1. Chapter 17
Antiparkinson Drugs

2. Degenerative Diseases
Medication is unable to cure degenerative diseases of the CNS
Cause is usually unknown
Includes:
Parkinson’s disease
Alzheimer’s disease
Multiple sclerosis (MS)
Huntington’s disease
Amyotrophic lateral sclerosis (ALS)

3. Parkinson’s
Symptoms develop due to destruction of dopamine producing neurons in brain
Brain depends on proper balance of dopamine (inhibitory) and acetylcholine (stimulatory) neurotransmitters
If dopamine is absent, acetylcholine is able to stimulate brain more

4. Neurotransmitters of the Basal Ganglia
Acetylcholine (ACH) & Dopamine (DA):
DA is an inhibitory neurotransmitter.
DA inhibits muscle tone and activity.
Parkinson’s disease is caused by the destruction of the DA neurons:
Deficiency of dopamine disturbs the balance between ACH and DA.
Increased activity of ACH produces excessive motor nerve stimulation.
Learning Outcomes
17 .1 List the major symptoms of Parkinson’s disease.
17 .2 Explain the relationship between dopamine and acetylcholine in the basal ganglia.
Normal function of the basal ganglia depends mainly upon the interaction between two neurotransmitters: acetylcholine (ACH) and dopamine (DA). ACH and DA help regulate the activity of the motor nerves that control voluntary muscle movements.
DA is an inhibitory neurotransmitter released by neurons from another of the basal ganglia, known as the substantia nigra. DA inhibits muscle tone and activity. Parkinson’s disease is caused by destruction of the DA neurons in the substantia nigra.
The deficiency of dopamine in Parkinson’s disease disturbs the balance between ACH and dopamine in favor of ACH. The increased activity of ACH produces excessive motor nerve stimulation, resulting in tremors, muscle rigidity, bradykinesia , and the other symptoms of Parkinson’s disease.

5. Symptoms Classic Triad Postural instability Tremors Muscle rigidity
Bradykinesia
Postural instability
1- hands and head develop palsy like motion of shakiness at rest. Pin rolling.
3- most noticable symptom. Pts have difficulty initiating movement and controlling fine muscle movements. Walking becomes difficult and pts shuffle their feet.
4- pts may hunch over and easily loose balance. Frequent falls.

7. Pharmacotherapy Drug therapy for Parkinson’s focuses on:
1. restoring dopamine function
Dopaminergic Agents
Enzyme Inhibitors
Dopamine Receptor Agonists
2. blocking effect of acetylcholine
Anticholinergics

8. Dopaminergic Agents Used to increase dopamine levels in brain
Drug of choice for Parkinson’s is levodopa
MOA: Precursor of (an agent that stimulates) dopamine synthesis
Levodopa can cross blood-brain barrier; dopamine cannot
Effectiveness of levodopa can be boosted by combining it with carbidopa (marketed as Sinemet)
Carbidopa prevents metabolism of levodopa, making it more available to enter CNS (MOA)
Learning Outcomes
17 .3 Explain the mechanism of action of levodopa and understand the common adverse effects and different movement disorders that occur over time with this drug.
When administered as a drug, dopamine does not readily cross the blood-brain barrier to enter the brain. However, the precursor of dopamine, l-dihydroxyphenylala-nine (levodopa or L-DOPA), does cross the blood-brain barrier into the brain.
As the level of dopamine increases, there is lessening of parkinsonian symptoms and a significant improvement in physical mobility. Many patients are able to resume normal physical activities. Although not all patients respond to levodopa, it is the most effective drug available.

9. Side Effects Involuntary movements Loss of appetite N & V
Orthostatic hypotension
On-off phenomenon
Nursing Considerations:
Several drug interactions
**D/C gradually…abrupt withdrawal can produce acute Parkinsonism
Different doses at different times of the day
Learning Outcomes
17 .3 Explain the mechanism of action of levodopa and understand the common adverse effects and different movement disorders that occur over time with this drug.
The most common adverse effects of levodopa are nausea, vomiting, and loss of appetite (anorexia). In the brain, high levels of dopamine interfere with cardiovascular reflexes that maintain blood pressure. Consequently, some patients experience orthostatic hypotension or fainting.
Another effect that may occur as drug treatment progresses is the on-off phenomenon. This is characterized by alternating periods of mobility and immobility during drug therapy.
A number of drugs interfere with the action of levodopa. The antipsychotic drugs (phenothiazines, haloperidol, drugs that block DA) decrease the effectiveness of levodopa because they block dopamine receptors.

