Parkinson disease

Parkinson disease is a degenerative disorder involving a progressive loss of dopaminergic neurons in the substantia nigra. This deficit in dopaminergic function results in resting tremor and difficulty in the control of voluntary movement. Cardiovascular function, bowel motility, and cognitive function are often compromised. Although not directly associated with the motor system pathology, the functional deficits are emotionally devastating to the patient, resulting in depression and other mood disorders. The predominant pharmacological approach in the management of Parkinson disease is the enhancement of dopaminergic function in the affected brain regions. Among the earliest successful approaches was the use of levodopa (l-dopa), a precursor of dopamine in the central nervous system (CNS). The use of this agent (and all agents to date) only enhances the dopaminergic function in remaining neurons. This approach has no effect on the progressive loss of neurons. In addition to central conversion of l-dopa to dopamine in the substantia nigra, a similar conversion occurs in the limbic system, a brain center associated with the regulation of behavior. Excessive dopaminergic influence in the limbic system has been associated with aberrant behaviors, including paranoia, delusions, hallucinations, and related psychiatric disturbances that may influence sleep and mood. These behavioral changes are obviously antagonistic to any therapeutic plan. In addition to l-dopa, a dopamine precursor, agents that inhibit the breakdown of dopamine, enhance the release of dopamine, or have dopaminergic agonist activity will have similar behavioral effects (Box 36-1). Dopaminergic agents may produce postural hypotension and syncope by virtue of their ability to produce vasodilation on the basis of CNS and peripheral actions.^3,4 If clients are unable to take their medication, an increasing danger exists (with extended therapy) that movement may be impossible and the normal chest wall expansion and contraction may be compromised (see Chapter 30).

Because Parkinson disease is progressive in nature, clients may have different presentations depending on the stage of the disease and the presence of pharmacological interventions. In the early months of the disease, the motor signs may be particularly subtle, and patients may report only slowness, stiffness, and trouble with handwriting. Particular attention to the history of tremor, slowness of fine motor control, a hunched and slightly flexed posture, and micrographia may lead the physician to diagnose Parkinson disease in its early phases.⁵ As Parkinson disease advances, patients have increasing difficulty in activities of daily living and gait as well as bradykinesia and distal tremor.

Once a definitive diagnosis has been made, controlling symptoms of the disease and the side effects of medications is balanced with the level of functional involvement. The physician and client may discuss the option of a number of medications (see Box 36-1) but must determine the best approach on the basis of the clinical presentation. One limitation is the side effect of involuntary movements (dyskinesias). These dyskinesias can be difficult to control and are different from the involuntary movements caused by the disease itself. As mentioned earlier, dopamine agonist regimens that do not cause dyskinesias can also be prescribed, but their effect on symptoms is not as potent.⁶ Often physicians may begin treatment with a dopamine agonist and continue with the agonist as long as symptoms are satisfactorily controlled. Later the physician can initiate treatment with l-dopa when the disease is in the advanced stages. With the elderly client who has cognitive deficits, combination therapy may be the initial choice. Once a medication regimen has been initiated, the client and therapist may notice improvement in Parkinson disease symptoms and therefore functional abilities. After taking a medication over time, clients may find that the effect of the medication begins to wear off before the next dose is scheduled. At this point consultation with the rehabilitation team is recommended to potentially change the medication timing or release ability or combine the treatment with other antiparkinsonian medications.

Great emphasis is placed on treating the motor features of Parkinson disease, but clients may have nonmotor manifestations, including depression, anxiety, cognitive impairment, and dementia. Often the client does not mention these difficulties because he or she does not link them to Parkinson disease. Clients may demonstrate some of these difficulties, and the therapist should recognize the symptoms and refer the client for further follow-up.

The major problems that patients have after 5 years of treatment for Parkinson disease are fluctuations (both motor and nonmotor), dyskinesias, and behavioral or cognitive changes.⁷ The mechanisms behind these complications relate both to the underlying Parkinson disease and to the effects of medications. Motor fluctuations take several forms. Most commonly, a predictable decline in motor performance occurs near the end of each medication dose (“wearing off”). Patients change gradually from “on” with a good medication response into an “off” period 30 minutes to 1 hour before the next medication dose is due. Often patients have involuntary movements (dyskinesias) as a peak-dose complication, and sometimes similar movements occur at the end of the dose. Sudden and severe cataclysms of motor fluctuation occur rarely, with ambulatory patients becoming immobilized over a period of seconds (“sudden on-off”).⁸ Because these fluctuations occur throughout the day, accurate detection requires the cooperation of the patient, who must be trained to complete diaries of function.⁹ These journals generally divide the 24-hour day into 30-minute segments to detect good medication response (“on”), poor medication response (“off”), disabling dyskinesias, and sleep.

In general, therapists working with clients taking antiparkinsonian medication must be aware of both the positive and the negative side effects of medications to meet functional goals and outcomes effectively. Learning the difference between tremor and dyskinesia is crucial. The therapist must coordinate therapy sessions during good medication response times to assist optimal outcomes. In addition, clients should be monitored for postural hypotension, dizziness, and cognitive changes. Therapists have the unique opportunity to determine the best timing, frequency, and duration of the treatment, and understanding the impact of a client’s drug regimen will only enhance the outcome. Therapists must also be aware that exercise increases metabolism. Increased metabolism may use up the medication faster; thus an individual who generally remains symptom free (no off times between doses) will again exhibit signs of the disease (distal tremors and axial or proximal rigidity). These increases in symptoms may be a drug dosage problem, not signs of further degeneration of the basal ganglia. All changes in symptoms should be discussed with both the pharmacist and the physician.

Cancer

Cancer is a general term for classifying disorders associated with abnormal and uncontrolled cell growth. Virtually any organ system in the body can be affected, either as the primary site of the disorder or as a secondary site associated with metastasis. Cancer may interfere with neurological rehabilitation in various ways. Tumors within the brain may interfere with cognitive and motor function as well as autonomic and metabolic control (see Chapter 25). Peripherally, tumors may interfere with peripheral nerve function and associated motor control or may produce pain. In addition, drugs that reduce cancer pain may interfere with cognitive and motor function.¹⁰ Among these, morphine and related opiate derivatives are notable (Box 36-2). A significant degree of tolerance to the CNS depressant effects of these agents will develop with long-term administration. In cancer chemotherapeutic regimens, many antiemetic agents are used. These include dopaminergic antagonists (which may produce motor deficits similar to Parkinson disease), dronabinol (a chemical component of marijuana, which can affect cognitive function), as well as high-dose corticosteroids (which affect mood). Some antitumor agents may be neurotoxic; a reduction in deep tendon reflex, paresthesias, and demyelination is associated with vincristine (Oncovin).¹¹ Naturally, any change in drugs that involves a cancer treatment regimen (directly or indirectly) requires the approval of the client’s oncologist.

The main role of rehabilitation specialists is to help patients with cancer recover from the physical changes that accompany their illness, promote function in activities of daily living, and help provide adaptations to activities within the limits of each patient’s function and the illness. Clinicians should be aware of chemotherapy side effects and the side effects of medications given to treat the toxic effects of chemotherapy.

