM OR P450?

Hepatic drug metabolism or P450?

The effect and duration of action of some drugs are increased, as both liver size and hepatic blood flow decrease along with subsequent hepatic inactivation.

In general, age-related decreases in liver mass, hepatic enzyme activity, and hepatic blood flow result in a decrease in the overall metabolic capacity of the liver in the elderly population.


Phase I reaction transform parent molecule◦ Oxidations◦ Reductions ◦ Hydrolytic reactions

Phase I reactions usually inactivate a bioactive molecule


Most studies support an age-related decline in phase I drug metabolism in elderly persons.

Age-related decreases in hepatic biotransformation are associated generally with the CYP monooxygenase system (CYP450) ◦ Alternate metabolic pathways do not appear to be

markedly affected by age.◦ Benzodiazepines subject to both phase I and II

metabolism have longer elimination times

Hepatic drug metabolism or P450? Phase II reactions◦ Glucuronide conjugation ◦ N-acetylation◦ Sulfate group

The range of capacity between individuals is greater than changes reported to occur in individuals as they age.

Phase II is unchanged in the elderly population◦ Evidenced by the elimination of sedative-hypnotics such

as oxazepam, a drug subject to only phase II metabolism, is unchanged in the aged

Oxazepam


For a drug to undergo substantial first-pass metabolism by the liver, it must be efficiently extracted from the blood.◦ Hepatic blood flow decreased from 12% to 14% in

the aged, thus decreasing extraction efficiency.◦ Drugs that have low hepatic clearance (≤0.3) are

substantially bound to plasma proteins with limited free-drug concentrations, and have relatively little first-pass metabolism.


At certain concentrations, ability of liver to extract and metabolize some drugs will be insufficient◦ Proportionately small increase in total drug dose will

result in a large increase in systemic drug concentration as the kinetics become dose dependent.

Hepatic drug metabolism or P450? Increased systemic bioavailability has been shown

for several highly extracted drugs in elderly persons.

Decreased rates of gastrointestinal absorption may reduce bioavailability of highly extracted drugs because a greater fraction of the drug is metabolized in the first pass through the liver.◦ Duration of action for such drugs may be prolonged

because of slow absorption and/or release from depots or because in situ, a longed-lived drug is derived from a short-lived prodrug

Hepatic drug metabolism or P450? Decreases in the hepatic

biotransformation of drugs with a high hepatic extraction ratio in elderly persons are predicted from the decrease in liver blood flow, ◦ There is significant variability

between individuals, though. Age-related decreases in hepatic

biotransformation are associated generally with the CYP monooxygenase system (CYP450) ◦ Alternate metabolic pathways do

not appear to be markedly affected by age.

Photo by Joxemai

Hepatic drug metabolism or P450? The CYP enzymes, a superfamily of heme proteins,

are found in all living species and are involved in metabolism of a wide variety of chemically diverse endogenous and exogenous compounds.

Biotransformation of drugs in the elderly population is more likely to be the basis of an adverse drug reaction when the hepatic P-450 family of enzymes is involved. ◦ In the normal healthy population, 6-fold differences in

rates of cytochrome P-450 (CYP) drug metabolism are observed.


The situation is further complicated because multiple reactions may occur for a given drug that involves CYP enzymes; many drugs are known to be inducers of selective CYP enzymes that may or may not be involved in their own metabolism.

Therefore, hypothetically, even a drug that a patient has tolerated well may have cause an adverse drug reaction after a second drug that alters the hepatic metabolism is added or discontinued.


Grapefruit juice, taken proximally to the administration of selected drugs, increases serum levels of numerous drugs known to be metabolized by CYP3A4.◦ Numerous drugs have had reports of increased

bioavailability due to grapefruit juice.


Any impairment of normal liver function potentially will alter hepatic biotransformation. ◦ Elderly patients have liver disease associated many

conditions.◦ Adverse drug reactions may suggest liver

dysfunction.

Renal Excretion of Drugs in the Elderly

Similar to hepatic blood flow in the elderly, renal blood flow is also reduced.◦ Occurs in the absence of nephropathy◦ Approximately 1% decrease per year after age of 50◦ Reduction affects the many drugs that are excreted

by the kidneys Assuming that more than 60% of the drug is excreted by

kidney Higher drug concentration in blood of primarily renal

excreted drugs typically found when glomerular filtration rate decreases


Insufficient to measure renal function by serum creatinine alone◦ Normal levels may be seem even though the

reduction in creatine clearance or glomerular filtration is substantial

Differences in creatinine clearance correlate with about a two-fold increase in the half-life of penicillin in the elderly


Overall, elderly typically have:◦ Declining renal function◦ Decreased renal blood flow◦ Decreased renal mass◦ Decreased creatinine clearance

Classes of Cyp450


Cytochrome P450 enzyme system◦ CYP1, CYP2, CYP3◦ Families of enzymes that metabolize drugs ◦ 9 other CYPs that metabolize endogenous

compounds in the body◦ Divided further into subclasses designating isoforms

that metabolize specific drugs/drug families

Hepatic drug metabolism or P450? Phase I (nonsynthetic) - major types◦ Oxidation by the cytochrome P450 system which is a family of

drug-metabolizing enzymes in the liver. The major function of this enzyme system is to add an oxygen atom to the drug substrate.

◦ drug + O2 --------> drug-OH◦ nonpolar, lipid-soluble) (polar, water-soluble)

Phase 1 Metabolism Hepatic drug metabolism or P450? Phase II (synthetic) reactions occur in the liver

and gut wall. The products of Phase II reactions arecalled conjugated metabolites, and are virtually alwaysinactive, very polar and/or ionized, and easily excreted.Several types of conjugation may occur:

i. glucuronide conjugation – liver ii. N-acetylation - liver, gut wall; addition of an

acetate group to a nitrogen atom. Individuals areclassified as either slow or fast acetylators dependingon genetic factors, e.g., sulfonamides, isoniazid,procainamide.

