THE APhA COMPLETE REVIEW FOR PHARMACY, 7th Ed

34. Geriatrics and Gerontology - William Nathan Rawls, PharmD

34-1. Overview

Introduction

Gerontology is the study of the problems of aging and all its aspects. Geriatrics focuses on the diseases associated with aging and the treatments for those conditions. Geriatrics is of particular concern for pharmacists.

More than 12% of the U.S. population is older than 65 years of age. By 2050, the percentage is expected to increase to over 20%.

Persons over 65 years of age have more chronic illnesses and take more prescription and nonprescription drugs than persons in younger age groups. The use of herbal or dietary supplements by older adults has increased significantly in the last 10 years, with the increased risk of adverse events and drug interactions.

Age-related physiologic changes and increased medication use contribute to a greater risk of adverse drug events. Changes in vision, hearing, and mental functioning can result in increased problems with medication compliance.

Adverse Drug Events in the Older Adult

Drug-related hospitalizations occur four times more often for older adults than for younger adults.

Older adults receiving multiple medications are at risk of a "prescribing cascade" that occurs when an unrecognized adverse effect of a medication is treated as a new illness and additional medications are prescribed.

Older adults are at increased risk of drug-drug interactions when taking multiple medications, and this potential is decreased by medication simplification.

The possibility that a newly developed medical condition or worsening of an existing illness is related to an older adult's medication or herbal use should be considered when a pharmacist is making medication recommendations.

Changes in Pharmacokinetics Associated with Aging

Decreased absorption of various drugs occurs secondary to decreased stomach acidity and changes in blood flow to the stomach (the least altered by aging).

Altered drug distribution is caused by a decrease in total body water, increased lipid storage, and decreased serum albumin in malnourished elderly persons. These factors can contribute to increased serum levels of drugs.

Decreased hepatic blood flow and reduced hepatic enzyme activity cause slower drug metabolism. Increased levels of drugs require increased metabolism by the liver.

Elimination of drugs by the kidneys is slowed because of decreased renal blood flow and lowered glomerular filtration. Thus, drug accumulation develops.

The Cockcroft-Gault formula for estimating creatinine clearance can be used to predict renal function in the elderly:

000074

Note: Use ideal body weight. The equation above is for males. For females, multiply the result by 0.85.

In dosing the elderly, the general rule is to start with lower doses than those used in younger patients and to increase doses at a slower rate.

34-2. Drugs of Concern

The following drugs can cause psychiatric symptoms:

• Anticholinergics

• Narcotics

• Tricyclic antidepressants

• Central nervous system stimulants

• Antiparkinson drugs

The following drugs can produce anxiety symptoms:

• Theophylline

• Nasal decongestants

• β-agonists

• Antiparkinson drugs

• Appetite suppressants

The following drugs can contribute to nutritional deficiencies:

• Diuretics

• Digoxin, digitalis

• Laxatives (overuse)

• Sedatives (overuse)

These specific drugs pose a risk to geriatric patients:

• Long-acting benzodiazepines (e.g., chlordiazepoxide [Librium] and diazepam [Valium]) should be avoided because of the risk of prolonged sedation and increased risks of falls and fractures.

• Amitriptyline (Elavil) has potent anticholinergic and sedating effects with risk to older patients.

• Digoxin (Lanoxin) at higher doses (> 0.125 mg daily) has an increased risk of toxicity without greater benefits.

• Meperidine (Demerol) taken orally has an increased risk of respiratory and circulatory depression.

• Antipsychotic use may result in the increased risk of heart events and infections.

34-3. Medication Compliance and the Older Adult

Types of noncompliant behavior in the elderly include the following:

• Failure to take medications

• Premature discontinuation of a medication

• Excessive consumption of a medication

• Use of medications not currently prescribed

Several strategies can improve patient medication compliance:

• Limit the number of different medications and decrease the dose frequency.

• Simplify dosage instructions.

• Tailor the regimen to the patient's schedule.

• Use compliance aids and telephone reminders.

• Enlist the assistance of family members and friends.

34-4. Basic Components of Evaluating Drug Therapy in Older Adults

These questions should be answered in an evaluation of drug therapy:

• Why is the drug being used? A diagnosis or reason should be given

• Is the drug being given correctly? The dosage, form, and schedule of administration should be analyzed.

• Are any symptoms or complaints related to drug therapy?

• Is monitoring of treatment ongoing?

• What is the endpoint of therapy?

34-5. Alzheimer's Disease and Related Dementias

Introduction

Dementia is the decline in intellectual abilities (e.g., impairment of memory, judgment, and abstract thinking) coupled with changes in personality. Dementia patients tend to be described as cognitively impaired.

Cognition is the mental process by which people become aware of objects of thought and perception, including all aspects of thinking and remembering. Impairment of cognition significantly affects the life of the dementia patient, his or her family members, and the community in general.

Types of Dementia

Alzheimer's disease accounts for approximately 70% of dementias. Vascular dementias account for approximately 15% of dementias. Patients may have both Alzheimer's disease and vascular dementia.

