N

INTRODUCTION

Indications

Treatment of nausea and vomiting due to chemotherapy that has not responded to other conventional antiemetics.

Action

Antiemetic action may be due to interaction with cannabinoid receptor system in the brain. Therapeutic Effects: Decreased nausea and vomiting due to emetogenic chemotherapy.

Adverse Reactions/Side Effects

CNS: concentration difficulty, drowsiness, euphoria, sleep disturbance, vertigo, altered mental state, anxiety, depression, detachment, disorientation, headache, panic, paranoia, psychotomimetic reactions. CV: hypotension, tachycardia. GI: dry mouth, increased appetite, nausea. Neuro: ataxia, physical dependence, psychologic dependence.

PHYSICAL THERAPY IMPLICATIONS

Examination and Evaluation

• Monitor improvements in GI symptoms (decreased nausea and vomiting, increased appetite) to help document whether drug therapy is successful.

• Assess vertigo or ataxia that might affect gait, balance, and other functional activities. Report balance problems and functional limitations to the physician and nursing staff, and caution the patient and family/caregivers to guard against falls and trauma.

• Monitor changes in mood and behavior such as anxiety, euphoria, depression, disorientation, paranoia, memory lapses, impaired concentration, paranoia, panic, psychosis-like reactions, or other changes in mental state. Notify physician if these changes become problematic.

• Assess heart rate, ECG, and heart sounds, especially during exercise (See Appendices G, H). Report fast heart rate (tachycardia) and symptoms of other arrhythmias, including palpitations, chest discomfort, shortness of breath, fainting, and fatigue/weakness.

• Assess blood pressure (BP) periodically and compare to normal values (See Appendix F). Report low BP (hypotension), especially if patient experiences dizziness, fatigue, or other symptoms.

Interventions

• Guard against falls and trauma (hip fractures, head injury, and so forth) caused by vertigo or ataxia; implement fall-prevention strategies (See Appendix E).

• Because of the risk of arrhythmias and abnormal BP responses, use caution during aerobic exercise and other forms of therapeutic exercise. Assess exercise tolerance frequently (BP, heart rate, fatigue levels), and terminate exercise immediately if any untoward responses occur (See Appendix L).

Patient/Client-Related Instruction

• Advise patient about the risk of daytime drowsiness and decreased attention and mental focus. Avoid driving, and use caution in other activities that require strong concentration.

• Educate patient about the risk of physical and psychologic dependence during excessive or prolonged use; encourage patient to adhere to proper dosing schedule.

• Instruct patient to report bothersome side effects such as severe or prolonged headache, nausea, increased appetite, or dry mouth.

Pharmacokinetics

Absorption: Completely absorbed following oral administration.

Distribution: Unknown.

Protein Binding: Highly protein bound.

Metabolism and Excretion: Highly metabolized with extensive first pass hepatic metabolism; metabolites excreted in feces (67%) and urine (22%).

Half-life: 2 hr.

Contraindications/Precautions

Contraindicated in: Hypersensitivity; OB: Lactation.

Use Cautiously in: History of substance abuse or mental illness/psychiatric disorder; Geri: Increased risk of hypotension, tachycardia, and psychoactive effects in patients >65 yr; OB: Use in pregnancy only if maternal benefit outweighs fetal risk; Pedi: Safe use in children <18 yr not established; increased risk of psychoactive reactions.

Interactions

Drug-Drug: ↑ risk of CNS depression with other CNS depressants, including alcohol, antihistamines, barbiturates, benzodiazepines, buspirone, lithium, muscle relaxants, opioids, sedative/hypnotics, or other CNS depressants. ↑ risk of hypertension, tachycardia, and cardiotoxicity with amphetamines, cocaine, and other sympathomimetic agents. ↑ risk of tachycardia or drowsiness with atropine, scopolamine, antihistamines, or other anticholinergics. ↑ risk of tachycardia, hypertension, and drowsiness with tricyclic antidepressants. May displace, be displaced by, or otherwise interfere with other highly protein-bound drugs. May cause reversible hypomanic reaction with disulfiram or fluoxetine. May ↓ clearance and ↑ effects of barbiturates. May ↑ clearance and ↓ effects of theophylline. Cross-tolerance and potentiation of effects may occur with opioids. Naltrexone may enhance effects. Alcohol may ↑ mood effects.

Route/Dosage

PO (Adults): 1 or 2 mg bid; initial dose should be given 1–3 hr prior to chemotherapy. May be given as 1 or 2 mg the night before. Not to exceed 6 mg/day (2 mg tid). May be used during entire course of each cycle of chemotherapy and for 48 hr after the last dose if needed.

Availability

Capsules: 1 mg.

INTRODUCTION

Indications

Symptomatic management of rheumatoid arthritis and osteoarthritis.

Action

Inhibits prostaglandin synthesis. Therapeutic Effects: Suppression of pain and inflammation.

Adverse Reactions/Side Effects

CNS: agitation, anxiety, confusion, depression, dizziness, drowsiness, fatigue, headache, insomnia, malaise, weakness. EENT: abnormal vision, tinnitus. Resp: dyspnea, hypersensitivity pneumonitis. CV: edema, fluid retention, vasculitis. GI: GI BLEEDING, abdominal pain, diarrhea, abnormal liver function tests, anorexia, constipation, dry mouth, dyspepsia, flatulence, gastritis, gastroenteritis, increased appetite, nausea, stomatitis, vomiting. GU: albuminuria, azotemia, interstitial nephritis. Derm: EXFOLIATIVE DERMATITIS, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, increased sweating, photosensitivity, pruritus, rash. Hemat: prolonged bleeding time. Metab: weight gain. Neuro: paresthesia, tremor. Misc: ALLERGIC REACTIONS, INCLUDING ANAPHYLAXIS, ANGIONEUROTIC EDEMA.

PHYSICAL THERAPY IMPLICATIONS

Examination and Evaluation

• Monitor signs of GI bleeding, including abdominal pain, vomiting blood, blood in stools, or black, tarry stools. Report these signs to the physician immediately.

• Monitor signs of allergic reactions and anaphylaxis or angioneurotic edema, including pulmonary symptoms (laryngeal edema, wheezing, cough, dyspnea) or skin reactions (rash, pruritus, urticaria, swelling in the face). Be especially alert for exfoliation, dermatitis, and other severe skin reactions that might indicate serious hypersensitivity reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis). Notify physician immediately if these reactions occur.

• Assess pain and other variables (range of motion, muscle strength) to document whether this drug is successful in helping manage the patient's pain and decreasing impairments.

• Assess blood pressure (BP) periodically and compare to normal values (See Appendix F). NSAIDs can increase BP in certain patients.

• Be alert for signs of difficult, labored breathing (dyspnea) or other signs of pneumonitis such as cough, shortness of breath, fever, and abnormal breath sounds (rales; See Appendix K). Report these signs to the physician.

• Be alert for signs of prolonged bleeding time such as bleeding gums, nosebleeds, and unusual or excessive bruising. Report these signs to the physician.

• Assess peripheral edema using girth measurements, volume displacement, and measurement of pitting edema (See Appendix N). Report increased swelling in feet and ankles or a sudden increase in body weight due to fluid retention.

• Monitor signs of interstitial nephritis (blood in urine, decreased urine output, weight gain from fluid retention) or signs of increased nitrogenous compounds in the blood (azotemia) such as confusion, decreased alertness, tachycardia, pallor, fatigue, dry mouth, thirst, and decreased/absent urine production. Notify physician of these signs.

• Assess any tremors or signs of paresthesia (numbness, tingling). Perform objective tests including electroneuromyography and sensory testing to document any drug-related neuropathic changes.

• Be alert for signs of vasculitis, including fatigue, weakness, muscle pain, joint pain, fever, loss of appetite, and weight loss. Report these signs to the physician.

• Assess dizziness and drowsiness that might affect gait, balance, and other functional activities (See Appendix C). Report balance problems and functional limitations to the physician, and caution the patient and family/caregivers to guard against falls and trauma.

• Monitor and report confusion, agitation, anxiety, depression, or other psychic disturbances.

Interventions

• Implement appropriate manual therapy techniques, physical agents, and therapeutic exercises to reduce pain and decrease the need for nabumetone and other NSAIDs.

• If treating arthritic conditions, recommend orthotic and assistive devices as needed to reduce pain, improve function, and augment the effects of drug therapy.

• Use caution with any physical interventions that could increase bleeding, including wound débridement, chest percussion, joint mobilization, and application of local heat.

• Help patient explore other nonpharmacologic methods to reduce chronic pain, such as relaxation techniques, exercise, counseling, and so forth.

• Causes photosensitivity; use care if administering UV treatments. Advise patient to avoid direct sunlight and use sunscreens and protective clothing, and to report any untoward skin reactions (rash, itching, excessive sweating).

Patient/Client-Related Instruction

• Advise patient that analgesics are usually more effective if given before pain becomes severe; emphasize that adequate pain control will allow better participation in physical therapy.

• Inform patient that NSAIDs may impair bone and cartilage healing. Advise patient to consult physician about NSAID use, especially after fractures, spinal fusion, and other bone surgeries.

• Caution patient about the use of over-the-counter products that contain NSAIDs or acetaminophen while taking prescription doses of nabumetone. Use of multiple NSAIDs increases the risk of toxicity and overdose.

• Instruct patient to report excessive or prolonged headache or ringing/buzzing in the ears (tinnitus); these signs may indicate drug toxicity.

• Advise patient about the risks of gastric irritation. Instruct patient to notify physician of GI reactions such as severe or prolonged nausea, vomiting, diarrhea, constipation, indigestion, heartburn, flatulence, and abdominal pain.

• Advise patient to reduce alcohol intake because alcohol increases the risk of gastric toxicity.

• Instruct patient and family/caregivers to report other troublesome side effects such as severe or prolonged sleep loss or vision disturbances.

Pharmacokinetics

Absorption: Nabumetone (a prodrug) is 80% absorbed after oral administration; 35% is rapidly converted to 6-methoxy-2-naphthylacetic acid (6-MNA), which is the active drug.

Distribution: Unknown.

Protein Binding: >99%.

Metabolism and Excretion: 6-MNA is metabolized by the liver to inactive compounds.

Half-life: 24 hr (increased in severe renal impairment).

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Use with other NSAIDs, including aspirin; cross-sensitivity may occur; Active GI bleeding or ulcer disease; Perioperative pain from coronary artery bypass graft (CABG) surgery.

Use Cautiously in: Severe renal, or hepatic disease; History of ulcer disease; OB/Lactation/Pedi: Safety not established; avoid using during 2nd half of pregnancy.

Interactions

Drug-Drug: ↑ adverse GI effects with aspirin, other NSAIDs, potassium supplements, corticosteroids, or alcohol. Chronic use with acetaminophen may ↑ risk of adverse renal reactions. May ↓ effectiveness of diuretics or antihypertensives. May ↑ hypoglycemic effects of insulins or oral hypoglycemic agents. ↑ risk of toxicity from methotrexate. ↑ risk of bleeding with cefotetan, cefoperazone, valproic acid, anticoagulants, ticlopidine, clopidogrel, eptifibatide, tirofiban, or thrombolytic agents. ↑ risk of adverse hematologic reactions with antineoplastics or radiation therapy. Concurrent use with cyclosporine may ↑ risk of renal toxicity.

Route/Dosage

PO (Adults): 1000 mg/day as a single dose or divided dose bid; may be increased up to 2000 mg/day; use lowest effective dose during chronic therapy.

Availability (generic available)

Tablets: 500 mg, 750 mg.

INTRODUCTION

Indications

Management of hypertension. Management of angina pectoris. Unlabeled Use: Arrhythmias. Migraine prophylaxis. Tremors (essential, lithium-induced, parkinsonian). Aggressive behavior. Antipsychotic-associated akathisia. Situational anxiety. Esophageal varices. Reduction of intraocular pressure.

Action

Blocks stimulation of beta₁ (myocardial) and beta₂ (pulmonary, vascular, and uterine) receptor sites. Therapeutic Effects: Decreased heart rate and blood pressure.

Adverse Reactions/Side Effects

CNS: fatigue, weakness, anxiety, depression, dizziness, drowsiness, insomnia, memory loss, mental status changes, nightmares. EENT: blurred vision, dry eyes, nasal stuffiness. Resp: bronchospasm, wheezing. CV: ARRHYTHMIAS, BRADYCARDIA, CHF, PULMONARY EDEMA, orthostatic hypotension, peripheral vasoconstriction. GI: constipation, diarrhea, nausea. GU: erectile dysfunction, decreased libido. Derm: itching, rashes. Endo: hyperglycemia, hypoglycemia. MS: arthralgia, back pain, muscle cramps. Neuro: paresthesia. Misc: drug-induced lupus syndrome.

PHYSICAL THERAPY IMPLICATIONS

Examination and Evaluation

• Assess heart rate, ECG, and heart sounds, especially during exercise (See Appendices G, H). Although intended to treat certain arrhythmias, this drug can unmask or precipitate new arrhythmias (proarrhythmic effect). Report an unusually slow heart rate (bradycardia) or signs of other arrhythmias, including palpitations, chest pain, shortness of breath, fainting, and fatigue/weakness.