Acetaminophen Glucuronidation Considerations of Metabolism

Age Induction Inhibition First-pass effect Nutritional status Disease state Enterohepatic circulation

EFFECTS OF AGING ON PHARMACODYNAMICS

Effects of Aging on Pharmacodynamics

Pharmacodynamics◦ Altered sensitivity◦ Modified response to a given stimulus◦ How homeostatic mechanisms contribute to altered

response

Effects of Aging on Pharmacodynamics: Altered sensitivity

Because of the changes in renal drug elimination, hepatic drug clearance, pharmacodynamics, and homeostatic mechanisms in elderly persons, discerning the role of intrinsic sensitivity is difficult.

Studies have shown elderly are more sensitive to:◦ Warfarin

◦ Sedative-hypnotics

◦ Narcotic analgesics

Effects of Aging on Pharmacodynamics: Pharmacodynamic Changes

As people age, responses to certain stimulant agents change.

Elderly patients have decreased variation of heart rate in the course of β-adrenergic blockade, indicating a decrease of parasympathetic function.

Decreased baroreceptor function. Drug sensitivity in elderly patients has been shown

to be reduced to both isoproterenol stimulation and β-adrenergic blockade.

Observations confirm decreased beta-adrenergic responses in elderly

Effects of Aging on Pharmacodynamics: Decreased Homeostatic Response Elderly patients with decreased plasma volume,

diminished vasomotor regulation, impaired glucose tolerance, greater morbidity from infections, and other limitations may be more susceptible to adverse effects of drugs.

ADRs and Why?

Adverse drug reactions in aged populations are typically not idiosyncratic◦ More likely extensions of the usual effects of the

drugs

ADRs and Why?

Frequent adverse drug reactions identified the elderly◦ Bleeding due to oral anticoagulants◦ Hypoglycemia from diabetes treatment◦ Gastropathy associated with non-steroidal anti-

inflammatory drugs

Because polypharmacy is common, the potential for adverse drug reactions has increased with every class

COMMON SIGNS OF ADVERSE DRUG REACTIONS IN THE OLDER PATIENT Restlessness Falls Depression Confusion Loss of memory Constipation Incontinence Extrapyramidal symptoms

WHICH PRESCRIPTION DRUGS ARE MOST LIKELY TO CAUSE AN ADR? Cardiovascular drugs Central nervous system (CNS)-active drugs Long-acting or sedating drugs Non-steroidal anti-inflammatory drugs

(NSAIDS) and other “blood thinners” Muscle relaxants

The Latest “Bad Guys”

A recent study linked almost 50% of adverse drug events in elderly outpatients to:◦ Warfarin◦ Aspirin◦ Insulin◦ Clopidogrel◦ Digoxin

Inappropriate use of these drugs was the main reason for the adverse event…

PATIENT ADVERSE EFFECTS IN THE LONG TERM CARE FACILITY MAIN ADRs SEEN◦ GI bleeds secondary to NSAID use◦ Falls resulting in fracture◦ Low fasting blood sugar◦ Dehydration

CAUSES OF ADRs◦ Polypharmacy◦ Failure to recognize renal impairment◦ Prior GI problems◦ Use of long-acting benzodiazepines, antipsychotics,

antidiabetic drugs, NSAIDS, narcotics

DRUG ERRORS IN THE ELDERLY

Frequency of Inappropriate Prescribing

Community-Dwelling Elderly◦ Inappropriate drugs used by 23.5%.

Board and Care Home Elderly◦ 20.2-27.4% had inappropriate prescriptions.

Outpatient Elderly◦ 4.45% outpatient visits resulted in an inappropriate

prescription.

Factors Contributing to Inappropriate Prescribing

Patients who had been referred◦ Increased rate by 73%

Had a number of prescriptions◦ Increased rate by 22% for each med

Were prescribed an antianxiety agent, sedative, antidepressant, analgesic, platelet inhibitor, antispasmodic◦ Increased rate by 6-284-fold!

Medication was prescribed by a provider in a nonmetropolitan area.

Patient Characteristics That Contribute

Number of active chronic medical diagnoses (>6) Nine or more medications Number of doses of medication per day (>12) Low body weight or body mass index (< 22 kg/sq

m) Recent transfer from hospital Advanced age (>85) Prior adverse drug reaction

Patient Characteristics That Contribute

Cancer Depression Cognitive impairment

including dementia Decreased renal

function (estimated creatinine clearance < 50 mL/min)

Beers List Updated by Fick, et al., in

2003 Includes drugs that are

dangerous “as is” Includes drugs that are

dangerous dependent on diagnosis

Link to this list is http://archinte.amaassn.org/cgi/reprint/163/22/2716

Drugs from Beers List Causing a High Degree of Bad Outcomes Pentazocine Indomethacin Trimethobenzamide Muscle relaxants Flurazepam Amitriptyline Doxepin Meprobamate

Trimethobenzamide

Drugs from Beers List Causing a High Degree of Bad Outcomes Short- and long-acting BZDs Disopyramide Methyldopa Chlorpropamide Gastrointestinal antispasmodics Anticholinergics Diphenhydramine All barbiturates except phenobarbital and those

used for seizures

BZDsPhoto by Josumiselunico

Drugs from Beers List Causing a High Degree of Bad Outcomes Meperidine Ticlopidine Ketorolac Amphetamines and anorexic agents Long-acting NSAIDs Daily fluoxetine Long-term use of stimulant laxatives Amiodarone

Drugs from Beers List Causing a High Degree of Bad Outcomes Orphenadrine Guanethidine Guanadrel Nitrofurantoin Methyltestosterone Thioridazine Mesoridazine

Drugs from Beers List Causing a High Degree of Bad Outcomes Short-acting nifedipine Mineral oil Desiccated thyroid Several more drugs cause a “low severity

rating” of bad outcomes and should also be avoided in the elderly patient.