Other Causes of Dementia

• Vascular disease, cerebrovascular accidents (strokes)

• Neurologic disorders such as Parkinson's disease, frontotemporal dementia, dementia with Lewy bodies, and Huntington's chorea

• Metabolic disorders such as hypothyroidism, alcoholism, and anemia

• Infectious diseases such as meningitis, syphilis, AIDS (acquired immune deficiency syndrome)

Clinical Presentation

Alzheimer's disease is a progressive neurologic disease that results in impaired memory and intellectual functioning and altered behavior. Alzheimer's disease is characterized by the slow onset of symptoms leading to loss of ability to function independently. Symptoms may include psychoses with hallucinations, illusions, and delusional thinking. As Alzheimer's disease progresses, the brain continues to deteriorate.

Depression can cause cognitive impairment similar to that of Alzheimer's disease and should be identified and treated.

Pathophysiology

Hallmark pathologic changes in the brain are linked to Alzheimer's disease (i.e., neuritic plaques and neurofibrillary tangles increase). Neuritic plaques are composed of amyloid proteins deposited on neurons. Neurofibrillary tangles exist within neurons and disrupt normal function.

Neurotransmitters are also altered in Alzheimer's disease. Acetylcholine concentrations decrease significantly.

Diagnostic Criteria

Diagnosis of Alzheimer's disease requires the presence of memory impairment and one or more of the following:

• Aphasia (language disturbance)

• Apraxia (impaired motor abilities)

• Agnosia (failure to recognize objects)

• Disturbance of executive function (e.g., planning, organizing)

Treatment Principles

When evaluating a patient for treatment of dementia and Alzheimer's disease, review the patient's medications and consider any that might cause mental confusion or worsen underlying disease states. Drugs that block activity of acetylcholine can worsen dementia and decrease the effectiveness of medications used to treat Alzheimer's disease.

Anticholinergic drugs are used for a variety of conditions, ranging from depression to incontinence. Indications should be identified before treating Alzheimer's disease. Anticholinergic effects can be additive (i.e., a combination of anticholinergic drugs can result in toxicity even when each is given at low doses; see

Table 34-1).

Provide support to caregivers, and treat the patient's behavioral and mood symptoms.

[Table 34-1. Anticholinergic Drugs That Can Worsen Alzheimer's Disease]

Consider a trial of a cholinesterase inhibitor and monitor for benefits to memory and cognitive functioning.

Monitoring

Monitor memory and cognitive functions every 6-12 months.

Routinely assess behaviors and ability to perform activities of daily living (e.g., bathing, feeding, toileting, dressing).

Monitor for focal neurologic signs and symptoms that may suggest other causes of changes in cognitive function.

Drug Therapy

The pharmacologic approach to treatment falls into two categories:

• Medications used to control behavioral and emotional symptoms

• Medications used to slow or reverse the disease process

Symptomatic therapy

Medications used to control behavioral and emotional symptoms are used to provide symptomatic improvement and do not affect the outcome of the disease.

Anxiolytics are used to decrease anxiety and possibly agitation, motor restlessness, and insomnia. Such medications include lorazepam (Ativan), oxazepam (Serax), and buspirone (Buspar). The benzodiazepines can increase the risk of falls and injury.

Antidepressants improve depression, which can worsen the cognitive functioning of a patient with Alzheimer's disease. Antidepressants include sertraline (Zoloft) and citalopram (Celexa).

Antipsychotics are used to decrease psychotic symptoms such as hallucinations and delusions. Antipsychotics such as haloperidol (Haldol), risperidone (Risperdal), and aripiprazole (Abilify) may reduce agitation and aggressiveness in dementia patients. A U.S. Food and Drug Administration (FDA) black box warning concerning the risk of increased mortality (cardiac events and infections) is associated with the use of antipsychotics in demented elderly patients.

Sedative-hypnotics are used for short-term treatment of insomnia but can increase confusion and memory impairment. These medications include trazodone (Desyrel), zolpidem (Ambien), and temazepam (Restoril).

Cholinesterase inhibitors

Medications used to slow or reverse the symptoms of Alzheimer's (see

Table 34-2) affect acetylcholine activity in the brain. Acetylcholine levels may be decreased by as much as 90% in Alzheimer's disease. These levels can be increased by inhibiting the enzyme acetylcholinesterase.

Acetylcholinesterase inhibitors increase acetylcholine but do not replace lost cholinergic neurons or change the underlying pathology. This class of medications is used to prevent or slow deterioration in cognitive functioning.

The first cholinesterase inhibitor approved to treat Alzheimer's disease was tacrine (Cognex), which proved beneficial but may cause hepatotoxicity (damage to the liver). Thus, tacrine requires regular liver function testing and is rarely prescribed.

[Table 34-2. Drugs Used to Treat Alzheimer's Disease]

Safer cholinesterase inhibitors include the following:

• Donepezil (Aricept) is selective for acetylcholinesterase in the brain (i.e., not in peripheral tissues) and is approved for mild to moderate and moderate to severe dementia.

• Rivastigmine (Exelon), a nonselective cholinesterase inhibitor, decreases both acetylcholinesterase and butyrylcholinesterase. It is approved for mild to moderate Alzheimer's disease and dementia associated with Parkinson's disease.

• Galantamine (Razadyne) is a selective acetylcholinesterase inhibitor that activates nicotinic receptors, which may increase acetylcholine. It is approved for mild to moderate Alzheimer's disease dementia.

