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Introductory Clinical Pharmacology Chapter 32 Antiparkinsonism Drugs Copyright © 2008 Lippincott Williams & Wilkins. Dopaminergic Drugs: Actions • Symptoms of parkinsonism are caused by depletion of dopamine in CNS • Amantadine: makes more of dopamine available at receptor site • Selegiline: inhibits monoamine oxidase type B, again making more dopamine available • Combining levodopa with another drug allows more levodopa to reach brain, providing better pharmacologic effect in patients with Parkinson’s disease Copyright © 2008 Lippincott Williams & Wilkins. Dopaminergic Drugs: Uses • Dopaminergic drugs are used to treat: – Parkinson’s disease – Parkinson-like symptoms as a result of injury, drug therapy, or encephalitis – Restless leg syndrome – Viral infections Copyright © 2008 Lippincott Williams & Wilkins. Dopaminergic Drugs: Adverse Reactions, Contraindications, and Precautions • Dry mouth, difficulty in swallowing, anorexia, nausea, and 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 Copyright © 2008 Lippincott Williams & Wilkins. Dopaminergic Drugs: Adverse Reaction Contraindications, and Precautions (cont’d) – Levodopa: Patients with narrow-angle glaucoma and those receiving MAOI antidepressants • Precautions – 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 opioids (meperidine) due to antimetabolite conversion Copyright © 2008 Lippincott Williams & Wilkins. Dopaminergic Drugs: Interactions Interactant drug Tricyclic antidepressants Antacids Effect of interaction Increased risk of hyperten sion and dyskines ia Increased effect of l e v o Copyright © 2008 Lippincott Williams & Wilkins. d Anticholinergics: Actions • Drugs with cholinergic blocking activity block Ach in CNS, enhancing dopamine transmission • Antihistimines such as diphenhydramine are used in elderly patients, as they produce fewer adverse effects Copyright © 2008 Lippincott Williams & Wilkins. Anticholinergics: Uses and Adverse Reactions • Uses – Used as adjunctive therapy in all forms of parkinsonism and in control of druginduced extrapyramidal disorders • Adverse Reactions – Dry mouth; blurred vision; dizziness; mild nausea; nervousness; skin rash; urticaria; urinary retention; dysuria; tachycardia; muscle weakness; disorientation; confusion Copyright © 2008 Lippincott Williams & Wilkins. 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; a tendency toward urinary retention; decreased liver or kidney function; obstructive disease of urinary system or gastrointestinal tract Copyright © 2008 Lippincott Williams & Wilkins. Anticholinergics: Interactions Interactant drug Amantadine Digoxin Effect of interaction Increased anticholinergic effects Increased digoxin serum Copyright © 2008 Lippincott Williams & Wilkins. COMT Inhibitors: Actions and Uses • Actions – 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 the levodopa • Uses – COMT inhibitors are used as adjuncts to levodopa/carbidopa in treating Parkinson’s disease Copyright © 2008 Lippincott Williams & Wilkins. COMT Inhibitors: Adverse Reactions, Contraindications, and Precautions • Dizziness, dyskinesias, hyperkinesias, nausea, anorexia, diarrhea, orthostatic hypotension, sleep disorders, excessive dreaming, somnolence, muscle cramps, liver failure • Contraindicated in patients with hypersensitivity to drugs and during pregnancy and lactation • Caution in patients with hypertension; hypotension; decreased hepatic or renal function Copyright © 2008 Lippincott Williams & Wilkins. COMT Inhibitors: Interactions Interactant drug MAOI antidepressants Effect of interaction I Copyright © 2008 Lippincott Williams & Wilkins. Dopamine Receptor Agonists: Actions and Uses • Actions – 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’s disease Copyright © 2008 Lippincott Williams & Wilkins. 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; patients with history of hallucinations or psychosis; cardiovascular disease; renal impairment Copyright © 2008 Lippincott Williams & Wilkins. Dopamine Receptor Agonists: Interactions Interactant drug Cimetidine, ranitidine Effect of interaction Increased agonist Copyright © 2008 Lippincott Williams & Wilkins. 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 comparing these observations with data obtained during initial physical assessment Copyright © 2008 Lippincott Williams & Wilkins. 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 Copyright © 2008 Lippincott Williams & Wilkins. Nursing Process: Implementation • 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 Copyright © 2008 Lippincott Williams & Wilkins. Nursing Process: Implementation • Monitoring and managing patient needs – Imbalanced nutrition: Less than bodily 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 • Monitor patient’s weight daily Copyright © 2008 Lippincott Williams & Wilkins. Nursing Process: Implementation • Monitoring and managing patient needs (cont’d) – 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 Copyright © 2008 Lippincott Williams & Wilkins. Nursing Process: Implementation • Monitoring and managing patient needs (cont’d) – Risk for injury •Carefully evaluate any sudden changes in patient’s behavior or activity and reports them to primary health care provider •Assist patient in getting out of bed or a chair, walking, and other self-care activities Copyright © 2008 Lippincott Williams & Wilkins. Nursing Process: Implementation • Monitoring and managing patient needs (cont’d) – Impaired physical mobility •If 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 Copyright © 2008 Lippincott Williams & Wilkins. Nursing Process: Implementation • 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 – Encourage family to create a home environment that is least likely to result in accidents or falls Copyright © 2008 Lippincott Williams & Wilkins. 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 Copyright © 2008 Lippincott Williams & Wilkins.