Drugs With Anticholinergic ActivityPOLYPHARMACY

DEFINITION: Concomitant use of many drugs. Excessive use of prescriptive medications.

Actual number of drugs varies in the literature. Ranges from 2,4,5,6,10 drugs used concomitantly.

Controversial as to whether this definition should also include OTC meds, herbal meds, alternative meds and pro re nata meds.

POLYPHARMACY

THE USE OF MORE PRESCRIBED MEDICINES THAN ARE CLINICALLY INDICATED.

Photo by BrokenSphere

FACTORS THAT INFLUENCE THE DEVELOPMENT OF POLYPHARMACY IN THE OLDER PATIENT

Increasing number of chronic illnesses Use of multiple medications Concept of a “pill for every ill” Susceptibility to product

advertisements Availability of nonprescription drugs Tendency toward self-treatment

FACTORS THAT INFLUENCE THE DEVELOPMENT OF POLYPHARMACY IN THE OLDER PATIENT

Hoarding of old medications Prohibitive cost of prescription products Use of multiple prescribers Use of different sources for medications Lack of knowledge about medications and

medical condition

OUTCOMES OF POLYPHARMACY

Decreased compliance Increased adverse drug effects Decreased social activity, increased depression Increased risk for nursing home placement Increased risk of prescribing errors

Photo by Thomas Bjørkan

OUTCOMES OF POLYPHARMACY

Increased morbidity (Increased mortality?) Increased incidence of iatrogenic illness

Increased cost

Graphic by Keith Evans

Culprits that complicate the polypharmacy problem:

• OTCs

• Herbal medications

OVER-THE-COUNTER MEDICATIONS TO WATCH IN THE OLDER PATIENT Cimetidine and other H2 blockers

NSAIDs

Decongestants

Antihistamines Laxatives

Antacids

OTC AGENTS THAT COMPLICATE THE POLYPHARMACY PROBLEM

Cimetidine (Tagamet): Inhibits enzymes in the liver, thereby prolonging the duration of other drugs in the body.

Decongestants: Cause increased blood pressure. These also have anticholinergic effects.

NSAIDs: May decrease renal blood flow thereby reducing elimination of drugs from the body; cause GI bleeds.

OTC AGENTS THAT COMPLICATE THE POLYPHARMACY PROBLEM

Antihistamines: Certain OTC preps (e.g., Diphenhydramine) are highly sedating and have pronounced anticholinergic effects.

Antacids: May adsorb to other drugs if taken at the same time, decreasing their absorbance.

Laxatives: May decrease GI transit time for drugs, decreasing their absorbance.

HERBAL PREPARATIONS TO WATCH IN THE OLDER PATIENT Aloe vera: Interacts with digoxin and diuretics.

Black cohosh: Interacts with sedatives and blood pressure meds.

Ephedra: Interacts BP meds, antidepressants. Feverfew: Interacts with warfarin, NSAIDS

Garlic: Interacts with anticoagulants and glucose-lowering agents.

Ginger: Interacts with warfarin and heart meds.

Ginkgo: Interacts with anticoagulants. Ginseng: Interacts with digoxin, furosemide, and blood glucose-

lowering agents.

HERBAL PREPARATIONS TO WATCH IN THE OLDER PATIENT Hawthorn: Interacts with digoxin and cardiovascular meds.

Kava: Interacts with sedatives and CNS depressants.

Licorice: Acts as a steroid.

Ma huang: Interacts with monoamine oxidase inhibitors, theophylline, decongestants, methyldopa and caffeine.

Mistletoe: Interacts with BP meds, antidepressants.

St. John’s Wort: Interacts with just about everything.

Saw palmetto: Do not take with meds for benign prostatic hypertrophy.

Yohimbe: Interacts with decongestants, antidepressants, and mood-altering drugs.

Drugs For Cardiovascular Problems

Lipid-lowering agents Antihypertensives Anticoagulants Drugs for heart failure

The Prevalence of Statins

In 2004, CV disease killed 870,000 people.◦ 1.6 X that of cancer deaths◦ 8 X higher than accidental deaths◦ 55 X more deaths than those due to HIV/AIDS

Congenital heart disease is the single leading cause of death in the US today.

Each year, 310,000 people die in an ER or without ever being hospitalized due to a heart attack.

16 million people alive today have a history of a myocardial infarction (MI).

Each year, 1.2 million Americans have a new or recurrent MI.

Mechanism of Action of Statins

Complex MOA◦ The inhibit HMGCoA reductase. This decreases

cholesterol synthesis. ◦ They increase the number of LDL receptors on

hepatocytes causing a removal of LDLs from blood.◦ They decrease apolipoprotein B-100 synthesis; a

decrease in VLDLs is seen.

Graphic by Jatlas2

Other Statin Benefits

They promote plaque stability by cholesterol removal and decreased calcification.

Decreased inflammation. Improvement of endothelial function. Decreased risk of atrial fibrillation. Decreased risk of thrombosis by decreasing

platelet aggregation and thrombin formation.

Statins In February, 2010, the FDA approved statins

(Crestor) for:◦ Men over 50 and women over 60.◦ + Elevated C reactive protein levels.◦ + Another CV risk factor such as HTN, low HDL,

smoking, family history. **Note: High LDLs are not on the list…◦ Half of all heart attacks and strokes happen in

people with low or normal LDLs.◦ Not sure if all statins will work the same…

Statins“Are these drugs too dangerous to use?” Risks associated with use include:◦ Myositis and rhabdomyolysis Mild injury may present as muscle weakness or tenderness, local

or diffuse. This is seen in 1 to 5% of cases. Rarely, this may progress to myositis with elevated creatinine

kinase. Check for CK levels 10 times the ULN—if >10, d/c the statin.