• Watch for signs of CHF and pulmonary edema, including dyspnea, rales/crackles, weight gain, peripheral edema, and jugular venous distention. Report any new or increased signs of heart failure, but also determine if drug therapy is effective in reducing these symptoms in patients with preexisting heart failure.

• Assess blood pressure (BP) periodically and compare to normal values (See Appendix F) to help document antihypertensive effects. Also assess BP when patient assumes a more upright position (lying to standing, sitting to standing, lying to sitting). Document orthostatic hypotension and contact physician when systolic BP falls >20 mm Hg, or diastolic BP falls >10 mm Hg.

• Assess exercise tolerance and episodes of angina pectoris. Document improvements in these variables, but also report any decline in exercise tolerance or increased frequency/severity of anginal attacks.

• Assess symptoms of bronchospasm (wheezing, coughing, tightness in chest). Perform pulmonary function tests to quantify suspected changes in ventilation and respiration (See Appendices I, J, K). Repeated or prolonged bronchoconstriction may require a change in dose or medication.

• Monitor signs of peripheral vasoconstriction, such as extreme coldness in the hands and feet, cyanosis, and muscle cramping. Notify physician of severe or prolonged signs of vasoconstriction.

• Assess dizziness and drowsiness that might affect gait, balance, and other functional activities (See Appendix C). Report balance problems and functional limitations to the physician, and caution the patient and family/caregivers to guard against falls and trauma.

• Monitor excessive fatigue or weakness. Beta blockers often cause some degree of fatigue and weakness, but any sudden or severe change in muscle strength or energy levels should be reported.

• Watch for signs of hypoglycemia (weakness, malaise, irritability, fatigue) or hyperglycemia (drowsiness, fruity breath, increased urination, unusual thirst). Medication may mask some signs of hypoglycemia, but dizziness and sweating may still occur. Patients with diabetes mellitus should check blood glucose levels frequently.

• Assess any back pain or joint pain to rule out musculoskeletal pathology; that is, try to determine if pain is drug-induced rather than caused by anatomic or biomechanical problems.

• Assess signs of paresthesia (numbness, tingling) or muscle twitching. Perform objective tests including electroneuromyography and sensory testing to document any drug-related neuropathic changes.

• If used to treat aggressive behavior, anxiety, or extreme restlessness (akathisia), document whether drug therapy is successful in decreasing these behaviors. Also notify physician of any worsening in mood or behavior, including increased depression, anxiety, nervousness, or memory loss.

• If used to prevent migraine headaches, monitor the incidence and severity of attacks to document whether this drug is successful in helping manage the patient's pain.

• Monitor signs of drug-induced lupus syndrome, including increased BP, fever, joint pain, skin rashes, and redness/irritation of the eye (uveitis). Notify physician promptly if these signs appear.

Interventions

• Design and implement aerobic exercise and endurance training programs to improve coronary perfusion, reduce angina, and improve myocardial pumping ability.

• Because of an increased risk of cardiac arrhythmias (bradycardia, others), use caution during aerobic exercise and endurance conditioning. Likewise, monitor patients closely during treatment of other cardiac problems (angina, CHF, recent MI). Terminate exercise if patient exhibits untoward symptoms (chest pain, shortness of breath, unusual fatigue) or displays other criteria for exercise termination (See Appendix L).

• Establish aerobic exercise workloads that account for the effects of beta blockers on heart rate. Some heart rate guidelines may not be appropriate because beta blockers typically decrease maximal HR by 20–30 bpm. Use other guidelines such as rating of perceived exertion (RPE, modified Borg scale) to determine exercise workloads.

• To minimize orthostatic hypotension, patient should move slowly when assuming a more upright position.

Patient/Client-Related Instruction

• Remind patients to take medication as directed to control hypertension even if they are asymptomatic.

• Counsel patients about additional interventions to help control BP, including regular exercise, weight loss, sodium restriction, stress reduction, moderation of alcohol consumption, and smoking cessation.

• Instruct patient or family/caregivers to report other troublesome side effects such as severe or prolonged insomnia, nightmares, skin rash/itching, blurred vision, dry eyes, stuffy nose, sexual problems (decreased libido, erectile dysfunction), or GI problems (nausea, constipation, diarrhea).

Pharmacokinetics

Absorption: 30% absorbed after oral administration.

Distribution: Minimal penetration of the CNS. Crosses the placenta and enters breast milk.

Metabolism and Excretion: 70% excreted unchanged by the kidneys.

Half-life: 10–24 hr (increased in renal impairment).

Contraindications/Precautions

Contraindicated in: Uncompensated CHF; Pulmonary edema; Cardiogenic shock; Bradycardia or heart block.

Use Cautiously in: Renal impairment (CCr <50 mL/min); Hepatic impairment; Geriatric patients (increased sensitivity to beta blockers; initial dosage reduction recommended); Pulmonary disease (including asthma); Diabetes mellitus (may mask signs of hypoglycemia); Thyrotoxicosis (may mask symptoms); Patients with a history of severe allergic reactions (intensity of reactions may be increased); Pregnancy, lactation, or children (safety not established; crosses the placenta and may cause fetal/neonatal bradycardia, hypotension, hypoglycemia, or respiratory depression).

Interactions

Drug-Drug: General anesthesia, IV phenytoin, diltiazem, and verapamil may cause additive myocardial depression. Additive bradycardia may occur with digoxin. Additive hypotension may occur with other antihypertensives, acute ingestion of alcohol, or nitrates. Concurrent use with amphetamines, cocaine, ephedrine, epinephrine, norepinephrine, phenylephrine, or pseudoephedrine may result in unopposed alpha-adrenergic stimulation (excessive hypertension, bradycardia). Concurrent use with clonidine ↑ hypotension and bradycardia. Concurrent thyroid administration may ↓ effectiveness. May alter the effectiveness of insulins or oral hypoglycemic agents (dosage adjustments may be necessary). May ↓ the effectiveness of theophylline. May ↓ the beneficial beta cardiovascular effects of dopamine or dobutamine. Use cautiously within 14 days of MAO inhibitor therapy (may result in hypertension). Concurrent NSAIDs may ↓ antihypertensive action.

Route/Dosage

PO (Adults): Antianginal—40 mg once daily initially; may increase by 40–80 mg/day q 3–7 days as needed (up to 240 mg/day). Antihypertensive—40 mg once daily initially; may increase by 40–80 mg/day q 7 days as needed (up to 320 mg/day).

Renal Impairment

PO (Adults): CCr 31–50 mL/min—increase dosing interval to 24–36 hr; CCr 10–30 mL/min—increase dosing interval to 24–48 hr; CCr <10 mL/min—increase dosing interval to 40–60 hr.

Availability (generic available)

Tablets: 20 mg, 40 mg, 80 mg, 120 mg, 160 mg. In combination with: bendroflumethiazide (Corzide). See Appendix B.

INTRODUCTION

Indications

Management of endometriosis. Management of central precocious puberty (gonadotropin-dependent) in children.

Action

Acts as a synthetic analogue of gonadotropin-releasing hormone (GnRH). Initially increases pituitary production of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which cause ovarian steroid production. Chronic administration leads to decreased production of gonadotropins. Endometriotic lesions are sensitive to ovarian hormones. Therapeutic Effects: Reduction in lesions and associated pain in endometriosis. Arrest and regression of puberty in children with central precocious puberty.

Adverse Reactions/Side Effects

CNS: emotional instability, headaches, depression, insomnia. EENT: nasal irritation. CV: edema. GU: vaginal dryness. Derm: acne, hirsutism, seborrhea. Endo: cessation of menses, impaired fertility, reduced breast size. MS: decreased bone density, myalgia. Misc: decreased libido, hot flashes, hypersensitivity reactions, weight gain.

PHYSICAL THERAPY IMPLICATIONS

Examination and Evaluation

• Monitor signs of hypersensitivity reactions, including pulmonary symptoms (tightness in the throat and chest, wheezing, cough, dyspnea) or skin reactions (rash, pruritus, urticaria). Notify physician immediately if these reactions occur.

• Assess peripheral edema using girth measurements, volume displacement, and measurement of pitting edema (See Appendix N). Report increased swelling in feet and ankles due to peripheral vasodilation.

• Monitor personality or behavioral changes, including emotional instability, depression, sleep loss, or other changes in mood. Notify physician if these changes become problematic.

• Assess any muscle pain to rule out musculoskeletal pathology; that is, try to determine if pain is drug induced rather than caused by anatomic or biomechanical problems.

• Periodically assess body weight and other anthropometric measures (body mass index, body composition). Report a rapid or unexplained weight gain or increased body fat.

Interventions

• Institute weight-bearing and resistance exercises as tolerated to maintain bone mineral density and prevent demineralization.

Patient/Client-Related Instruction

• Instruct patient or family/caregivers to report other troublesome side effects such as severe or prolonged headache, nasal irritation, hot flashes, menstrual irregularities, vaginal dryness, hot flashes, reduced breast size, decreased libido, or skin reactions (acne, oily skin increased hair growth).

Pharmacokinetics

Absorption: Well absorbed following intranasal administration.

Distribution: Unknown.

Metabolism and Excretion: 20–40% excreted in feces; 3% excreted unchanged by the kidneys.

Half-life: 3 hr.

Contraindications/Precautions

Contraindicated in: Hypersensitivity to GnRH, its analogues, or sorbitol; Pregnancy or lactation.

Use Cautiously in: Rhinitis.

Interactions

Drug-Drug: Concurrent topical nasal decongestants may reduce absorption of nafarelin (administer decongestant at least 2 hr after nafarelin).

Route/Dosage

Intranasal (Adults): Endometriosis—1 spray (200 mcg) in 1 nostril in the morning and 1 spray in the other nostril in the evening (400 mcg/day). May be increased to 1 spray in each nostril in the morning and evening (800 mcg/day).

Intranasal (Children): Central precocious puberty—2 sprays in each nostril in the morning and in the evening (1600 mcg/day); may be increased up to 1800 mcg/day (3 sprays in alternating nostrils 3 times daily).

Availability

Nasal spray: 2 mg/mL in 10-mL bottle (200 mcg/spray).

INTRODUCTION

Indications

Treatment of the following infections due to penicillinase-producing staphylococci: Respiratory tract infections; Sinusitis; Skin and skin structure infections; Bone and joint infections; Urinary tract infections; Endocarditis; Bacteremia; Meningitis.

Action

Bind to bacterial cell wall, leading to cell death. Not inactivated by penicillinase enzymes. Therapeutic Effects: Bactericidal action. Spectrum: Active against most gram-positive aerobic cocci. Spectrum is notable for activity against Penicillinase-producing strains of Staphylococcus aureus, S. epidermidis. Not active against methicillin-resistant bacteria.

Adverse Reactions/Side Effects

CNS: SEIZURES. GI: PSEUDOMEMBRANOUS COLITIS, diarrhea, epigastric distress, nausea, vomiting. GU: interstitial nephritis. Derm: rash, urticaria. Hemat: eosinophilia, leukopenia. Local: pain at IM site, phlebitis at IV site. Misc: ALLERGIC REACTIONS, INCLUDING ANAPHYLAXIS AND SERUM SICKNESS, superinfection.

PHYSICAL THERAPY IMPLICATIONS

Examination and Evaluation

• Watch for seizures; notify physician immediately if patient develops or increases seizure activity.

• Monitor signs of pseudomembranous colitis, including diarrhea, abdominal pain, fever, pus or mucus in stools, and other severe or prolonged GI problems (nausea, vomiting, heartburn). Notify physician or nursing staff immediately of these signs.

• Monitor signs of allergic reactions and anaphylaxis, including pulmonary symptoms (tightness in the throat and chest, wheezing, cough dyspnea) or skin reactions (rash, pruritus, urticaria). Notify physician or nursing staff immediately if these reactions occur.

• Assess muscle aches and joint pain (arthralgia) that may be caused by serum sickness. Notify physician if these symptoms seem to be drug-related rather than caused by musculoskeletal injury or if muscle and joint pain are accompanied by allergy-like reactions (fever, rashes, etc.)

• Monitor signs of eosinophilia (fatigue, weakness, myalgia) or leukopenia (fever, sore throat, signs of infection); report these signs to the physician.

• Monitor injection site for pain, swelling, and irritation. Report prolonged or excessive injection-site reactions to the physician or nursing staff.

Interventions

• Always wash hands thoroughly and disinfect equipment (whirlpools, electrotherapeutic devices, treatment tables, and so forth) to help prevent the spread of infection. Use universal precautions or isolation procedures as indicated for specific patients.

Patient/Client-Related Instruction

• Instruct patient to notify physician immediately if signs of the following occur:

  • ∘ Superinfection (black, furry overgrowth on tongue; vaginal itching or discharge; loose or foul-smelling stools).

  • ∘ Interstitial nephritis (blood in urine, decreased urine output, weight gain from fluid retention).

• Instruct patient and family/caregivers to report other troublesome side effects such as severe or prolonged skin problems (rash, itching) or GI problems (nausea, vomiting, diarrhea, heartburn).