10. Common Dopaminergic Agents
levodopa (Larodopa)
carbidopa-levodopa (Sinemet)
amantadine hydrochloride (Symmetrel)
Useful only in early stages
Believed to increase neuronal release of DA and decrease reuptake of DA
Adverse effects—dry mouth, dizziness, and confusion

11. Anticholinergics How do they work (MOA)? What about side effects?
NC: Not as effective as levodopa
Used early when symptoms not severe, in pts who cannot tolerate levodopa, and in combo therapy
Block the effect of acetylcholine- Inhibit the overactivity of this neurotransmitter.
SE- dry mouth, blurred vision, tachycardia, urinary retention, constipation

12. Common Anticholinergics
benztropine mesylate (Cogentin)
MOA: Block ACH and decrease cholinergic activity
Adverse effects —r/t F/F: HTN, tachycardia, dry mouth, constipation, and urinary retention
Used to use atropine…lg # of SE limited its use.

13. Enzyme Inhibitors
MOA: Inhibit certain enzymes, which leads to an increase of DA in the brain:
Monoamine oxidase-B inhibitors
Catechol-O-methyltransferase
Learning Outcomes
17 .4 Identify the mechanism of action of the MAO-B and COMT inhibitors and how they affect levodopa metabolism.
There are three different types of enzyme inhibitors that are used to increase the formation of dopamine in the brain and prolong the duration of dopamine once it is formed in the brain. Carbidopa inhibits DOPA decarboxylase to increase the amount of levodopa that enters the brain. Drugs that inhibit the enzymes monoamine oxidase-B and catechol-omethyltransferase also inhibit the metabolism of levodopa and dopamine to prolong the duration of action of dopamine in the brain.
Catechol-O-methyltransferase (COMT) is another enzyme that normally is involved in the metabolism of dopamine both peripherally and in the brain.

14. Enzyme Inhibitors Monoamine Oxidase-B Inhibitors:
selegiline (Eldepryl)
rasagiline (Azilect)
Catechol-O-Methyltransferase:
entacapone (Comtan)
Side Effects:
(r/t increased dopamine and levodopa levels)
nausea, orthostatic hypotension, mental distrurbances, dyskinesia, hepatotoxicity
Learning Outcomes
17 .4 Identify the mechanism of action of the MAO-B and COMT inhibitors and how they affect levodopa metabolism.
Selegiline is a drug that primarily inhibits the metabolism of dopamine in the brain. By inhibiting MAO-B, selegiline increases the concentration and prolongs the duration of action of the dopamine that is formed in the brain.
Rasagiline is also an MAO-B inhibitor that is more potent then selegiline and considered more effective. There is some evidence that rasagiline may slow the progression of Parkinson’s disease when used early in the disease.
Adverse effects of selegiline and rasagiline are associated with increased dopamine levels and are similar to those of treatment with levodopa, but occur with less frequency and intensity.
Drugs such as tolcapone (Tasmar) and entacapone (Comtan) inhibit COMT in the periphery and increase the amounts of levodopa that reach the brain.
Adverse effects caused by these drugs are due mostly to increased levodopa and dopamine levels and include nausea, orthostatic hypotension, mental disturbances, and dyskinesias –involuntary movement.

15. Dopamine Receptor Agonists
MOA: Bind to and stimulate dopamine receptors in basal ganglia:
Lower incidence of dyskinesia
Stimulates DA, alpha-adrenergic, and serotonin receptors
Adverse effects—nausea, postural hypotension, and hallucinations
bromocriptine (Parlodel)
New drugs include:
pramipexole (Mirapex) and ropinirole (Requip)
Learning Outcomes
17 .5 List the dopamine receptor agonist drugs and explain their mechanism of action and adverse effects.
Dopamine receptor agonists are drugs that enter the brain and bind to and stimulate dopamine receptors in the basal ganglia. Compared to levodopa, these drugs cause a lower incidence of movement disturbances and dyskinesias.
Bromocriptine ( Parlodel ) was the first DA agonist used in Parkinson’s disease and it produces a variety of other pharmacologic effects. In addition to stimulating DA receptors, bromocriptine also stimulates alpha-adrenergic and serotonin receptors.
Adverse effects are similar to levodopa and include nausea, vomiting, postural hypotension, dizziness, and CNS disturbances that include sleepiness, delusions, hallucinations, and related psychotic effects. The DA receptor agonists are claimed to cause less movement disturbances but more mental disturbances than levodopa.