Patient instructions and counseling

Donepezil

Give orally, 5 mg daily for 4-6 weeks. Increase dosage to 10 mg daily at bedtime. Take with or without food.

Rivastigmine

Oral doses are given with a gradual dosage increase. Begin at 1.5 mg twice daily and then 3.0 mg twice daily, 4.5 mg twice daily, and 6.0 mg twice daily, with a minimum of 2 weeks between dose increases. If rivastigmine is discontinued because of adverse effects, restart at beginning dose. Take with meals in divided doses. Transdermal patch dosing begins with 4.6 mg every 24 hours, once daily for 4 weeks. It then increases to 9.5 mg every 24 hours, once daily.

Galantamine

Doses begin with 4 mg twice daily for 4 weeks, 8 mg twice daily for 4 weeks, and then 12 mg twice daily. If galantamine is discontinued for more than a few days, restart at the beginning dose. In hepatic or renal dysfunction, doses should not exceed 16 mg per day. Do not use in instances of severe dysfunction. Take with meals in divided doses. Initiate therapy with extended-release capsules at 8 mg daily with a morning meal for 4 weeks. Increase the dose to 16 mg daily for 4 weeks and then 24 mg daily.

Adverse drug events

• Donepezil: Side effects include nausea, vomiting, and gastrointestinal (GI) symptoms. These side effects may be minimized by increasing the dose at 6 weeks.

• Rivastigmine: Side effects include nausea, vomiting, GI upset, and possibly significant weight loss. Adverse effects are dose related and may be lessened by increasing the dose at a slower rate.

• Galantamine: Adverse effects include nausea, vomiting, and GI upset. Slow dose titration will decrease side effects.

NMDA-receptor antagonists

Blocking the excitotoxicity effects of the neurotransmitter glutamate at N-methyl-D-aspartate (NMDA) receptors has been reported to be beneficial in Alzheimer's disease. Memantine (Namenda) is an NMDA-receptor antagonist used for moderate to severe Alzheimer's disease dementia. Doses begin with 5 mg daily for 1 week, increasing to 5 mg twice daily, with weekly increases to 10 mg twice daily.

The dose should be reduced to 5 mg twice daily in patients with renal impairment (creatinine clearance less than 30mL/min).

Side effects include drowsiness, dizziness, headache, blood pressure elevations, and motor restlessness.

Drug-drug interactions

Anticholinergic drugs will reduce the effectiveness of cholinesterase inhibitors and cause dry mouth, blurred vision, constipation, and mental confusion (i.e., conditions that are more problematic in the elderly).

Cytochrome P450 enzyme inhibitors of 2D6 and 3A4 increase levels of galantamine and donepezil by inhibiting their metabolism.

Dextromethorphan (Robitussin DM), a potent NMDA-receptor antagonist, should be used cautiously with memantine. Smoking and nicotine products may alter levels of memantine. Concurrent use of amantadine increases the potential for adverse effects.

Parameters to monitor

• Monitor cognitive function (e.g., poor results on mini-mental state exam, decline in performance of activities of daily living, incidence of behaviors that indicate cognitive decline).

• Watch for signs and symptoms of toxicity.

• Discontinue treatment with active peptic ulcer disease, severe bradycardia, and acute medical illness.

• Perform periodic complete blood cell count and basic chemistries.

• Look for expected benefits with the use of cholinesterase inhibitors and NMDA-receptor antagonists. Such benefits include improvement in memory, some stabilization of behaviors or mood, and possible slowing of the progression of the disease.

Nonprescription agents

High-dose vitamin E (2,000 units daily) has been recommended as an antioxidant to slow progression of Alzheimer's disease. Vitamin E may interfere with vitamin K absorption and result in increased risk of bleeding. Increased mortality has been reported with high-dose vitamin E. The potential toxicity of high-dose vitamin E may outweigh the benefits.

Ginkgo biloba, an herb, has been used to treat symptoms of Alzheimer's disease with reports of modest benefits. Ginkgo biloba is associated with increased risk of bleeding and hemorrhage, especially when combined with daily aspirin use, and is not recommended.

Nondrug Therapy

The treatment of Alzheimer's disease includes nonpharmacologic and pharmacologic therapies. Patients need to live in an environment that permits safe activities while minimizing risk.

Caregivers need training and support to deal with the behavioral and functional issues associated with this disease. Caregivers are at risk for depression and stress-related medical illnesses. Caregivers may also neglect their own health care needs and should be encouraged to maintain a healthy lifestyle.

34-6. Parkinson's Disease

Introduction

Parkinson's disease (PD) is a chronic progressive neurologic disorder with symptoms that present as a variable combination of rigidity, tremor, bradykinesia, and changes in posture and ambulation. An estimated 1 million persons in the United States suffer from PD. Approximately 60,000 new cases are diagnosed each year.

The risk of developing PD increases with age, and a substantial increase in the U.S. population of persons over 60 years of age is predicted.

Because medications are the primary treatment for PD, pharmacists play an important role in the care of these patients.

Classification

The two classes of PD are primary parkinsonism and secondary parkinsonism. Primary parkinsonism has no identified cause. Secondary parkinsonism can be the result of drug use (e.g., reserpine, metoclopramide, antipsychotics); infections; trauma; or toxins.