◦ Fatal rhabdo seen less than 0.15 cases in 1 million prescriptions. Rosuvastatin has the highest risk.◦ RISK BENEFIT RATIO STILL SWINGS IN FAVOR OF

USING A STATIN!!◦

Statins“Are these drugs too dangerous to use?” Risks associated with use include:◦ Diabetes (especially in patients over 60) CV benefit is greater than risk of diabetes. Check patient’s blood glucose regularly.

Liver injury◦ If serum transaminase stays at 3X the ULN with

monitoring, d/c the statin.◦ Safe and BENEFICIAL to use in patients with non-

alcoholic fatty liver disease. A possible benefit—do statins increase bone

formation?

Statin $$ Comparison

Atorvastatin generic◦ 100 10 mg tabs $75 (dose 10 mg at bedtime to

start)

Simvastatin generic◦ 120 10 mg $199 (dose 20 mg at bedtime to start)

Rosuvastatin generic◦ 90 10 mg $74 (dose 20 mg at bedtime to start)

Statin News

High-dose simvastatin recently relegated to restricted use.◦ 80-mg dose associated with increased risk of

myopathy.◦ Patients taking this dose for more than a year with

no symptoms of muscle pain or weakness may stay on it; do not escalate to this dose.◦ Higher risk in females.

More Statin News Do not use simvastatin with ketoconazole

(Nizoral), itraconazole (Sporanox), or posaconazole (Noxafil). Do not use with clarithromycin, erythromycin or telithromycin (Ketek); HIV protease inhibitors, nefazodone, gemfibrozil, cyclosporine, and danazol.

Do not exceed 10 mg dose with amiodarone, verapamil, and diltiazem, and the 20-mg dose should not be exceeded with amlodipine (Norvasc) and ranolazine (Ranexa).

Anything New? Recently approved combination of simvastatin

and sitagliptin (Januvia). Combination is called Juvisync. Gives good glucose control plus lipid-lowering

benefits in the type 2 patient. Watch for hypoglycemia, headache, URI, rhinitis,

muscle pain. Convenient, may help compliance. Dosed as 50/10, 50/20, 50/40 mg.

Blood Pressure Meds

Much to consider here! Quality of life. Look at reducing BP especially in the face of

compelling indications. Start low and slow. Consider combination drugs.

Diuretics--HCTZ

Cheapest, most effective way to lower elevated BP◦ Should be an initial drug of choice for most patients

with hypertension◦ Preferred in isolated systolic hypertension◦ Preferred in African Americans

Diuretics--HCTZ

Hydrochlorothiazide is preferred for mobilizing fluid in mild to moderate heart failure.

Lower blood pressure by decreasing blood volume and reducing arteriolar resistance.◦ Monitor electrolytes, monitor for hypokalemia, can

increase LDLs, total cholesterol, triglycerides, hyperglycemia in diabetic patients.

Hydrochlorothiazide

Diuretics - Furosemide

Furosemide lowers BP by causing a loss of fluid volume and by relaxing venous smooth muscle.

Used for CHF, edema of cardiac or renal origin, hypertension.◦ Monitor for hypotension, hypokalemia, transient

ototoxicity.

Diuretics - Furosemide

Reserved for patients who need greater diuresis than thiazides can offer.

Used for patients with low glomerular filtration rate.

Avoid in diabetes, gout, hypokalemia.

BP Medications with No Compelling Indications….. Stage 1 Hypertension◦ SBP 140-159 mm Hg or DBP 90-99 mm Hg◦ ACE inhibitors, angiotensin receptor blockers,

calcium channel blockers, diuretic or combination.

Stage 2 Hypertension◦ SBP > 160 mm Hg or DBP > 100 mm Hg◦ Consider combinations from the start; amlodipine

plus renin angiotensin aldosterone system blocker; or diuretic plus…

With Compelling Indications

Heart Failure◦ Thiazide, beta blocker, CCB, ACEI, ARB, aldosterone

antagonist.

Post-MI◦ Beta blocker, ACEI, aldosterone antagonist, ARB

CAD or high CVD risk◦ Thiazide, beta blocker, ACEI, CCB

Angina pectoris◦ Beta blocker, CCB

With Compelling Indications Aortopathy/Aortic aneurysm◦ Beta blocker, ARB, ACEI, thiazide, CCB

Diabetes◦ ACEI, ARB, CCB, thiazide, beta blocker

Chronic kidney disease◦ ACEI, ARB

Stroke prophylaxis◦ Thiazide, ACEI, ARB, CCB

Early Dementia◦ ACEI, ARB, thiazides, CCBs

Combination Therapy for Hypertension

More likely than unlikely in this patient population

Additive or synergistic effects Better compliance Decreased adverse events Prolonged duration of action More target organ protection

Heart Failure in the Older Patient

ACEI, ARBs, beta blockers and aldosterone antagonists reduce mortality.◦ If patient cannot tolerate ACEI/ARBs, vasodilator Tx

with hydralazine and nitrates.

Digoxin and diuretics are good for symptom control but require monitoring.◦ Orthostatic hypotension, renal function, electrolyte

imbalances, drug interactions, worsening of comorbid diseases.

Beta-Blockers: Atenolol & Metoprolol

Both are beta-1 blockers with no intrinsic sympathomimetic activity.

When used in patients undergoing ST-elevation MI (STEMI), they reduce pain, infarct pain, and short-term mortality.◦ Beta-receptor blockade reduces cardiac work and oxygen

demand; BP is lowered; risk of dysrhythmia is reduced.