16. Preferred Therapy for Parkinson’s
Treatment of Tremors:
Amantadine or anticholinergic drugs
Treatment of Mild-Moderate Disease:
Dopamine receptor agonist
Levodopa/carbidopa
Enzyme inhibitors
Treatment of Advanced Disease:
The most effective drug for treatment of Parkinson’s disease is the combination of levodopa and carbidopa. However, because of the movement disorders that occur with levodopa over time, levodopa therapy is often delayed in favor of other drugs until symptoms require more effective medications.
For Treatment of Tremors: In early stages of parkinsonism, tremor and rigidity may be the only symptoms. Often one of the anticholinergic drugs or amantadine may control these symptoms. In addition, rasagiline (MAO-B inhibitor) also may be considered.
For Treatment of Mild-Moderate Disease: As initial symptoms of tremor, rigidity, and bradykinesia worsen, either one of the dopamine receptor agonists or levodopa/carbidopa are added to treatment. Low doses of these drugs are initiated and increased until symptoms are controlled. COMT and MAO-B inhibitors also may be added to levodopa to increase brain drug levels and duration of action.
For Treatment of Advanced Disease: In advanced disease increased dosages and more frequent administrations of levodopa/carbidopa are usually required. COMT and MAO-B inhibitors are added if not already prescribed. Dopamine receptor agonists also can be added to the treatment. The severity of disease and patient response often determine which drugs are prescribed.

17. Question 1
A clients with Parkinson's disease has a new prescription of levodopa (Dopar). Which of the following findings should the nurse watch for in this client? (select all that apply.)
Immobility
Dyskinesia
Memory loss
Irregular heartbeats
Psychotic-like behaviors
A,B,D, & E
End-of-dose wearing-off effect causes immobility
Dyskinesia and dystonia can occur at different times, but particularly when drug concentrations in the basal ganglia are at the highest.
Memory loss is not a adverse effect of levodopa
Since Da stimulates bets-1-adrenergic receptors some patients may experience rapid or irregular heartbeats.
Psychotic behaviors which may occur in clients taking levodopa include visual hallucination, paranoid ideas, and vivid dreams or nightmares.

18. Question 2
What is the relationship between acetylcholine and dopamine in the area of the brain that affects balance, posture, and involuntary muscle movement? A. Both dopamine and acetylcholine stimulate this region B. Both dopamine and acetylcholine inhibit this region C. Dopamine stimulates and acetylcholine inhibits this region D. Dopamine inhibits and acetylcholine stimulates this region D

19. Question 3
A client who has Parkinson’s disease is prescribed levodopa/carbidopa (Sinemet) and pramipexole (Mirapex). for which of the following should the nurse monitor this client?
Urinary hesitancy
Watery diarrhea
Weight gain
Orthostatic hypotension D
see slide 17-4
Text page236 upper left corner.
In the brain, high doses of DA interfere with CV reflexes that maintain blood pressure, consequently, some patients may experience OH or fainting.
Orthostatic hypotension is an adverse effect of both levodopa/carbidopa and pramipexole. When both medications are prescribed, the incidence of OH is very high.

20. Question 4
Select the actions of bromocriptine (Parlodel). (Select all that apply)
Stimulates DA receptors
Inhibits alpha-adrenergic receptors
Inhibits decarboxylase
Stimulates serotonin receptors
A & D
Slide 17-7 Bromocriptine (generic)
Page 235
Stimulates alpha-adrenergic receptors
these select all, none or some are the pattern of many of the new NCLEX questions

21. Alzheimer’s Disease (AD)
Devastating, progressive, degenerative disorder
Generally begins after age 60
As many as 50% of people are affected by age 85
Pt generally lives 5-10 years after being diagnosed with AD (4th leading cause of death)
Is AD the same thing as dementia?