Pharmacokinetics

Absorption: Completely absorbed following IV administration; well absorbed from IM sites.

Distribution: Widely distributed; penetration into CSF is minimal but sufficient in the presence of inflamed meninges; cross the placenta and enter breast milk.

Metabolism and Excretion: Partially metabolized by the liver (60%), partially excreted unchanged by the kidneys.

Half-life: Neonates: 1–5 hr; Children 1 mo–14 yr: 0.75–1.9 hr; Adults: 0.5–1.5 hr (increased in renal impairment).

Contraindications/Precautions

Contraindicated in: Previous hypersensitivity to penicillins (cross-sensitivity exists with cephalosporins and other beta-lactam antibiotics).

Use Cautiously in: Severe renal or hepatic impairment.

Interactions

Drug-Drug: Nafcillin may ↓ effectiveness of oral contraceptive agents. Probenecid ↓ renal excretion and ↑ blood levels of nafcillin (therapy may be combined for this purpose). Concurrent use with methotrexate ↓ methotrexate elimination and ↑ risk of serious toxicity.

Route/Dosage

IM (Adults): 500 mg q 4–6 hr.

IM, IV (Children and Infants): 50–200 mg/kg/day divided q 4–6 hr, maximum: 12 g/day.

IM, IV (Neonates 0–4 wk, <1200 g): 50 mg/kg/day divided q 12 hr.

IV (Adults): 500–2000 mg q 4–6 hr.

IM, IV (Neonates 1.2–2 kg): 50 mg/kg/day divided q 12 hr for the first 7 days of life, then 75 mg/kg/day divided q 8 hr.

IM, IV (Neonates >2 kg): 75 mg/kg/day divided q 8 hr for the first 7 days of life, then 100 mg/kg/day divided q 6 hr.

Availability (generic available)

Powder for injection: 1-, 2-, and 10-g vials.

INTRODUCTION

Indications

Treatment of a variety of cutaneous fungal infections, including tinea pedis (athlete's foot), tinea cruris (jock itch), and tinea corporis (ringworm).

Action

Affects the synthesis of the fungal cell wall. Therapeutic Effects: Decrease in symptoms of fungal infection.

Adverse Reactions/Side Effects

Local: burning, dryness, itching, local hypersensitivity reactions, redness, stinging.

PHYSICAL THERAPY IMPLICATIONS

Examination and Evaluation

• Assess healing of skin lesions to help document drug effectiveness.

Interventions

• Avoid contact with cutaneous lesions when treating patient.

• Always wash hands thoroughly and disinfect equipment (whirlpools, electrotherapeutic devices, treatment tables, and so forth) to help prevent the spread of infection.

Patient/Client-Related Instruction

• Advise patient to report any increased local sensitivity to this drug (pain, burning, itching, swelling).

• Instruct patient about proper hygiene; e.g., thoroughly wash and dry the affected area, wear clean socks and ventilated shoes for tinea pedis, and so forth.

• Advise patient to apply the drug as directed for the full course of treatment even if feeling better.

• Inform patient that early relief of cutaneous symptoms may be seen in 2–3 days. Full therapeutic response may take up to 4 wk.

• Advise patient to seek medical help if infections persist or recur after the full treatment.

  Recurrent fungal infections may be a sign of systemic illness.

Pharmacokinetics

Absorption: Absorption through intact skin is minimal.

Distribution: Distribution after topical administration is primarily local.

Metabolism and Excretion: Systemic metabolism and excretion not known following local application.

Half-life: Not applicable.

Contraindications/Precautions

Contraindicated in: Hypersensitivity to active ingredients, additives, preservatives, or bases; Contains alcohol and should be avoided in patients with known intolerance.

Use Cautiously in: Nail and scalp infections (may require additional systemic therapy); OB/Lactation: Safety not established.

Interactions

Drug-Drug: Not known.

Route/Dosage

Topical (Adults): Apply cream once daily for up to 4 wk. Apply gel bid for up to 4 wk.

Availability

Cream: 1%. Gel: 1%.

INTRODUCTION

Indications

Moderate-to-severe pain. Also provides Analgesia during labor, Sedation before surgery, Supplement to balanced anesthesia.

Action

Binds to opiate receptors in the CNS. Alters the perception of and response to painful stimuli while producing generalized CNS depression. In addition, has partial antagonist properties, which may result in opioid withdrawal in physically dependent patients. Therapeutic Effects: Decreased pain.

Adverse Reactions/Side Effects

CNS: dizziness, headache, sedation, confusion, dysphoria, euphoria, floating feeling, hallucinations, unusual dreams. EENT: blurred vision, diplopia, miosis (high doses). Resp: respiratory depression. CV: hypertension, orthostatic hypotension, palpitations. GI: dry mouth, nausea, vomiting, constipation, ileus. GU: urinary urgency. Derm: clammy feeling, sweating. Misc: physical dependence, psychologic dependence, tolerance.

PHYSICAL THERAPY IMPLICATIONS

Examination and Evaluation

• Assess symptoms of respiratory depression, including decreased respiratory rate, confusion, bluish color of the skin and mucous membranes (cyanosis), and difficult, labored breathing (dyspnea). Monitor pulse oximetry and perform pulmonary function tests (See Appendix I) to quantify suspected changes in ventilation and respiratory function. Excessive respiratory depression requires emergency care.

• Be alert for excessive sedation or changes in mood and behavior (euphoria, dysphoria, confusion, hallucinations). Notify physician or nurse immediately if patient is unconscious or extremely difficult to arouse.

• Use appropriate pain scales (visual analogue scales, others) to document whether this drug is successful in helping manage the patient's pain.

• Assess blood pressure (BP) and compare to normal values (See Appendix F). Report a sustained increase in BP (hypertension) or a fall in BP when patient assumes a more upright position (lying to standing, sitting to standing, lying to sitting). Document orthostatic hypotension and contact physician when systolic BP falls >20 mm Hg, or diastolic BP falls >10 mm Hg.

• Assess dizziness that might affect gait, balance, and other functional activities (See Appendix C). Report balance problems and functional limitations to the physician and nursing staff, and caution the patient and family/caregivers to guard against falls and trauma.

Interventions

• Implement appropriate manual therapy techniques, physical agents, and therapeutic exercises to reduce pain and help wean patient off opioid analgesics as soon as possible.

• Because of the risk of abnormal BP responses, use caution during aerobic exercise and other forms of therapeutic exercise. Assess exercise tolerance frequently (BP, heart rate, fatigue levels), and terminate exercise immediately if any untoward responses occur (See Appendix L).

• Help patient explore other nonpharmacologic methods to reduce chronic pain, such as relaxation techniques, exercise, counseling, and so forth.

• Guard against falls and trauma (hip fractures, head injury). Implement fall-prevention strategies (See Appendix E), especially if patient exhibits sedation, dizziness, or blurred vision.

• To minimize orthostatic hypotension, patient should move slowly when assuming a more upright position.

Patient/Client-Related Instruction

• Advise patient that opioid analgesics are usually more effective if given before pain becomes severe; emphasize that adequate pain control will allow better participation in physical therapy.

• Educate patient about the dangers of opioid overdose; encourage patient to adhere to proper dosing schedule.

• Emphasize that the risk of physical addiction (tolerance and dependence) is usually minimal during short-term treatment of pain. Advise patient that addiction is more likely during excessive or inappropriate use of opioid analgesics.

• Advise patient to avoid alcohol and other CNS depressants because of the increased risk of sedation and decreased CNS function.

• Advise patient to increase fluid intake and dietary fiber to avoid constipation. Laxatives may also be helpful in patients susceptible to fecal impaction (e.g., people with spinal cord injury).

• Instruct patient to report other troublesome side effects such as severe or prolonged headache, unusual dreams, heart palpitations, excessive sweating, vision disturbances, increased urge to urinate, or GI problems (nausea, vomiting, dry mouth).

Pharmacokinetics

Absorption: Well absorbed after IM and SC administration.

Distribution: Probably crosses the placenta and enters breast milk.

Metabolism and Excretion: Mostly metabolized by the liver and eliminated in the feces via biliary excretion. Minimal amounts excreted unchanged by the kidneys.

Half-life: 5 hr.

Contraindications/Precautions

Contraindicated in: Hypersensitivity to nalbuphine or bisulfites; Patients who are physically dependent on opioids and have not been detoxified (may precipitate withdrawal).

Use Cautiously in: Head trauma; Increased intracranial pressure; Severe renal, hepatic, or pulmonary disease; Hypothyroidism; Adrenal insufficiency; Alcoholism; Geriatric or debilitated patients (dose reduction suggested); Undiagnosed abdominal pain; Prostatic hyperplasia; Patients who have recently received opioid agonists; OB: Pregnancy (has been used during labor but may cause respiratory depression in the newborn); Lactation or children (safety not established).

Interactions

Drug-Drug: Use with extreme caution in patients receiving MAO inhibitors (may result in unpredictable, severe reactions—reduce initial dose of nalbuphine to 25% of usual dose). Additive CNS depression with alcohol, antihistamines, and sedative/hypnotics. May precipitate withdrawal in patients who are physically dependent on opioid agonists. Avoid concurrent use with other opioid analgesic agonists (may diminish analgesic effect).

Drug-Natural: Concomitant use of kava, valerian, skullcap, chamomile, or hops can ↑ CNS depression.

Route/Dosage

Analgesia

IM, SC, IV (Adults): Usual dose is 10 mg q 3–6 hr (single dose not to exceed 20 mg; total daily dose not to exceed 160 mg).

Supplement to Balanced Anesthesia

IV (Adults): Initial—0.3–3 mg/kg over 10–15 min. Maintenance—0.25–0.5 mg/kg as needed.

Availability (generic available)

Injection: 10 mg/mL in 1- and 10-mL vials, 20 mg/mL in 1- and 10-mL vials and 1-mL preloaded syringes.

INTRODUCTION

Indications

Reversal of CNS depression and respiratory depression because of suspected opioid overdose. Unlabeled Use: Opioid-induced pruritus (low dose IV infusion). Management of refractory circulatory shock.

Action

Competitively blocks the effects of opioids, including CNS and respiratory depression, without producing any agonist (opioid-like) effects. Therapeutic Effects: Reversal of signs of opioid excess.

Adverse Reactions/Side Effects

CV: hypertension, hypotension, ventricular fibrillation, ventricular tachycardia. GI: nausea, vomiting.

PHYSICAL THERAPY IMPLICATIONS

Examination and Evaluation

• Report any remaining signs of opioid-induced CNS depression such as euphoria, dysphoria, confusion, and hallucinations.

• Be alert for any residual symptoms of respiratory depression, including decreased respiratory rate, confusion, bluish color of the skin and mucous membranes, and difficult/labored breathing. Monitor pulse oximetry and perform pulmonary function tests (See Appendix I) to document whether ventilation and respiratory function have returned to normal levels.

• Assess blood pressure (BP) and compare to normal values (See Appendix F). Report changes in BP, either a problematic decrease in BP (hypotension) or a sustained increase in BP (hypertension).

• Assess heart rate, ECG, and heart sounds, especially during exercise (See Appendices G, H). Report any rhythm disturbances or symptoms of arrhythmias, including palpitations, chest discomfort, shortness of breath, fainting, and fatigue/weakness.

• If used to treat opioid-induced itching (pruritus), monitor symptoms to help document whether drug therapy is successful in reducing itching.

Interventions

• Implement appropriate manual therapy techniques, physical agents, and therapeutic exercises to reduce pain and help wean patient off opioid analgesics as soon as possible.

• Because of the risk of arrhythmias and abnormal BP responses, use caution during aerobic exercise and other forms of therapeutic exercise. Assess exercise tolerance frequently (BP, heart rate, respiratory rate, fatigue levels), and terminate exercise immediately if any untoward responses occur (See Appendix L).

Patient/Client-Related Instruction

• Educate patient about the dangers of opioid overdose; encourage patient to adhere to proper dosing schedule.

• Instruct patient to report other troublesome side effects such as severe or prolonged GI problems (nausea, vomiting).

Pharmacokinetics

Absorption: Well absorbed after IM or SC administration.

Distribution: Rapidly distributed to tissues. Crosses the placenta.

Metabolism and Excretion: Metabolized by the liver.

Half-life: 60–90 min (up to 3 hr in neonates).

Contraindications/Precautions

Contraindicated in: Hypersensitivity.

Use Cautiously in: Cardiovascular disease; Patients physically dependent on opioids (may precipitate severe withdrawal); Pregnancy (may cause withdrawal in mother and fetus if mother is opioid dependent); Lactation (safety not established); Neonates of opioiddependent mothers.

Interactions

Drug-Drug: Can precipitate withdrawal in patients physically dependent on opioid analgesics. Larger doses may be required to reverse the effects of buprenorphine, butorphanol, nalbuphine, pentazocine, or propoxyphene. Antagonizes postoperative opioid analgesics.

Route/Dosage

Postoperative Opioid-Induced Respiratory Depression

IV (Adults): 0.02–0.2 mg q 2–3 min until response obtained; repeat q 1–2 hr if needed.