A number of chemotherapeutic and nonchemotherapeutic medications are used to fight cancer. Most therapies against cancer operate on the simple principle that because cells in tumors are actively dividing, agents that kill dividing cells will kill tumor cells.¹² Tissues that rapidly divide in the body are therefore at risk, including hair, mucosal lining, bone marrow, immune cells, and skin epithelial cells. Nonchemotherapy medications called biological response modifiers (BRMs) are naturally made by the body but delivered in large quantities and at higher doses than what the body is capable of producing.¹³ Interferon and interleukin are two of the most commonly used medications. Monoclonal antibodies are also used as chemotherapy to suppress the immune system.

Chemotherapy often has side effects that affect the integumentary, GI, hematological, and neurological systems. Each type of therapy has potential side effects as well as more general side effects of the treatment regimen. As a result of chemotherapeutic treatment of cancer, patients often have muscular weakness, fatigue, pain, immobility, and reduced flexibility. Often the therapist will have to be supportive and flexible with treatment plans to accommodate for changing physiological, psychological, and social factors during treatment.

GI symptoms such as nausea and vomiting may occur, and medications such as Compazine and Reglan may be given to help control these episodes. Symptoms of diarrhea may be addressed through prescriptions or the use of over-the-counter (OTC) medications including milk of magnesia and magnesium citrate. The development of mucositis or esophagitis is also possible. A prescription solution of three medications (Benadryl, nystatin, viscous lidocaine) can help relieve the pain, inflammation, and potential associated fungal infections. Bone marrow suppression from chemotherapeutic regimens may lead to increased risk of infections, increased risk of bleeding, and increased fatigue and lack of exercise capacity resulting in musculoskeletal weakness. Patients undergoing chemotherapy may receive one or more medications to signal the bone marrow to increase output of white blood cells (Neupogen), stimulate the production of red blood cells (Epogen), and stimulate increased production of platelets (Neumega). These therapies may be instituted to help the patient more quickly reverse suppression of bone marrow and allow the chemotherapy to continue without interruption.¹⁴ Generalized symptoms include fever, body aches and pains, and feelings of ill health and fatigue. No specific medications are used to improve these symptoms. In general, taking medications such as acetaminophen, ibuprofen, or narcotics for fever and pain may help. The use of exercise as an adjunct therapy for cancer treatment–related symptoms has gained favor in oncology rehabilitation as a promising intervention.^15,16 Exercise is thought to help improve endurance and functional abilities.¹⁵ The major side effects associated with BRMs and monoclonal antibodies are generalized as well and include fever and flulike symptoms with associated arthralgia and myalgia. Other side effects include lymphedema characterized by fluid retention caused by disruption of lymphatic drainage or removal of lymph nodes. As mentioned earlier, neurological changes may occur, with the development of neurological signs as well as forgetfulness, suicidal ideation, and depression. The rehabilitation professional is an important team member in oncology because he or she potentially affects quality of life.

Seizure disorders (epilepsy)

Epilepsy is associated with a diverse group of neurological disorders resulting in motor, psychic, and autonomic manifestations. Many antiseizure medications may produce drowsiness, ataxia, and vertigo (Box 36-3). Some may produce cognitive disorders in children and adults.^17,18 Although these adverse effects may be exhibited throughout therapy, they are most troublesome during initiation of drug therapy, addition of a drug, and dosage escalation. Sudden discontinuation of antiseizure medications may result in status epilepticus, which may be fatal. Many antiseizure medications are finding successful applications outside epilepsy, especially in the area of pain management.

The practicing clinician working with clients who have a history of seizure disorders must be prepared for the onset of a seizure and be aware of any adverse side effects of medications. Adverse side effects are typically determined on a clinical basis, signifying the importance of recognition by the health care provider. Many of the common side effects can also have negative implications for motor learning, especially while the client is getting used to the medication or the dosage is being elevated or tapered.

The treatment of seizure disorders with pharmacotherapy is typically intended to control the seizure activity completely without producing unwanted side effects. Pharmacological intervention usually begins with one medication (monotherapy); if this drug is unsuccessful a second is added while dosage of the first is tapered. Or a combination may be needed. The effects of the medications vary and may include enhancing the inhibitory effects of γ-aminobutyric acid (GABA) (benzodiazepines); reducing posttetanic potentiation, thereby reducing seizure spread (iminostilbenes); or modulating neuronal voltage-dependent sodium and calcium channels (hydantoin).¹⁹ The overall result is a reduction in abnormal electrical impulses in the brain. The choice of antiseizure drugs primarily depends on the seizure type and, if possible, the diagnosis of a specific syndrome. If seizures are recurrent and occur during critical periods of childhood, adolescence, and early adulthood, they may result in significant impairments in function and increased disability.

Some side effects may be slow to develop and difficult to diagnose because seizures can often be mistaken for sedation or cognitive dysfunction, especially in children, who may not report drug side effects. Practitioners can also mistakenly accept reversible drug toxicity as a necessary consequence of a seizure disorder. The number of seizures occurring during physical or occupational therapy should be tracked to assist in determining appropriate pharmacotherapy.

One common antiseizure medication, valproic acid (Depakene), may cause nausea, vomiting, hair loss, tremor, tiredness, dizziness, and headache. Valproic acid has also been reported to aggravate absence seizure in clients with absence epilepsy.²⁰ Metabolic side effects may include an increase in glucose-stimulated pancreatic insulin secretion, which may be followed by an increase in body weight.²¹ Long-term valproic acid use is known to increase bone resorption in adult epileptic patients and lead to a decreased bone mineral density.²²

Another seizure medication, carbamazepine (Tegretol), is considered a safe drug but has a long list of adverse events, most commonly ataxia and nystagmus.²³ Other systems frequently involved are the skin, the hematopoietic system, and the cardiovascular system. Gabapentin (Neurontin) is another well-tolerated antiseizure medication with proven clinical efficacy and a low incidence of adverse events in clinical trials. Common side effects include dizziness, fatigue, and headache. Phenytoin (Dilantin) has adverse reactions including ataxia, nystagmus, slurred speech, confusion, dizziness, and, at high doses, peripheral neuropathy.

Benzodiazepines (e.g., diazepam) are useful in managing status epilepticus, but their effects are not long lasting so they are often used along with a primary anticonvulsant. The most frequent side effects are dose-related sedation, difficulty with concentration, dizziness, and difficulty walking.

Pharmacological adverse events that occur under the influence of seizure medications must be recognized by the rehabilitation specialist to participate in a team approach to patient care. Therapists can assist in determination of effectiveness of a specific treatment regimen, appropriate timing of rehabilitation interventions, and the overall progress of the client during rehabilitation.