Clinical Presentation

Clinical signs and symptoms of PD develop insidiously, progress slowly, may fluctuate, and worsen with time despite pharmacologic therapy.

Symptoms

Tremors at rest may begin unilaterally and are present in 70% of PD patients. Tremors that do not occur during sleep may worsen with stress.

Rigidity of limbs and trunk may develop. The face may have a masklike expression. Patients may have difficulty dressing or standing from a seated position.

Akinesia (the absence of movement) and bradykinesia (slowed movements) can occur. Postural instability with abnormal gait and an increased risk of falls are often experienced.

Depression and possibly dementia are possible nonmotor symptoms of PD.

Other symptoms include micrographia (small writing), drooling, decreased blinking, constipation, and incontinence.

Pathophysiology

PD involves a progressive degeneration of the substantia nigra in the brain with a decrease in dopaminergic cells (more than the typical decrease that accompanies normal aging). The most significant neurotransmitter in PD is dopamine, but other neurotransmitters may play a role (e.g., acetylcholine, glutamate, GABA, serotonin, norepinephrine).

The etiology is unknown, but genetic susceptibility is possible. Environmental toxins combined with aging may also be responsible for the development of PD.

Diagnostic Criteria

Clinical diagnosis is based on the presence of bradykinesia and either rest tremor or rigidity. The stages of the disease are described in

Table 34-3.

Treatment Principles and Goals

The goal for treating PD is to relieve symptoms and maintain or improve quality of life for the patient. Treatment should be initiated when functional impairment and discomfort for the patient or caregiver occurs.

[Table 34-3. The Stages of Parkinson's Disease]

A safe environment and caregiver support programs in addition to medications will often allow patients to remain in the community.

Drug Therapy

Mechanism of action

Medications increase dopamine or dopamine activity by directly stimulating dopamine receptors or by blocking acetylcholine activity, which results in increased dopamine effects (

Table 34-4).

Selection of an initial medication to treat PD may vary with the prescriber. Some choose to begin

[Table 34-4. Drugs for Treating Parkinson's Disease]

therapy with selegiline (Eldepryl), which offers possible neuroprotection; others prescribe carbidopa-levodopa (Sinemet), which has proven benefits. Some experts will initiate therapy with a dopamine agonist in patients younger than 60 years of age.

Levodopa

Levodopa is the most effective drug in the treatment of PD and is converted to dopamine in the body. It is given with carbidopa, a decarboxylase inhibitor that prevents the peripheral conversion of levodopa to dopamine, thereby reducing nausea and vomiting while allowing more drug to pass through the blood-brain barrier.

Generally, doses are increased gradually to minimize the risk of side effects. Doses are given before meals to facilitate absorption. Carbidopa effectively inhibits peripheral conversion of levodopa at doses of 100 mg per day.

Levodopa provides benefits to all stages of PD, but chronic use is associated with adverse effects. Patients may have periods of good mobility alternating with periods of impaired motor function.

Dopamine agonists

Dopamine agonists work directly on dopamine receptors and do not require metabolic conversion. They may be used as monotherapy or as adjunctive therapy, allowing lower doses of carbidopa-levodopa.

Selective monoamine oxidase type B inhibitors

Monamine oxidase (MAO)-B inhibitors may be used as initial therapy in early PD and as adjunct treatment for more advanced disease. They may have neuroprotective properties.

With doses used for PD, adverse effects from consuming tyramine-containing foods would not be expected.

Catechol-O-methyl transferase inhibitors

Catechol-O-methyl transferase (COMT) inhibitors are ineffective when given alone and should always be given with carbidopa-levodopa. They are most often used to treat patients during end-of-dose wearing-off periods and patients experiencing motor fluctuations.

Treatment complications and strategies for improving patient response

• No initial response: If the patient does not initially respond to levodopa (carbidopa-levodopa combination), gradually increase the dose to at least 1,000-1,500 mg of levodopa.

• Suboptimal response: After increasing levodopa, add another drug (e.g., a dopamine agonist, selegiline, or a COMT inhibitor).

• "On and off" phenomenon: This type of response is associated with advancing disease and loss of benefits from a dose of medication. Use more frequent doses or sustained-release levodopa.

• Acute intermittent hypomobility "off" episodes: Such episodes are seen in advanced disease. They can be treated with subcutaneous injections of apomorphine, a direct-acting dopamine agonist.

• End-of-dose or "wearing-off" period: A decreased duration of benefit after a dose is experienced during a wearing-off period. Levodopa wanes after less than 4 hours; therefore, use combination therapy (two or more drugs), give levodopa more frequently, or use sustained-release levodopa (Sinemet CR).

Patient instructions and counseling

• Usually take medications on an empty stomach. Eat shortly afterward to avoid upset stomach.

• Take a missed dose as soon as possible. Skip the missed dose if the next scheduled dose is within 2 hours.

• Dizziness, drowsiness, and stomach upset may occur and make operating equipment dangerous.

• Report any confusion, mood changes, and uncontrolled movements to the prescriber as soon as possible.

• If taking a sustained-release product, do not crush.

Adverse effects and drug-drug interactions

Adverse effects of medications used to treat PD are described in

Table 34-5. See

Table 34-6 for information concerning drug-drug interactions.