IV (Children): 0.01 mg/kg; may repeat q 2–3 min until response obtained. Additional doses may be given q 1–2 hr if needed.

IM, IV, SC (Neonates): 0.01 mg/kg; may repeat q 2–3 min until response obtained. Additional doses may be given q 1–2 hr if needed.

Opioid-Induced Respiratory Depression during Chronic (>1 wk) Opioid Use

IV, IM, SC (Adults >40 kg): 20–40 mcg (0.02–0.04 mg) given as small, frequent (q min) boluses or as an infusion titrated to improve respiratory function without reversing analgesia.

IV, IM, SC (Adults and Children <40 kg): 0.005–0.02 mg/dose given as small, frequent (q min) boluses or as an infusion titrated to improve respiratory function without reversing analgesia.

Overdose of Opioids

IV, IM, SC (Adults): Patients not suspected of being opioid dependent—0.4 mg (10 mcg/kg); may repeat q 2–3 min (IV route is preferred). Some patients may require up to 2 mg. Patients suspected to be opioid dependent—Initial dose should be decreased to 0.1–0.2 mg q 2–3 min. May also be given by IV infusion at rate adjusted to patient's response.

IV, IM, SC (Children >5 yr or >20 kg): 2 mg/dose; may repeat q 2–3 min.

IV, IM, SC (Infants up to 5 yr or 20 kg): 0.1 mg/kg; may repeat q 2–3 min.

Opioid-Induced Pruritus

IV (Children): 2 mcg/kg/hr continuous infusion; may increase by 0.5 mcg/kg/hr every few hours if pruritus continues.

Availability (generic available)

Injection: 0.4 mg/mL in 1-mL prefilled syringes and 10-mL vials, 1 mg/mL in 2-mL prefilled syringes.

In combination with: pentazocine (Talwin NX). See Appendix B.

INTRODUCTION

Indications

Provides opioid antagonism in the management of opioid dependence (oral only). Management of alcohol dependence.

Action

Competitively blocks the effects of opioids, including CNS and respiratory depression, without producing any agonist (opioid-like) effects. Mechanism in managing alcohol dependence may involve the endogenous opioid system. Therapeutic Effects: Blocks the effects of opioids in previously dependent patients. Reduced alcohol-dependent behavior.

Adverse Reactions/Side Effects

CV: anxiety, fatigue, headache, insomnia, nervousness, depression, dizziness, increased energy, sedation, suicidal ideation. EENT: hoarseness, runny/stuffy nose, sinus problems, sneezing. Resp: EOSINOPHILIC PNEUMONIA (INJECTION), cough. CV: palpitations. GI: HEPATOTOXICITY, abdominal cramps/pain, nausea, constipation, ↓ appetite, diarrhea, vomiting. GU: delayed ejaculation, erectile dysfunction. Hemat: eosinophilia, thrombocytopenia. Derm: skin rash. Local: injection site reactions. MS: muscle/joint pain. Misc: chills, ↑ thirst.

PHYSICAL THERAPY IMPLICATIONS

Examination and Evaluation

• Monitor any breathing difficulties. Notify physician immediately if patient experiences signs of eosinophilic pneumonia, such as cough, fever, chills, night sweats, and chest pain during inspiration and expiration.

• Be alert for signs of hepatotoxicity, including anorexia, abdominal pain, severe nausea and vomiting, yellow skin or eyes, fever, sore throat, malaise, weakness, facial edema, lethargy, and unusual bleeding or bruising. Notify physician immediately if these signs occur.

• Monitor changes in mood and behavior such as anxiety, nervousness, depression, sedation, suicidal thoughts, or other changes in mental state. Notify physician if these changes become problematic.

• Monitor signs of eosinophilia (fatigue, weakness, myalgia) or thrombocytopenia (bruising, nose bleeds, and bleeding gums). Report these signs to the physician.

• Assess any muscle or joint pain to rule out musculoskeletal pathology; that is, try to determine if pain is drug induced rather than caused by anatomic or biomechanical problems.

• Assess dizziness that might affect gait, balance, and other functional activities (See Appendix C). Report balance problems and functional limitations to the physician, and caution the patient and family/caregivers to guard against falls and trauma.

• Monitor IM injection site for pain, swelling, and irritation. Report prolonged or excessive injection site reactions to the physician.

Patient/Client-Related Instruction

• Instruct patient to report bothersome side effects such as severe or prolonged headache, cough, nasal problems, palpitations, erectile dysfunction, skin rash, chills, or GI problems (nausea, vomiting, diarrhea, constipation, abdominal cramps, decreased appetite, increased thirst).

Pharmacokinetics

Absorption: Well absorbed orally, but undergoes extensive first-pass hepatic metabolism resulting in 5–40% bioavailability. Well absorbed following IM administration.

Distribution: Enters breast milk.

Metabolism and Excretion: Extensively metabolized by the liver. Major metabolite (6-beta-naltrexol) has opioid antagonist activity. Metabolites are excreted in urine.

Half-life: Oral: Naltrexone—4 hr; 6-beta-naltrexol—13 hr; IM: Naltrexone—5–10 days; 6-beta-naltrexol—5–10 days.

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Concurrent use of opioid analgesics or physiologic opioid dependence; Acute opioid withdrawal; Positive urine screen for opioids; Failure of a naloxone challenge test; Acute hepatitis/liver failure.

Use Cautiously in: History of hepatic impairment/damage; Moderate-to-severe renal impairment; History of depression or suicidal behavior/attempt; OB: Pregnancy (use only if maternal benefit outweighs fetal risk); Lactation/Pedi: Lactation or children <18 yr (safety not established).

Interactions

Drug-Drug: Concurrent use with thioridazine may ↑ CNS depression. May prevent therapeutic effects of opioid analgesics, antidiarrheals, and antitussives.

Route/Dosage

Opioid dependence

PO (Adults): Following a negative naloxone challenge and 7–10 days of opioid abstinence (longer for methadone), initial dose is 25 mg. If opioid withdrawal does not occur within 1 hr, additional 25 may be given. Maintenance dose is 50 mg daily as a single dose, or 50 mg once daily on weekdays and 100 mg on Saturday, or 100 mg every other day, or 150 mg every third day, or 100 mg on Monday and Wednesday and 150 mg on Friday.

Alcohol dependence

PO (Adults): 50 mg daily as a single dose, or 50 mg once daily on weekdays and 100 mg on Saturday, or 100 mg every other day, or 150 mg every third day, or 100 mg on Monday and Wednesday and 150 mg on Friday.

IM (Adults): 380 mg every 4 wk or once monthly.

Availability

Tablets: 50 mg. Microspheres for injection (requires diluent): 380 mg/vial.

INTRODUCTION

Indications

Treatment of anemia associated with renal insufficiency.

Action

Stimulates erythropoietin production and may have a direct stimulant action on bone marrow. Therapeutic Effects: Increased hemoglobin and RBC volume.

Adverse Reactions/Side Effects

CNS: insomnia. CV: edema. GI: abdominal fullness, diarrhea, hepatic dysfunction. GU: changes in libido, erectile dysfunction, prostatic hyperplasia. Derm: acne. Endo: virilism in women and prepubertal men. F and E: hypercalcemia. MS: muscle cramps. Misc: chills.

PHYSICAL THERAPY IMPLICATIONS

Examination and Evaluation

• Watch for signs of hepatic dysfunction, including anorexia, abdominal pain, severe nausea and vomiting, yellow skin or eyes, fever, sore throat, malaise, weakness, facial edema, lethargy, and unusual bleeding or bruising. Report these signs to the physician.

• Measure blood pressure periodically and compare to normal values (See Appendix F). Report a sustained increase in blood pressure (hypertension) to the physician.

• Assess peripheral edema using girth measurements, volume displacement, and measurement of pitting edema (See Appendix N). Report increased swelling in feet and ankles or a sudden increase in body weight due to fluid retention.

• Report signs of high calcium levels, including muscle pain, cramps, weakness, joint pain, confusion, and lethargy.

• Periodically assess body weight and other anthropometric measures (body mass index, body composition). A rapid or unexplained weight gain or increase in muscle mass may indicate androgen abuse.

• Monitor personality changes, including irritability and increased aggression. Aggressive behaviors (“roid rage”) may indicate inappropriate or excessive androgen use.

• Monitor IM injection site for pain, swelling, and irritation. Report prolonged or excessive injection site reactions to the physician.

Interventions

• Design and implement aerobic exercise programs as tolerated to capitalize on increased RBC production and help improve cardiovascular fitness and oxygen delivery to tissues.

• Do not apply physical agents (heat, cold, electrotherapeutic modalities) or massage over the injection site; these interventions can alter drug absorption from subcutaneous tissues.

Patient/Client-Related Instruction

• Advise patient against use of nandrolone and other androgens to artificially increase muscle mass and enhance athletic performance. Androgen abuse is not safe and can cause liver damage, cardiovascular disease, and other serious side effects.

• Advise men about the risk of sexual side effect, including erectile dysfunction and changes in libido. Notify physician if these side effects become persistent or troublesome.

• Instruct men to report signs of prostate enlargement, including difficulty urinating and increased urge to urinate.

• Advise women that masculine side effects are likely, including deepening of voice, unusual hair growth, clitoral enlargement, and menstrual irregularities.

• Instruct patient to report other troublesome side effects such as severe or prolonged sleep loss, chills, acne, or GI problems (diarrhea, abdominal pain/fullness).

Pharmacokinetics

Absorption: Well absorbed following IM administration.

Distribution: Unknown.

Metabolism and Excretion: Unknown.

Half-life: Unknown.

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Pregnancy or lactation; Some products contain sesame oil and should be avoided in patients with known hypersensitivity; Advanced breast cancer with associated hypercalcemia; Breast cancer in males; Severe hepatic impairment; Hypercalcemia; Nephrosis or nephrotic phase of nephritis; Prostate cancer.

Use Cautiously in: Cardiac or hepatic impairment; Coronary artery disease or history of MI; Diabetes mellitus; Benign prostatic hyperplasia; Children; Geriatric patients.

Interactions

Drug-Drug: ↑ risk of hepatotoxicity with other hepatotoxic agents. ↑ risk of bleeding with warfarin, NSAIDs, and salicylates.

Route/Dosage

IM (Adults and Children ≥14 yr): Women—50–100 mg q wk; men—100–200 mg q wk.

IM (Children 2–13 yr): 25–50 mg q 3–4 wk.

Availability (generic available)

Injection: 100 mg/mL in 2-mL vial, 200 mg/mL in 1-mL vial.

INTRODUCTION

Indications

Mild-to-moderate pain. Dysmenorrhea. Fever. Inflammatory disorders, including Rheumatoid arthritis (adults and children), Osteoarthritis.

Action

Inhibits prostaglandin synthesis. Therapeutic Effects: Decreased pain. Reduction of fever. Suppression of inflammation.

Adverse Reactions/Side Effects

CNS: dizziness, drowsiness, headache. EENT: tinnitus, visual disturbances. Resp: dyspnea. CV: edema, palpitations, tachycardia. GI: DRUG-INDUCED HEPATITIS, GI BLEEDING, constipation, dyspepsia, nausea, anorexia, diarrhea, discomfort, flatulence, vomiting. GU: cystitis, hematuria, renal failure. Derm: photosensitivity, rashes, sweating, pseudoporphyria (12% incidence in children with juvenile rheumatoid arthritis—discontinue therapy if this occurs). Hemat: blood dyscrasias, prolonged bleeding time. Misc: ALLERGIC REACTIONS, INCLUDING ANAPHYLAXIS AND STEVENS-JOHNSON SYNDROME.

PHYSICAL THERAPY IMPLICATIONS

Examination and Evaluation

• Monitor signs of GI bleeding, including abdominal pain, vomiting blood, blood in stools, or black, tarry stools. Report these signs to the physician immediately.

• Be alert for signs of drug-induced hepatitis, including anorexia, abdominal pain, severe nausea and vomiting, yellow skin or eyes, skin rashes, flu-like symptoms, and muscle/joint pain. Report these signs to the physician immediately.

• Monitor signs of allergic reactions and anaphylaxis, including pulmonary symptoms (laryngeal edema, wheezing, cough, dyspnea) or skin reactions (rash, pruritus, urticaria). Be especially alert for exfoliation, dermatitis, and other severe skin reactions that might indicate serious hypersensitivity reactions such as Stevens-Johnson syndrome. Notify physician immediately if these reactions occur.

• Assess pain and other variables (range of motion, muscle strength) to document whether this drug is successful in helping manage the patient's pain and decreasing impairments.

• Assess heart rate, ECG, and heart sounds, especially during exercise (See Appendices G, H). Report rapid heart rate (tachycardia) or symptoms of other arrhythmias such as palpitations, chest discomfort, shortness of breath, fainting, and fatigue/weakness.

• Assess blood pressure (BP) periodically and compare to normal values (See Appendix F). NSAIDs can increase BP in certain patients.

• Be alert for signs of prolonged bleeding time such as bleeding gums, nosebleeds, and unusual or excessive bruising. Report these signs to the physician.