Stroke, hypertension, and related disorders

Stroke, by virtue of the interference with blood flow and oxygenation, produces both reversible and irreversible neurological deficits (see Chapter 23). The loss of function associated with stroke has at least two major causes. The first involves loss of oxygenation to a critical brain region, followed by glutaminergic rebound and excessive calcium influx with apoptosis (programmed cell death). Current drugs and those under development are aimed at restoring blood flow and inhibiting glutaminergic hyperexcitability and intracellular apoptotic mechanisms.²⁴ The second pathogenic issue is related to reperfusion injury associated with oxygen radicals and associated cellular damage. In this case, free radical scavengers have shown some promise in animal models of stroke.²⁵ To reduce the damage associated with thromboembolism in such cases, tissue plasminogen activator has been recommended. However, this agent is most effective when given within an hour after the vascular insult. Drugs with other mechanisms used to improve the prognosis of stroke are under development. However, drugs used for concurrent conditions (atherosclerosis and hypertension) before and after a stroke are complicating factors for optimal outcomes from rehabilitation. These drugs include β-adrenergic antagonists, which reduce heart rate and correspondingly reduce exercise tolerance. Occasionally, calcium channel blockers, α-adrenergic blockers, and related agents may cause similar effects, including weakness, dizziness, syncope, and cognitive disorders. Changes in serum electrolytes induced by diuretics and the angiotensin-converting enzyme inhibitors may affect the heart, the vasculature, and skeletal muscle and ultimately cause impairments in areas such as strength of contraction.²⁶ Box 36-4 lists many of these drugs. Many of the cholesterol synthesis inhibitors (agents used to reduce serum cholesterol) may induce muscle weakness (Box 36-5).^27,28 Abrupt discontinuation of antihypertensive medications may result in a hypertensive crisis, dramatically increasing the risk of stroke and related disorders.

Clinicians caring for patients with stroke, hypertension, and cardiac disorders will benefit from understanding the impact of any medication on the therapeutic plan. These clients may be taking any number of medications to manage the acute and subacute complications of cardiovascular impairments and their resulting sequelae. Other complications after stroke that may require pharmacological intervention include urinary tract infections, musculoskeletal pain, deep vein thrombosis, pressure sores, shoulder subluxation, and depression. All these medications have their own issues, and health care providers must be aware of adverse events and any alteration in function of the heart that may occur in relation to exercise.

Anticoagulants such as heparin, warfarin, and aspirin (so-called blood thinners) are used to prevent another stroke after the first one has occurred. Side effects may include bleeding, allergic reactions, thrombocytopenia, and, in the case of aspirin, stomach irritation.²⁹ Blood thinners make the client more susceptible to bruising; therefore care must be taken in client handling and choice of activity. Antiarrhythmics are used to restore normal conduction patterns of the heart. Antiarrhythmic drugs may make some clients experience lightheadedness, dizziness, or faintness when they get up after sitting or lying down (orthostatic hypotension).³⁰ Antiarrhythmic drugs may also cause low blood sugar or changes in thermoregulation.³¹ The most common side effects are dry mouth and throat, diarrhea, and loss of appetite.³² These problems usually go away as the body adjusts to the drug and do not require medical treatment. Therapists must be prepared for hypotensive events and the need to educate clients on positions that will reduce the effects of orthostatic hypotension.

Hypertension is a common disorder that is frequently encountered when treating patients in the rehabilitation environment. Antihypertensive medications are used to lower blood pressure (see Box 36-4) by limiting plasma volume expansion, decreasing peripheral resistance, and decreasing plasma volume. Often clients under medical management will undergo changes in dose and additions or deletions of medication, which may lead to problems during rehabilitation. Side effects of these medications may include increased frequency of urination, increased urinary excretion of potassium, orthostatic hypotension, hypotension, dehydration, tiredness, fatigue, cold hands and feet, and dizziness.³³ When working with a client taking antihypertensive medications, health care providers should monitor for side effects, clinical signs, and the client’s perceived exertion. Generally, people on antihypertensive medications require careful cardiovascular monitoring during any physical activity.

Many clients may become depressed after a neurological disorder such as stroke or a cardiac event.³⁴ It may be attributable to a natural loss of physical function or a neurochemical response to changes in brain chemistry. Clients with signs and symptoms of depression (sadness, anxiousness, hopelessness, suicidal ideation) should be referred for further follow-up by the physician. Many antidepressant medications take at least 2 weeks to achieve a therapeutic level. Antidepressants may cause temporary side effects (sometimes referred to as adverse effects) in some people. These side effects are generally mild. Any unusual reactions, side effects, or behaviors that interfere with functioning should be reported to the doctor immediately. The most common side effects of tricyclic antidepressants (TCAs) are dry mouth, constipation, bladder problems, sexual problems, blurred vision, dizziness, and drowsiness.³⁵ The newer antidepressants have different types of side effects, including headache, nausea, nervousness, insomnia, agitation, and sexual problems.³⁶ Therapists working with clients who are depressed may need to delay rehabilitation until the depression is well managed.

Hyperlipidemia is considered a modifiable risk factor for heart disease and stroke. Many clients may be receiving pharmacological treatment to reduce their cardiovascular risk. Several types of drugs are available for cholesterol lowering, including statins, bile acid sequestrants, nicotinic acid, and fibric acids.³⁷ The statins are considered first-line drugs and are generally well tolerated but can produce myopathy under some circumstances.³⁷ An elevation of creatine kinase level is the best indicator of statin-induced myopathy and should be checked for when clients report leg pain. Bile acid sequestrants also produce moderate reductions in cholesterol. Sequestrant therapy can produce a variety of GI symptoms, including constipation, abdominal pain, bloating, fullness, nausea, and flatulence. Nicotinic acid (niacin) therapy can be accompanied by a number of side effects. Flushing of the skin is common with the crystalline form and is intolerable for some persons. However, most persons have tolerance to the flushing after more prolonged use of the drug. The fibrates have the ability to lower serum triglycerides and are generally well tolerated in most persons. GI symptoms are the most common reports, and fibrates appear to increase the likelihood of cholesterol gallstones.³⁷

Overall, clients taking cardiovascular medications need careful monitoring for any drug impact on cardiorespiratory or metabolic responses in relation to rehabilitation activities. Thus the effects of drugs must be considered in developing the rehabilitation plan (see Chapter 30).

Anxiety and depression

Agents used in the management of anxiety, whether from acute or chronic disease, must be carefully titrated. Among these agents are the benzodiazepines, whose anxiolytic (anxiety-reducing) dosage range immediately precedes a dose that may affect motor skills and cognitive function (Box 36-6). In subjects of all ages, but especially the geriatric population, administration of benzodiazepines may produce paradoxical excitement, confusion, and behavioral changes.³⁸ Geriatric subjects also have an increased incidence of injury from falls concurrent with use of benzodiazepines and other sedative-hypnotic drugs. Although benzodiazepines may have variable effects on learning and declarative memory, these effects may differ among the benzodiazepines, displaying considerable variation among individuals. If producing sleep alone is desired, zolpidem (Ambien) and zaleplon (Sonata) are attractive alternatives because these agents do not have anxiolytic effects. Although the anxiolytic agent buspirone (Buspar) is relatively free of benzodiazepine-like effects, the onset time for the desired anxiolytic effect is characteristically delayed.³⁹ Lack of compliance with anxiolytic agents may increase panic attacks and reduce effective interactions with a therapist.