Parameters to monitor

• Liver function, complete blood count, basic chemistries (periodically)

• Blood pressure, pulse, ECG (periodically)

• Reduction of rigidity, tremor, slowed movements

• Examination for mental confusion, mood changes, psychotic thinking

Nondrug Therapy for Parkinson's Disease

Educate the patient and caregiver about the benefits and side effects of PD medications. Provide aids for

[Table 34-5. Adverse Effects of Medications Used to Treat Parkinson's Disease]

compliance to enable the patient to participate in medication use as long as he or she is physically capable.

Physical therapy or occupational therapy may be important in maintaining physical activity and improving safety of working and living quarters. As PD progresses, speech therapy may be necessary to maintain communication ability.

Dietary consultation may assist the patient in nutritional concerns related to swallowing difficulties and food selections.

34-7. Glaucoma

Introduction

Glaucoma is a group of eye diseases characterized by an increase in intraocular pressure (IOP), which causes pathologic changes in the optic nerve and typical visual-field defects. Glaucoma affects over 4 million Americans, and as many as 15 million more people may have increased IOP but no clinical signs and symptoms of glaucoma.

The prevalence of glaucoma increases with age and is most often seen in those 65 years of age or older. The number of persons with glaucoma is expected to increase with the aging of the American population. With improved screening programs to identify those with increased IOP, an increase in the number of those diagnosed with glaucoma is expected.

Classification

Open-angle glaucoma is a form of primary glaucoma. The angle of the anterior chamber remains open in an eye, but filtration of aqueous humor is gradually diminished because of the tissues of the angle. Open-angle glaucoma accounts for approximately 80-90% of cases.

Angle-closure (narrow-angle) glaucoma is a form of primary glaucoma in an eye characterized by a shallow anterior chamber and a narrow angle. The filtration of aqueous humor is compromised because of the iris blocking the angle.

[Table 34-6. Drug-Drug Interactions with Medications Used to Treat Parkinson's Disease]

Congenital glaucoma results from defective development of the structures in and around the anterior chamber of the eye and results in impairment of aqueous humor.

Clinical Presentation

Clinical signs and symptoms of open-angle glaucoma develop slowly and may present with only minor symptoms, such as headache and mild eye pain. Optic nerve damage results from chronic elevations in IOP. Hence, early and consistent treatment is important to prevent loss of vision.

Acute angle-closure glaucoma presents with blurred vision, severe ocular pain, and possible nausea and vomiting. It should be considered a medical emergency, and immediate care should be recommended.

Chronic angle-closure glaucoma may have symptoms similar to those of open-angle glaucoma.

Tonometry is used to screen for IOP, but direct ophthalmoscopy (slit-lamp examination) is necessary to accurately evaluate the eye for changes in the optic nerve.

Pathophysiology

The pathogenesis of glaucoma results from changes in aqueous humor (the fluid filling the eye and in front of the lens) outflow that result in increased IOP. This increase in pressure leads to optic nerve atrophy and progressive loss of vision.

Increased IOP can result from decreased elimination or increased production of aqueous humor. Aqueous humor is secreted by the ciliary processes into the posterior chamber of the eye. It then flows through the trabecular meshwork and the canal of Schlemm.

Open-angle glaucoma is the result of decreased elimination of aqueous humor as it passes through the trabecular meshwork, thereby resulting in elevated IOP.

Angle-closure glaucoma is caused by papillary blockage of aqueous humor outflow. This blockage can result when a patient has a narrow anterior chamber in the eye or a dilated pupil where the iris comes into greater contact with the lens. With the blocking of outflow, aqueous humor accumulates in the posterior chamber, presses the lens forward, and further decreases drainage, with possible complete blockage as the outcome.

Diagnostic Criteria

• Elevated IOP as determined by tonometry

• Funduscopic assessment to identify characteristic changes in the optic disc and retina

Treatment Principles

Figure 34-1 illustrates the treatment of open-angle glaucoma. Treatment principles of glaucoma are as follows:

• Reduce IOP to prevent optic nerve damage and visual field loss.

• Use topical medications as first-line treatment.

• Consider acute angle-closure glaucoma as a medical emergency.

Monitoring

Periodic screening for increased IOP should be done, with yearly examinations for those over 65 years of age and as part of a routine eye examination.

Drug Therapy

Mechanism of action

Medications are considered the mainstay of therapy for the treatment of glaucoma (

Table 34-7). β-adrenergic

[Figure 34-1. Algorithm for the Treatment of Open-Angle Glaucoma]

[Table 34-7. Medications for the Treatment of Glaucoma]

blocking drugs (β-blockers) are considered first-line treatment for open-angle glaucoma. β-adrenergic antagonists can be nonselective (i.e., they block both β1 and β2 receptors) or selective (i.e., they block only β1 receptors). Drugs that block only β1 receptors are considered cardioselective and cause less decrease in blood pressure and heart rate.

β-adrenergic antagonists

Nonselective β antagonists include timolol, carteolol, levobunolol, and metipranolol. β1-selective antagonists include betaxolol and levobetaxolol.

Therapy is initiated with a single topical ophthalmic solution, and additional agents are added if decrease in IOP is less than acceptable. The effects of therapy on IOP should be apparent after a week of treatment.