If the patient continues to use these PO, long-term survival increases.

Metoprolol: Toprol is XL, Lopressor is IR.

Beta-Blocker Use

PO dosing should begin within 24 hours of STEMI and continue for at least 2-3 years thereafter.

Contraindications to use include overt HF, heart block >1st degree, pronounced bradycardia or persistent hypotension, and cardiogenic shock. Watch in patients with chronic obstructive pulmonary disease (COPD).

Beta-Blocker Use

These drugs will potentiate the blood pressure-lowering and cardiac effects of antihypertensives, calcium channel blockers, antithyroid medications.

They may cause cold extremities and exercise intolerance or sedation.

Do not discontinue abruptly!

Other Uses for Beta Blockers

Ventricular arrhythmias, atrial ectopy Migraine prophylaxis Essential tremor Aggressive behavior (not in dementia) Prevention of MI, atrial fibrillation/flutter,

hypertrophic obstructive cardiomyopathy

Anticoagulants

Warfarin still a mainstay.◦ Benefits outweigh risks in patients at risk for stroke

following atrial fibrillation.◦ Is risk of bleeds due to falls greater in the elderly?

Not really—benefits are STILL greater.

Newer anticoagulants offer some advantages.◦ Dabigatran◦ Rivaroxaban

Dabigatran

Direct thrombin inhibitor. Avoid use in patients taking NSAIDs or other

agents that promote bleeds.◦ Watch in history of GI bleeds; give with proton

pump inhibitor (PPI).

Do not need to do monitoring, but check liver enzymes at baseline and regularly.

Expensive!

Rivaroxaban Factor Xa inhibitor. Does not require monitoring, but has no reversing

agent, so must not be used in a patient with history of bleeds or with active bleeding.

Do not use in patient on other anticoagulants or NSAIDs.

Has drug interactions with CYP3A4 substrates. Expensive!!

Newer Anticoagulants

Apixaban, Edoxaban, Betrixaban are all in trials and development.

Cost may be prohibitive Warfarin will continue to be a mainstay.

When / Who to Treat With An Anticoagulant?

Compare risk/benefit. Complicated here by many things… Use assessment tools for stroke risk, bleeding

risk, consider gender, history, use your pharmacist or an antithrombotic risk assessment Tool.

Review the order frequently; review risk/benefit; review response and QOL.

Drugs for Benign Prostatic Hyperplasia

Affects 80% of men > 80 years old Increased urinary frequency Linked to QOL issues Linked to falls?

Drugs for BPH Finasteride (Proscar)—5-alpha-reductase inhibitors Dutasteride (Avodart) Dutasteride plus tamsulosin (Jalyn) Terazosin (Hytrin)—alpha blockers Doxazosin (Cardura) Tamsulosin (Flomax) Alfuzosin (Uroxatral) Silodosin (Rapaflo) Often taking both types of drugs in combination is

the best.

Mechanisms of Drugs for BPH

5-alpha reductase inhibitors◦ Inhibit the conversion of testosterone to

dihydrotestosterone (DHT), lowering serum levels of DHT. Since this hormone is trophic for the prostate, the gland no longer grows when DHT is decreased. Takes 6 to 12 months to work; works best in very enlarged

prostate. Decreased ejaculate volume and libido in 5-10%. Rarely, gynecomastia.

Dihydrotestosterone

Mechanisms of Drugs for BPH Alpha blockers◦ Blockade of alpha receptors in the smooth muscle

of the bladder neck decreases dynamic obstruction of the urethra These give relatively rapid improvement even in mild

enlargement; require lifelong use.

◦ Silodosin and tamsulosin are selective for alpha-1 receptors on the prostate; the others are not, and will lower BP as well.◦ Use caution with other BP-lowering drugs and with

phosphodiesterase inhibitors.

What’s New for BPH?? Tadalafil (Cialis)◦ A phosphodiesterase inhibitor used for ED.◦ Prescribed for BPH because it helps with urinary

urgency, weak urine stream, frequent urination especially at night.◦ Not for men who also take nitrates.◦ Not for concomitant use with alpha-blockers due to

significant drop in BP. Botulinum Toxin◦ A single injection into the prostate may decrease

symptoms for up to a year.

Drugs for Osteoarthritis

NSAIDs Disease-modifying antirheumatic drugs

(DMARDs) Drugs for neuromuscular pain

Phenylbutazone, a NSAID

Osteoarthritis Treatment

Non-pharmacologic means first Acetaminophen NSAIDs in combination with acetaminophen Low potency opioids Adjunctive analgesics◦ TCAs, anticonvulsants, serotonin-norepinephrine

reuptake inhibitors

Photo by Drahreg01

Osteoarthritis

Acetaminophen is drug of first choice.◦ No renal impairment at normal doses.◦ No GI bleed risk at normal doses.◦ May cause hepatic toxicity in patients with hepatic

impairment or alcohol use.

Dose at 4 g or less per day for osteoarthritis, back pain, dental pain, arthralgia, myalgia.

Acetaminophen


Acetaminophen Opiates◦ Use when other therapies fail.◦ SE include constipation, sedation, addictive potential.◦ Avoid codeine.◦ Consider tramadol (non-opiate).

Morphine, an opiate

NSAIDs for Osteoarthritis Concern about cardiovascular risk. COX-2 inhibitors are associated with highest risk.◦ Celecoxib (Celebrex)

Of the COX-1 COX-2 inhibitors, naproxen has the lowest CV risk but causes more GI bleeds.

Diclofenac causes more CV effects due to greater COX-2 inhibition.


Topical agents◦ Capsaicin, methyl salicylate, diclofenac gel◦ Reduce systemic SE of NSAIDs.