The emergence of the selective serotonin reuptake inhibitors (SSRIs) has revolutionized the treatment of depression. The older agents, such as the TCAs, are just as effective in the management of several forms of depression; however, their adverse effect profile is somewhat different. TCAs often produce drowsiness and orthostatic hypotension, effects that complicate any rehabilitation regimen.⁴⁰ Although these effects may be produced by SSRIs, their incidence is much reduced. Certain TCAs, by virtue of their ability to inhibit the reuptake of norepinephrine in adrenergic nerve terminals, may be used at lower doses for neuralgia. Although these low-dose regimens are usually not associated with the side effects previously mentioned, some patients may be more sensitive to these effects than others. This requires increased vigilance for the care team in determining iatrogenic versus pathological sources of somnolence and syncope. A partial list of antidepressants is presented in Box 36-7. Noncompliance with antidepressant therapy may result in lack of interest in any therapeutic regimen.

Patients with stroke and other neurological diagnoses often have depression, which reduces motivation and decreases compliance with a therapeutic regimen. Although obviously linked, the degree of functional restoration after a stroke does not always correlate with resolution of depression.

Many patients with neurological disorders are diagnosed with or experience anxiety and depression. The cause of affective symptomatology can be the result of cognitive and emotional deficits or impairment of brain function from the existing pathology.³⁴ In the rehabilitation environment many patients may show signs and symptoms of anxiety or depression that can make the process of recovery more difficult. The rehabilitation professional must recognize the manifestations of both anxiety and depression such as fear of dying or “going crazy,” heart palpitations, shortness of breath, difficulty concentrating, depressed mood, diminished interest or pleasure in activities, sleep disturbance, changes in appetite, psychomotor retardation and agitation, and suicidal ideation.⁴¹ Anxiety and depression may limit the client’s full participation in recovery of function and are associated with poorer outcomes.^36,42

Anxiety and depression can be managed well when treated with the medications discussed previously, but some drugs—including centrally acting hypotensives (methyldopa), lipid-soluble β-blockers (propranolol), benzodiazepines, and other CNS depressants—may cause a depressed mood.¹ Therefore review of the medication regimen in someone with depression is useful in case one of the medications may be implicated.

Pharmacological treatments for anxiety and depression should be administered at a dosage and time that ensure the best patient response during rehabilitation treatments. Antianxiety medications (see Box 36-6) act within a short time after ingestion, producing their effects of sedation and relaxation and thereby reducing anxiety. Higher levels may cause drowsiness, sleep, and anesthesia and are associated with falls, which may not be ideal when trying to promote recovery of function. Antidepressant medications (see Box 36-7) typically take weeks for therapeutic levels to be achieved in the brain and an improvement in mood to be demonstrated. Rehabilitation may be appropriate for a client taking these medications when they have improved the client’s mood and outlook. Side effects of antidepressants can also cause some difficulties, including lightheadedness, drowsiness, short-term memory loss, disturbed sleep, clumsiness, sedation, and low blood pressure.

Some evidence has shown that recovery from brain injury may be positively influenced by antidepressants^43,44 and that antidepressants can play a role in brain plasticity.⁴⁵ These studies suggest that recovery of function after brain injury can be influenced by experience and pharmacological intervention. Rehabilitation specialists need to be prepared to assess responses to pharmacotherapy, recognize adverse effects, manage minor side effects, and seek appropriate assistance for adverse events.

Arthritis and autoimmune disorders

In rheumatoid arthritis (RA), autoimmune mechanisms play an important role in the inflammatory process and progressive joint destruction. Because of the constant pain associated with movement, clients will seek nonprescription drugs (including dietary supplements) that often escape prescription drug monitoring programs in pharmacies. It is important for all health professionals to recognize this issue, particularly with RA. In the management of RA, the therapeutic approach may influence the progress of rehabilitation. Aggressive treatment with glucocorticoids may reduce joint pain and facilitate movement, but it may produce changes in mood and muscle wasting.⁴⁶ Although this is reversible and limited to systemic administration of high-dose corticosteroids, its impact cannot be overlooked and certainly affects physical or occupational therapy prognosis. Prednisone and related glucocorticoids may often produce a false sense of well-being that may exceed the ability of the patients to engage safely in certain exercise regimens. From the patient’s perspective, this pharmacological effect is perceived as a “cure” and does not provide the motivation to continue with exercise therapy. The same problems may exist with the use of corticosteroids in other autoimmune disorders.⁴⁷

Nonsteroidal antiinflammatory agents (NSAIDs) (Box 36-8) have long been used for the relief of pain with arthritis; however, depletion of prostaglandins in the gastric mucosa produces bleeding, which has limited their usefulness.⁴⁸ The development of newer agents that are more selective for isoforms of cyclooxygenase (COX-2 inhibitors) that are involved in joint inflammation is a major advance. An example is celecoxib. Although bleeding disorders are dramatically reduced, the incidence of ataxia with these agents may be increased.⁴⁹ Unfortunately, cardiovascular toxicity risk has led to the withdrawal of most of the COX-2 inhibitors from the market. Clients with neurological diseases or pathological processes with problems requiring antiinflammatory medications may develop side effects that interact with and complicate existing motor deficits. Failure to comply with the arthritis medication regimen will likewise reduce effective movement.

Clinically, clients with the onset of RA may have a number of systemic manifestations, including fatigue, anorexia, generalized weakness, and musculoskeletal symptoms followed by synovitis. These forewarning symptoms may continue over weeks or months before more specific symptoms occur. The initial evaluation of the patient with RA should document symptoms of active disease (e.g., presence of joint pain, duration of morning stiffness, degree of fatigue), functional status, objective evidence of disease activity (e.g., synovitis, as assessed by tender and swollen joint counts, and the erythrocyte sedimentation rate), mechanical joint problems (e.g., loss of motion, crepitus, instability, malalignment, or deformity), the presence of extraarticular disease, and damage detected radiographically.⁵⁰ Neurological complications of RA may occur in the CNS (cerebral vasculitis), the peripheral nervous system (nerve compression), the neuromuscular junction (myasthenic syndrome), and muscle (myopathy).⁵¹ Depending on the stage of involvement, the client may be undergoing nonpharmacological modalities (education, weight loss, range-of-motion exercises) and pharmacological therapy including analgesics, NSAIDs, steroids, disease-modifying antirheumatic drugs (DMARDs), and BRMs.