Prostaglandin analogues are also used as first-line treatment (or in combination with β-blockers). Topical carbonic anhydrase inhibitors and α2 agonists may be used in treatment.

Medications such as epinephrine, pilocarpine, and oral carbonic anhydrase inhibitors are prescribed less often, but they are considered to be effective adjunctive drugs.

Patient instructions and counseling

Multiple factors present obstacles that can interfere with good compliance. Patients are often asymptomatic and do not feel treatment is necessary. Because decreased vision is associated with glaucoma, patients may have difficulty with written instructions.

Adequate glaucoma therapy often requires two or more types of eye drops that may have to be given more than once daily. Correct administration of eye drops requires coordination and reasonable cognitive functioning.

Glaucoma is more common in the elderly, who may have more difficulty complying with prescribed medications.

Patient guidelines concerning the use of eye drops to treat glaucoma follow:

• Wash hands before administering eye drops, and avoid touching the dropper tip.

• Confirm that the medication is not outdated and has been stored properly.

• Looking upward, pull the lower lid down and instill the correct number of drops.

• Close the eye to allow the medication to have maximal effect.

• In most cases, wait 5 or more minutes between different medications.

Adverse drug events

Table 34-8 describes the adverse effects that may be seen with glaucoma medications.

Drug-drug interactions

Drug interactions between topical medications and systemic drugs are unlikely.

Acetazolamide interacts with the following:

• Aspirin to cause increased aspirin levels and possible toxicity

• Cyclosporine to cause increased cyclosporine levels

• Lithium to cause either increased or decreased lithium levels

• Phenytoin to cause an increased risk of osteomalacia

Parameters to monitor

Medication use is critical to the successful treatment of glaucoma and should be monitored by the health professional.

[Table 34-8. Classification, Mechanism of Action, and Adverse Effects of Glaucoma Medications]

Other aspects

A combination is available of timolol 0.5% and dorzolamide 2% (Cosopt). This combination effectively lowers IOP and requires only twice-daily doses. This simplified dosing should improve compliance with treatment. This combination (i.e., using two drugs from different categories) represents a sound treatment approach. Poor response to therapy may result in the prescribing of multiple medications, which may negatively affect the patient's ability to successfully use the more complex regimen.

Nondrug Therapy

Laser surgery

Argon laser trabeculoplasty has proven effective as adjunctive therapy that increases the flow of aqueous humor.

Surgery

A surgical procedure involves creating new means of drainage for aqueous humor to leave the anterior chamber.

34-8. Key Points

Alzheimer's Disease

• Alzheimer's disease is a progressive neurologic disease that results in impaired memory, intellectual functioning, and behavior.

• Alzheimer's disease has no cure, but therapies exist to decrease memory impairment as well as improve behavior and patient functioning.

• Other forms of dementia that are potentially reversible should be identified and treated accordingly.

• New drug therapies may slow the progression of Alzheimer's disease and allow patients to remain in the least restrictive environment possible.

• Caregiver support and education are important measures to ensure patient safety and well-being.

Parkinson's Disease

• Parkinson's disease is a chronic, progressive neurologic disease for which no cure exists; medications are available to slow the progression of symptoms.

• The etiology of Parkinson's disease is unknown but may involve genetic susceptibility combined with environmental toxins and age-related changes in the brain.

• Dopamine, the central neurotransmitter, is decreased in Parkinson's disease, and current drug therapy is primarily directed at increasing dopamine levels.

• Drug therapy monitoring in Parkinson's disease requires an understanding of a variety of different medications that may cause significant adverse effects.

• Physical therapy, occupational therapy, dietary considerations, and support counseling for caregivers are necessary components of treating Parkinson's disease.

Glaucoma

• Glaucoma, a group of eye diseases, is characterized by increased intraocular pressure resulting in damage to the optic nerve and possible blindness.

• Open-angle glaucoma is the most common form of this disease; angle-closure glaucoma can be a medical emergency.

• The goal of therapy is to reduce intraocular pressure with the simplest medication regimen possible.

• Drug therapy for glaucoma usually begins with a topical β-adrenergic antagonist; patients often require combination therapy.

• Medication compliance is essential in the control of glaucoma. Education of the patient and caregiver is required to overcome treatment barriers.

34-9. Questions

1.

Of the following pharmacokinetic processes, which is the least altered by aging?

A. Absorption

B. Distribution

C. Metabolism

D. Elimination

E. Excretion

 

2.

Which of the following is given as a once-daily oral dose?

A. Buspirone

B. Donepezil

C. Memantine

D. Rivastigmine

E. Tacrine

 

3.

Galantamine increases levels of which neurotransmitter?

A. Acetylcholine

B. Dopamine

C. Melatonin

D. Norepinephrine

E. Serotonin

 

4.

Weight loss is most often associated with which of the following?

A. Donepezil

B. Galantamine

C. Mirtazapine

D. Rivastigmine

E. Tacrine

 

5.

Which of the following statements concerning donepezil are correct?

I. It inhibits acetylcholinesterase but not butyrylcholinesterase.

II. It should be taken with meals in divided doses.

III. Side effects include tachycardia and blood pressure alterations.

A. I only

B. III only

C. I and II only

D. II and III only

E. I, II, and III

 

6.