Anticonvulsants◦ Carbamazepine, phenytoin, valproic acid, gabapentin,

pregabalin◦ May help with neuropathic pain.◦ Watch for allergies/rashes, sedation.

Medications for Arthritis/DMARDs

Daily supplementation with chondroitin sulfate has been useful for hand osteoarthritis.◦ Incidence greater than 50% in people over 60.

Takes several months for effects to develop. May be taken with NSAIDs.

Other Drugs for Osteoarthritis

Hyaluronic Acid◦ Causes some improvement in knee OA.

Topical diclofenac (Voltaren) gel◦ Avoids GI, CV, renal risks of NSAIDs.◦ Watch for dermatitis.◦ Apply to affected joints 4 times/day.


Antidepressants◦ Used when pain is associated with sleep disorders.◦ Used in cases of fibromyalgia.◦ May modulate nerve impulses.◦ TCAs, SSRIs, serotonin-norepinephrine reuptake

inhibitors.

Chronic Neuromuscular Pain

Consider mechanism. Duloxetine (Cymbalta) modulates neurogenic

mechanisms in neuromuscular pain. Also has an impact in osteoarthritis in some

patients.

GI Drugs

GERD Ulcer GI upset due to medications◦ NSAIDs

Proton Pump Inhibitors

Up to 44% of adults have heartburn at least once/month; 14% once a week; 7% every day.

Less than 50% of patients with GERD have the erosive form.◦ Most have NERD.◦ PPIs can work for both—daily for erosive GERD,

PRN for NERD.

Proton Pump Inhibitors

Mechanism of Action of PPIs

These drugs irreversibly inhibit the H/K-ATPase on the parietal cell.◦ Inhibit both basal and stimulated acid production.

Reduce acid production by almost 100% within 2 hours after a single dose.◦ Once pumps are inhibited, the effect lasts for days;

recovery may take weeks.

Nexium and Prevacid Vs. Prilosec

Nexium and Prevacid are the S-isomers only of Omeprazole.◦ They are metabolized more slowly and maintain

blood levels longer.◦ Cost: 90 Nexium (20 mg): $50 84 Prevacid (30 mg): $48 100 Prilosec (20 mg): $38

Nexium

PPIs—The Downsides Treatment for over 1 year in a patient over 50 is

associated with a 44% increase in hip fracture (and higher in patients over 60)—this study now being questioned, though warning still in place for Rx PPIs.◦ Make sure patient takes 1000-1500 mg calcium and 400-800

IU Vitamin D.

◦ Monitor bone density.

May cause rebound GERD if discontinued.◦ Seen even in healthy volunteers.

PPIs—The News

PPIs and clopidogrel—there was concern about an increase risk of GI bleeds. This seems unfounded, but research finds an overprescribing of PPIs to cardiac patients for extended periods.

Omeprazole has many drug-drug interactions due to its metabolic profile; lansoprazole may be a safer choice.

CNS-Active Drugs

Drugs for dementia Drugs for sleep/insomnia Drugs for depression Drugs for psychosis

Photo by Digimint

Dementia Tremendous problem worldwide—35 million

sufferers. This number will double every 20 years to 66 million

in 2030 and 115 million in 2050. Dementia currently has a price tag of $315

billion/year.◦ $422-604 when all social/caregiver/family costs are factored

in.

7th leading cause of death in the US.

Memantine ER N-methyl-D-aspartate blocker Recently approved by the FDA Once-a-day dosing Benefits for cognition, assessment, behavior, and

caregiver burden but not function Reserved for moderate-to-severe AD◦ Off-label for mild symptoms

Good for patients who suffer from neuropsychiatric or behavioral symptoms

Antidepressants in Dementia

Should they be used? Newer research seems to indicate little, if any

data. Commonly prescribed meds include sertraline,

mirtazapine. Side effect incidence is higher in the dementia

patient.

NSAIDs and AD

Heavy use of NSAIDs increases risk of AD by as much as 66%.

Heavy use defined as 500 standard daily doses over a 2-year period.

This seems to negate earlier data about a protective effect of NSAIDs.

In Women With Post-Menopausal Dementia… Conjugated equine estrogen has been shown to

have negative cognitive effects on the brain, made worse in patients with a history of impairment or familial risk.

17-beta-estradiol has positive or neutral effects. Helps especially with verbal memory

performance.

Compelling Old Drug for AD?

Low-dose lithium Early studies show benefit in a cohort who

took lithium at a low dose. These patients with amnestic mild cognitive

impairment (aMCI) had better cognitive response than placebo group. They had less phosphorylated tau (P-tau) protein in CSF after low-dose lithium treatment.

Polypharmacy as a Contributor to Dementia In the U.S., polypharmacy is found in 40% of those older than

65 years.

Residents of long-term care facilities are a small but important group of patients who ingest many daily medications, taking an average of six to eight drugs daily.

Use of multiple medications with anticholinergic effects can increase patients' total anticholinergic burden as evidenced by clinical signs such as dry mouth, sedation, confusion and even hallucinations and delirium.

Any Bright News for Dementia? Certain drugs for blood pressure management

have shown some improvement in cognition in patients with dementia.

Dihydropyridine CCBs decrease cognitive impairment .◦ Nifedipine, nicardipine, amlodipine, isradipine,

felodipine, nisoldipine ACEI (Captopril, Perindopril), ARBs, diuretics

do, too. NOT beta blockers.

Dihydropyridine

Future Directions in Treatment for AD

Anti-amyloid drugs to reduce the production of beta-amyloid (tau)◦ Beta- and gamma-secretase inhibitors, beta amyloid

antibodies

Drugs that block the phosphorylation of tau◦ Protein kinase inhibitors

Drugs that block the formation of neurofibrillary tangles

Drugs for Sleep

Options include OTC drugs and prescription. OTC◦ Antihistamines—not recommended because of long

half-lives, can cause dizziness, tolerance may develop within 3 days of consistent use.◦ Melatonin—variable success; lack of standardized

preps problematic. Helps with sleep initiation but not maintenance.