• Assess peripheral edema using girth measurements, volume displacement, and measurement of pitting edema (See Appendix N). Report increased swelling in feet and ankles or a sudden increase in body weight due to fluid retention.

• Monitor signs of kidney dysfunction such as painful urination or blood in the urine. Report signs of renal failure immediately, including decreased urine output, increased BP, muscle cramps/twitching, edema/weight gain from fluid retention, yellowish brown skin, and confusion that progresses to seizures and coma.

• Monitor unusual weakness and fatigue that might be due to anemia, or other symptoms such as fever, sore throat, mucosal lesions, or signs of infection that might be due to other blood dyscrasias. Notify physician if these signs occur.

• Assess dizziness and drowsiness that might affect gait, balance, and other functional activities (See Appendix C). Report balance problems and functional limitations to the physician, and caution the patient and family/caregivers to guard against falls and trauma.

Interventions

• Implement appropriate manual therapy techniques, physical agents, and therapeutic exercises to reduce pain and decrease the need for naproxen and other NSAIDs.

• Because of the risk of arrhythmias, use caution during aerobic exercise and other forms of therapeutic exercise. Assess exercise tolerance frequently (BP, heart rate, fatigue levels), and terminate exercise immediately if any untoward responses occur (See Appendix L).

• If treating arthritic conditions, recommend orthotic and assistive devices as needed to reduce pain, improve function, and augment the effects of drug therapy.

• Use caution with any physical interventions that could increase bleeding, including wound débridement, chest percussion, joint mobilization, and application of local heat.

• Help patient explore other nonpharmacologic methods to reduce chronic pain, such as relaxation techniques, exercise, counseling, and so forth.

• Causes photosensitivity; use care if administering UV treatments. Advise patient to avoid direct sunlight and use sunscreens and protective clothing, and to report any untoward skin reactions (rash, excessive sweating).

Patient/Client-Related Instruction

• Advise patient that analgesics are usually more effective if given before pain becomes severe; emphasize that adequate pain control will allow better participation in physical therapy.

• Inform patient that NSAIDs may impair bone and cartilage healing. Advise patient to consult physician about NSAID use, especially after fractures, spinal fusion, and other bone surgeries.

• Caution patient about the use of over-the-counter products that contain NSAIDs or acetaminophen while taking prescription doses of naproxen. Use of multiple NSAIDs increases the risk of toxicity and overdose.

• Instruct patient to report excessive or prolonged headache or ringing/buzzing in the ears (tinnitus); these signs may indicate drug toxicity.

• Advise patient about the risks of gastric irritation. Instruct patient to notify physician of GI reactions such as severe or prolonged nausea, vomiting, constipation, diarrhea, indigestion, flatulence, loss of appetite, and abdominal pain.

• Advise patient to reduce alcohol intake because alcohol increases the risk of gastric toxicity.

• Instruct patient and family/caregivers to report other troublesome side effects such as severe or prolonged vision disturbances or difficult, labored breathing.

Pharmacokinetics

Absorption: Completely absorbed from the GI tract. Sodium salt (Anaprox) is more rapidly absorbed.

Distribution: Crosses the placenta; enters breast milk in low concentrations.

Protein Binding: >99%.

Metabolism and Excretion: Mostly metabolized by the liver.

Half-life: Children <8 yr: 8–17 hr; Children 8–14 yr: 8–10 hr; Adults: 10–20 hr.

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Cross-sensitivity may occur with other NSAIDs, including aspirin; Active GI bleeding; Ulcer disease; Lactation: Passes into breast milk and should not be used by nursing mothers.

Use Cautiously in: Severe cardiovascular, renal, or hepatic disease; History of ulcer disease or any other history of gastrointestinal bleeding (may ↑ risk of GI bleeding); Underlying cardiovascular disease (may ↑ risk of MI or stroke); Chronic alcohol use/abuse; Geri: Increased risk of adverse reactions; OB: Avoid using during 3rd trimester of pregnancy; may cause premature closure of the ductus arteriosus; Pedi: Children <2 yr (safety not established).

Interactions

Drug-Drug: Concurrent use with aspirin ↓ naproxen blood levels and may ↓ effectiveness. ↑ risk of bleeding with anticoagulants, thrombolytic agents, eptifibatide, tirofiban, cefotetan, cefoperazone, valproic acid, clopidogrel, and ticlopidine. Additive adverse GI side effects with aspirin, corticosteroids, and other NSAIDs. Probenecid ↑ blood levels and may ↑ toxicity. ↑ risk of photosensitivity with other photosensitizing agents. May ↑ risk of toxicity from methotrexate, antineoplastics, or radiation therapy. May ↑ serum levels and risk of toxicity from lithium. ↑ risk of adverse renal effects with cyclosporine or chronic use of acetaminophen. May ↓ response to ACE inhibitors, angiotensin II antagonists, or furosemide. May ↑ risk of hypoglycemia with insulin or oral hypoglycemic agents. Oral potassium supplements may ↑ GI adverse effects.

Drug-Natural: ↑ anticoagulant effect and bleeding risk with anise, arnica, chamomile, clove, dong quai, feverfew, garlic, ginger, ginkgo, Panax ginseng, licorice, and others.

Route/Dosage

275 mg naproxen sodium is equivalent to 250 mg naproxen.

Anti-inflammatory/Analgesic/Antidysmenorrheal

PO (Adults): Naproxen—250–500 mg bid (up to 1.5 g/day). Delayed-release naproxen—375–500 mg bid. Naproxen sodium—275–550 mg bid (up to 1.65 g/day).

PO (Children >2 yr): Analgesia: 5–7 mg/kg/dose every 8–12 hr. Inflammatory disease: 10–15 mg/kg/day divided q 12 hr, maximum: 1000 mg/day.

Antigout

PO (Adults): Naproxen—750 mg naproxen initially, then 250 mg q 8 hr. Naproxen sodium—825 mg initially, then 275 mg q 8 hr.

OTC Use (naproxen sodium)

PO (Adults): 200 mg q 8–12 hr or 400 mg followed by 200 mg q 12 hr (not to exceed 600 mg/24 hr).

PO (Geriatric Patients >65 yr): Not to exceed 200 mg q 12 hr.

Availability

Naproxen (generic available)

Tablets (Naprosyn [Apo-Naproxen, Naxen, Novo-Naprox, Nu-Naprox]): 125 mg, 250 mg, 375 mg, 500 mg. Controlled-release tablets (Naprelan): 375 mg, 500 mg. Delayed-release tablets

(EC-Naprosyn, Naprosyn-E): 250 mg, 375 mg, 500 mg. Extended-release tablets (Naprosyn-SR): 750 mg. Oral suspension (Naprosyn): 125 mg/5 Ll. Suppositories (Naprosyn, Naxen): 500 mg.

Naproxen Sodium

Tablets (Aleve, Anaprox, Anaprox DS, Apo-Napro-Na, Novo-Naprox Sodium, Novo-Naprox Sodium DS, Synaflex, Synaflex DS): 220 mg OTC, 275 mg, 550 mg. In combination with: lansoprazole in a combination package (Prevacid NapraPac), pseudoephedrine (Aleve Cold and Sinus Tablets, Aleve Sinus and Headache Tablets), sumatriptan (Treximet). See Appendix B.

INTRODUCTION

Indications

Acute treatment of migraine headache.

Action

Acts as an agonist at specific 5-HT₁ receptor sites in intracranial blood vessels and sensory trigeminal nerves. Therapeutic Effects: Cranial vessel vasoconstriction with resultant decrease in migraine headache.

Adverse Reactions/Side Effects

CNS: dizziness, drowsiness, malaise/fatigue. CV: CORONARY ARTERY VASOSPASM, MI, VENTRICULAR FIBRILLATION, VENTRICULAR TACHYCARDIA, myocardial ischemia. GI: nausea. Neuro: paresthesia. Misc: pain/pressure sensation in throat/neck.

PHYSICAL THERAPY IMPLICATIONS

Examination and Evaluation

• Continually monitor for signs of coronary artery vasospasm and MI, including sudden chest pain, pain radiating into the arm or jaw, shortness of breath, dizziness, sweating, anxiety, and nausea. Seek immediate medical assistance if patient develops these signs.

• Assess heart rate, ECG, and heart sounds, especially during exercise (See Appendices G, H). Report any rhythm disturbances or symptoms of increased arrhythmias, including palpitations, chest discomfort, shortness of breath, dizziness, fainting, and fatigue/weakness.

• Assess the frequency and severity of headaches, and document whether drug therapy is successful in decreasing the intensity of migraine attacks.

• Watch for dizziness that affects gait, balance, and other functional activities (See Appendix C). Report balance problems and functional limitations to the physician, and caution the patient and family/caregivers to guard against falls and trauma.

• Assess any neck or throat pain and pressure to rule out musculoskeletal pathology; that is, try to determine if pain is drug induced rather than caused by anatomic or biomechanical problems.

• Assess signs of paresthesia (numbness, tingling). Perform objective tests, including electroneuromyography and sensory testing to document any drug-related neuropathic changes.

Interventions

• Because of the risk of MI and ventricular arrhythmias, use extreme caution during aerobic exercise and other forms of therapeutic exercise. Assess exercise tolerance frequently (blood pressure, heart rate, respiration, fatigue levels), and terminate exercise immediately if any untoward responses occur (See Appendix L).

• Implement appropriate interventions (manual techniques, physical agents, therapeutic exercise) to manage headache pain and reduce the need for drug therapy. Help patient also explore other nonpharmacologic methods to reduce chronic headache pain, such as relaxation techniques, imagery, and so forth.

• If a headache occurs and drug treatment is needed during a rehabilitation session, allow patient to recover in a quiet, darkened room to allow the drug to achieve maximal effects.

Patient/Client-Related Instruction

• Advise patient and family or caregiver about the signs of MI (see above under Examination and Evaluation), and to seek immediate medical assistance if these signs develop.

• Advise the patient to bring this drug to each therapy session; this drug is most effective when taken at the first signs of a migraine attack.

• Advise patient to adhere to the correct dosing schedule, and to not exceed the recommended frequency and number of doses per 24-hr period.

• Instruct patient to report other troublesome side effects such as severe or prolonged drowsiness, malaise, fatigue, or nausea.

Pharmacokinetics

Absorption: Well absorbed (70%) following oral administration.

Distribution: Unknown.

Metabolism and Excretion: 60% excreted unchanged in urine; 30% metabolized by the liver.

Half-life: 6 hr (increased in renal impairment).

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Geriatric patients; Ischemic cardiovascular, cerebrovascular, or peripheral vascular syndromes; History of significant cardiovascular disease; Uncontrolled hypertension; Severe renal impairment (CCr <15 mL/min); Severe hepatic impairment; Should not be used within 24 hr of other 5-HT₁ agonists or ergot-type compounds (dihydroergotamine).

Use Cautiously in: Mild-to-moderate renal or hepatic impairment (dose should not exceed 2.5 mg/24 hr; initial dose should be decreased); Pregnancy, lactation, or children (safety not established).

Exercise Extreme Caution in: Cardiovascular risk factors (hypertension, hypercholesterolemia, cigarette smoking, obesity, diabetes, strong family history, menopausal women or men >40 yr); use only if cardiovascular status has been evaluated and determined to be safe and 1st dose is administered under supervision.

Interactions

Drug-Drug: Concurrent use with SSRI antidepressants may result in weakness, hyperreflexia, and incoordination. Cigarette smoking increases the metabolism of naratriptan. Blood levels and effects are increased by hormonal contraceptives. Avoid concurrent use (within 24 hr of each other) with ergot-containing drugs (dihydroergotamine); may result in prolonged vasospastic reactions. Avoid concurrent (within 2 wk) use with MAO inhibitors; produces increased systemic exposure and risk of adverse reactions to naratriptan. Serotonin syndrome may occur with sibutramine.

Drug-Natural: ↑ risk of serotonergic side effects, including serotonin syndrome with St. John's wort and SAMe.

Route/Dosage

PO (Adults): 1 or 2.5 mg; dose may be repeated in 4 hr if response is inadequate (not to exceed 5 mg/24 hr or treatment of more than 4 headaches/mo).

Availability

Tablets: 1 mg, 2.5 mg.

INTRODUCTION

Indications

To reduce the frequency of exacerbations of relapsing multiple sclerosis (MS).

Action

Binds to integrin receptors on nonneutrophil leukocytes which may alter adhesion and migration characteristics involved in the crossing of activated inflammatory cells into the CNS. Therapeutic Effects: Fewer exacerbations of relapsing multiple sclerosis.

Adverse Reactions/Side Effects

CNS: depression, fatigue. GI: cholelithiasis. Misc: allergic reactions, including anaphylaxis, infections, PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML), infusion-related reactions.

PHYSICAL THERAPY IMPLICATIONS

Examination and Evaluation

• Be alert for signs of PML. Signs include memory lapses, decreased cognition, vision loss, speech problems, incoordination, ataxia, and muscle weakness that can progress to paralysis, seizures, and coma. Report these signs to the physician or nursing staff immediately.