22. Dementia AD is responsible for 70% of all dementia
Dementia- disorder characterized by progressive memory loss, confusion, and inability to think or communicate effectively
Cause of AD is unknown
but atrophy or other structural changes within brain are usual
Plaques are noted on CT scans
Other causes- multiple strokes, severe infections, and toxins (less frequent)

23. Alzheimer’s and Acetylcholine
Acetylcholine is major neurotransmitter within hippocampus (area of brain responsible for learning and memory) and other parts of cerebral cortex
AD pts experience a dramatic loss of ability to perform tasks that require acetylcholine
Impaired memory and judgment
Confusion or disorientation
Inability to recognize family and friends
Aggressive behavior
Depression
Psychoses
Anxiety
Drug therapy?
Drugs are used to slow memory loss and other progressive symptoms
Do not cure AD- only slow progression
Therapy begun as soon as diagnosis is established
Not effective in treating severe stages (probably b/c so many neurons have died)

24. Pharmacotherapy Continued
Most widely treated with acetylcholineresterase inhibitors
What is acetylcholineresterase?
What happens when acetylcholineresterase is inhibited?
Enzyme that breaks down ACH.
More ACH in system.
Direct or indirect agents?

25. Acetylcholineresterase inhibitors
Acetylcholine is naturally degraded in the synapse by the enzyme acetylcholineresterase
MOA: When acetylcholineresterase is inhibited, acetylcholine levels increase and affect receptors –which brings about more rest and digest.
They are indirect acting cholinergic agents!
Indirectly mimics acetylcholine (cholinergic agent).

26. Side Effects
Those expected of drugs that enhance the parasympathetic NS
N, V, D
Fatigue
Increased libido
Urinary incontinence
Bradycardia

27. Common Acetylcholineresterase Inhibitors
Donepexil hydrochloride (Aricept)
Tacrine (Cognex)
Nursing Condsiderations:
D/C as disease progresses

28. Multiple Sclerosis (MS)
Autoimmune disorder of CNS
Antibodies target and slowly destroy tissues in brain and spinal cord
As tissues are damaged, inflammation of nervous tissue causes demyelination (loss of myelin)
Loss of myelin leaves multiple areas of hard scarred tissue called plaques along the covering of nerve cells
Axons are gradually destroyed, disrupting the ability of the nerves to conduct electrical impulses to and from brain
Myelin- fatty material that acts as a protective insulator of nerve fibers.
Result from demyelination of central nerve fibers
Course of MS is unpredictable, and each pt will experience a variety of symptoms
Symptoms may include:
Fatigue
Heat sensitivity
Pain
Spasticity (muscle cramps and spasms)
Cognitive problems
Balance coordination problems
Bowel and bladder symptoms

29. Pharmacotherapy 2 basic strategies:
1. attempt to reduce inflammation and prevent attacks on the nervous system
Immuno-modulators
Myelin Protein Builders
2. relieve symptoms
Muscle Relaxants

30. Immunomodulators Interferon beta- 1a (Avonex, Rebif)
Interferon beta- 1b (Betaseron)
MOA: Changes immunity (MS is autoimmune, so we want to stop the body from attacking itself)
Use:
Only clinically proven drugs for treating underlying causes of MS SE
Flu-like symptoms
Pain at injection site
hepatotoxicity
Nursing Considerations : Monitor LFTs

31. Myelin protein builder
Glatiramer acetate (Copaxone)
MOA:
Synthetic protein that simulates myelin basic protein, as essential part of the nerve’s myelin coating
Since glatiramer acetate resembles myelin, it is thought to curb the body’s attack on the myelin covering and reduce the creation of new lesions
SE: discomfort at inj site; NC: monitor site

32. Question 1
A patient is started on levodopa for Parkinson’s disease. What type of side effect would be expected?
A. Sleep disorders, such as insomnia
B. Sedation
C. Seizures
D. Orthostatic hypotension D

33. Question 2 Drugs that inhibit the enzyme acetylcholinesterase (AchE):
A. Increase levels of dopamine
B. Increase levels of acetylcholine
C. Decrease levels of dopamine
D. Decrease levels of acetylcholine B

34. Question 3
What drug has been prescribed more extensively than any other drug for patients with Parkinson’s disease?
A. Carbidopa (Lopdosyn)
B. Levodopa (Larodopa)
C. Benztropine (Cogentin)
D. Tacrine (Cognex) B