Drugs for Sleep Prescription options

Ramalteon (Rozerem)—melatonin agonist; lasts for about 4 hours

Benzodiazepines may be used, but short-term only; rebound insomnia◦ Triazolam (Halcion), Estazolam (ProSom), Temazepam (Restoril),

Flurazepam (Dalmane)*, Quazepam (Doral)*

Non-Benzodiazepines—watch for sleep-eating, walking, driving; must be discontinued if sleep-driving occurs. Do not use long-acting or sustained-release preparations*◦ Zolpidem (Ambien)*, Zalaplon (Sonata), Eszopiclone (Lunesta)

Drugs for Sleep

Occasionally, antidepressants may be used.◦ In patients with refractory insomnia.◦ In patients with a history of substance abuse.◦ Along with stimulant daytime antidepressants.

Consider trazodone (Desyrel), nefazodone (Serzone), amitriptyline and nortriptyline (Aventil).

Benzodiazepines in the Elderly

Use is associated with episodic memory problems, poor concentration, disinhibition, drowsiness, dysarthria, motor incoordination, and falls.

Risks associated with use include slowed reaction time, visuospatial deficits, impaired driving skills, and increased MVA.

On Beers’ list for these risks!

Antipsychotics in the Older Adult

In 2001, more than 70% of US atypical antipsychotic prescriptions were written for off-label indications such as dementia.

In 2002, however, growing safety concerns, including reported increases in diabetes and stroke risk, began to emerge. These concerns eventually culminated in an FDA black box warning in 2005.

Antipsychotics in the Older Adult

Why were they prescribed?◦ Crying, wandering, agitation.◦ These are NOT indications for use.

Overt aggression, true psychosis, risk of harm to self or others◦ Consider risk/benefit.

Do we have anything else for these patients?◦ Not really….make the environment the best

possible!

Antipsychotics in the Older Adult Linked to increase risk of CVAs.◦ Especially in patients with dementia.

First-generation antipsychotics are highest risk drugs to use.◦ Thioridazine, prochlorperazine, haloperidol.◦ Risk is reduced if drug is discontinued.

Second-generation antipsychotics most often prescribed in this population are risperidone and olanzapine.◦ Also associated with CVAs, but risk is less.

Opioid Use

Chronic and acute use are associated with deficits in executive functions, attention, concentration, recall, visuospatial skills, and psychomotor speed.

Conditions That May be Treated with OTC Medications in the Older Adult Allergy Common cold Osteoarthritis Heartburn Insomnia

Allergy Consider inhaled cromolyn sodium drugs.◦ Local effects only so no drug interactions.◦ No adjustment in dose for renal, hepatic disease.

Ketotifen◦ OTC antihistamine for ocular conjunctivitis.◦ Conjunctive congestion, headache, rhinitis may be SE,

but no drug interactions. Loratidine (Claritin)◦ Does not penetrate the BBB well so not as sedating.◦ No anticholinergic SE.

Photo by Wolfgang Ihloff

Common Cold

Most systemic medications interact with Rx drugs the older patient may be taking for HTN, CV ailments or diabetes.

Consider Oxymetazoline spray decongestant for short-term use (3-5 days).◦ No systemic effects due to lack of absorption.◦ Promotes drainage, improves breathing.◦ Rebound stuffiness WILL occur.

Heartburn Famotidine and nizatidine are recommended H2

receptor blockers. Main drug interactions are related to acid-lowering

effects.◦ Dosage adjustments needed for patients with renal

impairment. Omeprazole is a PPI that may be used but consider…◦ Takes up to 4 days before relief is felt.◦ Interacts with Cyp450 enzymes so drug-drug interactions are

common. Lansoprazole may be a safer choice??

◦ Patient should not take for longer than 14 days—rebound reflux common!

Constipation Bulk-forming laxatives are among the safest.◦ Psyllium, methylcellulose

Emollient laxatives (e.g., Docusate)◦ Should be reserved for the patient who should not

strain during defecation. Patient with MI, hemorrhoids, following rectal surgery.

Polyethylene glycol 3550 is osmotic, but does not cause electrolyte disturbances.◦ Safe to use in the cardiac patient, in renal failure.

Glycerin suppositories

Insomnia

Most OTC products for insomnia contain antihistamines and should be AVOIDED in the elderly.

Some promising studies with melatonin.◦ May improve sundowning in patients with dementia.

Check sleep hygiene before initiating Rx therapy.

Photo by Chad fitz

What About Illicit Drugs?

35 million people are 65 or older. Substance abuse affects about 17% of this

population.◦ This is expected to double by 2020.◦ Includes abuse of prescription drugs: opioids,

benzodiazepines.

Regional Differences Affecting Drug of Abuse Use Socioeconomic factors influence access to

healthcare, overall health, drug of abuse use, education level, etc.

Lifestyle factors—healthy choices with respect to alcohol, tobacco, recreational drugs, diet

Areas of concern….

Cannabis Use in the Elderly

May cause a protracted impairment even after discontinuance and years of abstinence.

Attention and short-term memory may be especially affected.◦ These are most affected acutely as well, as is

executive function.

Where Does Marijuana Work in the Brain?

Effects of Marijuana are Dose-Dependent Causes three effects on the brain: euphoria,

sedation, and hallucinations. Low-Moderate dose: euphoria, relaxation,

appetite stimulation, impairment of short-term memory, impairment of driving skills, depersonalization.

High dose: hallucinations, paranoia, delusions.