The goals of pharmacological treatment of RA are to prevent or control joint damage, prevent loss of function, decrease pain, and improve joint function.⁵⁰ NSAIDs assist in analgesia and decrease inflammation, thus allowing the therapist to work on range of motion and strengthening, but they do not alter the disease process. Because NSAIDs regulate the production of chemicals (prostaglandins) in the body that help trigger inflammation by inhibition of an enzyme (COX), they sometimes lead to unwanted side effects previously discussed. Data suggest that although selective COX-2 inhibitors have a significantly lower risk of serious adverse GI effects than do nonselective NSAIDs, they are no more effective than nonselective NSAIDs, are related to cardiovascular events, and may cost as much as 15 to 20 times more per month of treatment than generic NSAIDs.^52,53

Steroids are synthetic forms of naturally occurring hormones produced by the adrenal glands and are typically administered orally or by injection. They provide rapid and powerful reduction of pain and inflammation, thus resulting in improved function. Recent evidence suggests that low-dose glucocorticoids slow the rate of joint damage and therefore appear to have disease-modifying potential.⁵⁴ Side effects include blood sugar elevations, cataracts, hypertension, increased susceptibility to infection and bruising, osteoporosis, and weight gain, depending on the dosage and length of treatment. They are often used at disease onset or with disease flares as a temporary aid in obtaining control. Disabling synovitis frequently recurs when glucocorticoids are discontinued, even in patients who are receiving combination therapy with one or more DMARDs. Therefore many patients with RA are functionally dependent while taking glucocorticoids and continue them long term.⁵⁰

An important foundation in the treatment of RA is the use of DMARDs, which are medications that reduce signs and symptoms, reduce or prevent joint damage, and preserve the structure and function of the joints. Their use alone or in combination has been reported to allow patients to remain active and productive.⁵⁵ The most common DMARDs in current use include methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, and cyclosporine. Others include gold salts, azathioprine, and d-penicillamine. Side effects may include diarrhea, eye damage, liver damage, nausea, and vomiting and depend on the DMARD taken.

Finally, BRMs are a newly developed class of medicines that restore or stimulate the immune system to fight disease. BRMs target specific parts of the immune system that destroy joints. Some do so by blocking the effects of tumor necrosis factor (TNF), a protein involved in RA through the inflammatory cascade, and are credited with improving signs, symptoms, and function in patients with RA.⁵⁶

Rehabilitation therapy is important in maintaining physical function in clients with RA. With combinations of medications, health care providers can reach goals of increasing or maintaining joint mobility; decreasing pain; improving functional abilities; improving cardiovascular fitness; and educating clients on the use of assistive devices, joint protection, and energy conservation.

Infectious diseases

Both bacterial and viral diseases may produce neurological disorders (see Chapter 26). The neurological impact of treatments and prophylactic measures must be understood. Although this may be readily apparent for drugs, vaccines have also been implicated in causing similar problems. The association of a hypotonic-hyporesponsive episode with the pertussis vaccine is such an example.⁵⁷

In the course of treating bacterial diseases, many antibiotics and antiinfective agents may compromise sensory, motor, and cognitive function. These functions may be compromised temporarily or permanently and may be patient specific. First, in the critically ill patient, aminoglycosides (gentamicin, tobramycin, and amikacin) and vancomycin may produce ototoxicity, such as hearing loss (reversible and irreversible) and vestibular damage (dizziness, vertigo, and ataxia). Minocycline is also associated with vestibular toxicity.⁵⁸ Extra precautions may be necessary to prevent falls during and after therapeutic exercise sessions. Fall-prevention programs must be developed in these cases as well as with the use of sedative-hypnotics, as previously noted.

A wide variety of viral diseases interfere with neurological function. Polio is historically the most widely recognized (see Chapter 35). Acquired immunodeficiency syndrome (AIDS) may manifest as a wide variety of neurological disorders (see Chapter 31). A recent finding is that protease inhibitors, which reduce the assembly of viral particles, may dramatically reduce and possibly reverse the neurological manifestations of AIDS.⁵⁹ Although adverse effects associated with antiviral and antibiotic agents may be intolerable, noncompliance may result in increased resistance of the virus or microorganism to retreatment.

The guiding principle of chemotherapy for infection is selective toxicity, in which the agent must cause more harm to the pathogen than to the host. Problems associated with antimicrobial therapy include resistance to drugs, side effects, allergies, and suppression of normal flora. Clinicians ask clients to exercise under conditions in which they may potentially have a compromised immune response because of trauma, a pathological condition, or surgery. These conditions may make clients more susceptible to infection, slow healing, and slow recovery.⁶⁰

An increasing number of strains of antibiotic-resistant bacteria are now emerging, in large part because of the overuse and misuse of antimicrobial drugs by health care providers.⁶¹ Overuse of antimicrobial drugs exerts a selective pressure among bacteria, encouraging the emergence of antibiotic-resistant strains by eliminating antibiotic-sensitive strains, promoting the establishment of bacteria with rare mutations of resistance, and permitting the spread of resistant strains from infected individuals.⁶² One example is the use of antibiotics for upper respiratory tract infections caused by viruses. This has been shown to have no beneficial impact on the course of the disease.⁶³ Infection control in the rehabilitation environment is essential to stop the spread of disease. Therapists must be diligent with infection control procedures such as handwashing, updating vaccinations, and cleaning all equipment. Educating clients to use antibiotics only when needed and complete the entire course of medication can potentially slow the proliferation.

Common adverse effects from the use of antimicrobials and antiviral drugs include nephrotoxicity and ototoxicity (aminoglycosides), GI complications (cephalosporins, clindamycin), thrombophlebitis and vertigo (tetracyclines), jaundice (erythromycin), photophobia (vidarabine), neurotoxicity (metronidazole), and allergic reactions (β-lactam antibiotics). The therapist must be aware of adverse side effects to assist with early recognition and referral to the physician.

Antibiotics kill various normal commensal bacteria in the gut, altering the balance and allowing overgrowth of pathogens.⁶⁴ This change of bacterial flora is believed to result in increased toxins from pathogens and can cause infection with resistant microbes.⁶⁴ When clients are taking drugs to fight infection or undergoing procedures or surgeries that place them at risk for infection (indwelling catheters), they can be more susceptible to infectious agents. Abscesses or contamination as a result of the normal flora into a normally sterile body site is often the reason for perioperative antimicrobial prophylaxis.⁶⁵ Rehabilitation specialists will most likely see many clients who are undergoing chemotherapy with antiinfective medications and play a crucial role in preventing and controlling infectious disease in the health care setting. Therapists need to update their knowledge foundation with evidence-based protocols for specific diagnoses and treatments as well as understand when infections may or may not need antimicrobial medications. In addition, education of patients about why antimicrobial agents are not indicated in specific situations, how to alleviate symptoms, and what signs indicate further follow-up may help them understand the growing problem of antibiotic resistance.

Diabetes

Diabetes, as a disorder of insulin production and sensitivity, has two major forms. Type 1 has an autoimmune component based on destruction of pancreatic islets, but success in modulating this pathogenic feature has been limited. As a result, clients with type 1 diabetes are necessarily insulin dependent. The pathogenic features of insulin insensitivity characteristic of type 2 are not well understood, but a wide array of therapeutic agents have been developed for management of this condition. Although the metabolic states of type 1 and 2 pathologies may differ somewhat, the chronic pathologies associated with poorly controlled hyperglycemia are remarkably similar. The development of peripheral neuropathy (see Chapter 18) is a progressive problem in patients with diabetes. This neuropathy compromises sensory and motor control. In addition to long-term management of diabetes from a glucohomeostatic perspective, other agents show promise. Treatment of diabetic neuropathy with trazodone or mexiletine is an example.^66,67

A more acute problem is swings in blood glucose level from inappropriate diet, exercise, insulin, and oral hypoglycemic drug administration. The balance of these factors is important, and monitoring of blood glucose level is essential. Swings in blood glucose level are often associated with changes in behavior and sensorium. This may pose a safety concern because cognitive and motor function may be impaired as a result. An increase in exercise will decrease the blood glucose concentration, thereby reducing insulin requirements. These factors should be carefully considered in any exercise regimen for the client with diabetes.⁶⁸ A list of oral hypoglycemic agents is presented in Box 36-9. Lack of glucose control because of noncompliance with medications that are useful in controlling diabetes will only return the client to an accelerated course to peripheral neuropathies and related sequelae.