• Monitor signs of allergic reactions and anaphylaxis, including pulmonary symptoms (tightness in the throat and chest, wheezing, cough, dyspnea) or skin reactions (rash, pruritus, urticaria, dermatitis). Be especially alert for responses that occur during and after administration (infusion related reactions). Notify physician or nursing staff immediately if these reactions occur.

• Periodically assess balance, coordination, spasticity, and other aspects of neuromuscular function to help document this drug's effectiveness in reducing MS exacerbations.

• Monitor personality changes, including depression and increased thoughts of suicide. Notify physician if these changes become problematic.

• Report signs of gallstones (cholelithiasis), including sudden intense pain in the abdomen or right side, jaundice, chills, and fever.

Interventions

• Design and implement coordination, balance, and other therapeutic exercises to maintain function, and complement drug effects in patients with MS.

Patient/Client-Related Instruction

• Advise patient to guard against infection (frequent hand washing, etc.), and to avoid crowds and contact with persons with contagious diseases.

• Instruct patient to report other troublesome side effects such as prolonged or severe fatigue or signs of infection.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism and Excretion: Unknown.

Half-life: 7–15 days.

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Concurrent use of immunosuppressants; History of PML; Children <18 yr.

Use Cautiously in: History of depression or suicide attempt; Pregnancy (use only if clearly needed).

Interactions

Drug-Drug: ↑ risk of infections with immunosuppressants (avoid concurrent use).

Route/Dosage

NOTE: Because of the risk of PML, natalizumab is available only under a special restricted distribution program, the TOUCH Prescribing Program. Prescribers, pharmacies, and patients must be enrolled in the program to obtain the drug.

IV (Adults): 300 mg q 4 wk.

Availability

Concentrate for IV infusion: 300 mg/15-mL vial.

INTRODUCTION

Indications

To improve glycemic control in patients with type 2 diabetes (with diet and exercise); may also be used with metformin or a thiazolidinedione (pioglitazone, rosiglitazone).

Action

Stimulates the release of insulin from pancreatic beta cells by closing potassium channels, which results in the opening of calcium channels in beta cells. This is followed by release of insulin. Requires functioning pancreatic beta cells. Therapeutic Effects: Lowering of blood glucose.

Adverse Reactions/Side Effects

CNS: dizziness. Resp: bronchitis, coughing, upper respiratory infection. GI: diarrhea. Endo: HYPOGLYCEMIA. MS: arthropathy, back pain. Misc: flu symptoms.

PHYSICAL THERAPY IMPLICATIONS

Examination and Evaluation

• Be alert for signs of hypoglycemia, especially during and after exercise. Common neuromuscular signs include anxiety; restlessness; tingling in hands, feet, lips, or tongue; chills; cold sweats; confusion; difficulty in concentration; drowsiness; excessive hunger; headache; irritability; nervousness; tremor; weakness; unsteady gait. Report episodes of severe hypoglycemia to the physician immediately.

• Monitor symptoms of upper respiratory tract infection and bronchitis, including cough, production of mucous, wheezing, chest discomfort, shortness of breath, fatigue, chills, and fever. Report severe or prolonged symptoms to the physician.

• Assess dizziness that might affect gait, balance, and other functional activities (See Appendix C). Report balance problems to the physician, and caution the patient and family/caregivers to guard against falls and trauma.

• Assess any back or joint pain to rule out musculoskeletal pathology; that is, try to determine if pain is drug induced rather than caused by anatomic or biomechanical problems.

• Assess blood pressure periodically (See Appendix F). A sudden or sustained increase in blood pressure (hypertension) may indicate problems in diabetes management, and should be reported to the physician.

Interventions

• Implement aerobic exercise and endurance training programs to maintain optimal body weight, improve insulin sensitivity, and reduce the risk of macrovascular disease (heart attack, stroke) and microvascular problems (reduced blood flow to tissues and organs that causes poor wound healing, neuropathy, retinopathy, and nephropathy).

• Provide a source of oral glucose (fruit juice, glucose gels/tablets, etc.) to treat mild hypoglycemia. Call for emergency assistance if symptoms persist or in cases of severe hypoglycemia. Emergency treatment typically consists of IV glucose, glucagon, or epinephrine.

Patient/Client-Related Instruction

• Encourage patient to monitor blood glucose before and after exercise and to adjust food intake to maintain normal glycemic levels.

• Emphasize the importance of adhering to nutritional guidelines, and the need for periodic assessment of glycemic control (serum glucose and glycosylated hemoglobin levels) throughout the management of diabetes mellitus.

• Advise patient about symptoms of hyperglycemia (confusion, drowsiness; flushed, dry skin; fruit-like breath odor; rapid, deep breathing, polyuria; loss of appetite; unusual thirst). Drug dosages may need to be adjusted to prevent repeated episodes of hyperglycemia.

• Instruct patient to report other troublesome side effects such as severe or prolonged diarrhea or flulike symptoms.

Pharmacokinetics

Absorption: Well absorbed (73%) following oral administration; absorption is rapid.

Distribution: Unknown.

Protein Binding: 98%.

Metabolism and Excretion: Mostly metabolized by the liver (cytochrome P2C9 and P3A4 [CYP2C9 and CYP3A4] enzyme systems); 16% excreted unchanged in urine.

Half-life: 1.5 hr.

Contraindications/Precautions

Contraindicated in: Hypersensitivity; OB: Pregnancy or lactation (insulin recommended to control diabetes during pregnancy); Diabetic ketoacidosis; Type 1 diabetes.

Use Cautiously in: Geri: Elderly patients, malnourished patients, patients with pituitary or adrenal insufficiency (increased susceptibility to hypoglycemia); Strenuous physical exercise, insufficient caloric intake (increased risk of hypoglycemia); Autonomic neuropathy (hypoglycemia may be masked); Moderate-to-severe liver impairment; Fever, infection, trauma, or surgery (may lead to transient loss of glycemic control; insulin may be required); Pedi: Children (safety not established).

Interactions

Drug-Drug: Concurrent use with beta blockers may mask hypoglycemia. Alcohol, combination with other antidiabetics, NSAIDs, MAO inhibitors, or nonselective beta blockers may ↑ the risk of hypoglycemia. Hypoglycemic effects may be ↓ by thiazide diuretics, corticosteroids, thyroid supplements, or sympathomimetic (adrenergic) agents.

Drug-Food: Blood levels and effects are significantly ↓ when administered prior to a liquid meal.

Route/Dosage

PO (Adults): 120 mg tid before meals; patients who are approaching glycemic control may be started at 60 mg tid.

Availability

Tablets: 60 mg, 120 mg.

INTRODUCTION

Indications

Hypertension (alone and with other antihypertensives).

Action

Blocks stimulation of beta-adrenergic receptor sites; selective for beta₁ (myocardial) receptors in most patients. In some patients (poor metabolizers, higher blood levels may result in some beta₂ [pulmonary, vascular, uterine] adrenergic) blockade. Therapeutic Effects: Lowering of blood pressure.

Adverse Reactions/Side Effects

CNS: dizziness, fatigue, headache.

PHYSICAL THERAPY IMPLICATIONS

Examination and Evaluation

• Assess blood pressure periodically and compare to normal values (See Appendix F) to help document antihypertensive effects.

• Assess dizziness that might affect gait, balance, and other functional activities (See Appendix C). Report balance problems and functional limitations to the physician, and caution the patient and family/caregivers to guard against falls and trauma.

• Monitor excessive fatigue or weakness. Beta blockers often cause some degree of fatigue and weakness, but any sudden or severe change in muscle strength or energy levels should be reported.

Interventions

• Establish aerobic exercise workloads that account for the effects of beta blockers on heart rate. Some heart rate guidelines may not be appropriate because beta blockers typically decrease maximal HR by 20–30 bpm. Use other guidelines such as rating of perceived exertion (RPE, modified Borg scale) to determine exercise workloads.

• To minimize orthostatic hypotension, patient should move slowly when assuming a more upright position.

Patient/Client-Related Instruction

• Remind patients to take medication as directed to control hypertension even if they are asymptomatic.

• Counsel patients about additional interventions to help control blood pressure such as regular exercise, weight loss, sodium restriction, stress reduction, moderation of alcohol consumption, and smoking cessation.

Pharmacokinetics

Absorption: Well absorbed following oral administration.

Distribution: Unknown.

Protein Binding: 98%.

Metabolism and Excretion: Mostly metabolized by the liver, including the CYP2D6 enzyme system; some have antihypertensive action; minimal excretion of unchanged drug.

Half-life: Extensive metabolizers—12 hr; poor metabolizers—19 hr.

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Severe bradycardia, heart block greater than 1st degree, cardiogenic shock, decompensated heart failure or sick sinus syndrome (without pacemaker); Severe hepatic impairment (Child-Pugh >B); Bronchospastic disease; OB: Lactation.

Use Cautiously in: Coronary artery disease (rapid cessation should be avoided); Compensated congestive heart failure; Major surgery (anesthesia may augment myocardial depression); Diabetes mellitus (may mask signs of hypoglycemia); Thyrotoxicosis (may mask symptoms); Moderate hepatic impairment (↓ metabolism); Severe renal impairment (↓ initial dose if CCr <30 mL/min); History of severe allergic reactions (↑ intensity of reactions); Pheochromocytoma (alpha blockers required prior to beta blockers); Geri: Consider increased sensitivity, concurrent chronic diseases, medications, and presence of age-related decrease in clearance; OB: Use in pregnancy only if maternal benefit outweighs fetal risk; Pedi: Safe use in children <18 yr not established.

Interactions

Drug-Drug: Drugs that affect the CYP2D6 enzyme system are expected to alter levels and possibly effects of nebivolol; dose alterations may be required. Fluoxetine, a known inhibitor of CYP2D6, ↑ levels and effects; similar effects may be expected from quinidine, propafenone, and paroxetine. Blood levels are also ↑ by cimetine. Anesthetic agents, including ether, trichloroethylene, and cyclopropane as well as other myocardial depressants or inhibitors of AV conduction such as diltiazem and verapamil, may ↑ risk of myocardial depression and bradycardia. Avoid concurrent use with beta blockers. Concurrent use with reserpine or guanethidine may excessively reduce sympathetic activity. If used concurrently with clonidine, nebivolol should be tapered and discontinued several days prior to gradual withdrawal of clonidine.

Route/Dosage

PO (Adults): 5 mg once daily initially; may increase at 2-wk intervals up to 40 mg/day.

Hepatic/Renal Impairment

PO (Adults): 2.5 mg once daily initially; titrate upward cautiously.

Availability

Tablets: 2.5 mg, 5 mg, 10 mg.

INTRODUCTION

Indications

Major depression. Unlabeled Use: Panic disorder, posttraumatic stress disorder (PTSD).

Action

Inhibits the reuptake of serotonin and norepinephrine by neurons. Antagonizes alpha₁-adrenergic receptors. Therapeutic Effects: Antidepressant action, which may develop only after several weeks.

Adverse Reactions/Side Effects

CNS: dizziness, insomnia, somnolence, agitation, confusion, weakness. EENT: abnormal vision, blurred vision, eye pain, tinnitus. Resp: dyspnea. CV: bradycardia, hypotension. GI: HEPATIC FAILURE, HEPATOTOXICITY, constipation, dry mouth, nausea, gastroenteritis. GU: erectile dysfunction. Derm: rashes. Hemat: decreased hematocrit.

PHYSICAL THERAPY IMPLICATIONS

Examination and Evaluation

• Be alert for signs of hepatotoxicity and liver failure, including anorexia, abdominal pain, severe nausea and vomiting, yellow skin or eyes, fever, sore throat, malaise, weakness, facial edema, lethargy, and unusual bleeding or bruising. Report these signs to the physician immediately.

• Be alert for increased depression and suicidal thoughts and ideology, especially when initiating drug treatment or in children and teenagers. Notify physician or other mental health care professional immediately if patient exhibits worsening depression or other changes in mood and behavior.

• Assess blood pressure periodically and compare to normal values (See Appendix F). Report low blood pressure (hypotension), especially if patient experiences dizziness or syncope.

• Assess heart rate, ECG, and heart sounds, especially during exercise (See Appendixes G, H). Report an unusually slow heart rate (bradycardia) or signs of other arrhythmias, including palpitations, chest discomfort, shortness of breath, fainting, and fatigue/weakness.

• Assess dizziness and drowsiness that might affect gait, balance, and other functional activities (See Appendix C). Report balance problems and functional limitations to the physician, and caution the patient and family/caregivers to guard against falls and trauma.

• Be alert for agitation, confusion, or other alterations in mental status. Notify physician promptly if these symptoms develop (See Appendix D).

Interventions

• Guard against falls and trauma (hip fractures, head injury, and so forth), and implement fall prevention strategies (See Appendix E).

• Because of the risk of bradycardia and other arrhythmias, use caution during aerobic exercise and other forms of therapeutic exercise. Assess exercise tolerance frequently (blood pressure, heart rate, fatigue levels), and terminate exercise immediately if any untoward responses occur (See Appendix L).

• To minimize orthostatic hypotension, patient should move slowly when assuming a more upright position.