Of the following medications used to treat behavioral and emotional symptoms in Alzheimer's patients, which has an FDA black box warning of increased mortality?

A. Buspirone

B. Citalopram

C. Lorazepam

D. Risperidone

E. Zolpidem

 

7.

The maximum daily dose of galantamine in patients with renal impairment is

A. 8 mg/d.

B. 12 mg/d.

C. 16 mg/d.

D. 24 mg/d.

E. 32 mg/d.

 

8.

All of the following could worsen cognition in Alzheimer's disease patients except

A. dicyclomine.

B. dimenhydrinate.

C. meclizine.

D. trazodone.

E. trihexyphenidyl.

 

9.

Memantine's reported benefit in treating the symptoms of Alzheimer's disease is thought to be the result of

A. increasing serotonin receptor activity.

B. blocking the effect of glutamate on receptors.

C. direct blocking of acetylcholine receptors.

D. decreasing intracellular dopamine activity.

E. decreasing amyloid deposits in the brain.

 

10.

Which works by direct stimulation of dopamine receptors?

A. Amantadine

B. Benztropine

C. Entacapone

D. Ropinirole

E. Selegiline

 

11.

Which of the following has a risk of causing a significant drug interaction if taken with ondansetron?

A. Amantadine

B. Apomorphine

C. Carbidopa-levodopa

D. Pramipexole

E. Entacapone

 

12.

What would be the most likely outcome if a Parkinson's patient on levodopa were also prescribed haloperidol?

A. Excessive nausea and vomiting

B. Hypertensive crisis

C. Tachycardia and possible chest pain

D. Worsening symptoms of Parkinson's disease

E. Excessive somnolence

 

13.

Which inhibits monoamine oxidase (MAO)?

A. Benztropine

B. Bromocriptine

C. Pramipexole

D. Rasagiline

E. Tolcapone

 

14.

How does carbidopa affect levodopa?

A. It slows the release from presynaptic neurons.

B. It prevents the excretion of dopamine.

C. It increases stimulation of dopamine receptors.

D. It decreases tolerance to normal doses.

E. It inhibits the peripheral conversion to dopamine.

 

15.

A patient with Parkinson's disease currently taking selegiline has been prescribed mirtazapine (Remeron). What would be the most likely outcome of this combination?

A. Inhibition of benefits with worsening parkinsonism

B. No significant drug interaction

C. Risk of serotonin syndrome

D. Increased benefits with improved parkinsonism

E. Hypertensive episode

 

16.

Which of the following statements are true concerning the treatment of Parkinson's disease?

I. Entacapone is not used as monotherapy except for patients with end-of-dose wearing-off periods and for those experiencing motor fluctuations.

II. Pramipexole has been reported to cause "sleep attacks."

III. Food-drug interactions would not be expected with selegiline when given at doses of 10 mg daily.

A. I only

B. III only

C. I and II only

D. II and III only

E. I, II, and III

 

17.

Timolol ophthalmic drops would be more likely to cause which adverse effect as compared to levobetaxolol ophthalmic drops?

A. Agitation and restlessness

B. Nausea and vomiting

C. Confusion

D. Change in heart rate and blood pressure

E. Altered intraocular pressure

 

18.

Which of the following would not be considered for monotherapy of glaucoma?

A. Latanoprost

B. Dorzolamide

C. Carteolol

D. Methazolamide

E. Brimonidine

 

19.

Which of the following can cause iris pigmentation changes?

A. Acetazolamide

B. Betaxolol

C. Brimonidine

D. Latanoprost

E. Pilocarpine

 

20.

Which of the following is available as a fixed combination product?

A. Dorzolamide and timolol

B. Betaxolol and bimatoprost

C. Bimatoprost and levobunolol

D. Latanoprost and timolol

E. Methazolamide and latanoprost

 

21.

All of the following are available as an ophthalmic solution except

A. brimonidine.

B. dipivefrin.

C. dorzolamide.

D. methazolamide.

E. metipranolol.

 

22.

Which should not be used if a patient has a sulfa allergy?

A. Betaxolol

B. Bimatoprost

C. Brimonidine

D. Brinzolamide

E. Unoprostone

 

23.

Which of the following is true about α2-adrenergic agonists?

A. They cause an increase in aqueous humor synthesis.

B. They cause a decrease in aqueous humor formation.

C. They cause an increase in uveoscleral outflow.

D. They cause an increase in aqueous humor outflow.

E. They cause a decrease in uveoscleral outflow.

 

24.

Which of the following statements concerning glaucoma therapy is correct?

I. Carteolol is available as an ophthalmic solution and as a gel-forming solution.

II. Latanoprost and metipranolol ophthalmic solutions should be stored in the refrigerator.

III. Prostaglandin analogues, β-adrenergic antagonists, and α-adrenergic agonists can be used as monotherapy.

A. I only

B. III only

C. I and II only

D. II and III only

E. I, II, and III

 

34-10. Answers

1.

A. Of all the age-related changes of the pharmacokinetic process, absorption is the least altered, perhaps because most drugs are passively absorbed.

 

2.