In the clinical setting the health care practitioner must remember that the main goal of diabetes management is to prevent both the small-vessel complications (e.g., retinopathy and neuropathy) and large-vessel complications (e.g., heart disease and amputation) of the disease linked with elevated blood glucose levels. Diabetes is therefore often controlled through intensive, tailored treatment regimens of diet and physical activity, oral agents, and insulin.⁶⁹ Each of these regimens is designed to potentially reduce hyperglycemia and can result in hypoglycemia if not monitored.

Initially, the physician and client with diabetes can work together on a treatment plan to manage the disease. An important first step includes diet, physical activity, and a program to reduce body weight by 5% to 10%.⁷⁰ The effects of exercise as a cause of hypoglycemia deserve particular consideration because physical activity represents the most variable factor in the routine of many clients, especially those in rehabilitation.⁷¹ With vigorous exercise, glucose use can increase severalfold, and this increase can persist long after the completion of the exercise, resulting in a fall in blood glucose long afterward. Although diet and activity are important cornerstones for diabetes care, oral agents and/or insulin may eventually be required to achieve glycemic control.

Five classes of oral agents are available to help or make the body use its own insulin, including sulfonylureas (chlorpropamide), meglitinides (repaglinide), biguanides (metformin), glitazones (rosiglitazone), and α-glucosidase inhibitors (acarbose). These classes of medications have specific regimens and may be prescribed as monotherapy or taken in combinations that may include insulin. Side effects vary from weight gain to GI symptoms to hypoglycemia. Hypoglycemia as a side effect of pharmacotherapy is of concern in the rehabilitation setting because abnormally low glucose levels can cause alterations in cognition, cardiovascular hemodynamic changes, and an increased risk of physical injury.⁷² The signs and symptoms of hypoglycemia can vary from person to person and may depend on how fast the blood sugar drops. Early signs include shaking, sweating, fatigue, and weakness. Later signs may include confusion, combativeness, and exhaustion that inhibits eating, which may lead to loss of consciousness.

Insulin is a primary therapy in type 1 diabetes, in which the body has no ability to produce its own insulin. When oral antidiabetic agents no longer assist in maintaining glycemic targets, insulin is usually instituted in the diabetic with low production or resistance to insulin (type 2 diabetes).⁷³ Many forms of insulin are available, and administration is typically through subcutaneous injection or insulin pumps. Insulin can be long acting or short acting and is often used in combinations to maintain the optimal level of glycemic control. Hypoglycemia is the primary problem associated with insulin use because of its ability to lower blood sugar.⁷³

Health professionals working with clients who have diabetes should consider a number of strategies for prevention of hypoglycemia and be able to analyze the risk and benefits of exercise. Because glycemic control is individualized, each client must be addressed uniquely, and as a member of the health care team the rehabilitation specialist can potentially assist in education of all those involved in the care of the client. The following are guidelines published by the American Diabetes Association (ADA) and should be implemented in clients with known type 2 diabetes.⁷⁴ Medical evaluation of the client before exercise begins is important to determine the extent of involvement and complications present. Prepare the client for exercise by monitoring glycemic control before, during, and after exercise. Exercise is contraindicated if fasting glucose levels are more than 250 mg/dL and ketosis is present; use caution if glucose levels are greater than 300 mg/dL and no ketosis is present. The patient should ingest added carbohydrate if glucose levels are less than 100 mg/dL. Document when changes in insulin or food intake are necessary, and learn the glycemic response to different exercise conditions (e.g., light, moderate, heavy). Food intake should include consumption of carbohydrates as needed to avoid hypoglycemia. Carbohydrate-based foods should be readily available during and after exercise.

Clinicians need to have an understanding of what causes diabetes, the effects of medications and exercise on the regulation of blood sugar levels, signs and symptoms of hypoglycemia, and what should be done in a diabetic emergency.

Pulmonary diseases

Many clients with neurological problems have pulmonary disease as well (see Chapter 30). The treatment of pulmonary diseases presents an unusual challenge. Many drugs used for treatment of asthma, emphysema, and chronic obstructive pulmonary disease (COPD) are intended to have direct effects on the lung, yet systemic effects are often unavoidable. Adrenergic bronchodilators, such as albuterol, epinephrine, and metaproterenol, may increase heart rate and tremor.⁷⁵ If tremor first manifests because of a neurological insult, then these drugs may exaggerate the motor impairment. Although ipratropium is an anticholinergic with bronchodilating properties, the associated systemic anticholinergic effects (such as urinary retention with prostatic hypertrophy) are not well tolerated in geriatric men.⁷⁶ Prednisone and related corticosteroids may dramatically reduce the degree of pulmonary hyperresponsiveness but often produce systemic effects as previously noted. These are often reduced (but not necessarily eliminated) with the use of inhaled corticosteroids such as beclomethasone, budesonide, flunisolide, and triamcinolone. Although the use of xanthines in asthma is declining, theophylline in asthma and obstructive pulmonary diseases can produce changes in cognitive function, including delusions and hallucinations with higher doses. General CNS stimulation, including nervousness, insomnia, and seizures, is well recognized.⁷⁷ Tremor and nausea are often produced with theophylline, even with clinical dosage regimens commonly accepted. Finally, the increase in diuresis caused by theophylline in patients with prostatic hypertrophy is certainly troublesome. The metabolism of this drug is often changed by other medications, which complicates therapy. These changes in drug metabolism may increase toxicity or decrease efficacy.⁷⁸ Newer classes of disease-modifying agents known as leukotriene modifiers (montelukast and zafirlukast) are being favored in many regimens for the management of asthma. Although cardiovascular and neurological side effects of these drugs appear to be dramatically reduced when compared with other agents, they have been implicated in several important drug interactions.⁷⁸ Lack of compliance with these medications decreases pulmonary gas exchange, ultimately decreasing motor performance.

Clients may have signs and symptoms of lung dysfunction during exercise, including nonproductive cough, dyspnea, alterations in breathing rate and chest expansion, changes in skin color, as well as changes in auscultation and percussion findings. Symptomatic pharmacotherapy may be required to reduce disease-related symptoms such as shortness of breath and improve exercise tolerance.⁷⁹ The client should begin exercise after medications to improve exercise tolerance. Often with chronic lung disease, exacerbations may be caused by an infection; therefore antibiotics may be prescribed.⁸⁰ In addition, thinning and mobilization of secretions in airways with mucolytics and chest therapy may be necessary.⁸¹ Oxygen therapy is a secondary therapy that may be necessary for hypoxemic patients.⁸⁰ This therapy reduces the hematocrit level to more normal levels, moderately improves neuropsychological factors, and ameliorates pulmonary hemodynamic abnormalities.⁸² Oxygen therapy may be indicated during exercise for patients whose levels become desaturated during low-level activity.⁸³ Understanding the use of pharmacological treatments for pulmonary dysfunction can assist the rehabilitation professional in promoting improved strength, exercise tolerance, and functional abilities in clients with pulmonary dysfunction.

