1. Introduction to Clinical Pharmacology Chapter 28 Antiparkinson Drugs

2. 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

3. Dopaminergic Drugs: Actions
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

4. 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

5. 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

6. Dopaminergic Drugs: Adverse Reactions, Contraindications, and Precautions #2
Levodopa: patients with narrow-angle glaucoma, 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 opioid meperidine due to antimetabolite conversion

7. 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

8. 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

9. 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

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

11. 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

12. 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

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

14. 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

15. 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; blurred vision; dizziness; mild nausea; nervousness; skin rash; urticaria; urinary retention; dysuria; tachycardia; muscle weakness; disorientation; confusion

16. 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

17. 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

18. 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

19. 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.

20. 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

21. 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

22. 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
Monitor patient’s weight daily

23. 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

24. 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

25. 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

26. 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
Encourage family to create a home environment that is least likely to result in accidents or falls

27. 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

28. Question #1 Is the following statement true or false?
Parkinson disease is a progressive neurologic disease caused by an increase in dopamine in the brain.

29. Answer to Question #1 False
Parkinson disease is a progressive neurologic disease caused by a reduction in dopamine in the brain. Cardinal signs include tremors, rigidity, and bradykinesia.

30. Question #2 Is the following statement true or false?
When drugs or other illnesses cause Parkinson-like symptoms, these are termed parkinsonism or extrapyramidal symptoms.

31. Answer to Question #2 True
When drugs or other illnesses cause Parkinson-like symptoms, these are termed parkinsonism or extrapyramidal symptoms.

32. Question #3 Is the following statement true or false?
The drugs used to treat Parkinson disease and parkinsonism either supplement dopamine or block excess acetylcholine to enhance neurotransmission.

33. Answer to Question #3 True
The drugs used to treat Parkinson disease and parkinsonism either supplement dopamine or block excess acetylcholine to enhance neurotransmission. Blood–brain barrier issues make supplementing dopamine difficult.