B. All of these drugs except donepezil require at least twice-daily dosing. Donepezil has a long half-life, which allows once-daily doses. None of these agents is available in sustained-release forms, although rivastigmine has a once-daily patch. Buspirone is an antianxiety drug that is dosed twice or three times daily.

 

3.

A. Galantamine is a cholinesterase inhibitor, and all cholinesterase inhibitors increase levels of acetylcholine, the neurotransmitter that appears to be involved with memory function.

 

4.

D. Weight loss, probably because of nausea and vomiting, is a warning for rivastigmine. In controlled trials, approximately 26% of women on doses of 9 mg/d or greater had weight loss of equal to or greater than 7% of their baseline weight.

 

5.

A. Donepezil is selective for acetylcholinesterase and does not inhibit butyrylcholinesterase. Donepezil does not have to be taken with meals and is given once daily. Donepezil does not increase heart rate, and this class of medications that increase acetylcholine should be used with caution in patients with bradycardia.

 

6.

D. Risperidone, as well as other atypical antipsychotics, increases mortality risk when given to dementia patients with agitation or aggressive behaviors. This is probably a class effect, and any antipsychotic should be used only if no alternative medication is effective.

 

7.

C. With renal or hepatic dysfunction, galantamine doses should not exceed 16 mg/d. With severe renal or hepatic dysfunction, galantamine should not be used.

 

8.

D. All of the drugs listed—with the exception of trazodone—have anticholinergic activity. Decreasing the activity of acetylcholine could worsen dementia and block benefits of cholinesterase inhibitors. Trazodone is an antidepressant with sedating properties but little anticholinergic activity. It may be given at bedtime to help with sleep. Trazodone does have a side effect of orthostatic hypotension.

 

9.

B. Glutamate is the main excitatory neurotransmitter in the central nervous system, and one theory states that blocking the effects of glutamate on NMDA receptors will decrease symptoms of Alzheimer's disease.

 

10.

D. Ropinirole directly stimulates dopamine receptors; the other drugs increase dopamine activity by different mechanisms.

 

11.

B. Apomorphine can cause severe hypotension and loss of consciousness when taken with ondansetron and other serotonin-receptor antagonists.

 

12.

D. Haloperidol and other antipsychotics block dopamine activity and can worsen PD. They can also block the benefits of PD medications, which increase dopamine activity.

 

13.

D. Rasagiline is an MAO inhibitor that is selective for MAO-B, which decreases the potential for drug-drug and drug-food interactions. At higher doses, this selectivity lessens.

 

14.

E. Carbidopa inhibits the peripheral conversion of levodopa to dopamine, thus allowing more levodopa to cross the blood-brain barrier, and decreases adverse effects from dopamine.

 

15.

C. The combination of two drugs that increase serotonin levels can result in serotonin syndrome, which can cause confusion, agitation, tremor, seizures and coma.

 

16.

D. Entacapone should always be given with carbidopa-levodopa because benefits depend on carbidopa inhibiting the peripheral conversion of levodopa.

 

17.

D. Timolol is a nonselective β-adrenergic antagonist that causes a reduction in heart rate and blood pressure. There is enough absorption from eye drops to produce these cardiac effects.

 

18.

D. All of the other choices could be considered as monotherapy for glaucoma. Methazolamide is an oral carbonic anhydrase inhibitor and is used in conjunction with ophthalmic drops.

 

19.

D. Latanoprost, a prostaglandin analogue, is known to change iris pigmentation and to darken eyelashes.

 

20.

A. Dorzolamide plus timolol (Cosopt) is the only combination ophthalmic solution for treating glaucoma. An advantage for using a combination product would be increased compliance.

 

21.

D. Methazolamide and acetazolamide are both available only as oral tablets or capsules. Topical carbonic anhydrase inhibitors are brinzolamide and dorzolamide.

 

22.

D. Patients with sulfa allergy should not be given a carbonic anhydrase inhibitor.

 

23.

B. Brimonidine and other α2-adrenergic agonists cause a decrease in aqueous humor formation.

 

24.

B. All of these drugs can be used as monotherapy in glaucoma. Timolol and pilocarpine are available as gel forms. Latanoprost (but not metipranolol) should be stored in a refrigerator before dispensing.

 

34-11. References

Chen JJ, Shimomua SK. Parkinsonism. In: Herfindal ET, Gourley DR, eds. Textbook of Therapeutics. 8th ed. Philadelphia: WB Saunders; 2006:839-54.

Grutzendler J, Morris JC. Cholinesterase inhibitors for Alzheimer's disease. Drugs. 2001;61:41-52.

Khaw P, Shah P, Elkington A. Glaucoma-1 treatment. BMJ. 2004;328(7432):156-8.

Olanow CW, Watts RL, Koller WC. An algorithm for the management of Parkinson's disease. Neurology. 2001;56:872-91.

Rawls WN. Alzheimer's disease. In: Herfindal ET, Gourley DR, eds. Textbook of Therapeutics. 8th ed. Philadelphia: WB Saunders; 2006:1811-28.

Scarpini E, Scheltens P, Felman H. Treatment of Alzheimer's disease: Current status and new perspectives. Lancet Neurol. 2003;2:539-47.

Steinman MA, Landefeld C, Rosenthal GE, et al. Polypharmacy and prescribing quality in older people. J Am Geriatr Soc. 2006;54:1516.