Gastrointestinal disorders

Among the wide variety of agents used in the treatment of GI disorders, problems with agents affecting GI motility are among the most frequently encountered. Antiemetics that are dopaminergic antagonists, such as prochlorperazine (Compazine), chlorpromazine (Thorazine), and promethazine (Phenergan), may produce extrapyramidal side effects resembling Parkinson disease through the drug’s actions on the basal ganglia.⁸⁴ Dronabinol (Marinol), a cannabinoid derivative from marijuana, is an effective antiemetic but may produce cognitive and sensory disturbances, including drowsiness, dizziness, ataxia, disorientation, orthostatic hypotension, and euphoria.⁸⁵ The selective serotonin antagonists dolasetron (Anzemet), granisetron (Kytril), and ondansetron (Zofran) are effective and valuable antiemetics, especially in cancer chemotherapy. The most common adverse effect is severe headache.⁸⁶ The benzodiazepine lorazepam is an effective adjunct for control of emesis. Problems associated with benzodiazepines have been previously discussed. Corticosteroids such as dexamethasone should be included among the antiemetic agents; their adverse effects have also been previously discussed.

In producing normal motility, metoclopramide (Reglan), domperidone (Motilium), and cisapride (Propulsid) are often used. The adverse effects of metoclopramide are primarily through dopaminergic antagonism. Domperidone was developed to reduce these CNS effects and has been used to treat diabetic gastroparesis with some success.⁸⁷ Cisapride, a restricted-use prokinetic agent, may have a wide variety of CNS effects, including dizziness, mood disorders, vision changes, hallucinations, and amnesia, although with low incidence compared with concerns of arrhythmias induced by this drug.⁸⁸ Compliance with medications that reduce problems with the GI system may have little direct effect on motor performance but may prove troublesome to the client’s quality of life.

In the rehabilitation setting, GI signs and symptoms are common problems for many clients. The side effects of drugs reported in formularies show that almost all oral preparations are the potential cause of some form of GI disturbance.⁸⁹ Signs and symptoms include upper GI effects such as nausea, vomiting, indigestion, gastric reflux, and stomach pain or lower GI effects such as diarrhea, constipation, colonic pain, and blood in stools. These symptoms may be caused by an underlying GI condition (gallstones and acid reflux) or side effects from medications (nausea and vomiting). Because GI problems can be prevalent and challenging, cause poor compliance, and be a signal for a more serious condition, the causes and potential approaches used to ameliorate the symptoms must be understood.

Medications can modify GI absorption, cause dysmotility, damage the mucosal lining, or change the bioavailability and resulting effectiveness of drugs. Some drugs modify the absorption or activity of nutrients, ions, and drugs. Drugs such as metformin (used in the treatment of diabetes) may reduce the absorption of vitamin B₁₂, with the potential development of megaloblastic anemia, necessitating exercise precautions.⁹⁰ Other drugs that damage the mucosal lining (methotrexate, allopurinol, neomycin, colchicine, methyldopa) may reduce nutrient absorption, leading to deficiencies.⁶⁴ One class of agents, NSAIDs, is estimated to be regularly used by 5% to 10% of the U.S. population, with more than 70 million prescriptions filled annually and more than 30 billion OTC tablets sold.⁹¹ These drugs are implicated in patients reporting gastric dyspepsia (pain or discomfort in the upper abdomen), and concomitant administration of proton pump inhibitors (which block production of stomach acid) and prostaglandin analogs (which protect the stomach lining) may often reduce mucosal erosion.⁶⁴

Drugs that cause dysmotility of the small intestine such as TCAs (for depression), anticholinergics (for asthma), calcium channel blockers (for heart failure), and opiates (for pain) may be commonly administered to patients within the rehabilitation population.⁶⁴ The large intestine is more likely to have reduced motility, with abdominal pain, constipation, nausea, vomiting, and abdominal distention present. Many patients require increased activity, change of dietary habits, or laxatives to improve motility.⁹² Precautions must be taken because of the potential for chronic use of laxatives, fluid and electrolyte imbalance, steatorrhea, protein-losing gastroenteropathy, osteomalacia, and vitamin and mineral deficiencies.⁶⁴

It is important to note that some supplements and fluids (e.g., grapefruit juice) taken with medications can potentially cause changes in the bioavailability of drugs. Concurrent ingestion of iron causes a marked decrease in the bioavailability of a number of drugs such as tetracycline (an antibiotic), methyldopa (an antihypertensive agent), levodopa (for Parkinson disease), and ciprofloxacin (an antimicrobial).⁹³ Grapefruit juice is also known to change the bioavailability of some medications, leading to an elevation of their serum concentrations; these drugs include cyclosporine (an immunosuppressive agent), calcium antagonists (for hypertension), and coenzyme A reductase inhibitors (statins).⁹⁴

Most medications have the potential to cause some form of GI difficulties, whether taken systemically, topically applied, or given by the parenteral route.⁶⁴ Most adverse effects can be reduced with identification of the causal relation, proper administration of the drug, and administration according to all the guidelines on the label. Therapists may suggest specific timing of medication administration to relieve symptoms and increase participation in therapy. The role of physical and occupational therapists should be recognized in observing adverse drug events to warn patients of early signs of potential problems, provide education, and refer for further follow-up by the pharmacist or physician.

Sensory impairment

Drugs that affect hearing, vision, and touch may influence any type of sensory, cognitive, and motor impairment. In any impairment, the processing of accurate sensory information is crucial to modify and adjust procedural programming during movement. A subject must be able, through visual, manual, or auditory cues (even through olfactory means), to relate to or recognize the relevance of the external environment, engage the specific motor programming centers that reach consensus regarding the specific motor response, and produce the series of signals that may progress uninterrupted through spinal mechanisms and the motor endplate to a regional muscle group for an appropriate response. Any impairment or drug that affects any component within these systems, whether early or late in this sequence, will affect the motor performance. Clients with sensory integrative problems are often given medications such as those for attention-deficit disorder, anxiety, seizure, and depression.⁹⁵ As previously discussed, certain drugs may influence hearing (as previously indicated regarding infectious diseases) or produce tinnitus (e.g., aspirin), which may be distracting and thus ultimately affect motor performance.⁵⁸ Changes in the visual field (e.g., with ethambutol and anticonvulsants) are likewise important. Analgesics and topical anesthetics may dangerously affect surface heat or cold discomfort and undermine avoidance cues. However, elimination of excessive pain (peripheral and central) may enhance cognitive focus and learning as well as allow an individual to move as part of daily living, which will help maintain power, range, balance, and thus quality of life. The CNS functions with the consensus of multiple interactions. Because the branched as well as sequential nature of systems links sensory and motor functions, the peripheral effects of drugs commonly modify the function of central systems. This is a relatively unappreciated reason why drug therapy can modify rehabilitation techniques both positively and negatively (see Chapter 9). Therapists must be aware of medications when working with clients who have sensory impairments. Medications can increase or alleviate signs and symptoms, as well as produce unwanted side effects. Clients may benefit from alterations in the environment to limit sensory sensitivities, timing of treatment to coincide with the most effective dose of medications, and monitoring for unwanted side effects.