• Help patient explore nonpharmacologic methods reduce depression and other psychologic disorders (exercise, counseling, support groups, and so forth).

Patient/Client-Related Instruction

• Advise patient that antidepressant effects may not occur immediately; it may take 2 wk or more before an improvement in mood is observed.

• Advise patient to avoid alcohol and other CNS depressants because of the increased risk of sedation and adverse effects.

• Instruct patient to report other problematic side effects such as severe or prolonged insomnia, vision disturbances, ringing/buzzing in the ears (tinnitus), erectile dysfunction, skin rashes, GI problems (nausea, constipation, dry mouth), or signs of GI infection (diarrhea, vomiting, abdominal cramps, fever).

Pharmacokinetics

Absorption: Well absorbed but undergoes extensive and variable first-pass hepatic metabolism (bioavailability about 20%).

Distribution: Widely distributed; enters the CNS.

Protein Binding: ≥99%.

Metabolism and Excretion: Extensively metabolized. One metabolite (hydroxynefazodone) has antidepressant activity.

Half-life: Nefazodone—2–4 hr; hydroxynefazodone—1.5–4 hr.

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Concurrent MAO inhibitor therapy; Active liver disease or baseline elevated serum transaminases.

Use Cautiously in: May ↑ risk of suicide attempt/ideation, especially during dose early treatment or dose adjustment; History of suicide attempt or drug abuse; Underlying cardiovascular or cerebrovascular disease; History of mania; OB: Safety no established; Lactation: Discontinue drug or bottle-feed; Pedi: Safety not established in children; suicide risk may be greater in children and adolescents; Geri: Initiate therapy at lower doses.

Interactions

Drug-Drug: Serious, potentially fatal reactions may occur during concurrent use with MAO inhibitors (do not use concurrently or within 2 wk of MAO inhibitors; discontinue nefazodone at least 14 days before starting MAO inhibitor therapy). ↑ CNS depression with other CNS depressants, including alcohol, antihistamines, opioid analgesics, and sedative/hypnotics. May ↑ blood levels and effects of alprazolam or triazolam. May increase serum digoxin levels. Additive hypotension may occur with antihypertensives, nitrates, or acute ingestion of alcohol. May ↑ risk of myopathy with HMG CoA reductase inhibitors. Decreased antidepressant action with concomitant use of carabazepine. May reduce clearance of haloperidol, so haloperidol dose may need to be decreased.

Drug-Natural: ↑ risk of seritonergic side effects, including serotonin syndrome with St. John's wort and SAMe. Kava, valerian, or chamomile can ↑ CNS depression.

Route/Dosage

PO (Adults): 100 mg bid initially; may be ↑ weekly up to 600 mg/day in 2 divided doses.

PO (Geriatric Patients): 50 mg bid initially; may be ↑ weekly as tolerated.

Availability (generic available)

Tablets: 50 mg, 100 mg, 150 mg, 200 mg, 250 mg.

INTRODUCTION

Indications

T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma unresponsive to at least 2 other previous chemotherapy regimens.

Action

Converted intracellularly to arabinosylguanine (ara-G) and then to arabinosylguanine triphosphate (ara-GTP). In leukemic cells, it is incorporated into DNA, leading to inhibition of DNA synthesis and cell death.Therapeutic Effects: Decreased proliferation of leukemic cells.

Adverse Reactions/Side Effects

Hemat: anemia, leukopenia, neutropenia, thrombocytopenia. Neuro: SEVERE NEUROLOGIC EVENTS.

PHYSICAL THERAPY IMPLICATIONS

Examination and Evaluation

• Be alert for signs of CNS neurotoxicity, including confusion, agitation, severe headache, hearing loss, visual disturbances, decreased consciousness, and seizures. Notify physician immediately, especially if patient becomes unresponsive or difficult to arouse.

• Monitor signs of leukopenia and neutropenia (fever, sore throat, signs of infection), thrombocytopenia (bruising, nose bleeds, bleeding gums), or anemia (unusual weakness, fatigue, shortness of breath, pallor). Report these signs to the physician.

Interventions

• For patients who are medically able to begin exercise, implement appropriate resistive exercises and aerobic training to maintain muscle strength and aerobic capacity during cancer chemotherapy or to help restore function after chemotherapy.

Patient/Client-Related Instruction

• Advise patient to decrease risk of infections (frequent hand washing, etc.) and to avoid contact with persons with contagious diseases.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability. Intracellular conversion is required for activation of prodrug.

Distribution: Extensively distributed.

Metabolism and Excretion: Mostly metabolized intracellularly. Partially eliminated by the kidneys as nelarabine and ara-G.

Half-life: Unknown.

Contraindications/Precautions

Contraindicated in: Hypersensitivity; CCr <50 mL/min; OB: Pregnancy, lactation.

Use Cautiously in: OB: Patients with childbearing potential; Geri: Risk of neurologic events may be ↑; Severe hepatic impairment (bilirubin >3.0 mg/dL).

Interactions

Drug-Drug: Decreases antibody response to and ↑ risk of adverse reactions from live-virus vaccines.

Route/Dosage

IV (Adults): 1500 mg/m² on days 1, 3, and 5 of every 21-day cycle.

IV (Children): 650 mg/m²/day for first 5 days of every 21-day cycle.

Availability

Solution for IV injection: 5 mg/mL in 50-mL vials (250 mg/vial).

INTRODUCTION

Indications

HIV infection (with other antiretrovirals).

Action

Inhibits HIV protease and prevents cleavage of viral polyproteins. Therapeutic Effects: Increased CD4 cell count and decreased viral load. Slowed progression of HIV infection with less sequela.

Adverse Reactions/Side Effects

CNS: SEIZURES, anxiety, depression, dizziness, drowsiness, emotional lability, headache, hyperkinesia, malaise, migraine headache, sleep disorders, suicidal ideation, weakness. EENT: acute iritis, pharyngitis, rhinitis, sinusitis. Resp: dyspnea. GI: diarrhea, anorexia, dyspepsia, elevated liver function studies, epigastric pain, flatulence, GI bleeding, hepatitis, nausea, oral ulcerations, pancreatitis, vomiting. GU: nephrolithiasis, sexual dysfunction. Derm: pruritus, rash, sweating, urticaria. Endo: fat redistribution, hyperglycemia. F and E: dehydration. Hemat: anemia, leukopenia, thrombocytopenia. Metab: hyperlipidemia, hyperuricemia. MS: arthralgia, arthritis, back pain, myalgia, myopathy. Neuro: myasthenia, paresthesia. Misc: allergic reactions, fever.

PHYSICAL THERAPY IMPLICATIONS

Examination and Evaluation

• Be alert for new seizures or increased seizure activity, especially at the onset of drug treatment. Document the number, duration, and severity of seizures, and report these findings immediately to the physician.

• Be alert for signs of peripheral neuropathy (numbness, tingling) and myopathy (muscle pain, weakness). Establish baseline electroneuromyographic values using EMG and nerve conduction at the beginning of drug treatment whenever possible, and reexamine these values periodically to document drug-induced changes in nerve and muscle function.

• Assess any back pain or joint pain to rule out musculoskeletal pathology; that is, try to determine if pain is drug induced rather than caused by anatomic or biomechanical problems.

• Monitor signs of allergic reactions, including pulmonary symptoms (tightness in the throat and chest, wheezing, dyspnea) or skin reactions (rash, pruritus, urticaria). Notify physician or nursing staff immediately if these reactions occur.

• Be alert for signs of hyperglycemia, including confusion, drowsiness, flushed/dry skin, fruit-like breath odor, rapid/deep breathing, polyuria, loss of appetite, and unusual thirst. Patients with diabetes mellitus should check blood glucose levels frequently.

• Monitor signs of leukopenia (fever, sore throat, signs of infection), thrombocytopenia (bruising, nose bleeds, and bleeding gums), or unusual weakness and fatigue that might be due to anemia. Report these signs to the physician.

• Monitor and report signs of kidney stones (nephrolithiasis), including severe pain in the side and back, pain on urination, bloody urine, and a persistent urge to urinate.

• Assess dizziness and drowsiness that might affect gait, balance, and other functional activities (See Appendix C). Report balance problems and functional limitations to the physician and nursing staff, and caution the patient and family/caregivers to guard against falls and trauma.

• Monitor personality changes, including anxiety, depression, mood swings, severe restlessness, and increased thoughts of suicide. Notify physician if these changes become problematic.

Interventions

• Implement resistive exercises and other therapeutic exercises as needed to maintain muscle strength and function and prevent muscle wasting associated with HIV infection and AIDS.

• Design and implement aerobic exercise and endurance training programs to help prevent heart disease associated with drug-related hyperlipidemia and other problems with lipid and glucose metabolism.

• Make sure that fluid intake is adequate during and after exercise; this drug increases the risk of dehydration.

Patient/Client-Related Instruction

• Emphasize the importance of taking nelfinavir as directed even if the patient is asymptomatic, and that this drug must always be used in combination with other antiretroviral drugs. Do not take more than prescribed amount, and do not stop taking nelinavir without consulting a health care professional.

• Inform patient that nelfinavir does not cure HIV or AIDS or prevent associated or opportunistic infections. Nelfinavir does not reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom, and to avoid sharing needles or donating blood to prevent spreading the AIDS virus to others.

• Advise patient that this drug may cause problems in fat metabolism (hyperlipidemia). Remind patient that periodic blood tests may be needed to monitor plasma lipids.

• Inform patient that redistribution and accumulation of body fat may occur, causing central obesity, thin arms and legs, dorsocervical fat enlargement (buffalo hump), breast enlargement, and other symptoms that resemble Cushing's syndrome (moon face, striations on abdominal skin). Discuss possible effects on body image, and help patient explore coping mechanisms.

• Instruct patient to immediately report signs of GI bleeding, including abdominal pain, vomiting blood, blood in stools, or black, tarry stools.

• Advise patient about the likelihood of other GI reactions, including diarrhea, nausea, vomiting, flatulence, heartburn, oral ulcerations, and loss of appetite. Instruct patient to report severe or prolonged GI problems, signs of liver toxicity (yellow skin or eyes, abdominal pain, severe nausea and vomiting, fever, sore throat, malaise, weakness, facial edema), or pancreatitis (upper abdominal pain especially after eating, indigestion, weight loss, oily stools).

• Instruct patient to report other troublesome side effects such as prolonged or severe headache, migraines, sleep loss, vision problems, sexual dysfunction, or upper respiratory tract irritation (rhinitis, sinusitis, pharyngitis).

Pharmacokinetics

Absorption: Well absorbed after oral administration.

Distribution: Unknown.

Protein Binding: >98%.

Metabolism and Excretion: Mostly metabolized (CYP3A4 enzyme system) and excreted in feces as metabolites (78%) or unchanged drug (22%); minimal renal excretion.

Half-life: 3.5–5 hr.

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Concurrent amiodarone, ergot derivatives, midazolam, quinidine, rifampin, pimozide, simvastatin, lovastatin, St. John's wort, or triazolam; Lactation: Breast-feeding should be avoided by HIV-infected patients.

Use Cautiously in: Hemophiliacs (↑ risk of bleeding); Diabetes mellitus (may exacerbate condition); Hepatic impairment.

Interactions

Drug-Drug: Concurrent amiodarone, dihydroergotamine, ergotamine, methylergonovine, ergonovine, midazolam, simvastatin, lovastatin, pimozide, quinidine, or triazolam should be avoided; nelfinavir inhibits the action of the CYP3A4 enzyme system and concurrent use may result in excess sedation, vasoconstriction, rhabdomyolysis or serious cardiac arrhythmias. Since nelfinavir is also metabolized by the CYP3A4 enzyme system, potent inducers of the enzyme such as rifampin may ↓ blood levels of nelfinavir and promote resistance to its effects; concurrent use should be avoided. ↓ metabolism may ↑ effects of rifabutin (dose of rifabutin should be ↓ by 50%), carbamazepine, phenobarbital, or phenytoin (concurrent use with rifampin should be avoided). Plasma levels and effectiveness may be ↑ by ketoconazole, indinavir, delavirdine, or ritonavir. May ↓ levels of methadone; dose of methadone may need to be ↑. ↑ plasma levels of indinavir, saquinavir, cyclosporine, tacrolimus, sirolimus, and azithromycin. ↑ levels and effects of sildenafil (sildenafil dose should not exceed 25 mg in 48 hr). ↑ levels and risk of toxicity from atorvastatin (use lowest dose of these agents or consider fluvastatin or pravastatin). Blood levels may be ↓ by nevirapine. Should not be given at the same time as didanosine. May ↓ plasma levels and effectiveness of hormonal contraceptives or delavirdine. May ↑ concentrations of phosphodiesterase type 5 inhibitors (PDE5) causing hypotension, visual changes, priapism; ↓ starting doses not to exceed 25 mg within 48 hr for sildenafil, 2.5 mg every 72 hr for vardenafil and 10 mg every 72 hr for tadalafil.

Drug-Natural: St. John's wort induces metabolism of nelfinavir, ↓ blood levels, and may promote resistance to its effects.

Drug-Food: Food ↑ absorption.