Alcohol Use in the Older Population

Alcohol is the most commonly used recreational drug in older adults. Among 40,556 U.S. adults age 60 years and older, 52.8% of men and 37.2% of women were current drinkers.

A safe amount of alcohol intake for individuals over age 65 would be no more than seven drinks per week and no more than four at one sitting for both men and women.

Photo by Fiona Shields

The J-Curve Deaths Due to Alcohol by County

Alcohol Plus…..

In a survey of 83,321 older outpatients, 19% of those taking prescription medications known to adversely interact with alcohol reported concomitant alcohol use.

• Photo by Tim “Avatar” Bartel

Alcohol-Related Dementia

Deficits in abstracting abilities, short-term memory, executive control.◦ This is in contrast to AD, where word-finding ability

is hampered, there is profound memory loss, and recognition and recall are affected.

With abstinence, physical and mental function do NOT continue to deteriorate (as they do in AD).◦ However, ARD may contribute to worsening of AD.

Non-Medical Use of Pain Relievers in Persons Aged 12 and Older Other Drugs of Abuse

Which Drugs are the Worst?

Drugs of abuse are problematic. Sometimes the prescription drugs may become

the drugs of abuse. The most-prescribed have issues of their own,

including “black box” warnings that have to be taken into account.

Medication Adherence

40% or more of the elderly fail to take drugs as prescribed.◦ May not fill or refill prescriptions.◦ May not follow dosing directions.

Outcomes of non-adherence may be toxicity or therapeutic failure (90%).

Much of the time non-adherence is intentional.◦ “I don’t need this drug.”

GUIDELINES FOR PRESCRIBING IN THE ELDERLY--SAIL PROTOCOL

S Simplify regimens (q day drugs) A Adverse effects, both side effects and

interactions I Indications for drug use must be well-defined L List all current meds, including OTC drugs,

herbal and alternative medicines

Steps for Reducing Medication Errors in the Elderly

Consider a “brown bag” session. Reduce medications wherever possible. Check indications--are all meds necessary? Communicate with other caregivers. Check OTC and herbal use. Ascertain compliance. EDUCATE!

PREVENTION OF POLYPHARMACY

Recognition of polypharmacy is key. “Brown bag” approach is useful.

Educate patients with respect to medication use. Clinical pharmacist consult may be useful.

Communication between prescribers is key. “Essential medication only” approach may prevent

polypharmacy.

REVIEW MEDICATION REGIMENS

Review drug regimens regularly. Is drug being taken as prescribed? Are all agents still needed? Can the regimen be simplified?

WHAT CAN BE DONE TO LIMIT ADVERSE DRUG REACTIONS IN OLDER PATIENTS?

Anticipate more side effects, and maybe more toxicity.

Recognize that many drugs may be effective in doses LOWER than what the manufacturer recommends.

ALWAYS communicate side effects or a desire to change a dose with the prescriber.

DRUGS SHOWN TO BE EFFECTIVE AT DOSES LOWER THAN THE MANUFACTURER RECOMMENDS

Amlodipine (2.5 mg/d vs 5 mg/d) Atenolol (25 mg/d vs 50 mg/d) Atorvastatin (2.5-5 mg/d vs 10 mg/d) Bupropion (50 mg bid vs 100 mg bid) Captopril (12.5 mg qd or bid vs 50-75 mg/d) Diclofenac (75 mg /d vs 100-200 mg/d) Enalapril (2.5 mg/d vs 5 mg/d)


Fexofenadine (20 tid vs 60 mg bid) Fluoxetine (2.5-10 mg/d vs 20 mg/d) Flurazepam (15 mg qhs vs 30 mg qhs) Hydrochlorothiazide (12.5 mg/d vs 25-50 mg/d) Ibuprofen (200 mg tid-qid vs 400 mg tid-qid) Lisinopril (5 mg/d vs 10 mg/d)


Lovastatin (10 mg/d vs 20 mg/d) Metaprolol (50 mg/d vs 100 mg/d) Misoprostol (50-100 mcg qid vs 200 mcg qid) Nefazodone (50 mg/d or bid vs 100 mg bid) Nizatidine (25-50 mg bid or 100 mg qhs vs 150

mg bid or 300 mg qhs) Omeprazole (10 mg/d vs 20 mg/d)


Ondansetron (1-4 mg tid vs 8 mg bid-tid) Pravastatin (5-10 mg/d vs 20 mg/d) Ranitidine (100 mg bid vs 150 mg bid) Simvastatin (2.5-5 mg/d vs 10 mg/d) Trazodone (25-100 mg/d vs 150 mg/d) Zolpidem 5-7.5 mg qhs vs 10 mg qhs

WHAT IS A PATIENT TO DO?

Be aware of polypharmacy and learn steps to reduce it.

Be aware that many drugs are effective in lower dosages than prescribed (but ALWAYS consult a physician before altering your dose).

Be aware of drugs that should be avoided in the older patient.

Remember drugs should make one feel better, not worse.

Communicate with all prescribers.

Check drug name against prescription!

Some Final Rules

Dose reduction is likely (start low!). An increased incidence of toxicity is likely. Avoid poly-clinic, poly-prescriber situations. Avoid treating non-medical problems with

drugs.

Your Enemy, Your Friend

The self-empowered patient◦ “My friend tells me…”◦ “My other HCP said…”◦ “I read in a magazine that…”◦ “I saw on TV that…”◦ “I saw on the INTERNET….”

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CONSIDERATIONS GERONTOLOGICAL PHARMACOLOGY UPDATE Handout Samples/Full Handouts... · GERONTOLOGICAL PHARMACOLOGY UPDATE Thomas W. Barkley, Jr., DSN, ACNP-BC, FAANP Professor of Nursing