Cognitive and central motor control impairment

Disorders of mood (anxiety and depression) reduce initiative in the rehabilitation process. In this context, anxiolytics and antidepressants may have a positive impact. However, if the dose is not carefully titrated, drowsiness and anterograde amnesia will cloud effective response and learning. Both antidepressants and many of the benzodiazepines may cause these effects, as previously discussed. Behavioral disorders, especially those associated with untreated psychoses or dementia, impede cognitive function. Although antipsychotics may correct these disorders, the dopaminergic antagonism associated with these may interfere with the function of the basal ganglia and facilitation of movement. Many newer antipsychotic agents (also known as the atypical antipsychotics) have, in addition to dopaminergic antagonism, serotonin antagonist activity, which may reduce the extrapyramidal side effects of the earlier agents when analyzed as movement dysfunction (Box 36-10) (see Chapter 20). The therapist should be monitoring for signs of depression, which is common in clients who have had loss of function. Effective management of depression is dependent on finding an appropriate formulation and therapeutic dose, which may take weeks, and clients will need education and support. Extrapyramidal motor signs should be monitored and reported to the health care team.

Vertigo, dizziness, balance, and coordination

Many agents with histamine antagonist and anticholinergic activity have been used for treatment of vertigo and dizziness. Meclizine and related antihistamines are primary examples. Occasionally, sinus congestion can result in impaired vestibular function and dizziness. In the absence of hypertension or related autonomic dysfunction, an indirect-acting adrenergic agonist such as ephedrine or pseudoephedrine can reduce this congestion and improve this condition (see Chapter 22).⁹⁶ Dizziness is a common clinical problem, affecting at least a third of the population in one form or another at some point during their lives.⁹⁷ Medications should be reviewed in all patients with dizziness, as numerous medications can be associated with this effect, including alcohol and other CNS depressants, aminoglycoside antibiotics, anticonvulsants, antidepressants, antihypertensives, chemotherapeutics, loop diuretics, and salicylates.⁹⁸ Clients should be monitored for orthostatic hypotension and hyperventilation. Depending on the cause of dizziness, clients with dizziness may benefit from canalith repositioning procedures,⁹⁹ vestibular exercises,¹⁰⁰ instrumental rehabilitation training on a moving platform,¹⁰¹ positional education (sitting at bedside before standing), use of compression garments, dietary changes (salt and fluid intake), and use of simple physical counter-maneuvers such as squatting to temporarily but rapidly raise blood pressure.¹⁰² Symptoms of dizziness and balance dysfunction should be reported to the health care team for determination of the underlying cause and best management strategies.

Cardiovascular impairment

In the management of hypercholesterolemia, the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (see Box 36-5) may produce myopathies to various degrees. Changes in hemodynamics caused by antihypertensive regimens must be monitored because these agents can produce syncope and lower exercise tolerance. Weakness from intermittent claudication is a challenge that can be managed in part with cilostazol.¹⁰³ Any drug that is used to decrease spasticity as a consequence of stroke and related cerebrovascular disorders may impair motor control and thus affect motor learning. A discussion of these drugs is outlined in the next section (see also Chapters 23 and 30). Cardiovascular impairments are common in the rehabilitation setting. Knowing the pharmacological management for and side effects of medications related to the cardiovascular system will assist the therapist in providing high-quality care. Clients will benefit from education on modifiable and nonmodifiable risk factors, monitoring blood pressure and heart rate, signs of heart failure, vascular effects of modalities, and responses to exercise and positional changes.

Spasticity and muscle tone

Muscle spasms may be controlled with centrally acting and peripherally acting agents, all of which produce drowsiness, dizziness, and muscle weakness to various degrees.¹⁰⁴ Commonly used agents are listed in Box 36-11. Pharmacological management of muscle tone, spasticity, and coordination of movement is of primary importance in neurological rehabilitation.

With regard to spasticity, several additional options are available. Tizanidine (Zanaflex) is the newest of the α-adrenergic agonists available to reduce spasticity, primarily through activation of descending noradrenergic inhibitory pathways.¹⁰⁵ Clonidine (Catapres) has similar actions. Intrathecal administration of baclofen (Lioresal) produces an antispasmodic effect through enhancement of GABAergic function, both central and spinal.¹⁰⁶ Likewise, enhancement of GABAergic function and reduced spasticity can be realized through the antiseizure drug gabapentin.¹⁰⁷ Selective motor neurons can be inactivated through local injection of botulinum toxins.¹⁰⁸ These agents inhibit the release of acetylcholine at the neuromuscular junction. The investigational agent 4-aminopyridine has been shown to reduce spasticity in patients with spinal cord injury.¹⁰⁹

The involvement of serotonin in maintenance of muscle tone and spasticity is complex and controversial. Cyproheptadine, a relatively nonselective serotonergic antagonist, can reduce spasticity and maintain muscle tone.¹¹⁰ However, SSRIs used as antidepressants may occasionally increase spasticity,¹¹¹ and clozapine (Clozaril), a selective serotonin antagonist, may produce muscle weakness.¹¹²

In addition to spinal cord injuries, multiple sclerosis (MS) may cause spasticity as a complication. Although several interferons have been used in the management of MS, interferon beta-1b has been shown to increase spasticity (see Chapters 19 and 24).¹¹³ Therapists often work closely with clients who are undergoing treatment with antispasticity medications. Knowing the underlying cause of the spasticity in the client with neurological impairments (disruptions of inhibitory control) and using concomitant rehabilitation therapy may assist with decreasing pain and improving range of motion and functional ability. Therapists should have an understanding of the desired effects of agents and the adverse effects, including sedation and addictive properties.

Neuroplasticity

The effects of drugs on plasticity are highly controversial. In Alzheimer disease a loss of plasticity may occur through deficits in hippocampal and cortical function, leading to memory loss (see Chapters 4, 5, and 27). Many anticholinesterase agents improve memory, which may provide evidence that they enhance neuroplasticity.¹¹⁴ At the time of this publication, the primary agents used in the management of Alzheimer disease are anticholinesterase agents. Within the past few years, agents affecting the glutaminergic system have shown promise.¹¹⁵ Based on the putative molecular mechanisms of the pathology, inhibitors of β-amyloid formation and related modulators may hold additional promise.¹¹⁶ This rapidly evolving area of research may provide interesting avenues for treatment of Alzheimer disease. Neuroprotective agents that aim to prevent neuronal death by inhibiting one or more pathophysiological steps in the process that follows brain injury or ischemia are currently under development for neurological disorders including stroke, spinal cord injury, traumatic brain injury, and Parkinson disease. In addition, studies on enriched environments are providing knowledge related to neuronal capacity for regeneration and repair in the adult and ageing brain and spinal cord.¹¹⁷ The future of neuroplasticity in rehabilitation may be enriched when medications that protect or promote neurological recovery can be paired with techniques to improve function.