Route/Dosage

PO (Adults and Children >13 yr): 750 mg tid or 1250 mg bid.

PO (Children 2–13 yr): 20–30 mg/kg tid (not to exceed 750 mg tid).

Availability

Tablets: 250 mg, 625 mg. Oral powder: 50 mg nelfinavir/1 g powder (1 g powder/level scoopful).

INTRODUCTION

Indications

Preparation of the GI tract for surgery. Treatment of diarrhea caused by Escherichia coli. To decrease the number of ammonia-producing bacteria in the gut as part of the management of hepatic encephalopathy.

Action

Inhibits protein synthesis in bacteria at level of 30S ribosome. Therapeutic Effects: Bactericidal action. Spectrum: Notable for activity against Klebsiella pneumoniae, E. coli, Proteus, Serratia, Acinetobacter, Staphylococcus aureus.

Adverse Reactions/Side Effects

GI: diarrhea, nausea, vomiting. Misc: hypersensitivity reactions.

PHYSICAL THERAPY IMPLICATIONS

Examination and Evaluation

• Monitor signs of hypersensitivity reactions, including pulmonary symptoms (tightness in the throat and chest, wheezing, cough dyspnea) or skin reactions (rash, pruritus, urticaria). Notify physician or nursing staff immediately if these reactions occur.

Interventions

• Always wash hands thoroughly and disinfect equipment (whirlpools, electrotherapeutic devices, treatment tables, and so forth) to help prevent the spread of infection. Use universal precautions or isolation procedures as indicated for specific patients.

Patient/Client-Related Instruction

• Advise patient about the likelihood of GI reactions, including diarrhea, nausea, and vomiting. Instruct patient to report severe or prolonged GI problems.

Pharmacokinetics

Absorption: Minimal systemic absorption, but may accumulate in patients with renal failure.

Distribution: Widely distributed throughout extracellular fluid; crosses the placenta; small amounts enter breast milk. Poor penetration into CSF.

Metabolism and Excretion: Excretion is >90% renal.

Half-life: 2–4 hr (increased in renal impairment).

Contraindications/Precautions

Contraindicated in: Hypersensitivity to neomycin or other aminoglycosides; Intestinal obstruction.

Use Cautiously in: Renal impairment (lower doses are recommended); Hearing impairment; Geriatric patients; Neuromuscular diseases such as myasthenia gravis; Pregnancy, lactation, infants, and neonates (safety not established).

Interactions

Interactions are listed for systemically absorbed drug

Drug-Drug: May enhance possible respiratory paralysis after inhalation anesthetics or neuromuscular blockers. ↑ incidence of ototoxicity with loop diuretics. ↑ incidence of nephrotoxicity with other nephrotoxic drugs. May ↑ the anticoagulant effects of warfarin. May ↓ the absorption of digoxin and methotrexate.

Route/Dosage

Preoperative Intestinal Antisepsis

PO (Adults): 1 g q hr for 4 doses, then 1 g q 4 hr for 5 doses or 1 g at 1 PM, 2 PM, and 11 PM on day before surgery.

PO (Children): 15 mg/kg q 4 hr for 2 days or 25 mg/kg at 1 PM, 2 PM, and 11 PM on day before surgery.

Hepatic Encephalopathy

PO (Adults): 1–3 g q 6 hr for 5–6 days; may be followed by 4 g/day chronically.

PO (Children): 12.5–25 mg/kg q 6 hr for 5–6 days (max dose 12 g/day).

Availability (generic available)

Oral solution: 125 mg/5 mL. Tablets: 500 mg. In combination with: other topical antibiotics or anti-inflammatory agents for skin, ear, and eye infections. See Appendix B.

INTRODUCTION

Indications

Acutely decompensated CHF in hospitalized patients who have dyspnea at rest or with minimal activity; has been used with digoxin, diuretics, and angiotensin-converting enzyme (ACE) inhibitors. Should not be used for intermittent outpatient infusion, scheduled repetitive use, as a diuretic or to improve renal function.

Action

Binds to guanyl cyclase receptors in vascular smooth muscle and endothelial cells, producing increased intracellular guanosine 3′5′-cyclic monophosphate (cGMP) and smooth muscle cell relaxation. cGMP acts as a “second messenger” to dilate veins and arteries. Therapeutic Effects: Dose-dependent reduction in pulmonary capillary wedge pressure (PCWP) and systemic arterial pressure in patients with heart failure with resultant decrease in dyspnea.

Adverse Reactions/Side Effects

CNS: anxiety, confusion, dizziness, headache, insomnia, drowsiness. EENT: amblyopia. Resp: APNEA, cough, hemoptysis. CV: hypotension, arrhythmias, bradycardia. GI: abdominal pain, nausea, vomiting. GU: ↑ creatinine, renal failure. Derm: itching, rash, sweating. Hemat: anemia. Local: injection site reactions. MS: back pain, leg cramps. Neuro: paresthesia, tremor. Misc: fever.

PHYSICAL THERAPY IMPLICATIONS

Examination and Evaluation

• Assess respiration, and notify physician or nursing staff immediately if patient exhibits any interruption in respiratory rate (apnea) or other severe respiratory symptoms (coughing up blood).

• Assess signs and symptoms of CHF (dyspnea, rales/crackles, peripheral edema, jugular venous distention, exercise intolerance) to help document whether drug therapy is effective in reducing these symptoms.

• Assess heart rate, ECG, and heart sounds, especially during exercise (See Appendices G, H). Report a slow heart rate (bradycardia) or symptoms of other arrhythmias, including palpitations, chest pain, shortness of breath, fainting, and fatigue/weakness.

• Assess blood pressure periodically and compare to normal values (See Appendix F). Report low blood pressure (hypotension), especially if patient experiences dizziness, fatigue, or other symptoms.

• Monitor signs of anemia, including unusual fatigue, shortness of breath with exertion, and bruising. Notify physician or nursing staff immediately if these signs occur.

• Monitor signs of renal failure, including decreased urine output, increased blood pressure, muscle cramps/twitching, edema/weight gain from fluid retention, yellowish brown skin, and confusion that progresses to seizures and coma. Report these signs to the physician or nursing staff immediately.

• Assess signs of parasthesia (numbness, tingling). Perform objective tests, including electroneuromyography and sensory testing to document any drug-related neuropathic changes.

• Assess any back pain or leg cramps to rule out musculoskeletal pathology; that is, try to determine if pain is drug induced rather than caused by anatomic or biomechanical problems.

• Assess dizziness and drowsiness that might affect gait, balance, and other functional activities (See Appendix C). Report balance problems and functional limitations to the physician and nursing staff, and caution the patient and family/caregivers to guard against falls and trauma.

• Monitor personality or behavioral changes, including anxiety, confusion, or other changes in mood. Notify physician if these changes become problematic.

• Monitor IV injection site for pain, swelling, and irritation. Report prolonged or excessive injection site reactions to the physician or nursing staff.

Interventions

• Design and implement aerobic exercise and endurance training programs as tolerated to help improve myocardial pumping ability.

• Because of an increased risk of bradycardia and other arrhythmias, use caution during aerobic exercise and endurance conditioning. Terminate exercise if patient exhibits untoward symptoms (chest pain, shortness of breath, unusual fatigue) or displays other criteria for exercise termination (See Appendix L).

• Avoid physical therapy interventions that cause systemic vasodilation (large whirlpool, Hubbard tank). Additive effects of this drug and the intervention may cause a dangerous fall in blood pressure.

• To minimize orthostatic hypotension, patient should move slowly when assuming a more upright position.

Patient/Client-Related Instruction

• Counsel patients about additional interventions to help cardiac dysfunction, including regular exercise, weight loss, sodium restriction, stress reduction, moderation of alcohol consumption, and smoking cessation.

• Instruct patient or family/caregivers to report other troublesome side effects such as severe or prolonged headache, double vision, tremor, fever, skin problems (rash, itching, sweating), or GI problems (nausea, vomiting, abdominal pain).

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism and Excretion: Cleared from circulation by binding to cell surface clearance receptors resulting in cellular internalization and proteolysis, proteolytic breakdown by endopeptidases, and renal filtration.

Half-life: 18 min.

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Cardiogenic shock; Systolic blood pressure (BP) <90 mm Hg; Low cardiac filling pressure, significant valvular stenosis, restrictive/subtractive cardiomyopathy, constrictive pericarditis/cardiac tamponade, or other conditions in which cardiac output is dependent on venous return.

Use Cautiously in: Heart failure where renal function is dependent on activity of the renin/angiotensin/aldosterone system (may cause azotemia); BP <90 mm Hg (increased risk of hypotension); Geri: Geriatric patients (some may be more sensitive to effects); Cardiogenic shock (should not be used as primary therapy); OB: Pregnancy, lactation; Pedi: Children (safety not established).

Interactions

Drug-Drug: None reported.

Route/Dosage

IV (Adults): 2 mcg/kg bolus followed by 0.01 mcg/kg/min as a continuous infusion. May increase by 0.005 mcg/kg/min every 3 hr up to a maximum infusion rate of 0.03 mcg/kg/min (based on response).

Availability

Lyophilized powder for injection (requires reconstitution): 1.5 mg/vial.

INTRODUCTION

Indications

Induction of skeletal muscle paralysis and facilitation of intubation after induction of anesthesia in surgical procedures. Facilitation of compliance during mechanical ventilation. Metocurine, tubocurarine: Adjunct to electroconvulsive therapy. Tubocurarine: Diagnostic agent for myasthenia gravis.

Action

Prevent neuromuscular transmission by blocking the effect of acetylcholine at the myoneural junction. Have no analgesic or anxiolytic properties. Therapeutic Effects: Skeletal muscle paralysis.

Adverse Reactions/Side Effects

Resp: bronchospasm. CV: tubocurarine: arrhythmias; atracurium, metocurine, tubocurarine: hypotension (↑ with tubocurarine); pancuronium, gallamine: hypertension (↑ with gallamine); atracurium, pancuronium, gallamine: tachycardia (↑ with gallamine). GI: pancuronium: excessive salivation. Derm: rash; atracurium: skin flushing. Misc: ALLERGIC REACTIONS, INCLUDING ANAPHYLAXIS.

PHYSICAL THERAPY IMPLICATIONS

Examination and Evaluation

• Monitor signs of allergic reactions and anaphylaxis, including pulmonary symptoms (tightness in the throat and chest, wheezing, cough, dyspnea) or skin reactions (rash, pruritus, urticaria). Notify physician or nursing staff immediately if these reactions occur.

• Be alert for residual skeletal muscle weakness that persists after the patient recovers from surgery. Report any strength deficits that might affect gait, balance, and other functional activities.

• Assess blood pressure (BP) and compare to normal values (See Appendix F). Report changes in BP, either a problematic decrease in BP (hypotension) or a sustained increase in BP (hypertension).

• Assess symptoms of bronchospasm (wheezing, coughing, tightness in chest) or decreased respiratory muscle function. Perform pulmonary function tests to quantify suspected changes in ventilation and respiration (See Appendix I).

• Assess heart rate, ECG, and heart sounds, especially during exercise (See Appendices G, H). Report any rhythm disturbances or symptoms of increased arrhythmias, including palpitations, chest discomfort, shortness of breath, fainting, and fatigue/weakness.

• If used during mechanical ventilation, observe whether the chest wall is relaxed and compliant with ventilation. Notify physician or nursing staff if the patient is agitated or appears to be resisting mechanical ventilation.

Patient/Client-Related Instruction

• Instruct patient to report other troublesome side effects such as excessive salivation or skin problems (rash, flushing).

Pharmacokinetics

Absorption: Following IV administration, absorption is essentially complete. Tubocurarine—Although well absorbed following IM administration, effect is delayed as compared with IV administration.

Distribution: Atracurium, gallamine—Distribute into extracellular space; cross the placenta. Metocurine—Extensively distributed; crosses the placenta. Mivacurium—Tissue distribution is limited. Pancuronium—Rapidly distributes into extracellular fluid; small amounts cross the placenta. Tubocurarine—Extensively distributed and subsequently redistributed to various tissue compartments; saturation of compartments occurs, explaining prolonged duration of action following repeated doses. Vecuronium—Rapidly distributed in extracellular fluid; minimal penetration of the CNS.

Metabolism and Excretion: Atracurium, mivacurium—Metabolized in plasma. Cisatracurium—Undergoes pH-dependent breakdown, which is responsible for 80% of metabolism; remainder eliminated by liver and kidneys. Doxacurium—Excreted primarily unchanged in urine and bile. Gallamine—Excreted almost entirely unchanged by the kidneys. Metocurine—50% excreted unchanged in urine. Pancuronium—Excreted mostly unchanged by the kidneys; small amounts are eliminated in bile. Pipecuronium—>75% excreted by the kidneys, mostly as unmetabolized drug. Rocuronium—Mostly metabolized by the liver. Tubocurarine—30–75% excreted unchanged by the kidneys; 11% excreted in bile; small amounts are metabolized by the liver. Vecuronium—Some metabolism by the liver (20%), with conversion to at least 1 active metabolite; 35% excreted unchanged by the kidneys.