Introduction to Clinical Pharmacology Chapter 28 Antiparkinson Drugs

Definitions Parkinsonism: referring to a cluster of symptoms associated with Parkinson disease (i.e., fine tremors, slowing of voluntary movements, muscular weakness) Parkinson disease: degenerative disorder caused by an imbalance of dopamine and acetylcholine in the CNS The cardinal signs of Parkinson disease include tremors, rigidity, and slow movement (bradykinesia). Other symptoms of Parkinson disease include slurred speech, a mask-like and emotionless appearance of the face, and difficulty chewing and swallowing. The client assumes a rigid, bent-forward posture and the gait becomes unsteady and shuffled.

Dopaminergic Drugs: Actions Review the Summary Drug Table Symptoms of parkinsonism are caused by depletion of dopamine in CNS Amantadine: makes more dopamine available at receptor site; selegiline and rasagiline: inhibit monoamine oxidase type B, again making more dopamine available Combining levodopa with another drug allows more levodopa to reach brain, hence provide better pharmacologic effect in patients with Parkinson disease

Dopaminergic Drugs: Uses Dopaminergic drugs are used to treat: Parkinson disease Parkinson-like symptoms as a result of injury, drug therapy, or encephalitis Restless leg syndrome Viral infections

Dopaminergic Drugs: Adverse Reactions, Contraindications, and Precautions #1 Dry mouth, difficulty in swallowing, anorexia, nausea, vomiting, abdominal pain, constipation, increased hand tremor, headache, dizziness Adverse reactions seen with levodopa: choreiform movements, dystonic movements Contraindications: Dopaminergic drugs: patients with known hypersensitivity to the drugs

Dopaminergic Drugs: Adverse Reactions, Contraindications, and Precautions #2 Carbidopa/Levodopa: patients with narrow-angle glaucoma, those receiving MAOI antidepressants Precautions: Carbidopa/Levodopa is used cautiously in patients with cardiovascular or pulmonary diseases; peptic ulcer disease; renal or hepatic disease; and psychosis Dopamine agonist selegiline should not be used with opioid meperidine due to antimetabolite conversion

Dopaminergic Drugs: Interactions Interacting drug Effect of interaction Tricyclic antidepressants Increased risk of hypertension and dyskinesia Antacids Increased effect of levodopa Anticonvulsants Decreased effect of levodopa

Dopamine Receptor Agonists: Actions and Uses Act directly on postsynaptic dopamine receptors of nerve cells in brain, mimicking effects of dopamine in brain Uses: Used for treatment of signs and symptoms of Parkinson disease and Restless Leg Syndrome

Dopamine Receptor Agonists: Adverse Reactions, Contraindications, Precautions Nausea; dizziness; vomiting; somnolence; hallucinations; confusion; visual disturbances; postural hypotension; abnormal involuntary movements; headache Contraindications: patients with known hypersensitivity to drugs Precautions: used with caution in patients with dyskinesia; orthostatic hypotension; hepatic or renal impairment; history of hallucinations or psychosis; cardiovascular disease; renal impairment

Dopamine Receptor Agonists: Interactions Interacting drug Effect of interaction Cimetidine, ranitidine Increased dopamine agonist effectiveness Verapamil, quinidine Estrogen Phenothiazines Decreased dopamine agonist effectiveness

COMT Inhibitors: Actions and Uses Prolong the effect of levodopa by blocking an enzyme, catechol-O-methyltransferase, which eliminates dopamine With levodopa: increased plasma concentration and duration of action of levodopa Uses: COMT inhibitors are used as adjuncts to levodopa/carbidopa in treating Parkinson disease

COMT Inhibitors: Adverse Reactions, Contraindications, and Precautions Dizziness, dyskinesias, hyperkinesias, akathisia, nausea, anorexia, diarrhea, orthostatic hypotension, sleep disorders, excessive dreaming, somnolence, muscle cramps Contraindicated: patients with hypersensitivity to drugs, during pregnancy and lactation Caution: patients with hypertension; hypotension; decreased hepatic or renal function If hepatic function need to think about checking glucose levels If renal function need to think about checking renal function

COMT Inhibitors: Interactions Interacting drug Effect of interaction MAOI antidepressants Increased risk of toxicity of both drugs Adrenergic drugs Increased risk of cardiac symptoms

Cholinergic Blocking Drugs/ Anticholinergics: Actions Drugs with cholinergic blocking activity; block ACh in CNS, enhancing dopamine transmission Antihistamines, such as diphenhydramine, are used in elderly patients as they produce fewer adverse effects

Cholinergic Blocking Drugs/ Anticholinergics: Uses and Adverse Reactions Used as adjunctive therapy in all forms of parkinsonism and in control of drug-induced extrapyramidal disorders Adverse reactions: Dry mouth as seen when taking amantadine; blurred vision; dizziness; mild nausea; nervousness; skin rash; urticaria; urinary retention; dysuria; tachycardia; muscle weakness; disorientation; confusion

Cholinergic Blocking Drugs/ Anticholinergics: Contraindications and Precautions Contraindicated in patients : With hypersensitivity to anticholinergic drugs; glaucoma; pyloric or duodenal obstruction; peptic ulcers; prostatic hypertrophy; achalasia; myasthenia gravis; megacolon Used with caution in patients with: Tachycardia; cardiac arrhythmias; hypertension; hypotension; tendency toward urinary retention; decreased liver or kidney function; obstructive disease of urinary system or gastrointestinal tract

Cholinergic Blocking Drugs/ Anticholinergics: Interactions Interacting drug Effect of interaction Amantadine Increased anticholinergic effects Digoxin Increased digoxin serum levels Haloperidol Increased psychotic behavior Phenothiazines Increased anticholinergic effects

Nursing Process: Assessment Preadministration assessment: Obtain health history from family member Perform physical assessment of patient to provide baseline for future evaluations of drug therapy Ongoing assessment: Evaluate patient’s response to drug therapy by observing patients for various neuromuscular signs and compare these observations with data obtained during initial physical assessment. If noted improvement of bradykinesia effectiveness of drug therapy is working.

Nursing Diagnoses Imbalanced Nutrition: Less Than Body Requirements related to nausea, dry mouth Constipation related to neurologic changes in the bowel Risk for Injury related to dizziness, lightheadedness, orthostatic hypotension, loss of balance Impaired Physical Mobility related to alterations in balance, unsteady gait, dizziness Disturbed Sleep Pattern related to involuntary movement at rest.

Nursing Process: Planning Expected outcomes for patient may include: Optimal response to drug therapy Support of patient needs related to management of adverse reactions Absence of injury Understanding of and compliance with prescribed therapeutic regimen

Nursing Process: Implementation #1 Promoting an optimal response to therapy: Carefully monitor drug therapy; provide psychological support; emphasize patient and family teaching Requires titration of doses based on patient activities Withhold next dose of drug and immediately notify primary health care provider if sudden behavioral changes are noted

Nursing Process: Implementation #2 Monitoring and managing patient needs: Imbalanced Nutrition: Less Than Body Requirements Help patient relieve dry mouth by offering frequent sips of water, ice chips, or hard candy Create calm environment; serve small, frequent meals; serve foods patient prefers to help improve nutrition If GI distress with carbidopa/levodopa administer with meals Monitor patient’s weight daily

Nursing Process: Implementation #3 Monitoring and managing patient needs (cont.) Constipation: Observe patient with parkinsonism for outward changes that may indicate one or more adverse reactions Stress need for diet high in fiber and increasing fluids in diet

Nursing Process: Implementation #4 Monitoring and managing patient needs (cont.) Risk for injury: Carefully evaluate any sudden changes in patient’s behavior or activity and report them to primary health care provider Assist patient in getting out of bed or a chair, walking, and other self-care activities

Nursing Process: Implementation #5 Monitoring and managing patient needs (cont.) Impaired physical mobility: If the symptoms occur, primary health care provider may order a drug holiday that includes complete withdrawal of levodopa for 5 to 14 days, followed by gradually restarting drug therapy at lower dose

Nursing Process: Implementation #6 Educating the patient and family: Evaluate patient’s ability to understand therapeutic drug regimen; ability to perform self-care in the home environment; ability to comply with prescribed drug therapy Teach the client to be alert for those such as facial grimacing, protruding tongue, exaggerated chewing motions and head movements, and jerking movements of the arms and legs Encourage family to create a home environment that is least likely to result in accidents or falls

Nursing Process: Evaluation Therapeutic effect is achieved, and the symptoms of parkinsonism are controlled Adverse reactions are identified, reported, and managed successfully through appropriate nursing interventions No evidence of injury is seen Patient verbalizes an understanding of treatment modalities, adverse reactions, and importance of continued follow-up care Patient and family demonstrate an understanding of drug regimen