NU 370: Parkinson's Disease & Anti-Parkinson Agents

• NU 370 covers Parkinson's and Alzheimer's Disease

Parkinson's Disease (PD)

• PD is a movement disorder characterized by the degeneration of dopamine-producing neurons in the substantia nigra
• Anti-Parkinson medications are used to manage the condition
• PD is a common degenerative central nervous system disease
• PD involves a progressive loss of dopamine
• Symptoms include tremors, muscle rigidity, bradykinesia, postural instability, and affective flattening
• Primarily affects muscle movement
• Patients often experience anxiety, depression, sleep disturbances, dementia, and autonomic nervous system disturbances such as difficulty urinating
• Disease management is often complex

Anti-Parkinson Agents

• These agents restore the balance of dopamine and acetylcholine in the brain
• Dopaminergic drugs are a primary category:
  • Levodopa is a dopamine synthesis drug
  • Carbidopa is a dopamine agonist
  • Levodopa/carbidopa is a combination drug
  • Ropinirole and pramipexole activate dopamine receptors
  • MAO-B inhibitors such as selegiline prevent dopamine breakdown
• Concurrent use of these medications can increase beneficial effects

Dopamine Agonists

• Examples of dopamine agonists are levodopa-carbidopa (Parcopa, Sinemet), levodopa-carbidopa-entacapone (Stalevo), pramipexole (Mirapex), and ropinirole (Requip)
• May cause skin irritation, dizziness, light-headedness, difficulty concentrating, confusion, anxiety, headache, and sleep disturbances
• Other adverse effects include dysfunction, weight loss, fatigue, nausea, vomiting, constipation, orthostatic hypotension, choreiform movements, involuntary movements, dystonia, dyskinesia, acute myocardial infarction (MI), shock, neuroleptic malignant syndrome, hallucinations, agranulocytosis, depression with suicidal tendencies, extrapyramidal syndrome (EPS), and liver failure or injury

Factors Underlying Motor Complications

• Pharmacokinetic factors include delayed gastric emptying, amino acids competing for absorption, and the short half-life of levodopa (approximately 90 minutes)
• Pharmacodynamic factors include the loss of presynaptic 'buffering' as the nigrostriatal pathway degenerates and plastic changes in the postsynaptic receptor population

Wearing Off - On/Off Fluctuations

• Levodopa medication can "wear off" during the day in a typical pattern

Complications Associated with Therapy (OPAS)s

• Motor fluctuations: wearing off, delayed 'on' or no 'on' at all, and 'on'/'off' fluctuations that can be predictable or unpredictable
• Dyskinesias: involuntary movements, peak dose, diphasic, and 'off' period dystonia

MAO-B Inhibitors

• First-line medication used in conjunction with carbidopa/levodopa to reduce the "wear off" effect
• Selegiline can preserve dopamine produced from levodopa and prolong its effects for up to 2 years
• Examples include selegiline (Eldepryl, Zelapar)
• Side effects include nausea, vomiting, cramps, heartburn, headache, joint pain, muscle pain, dry mouth, insomnia, mental confusion, constipation, gastric upset, mouth sores, hallucinations, hepatotoxicity, seizures, convulsions, and sudden numbness

General Principles of PD Drug Therapy

• Drug therapy may take several weeks or months for full effect and should be gradual
• Safety and awareness of orthostatic hypotension are important
• Promote independence and address behavior changes, including suicidal thoughts
• Care for the caregiver is essential
• Maintain a symptom diary and pay attention to nutrition
• Take PD medication on an empty stomach, avoiding high-protein meals and pyridoxine
• Monitor liver and kidney function

Consequences of Poor Medication Management

• Increased anxiety, reduced motor function, exacerbated motor and cognitive symptoms, loss of confidence in self and clinicians, a vicious cycle of decline, reduced rehabilitation potential, delayed discharge, prolonged time to regain previous function, and reduced confidence in self and hospital

Checklist for Medication Management

• Verify the medications the patient is taking
• The timing of medication is very important, especially for levodopa drugs
• Interaction of medication with food, especially protein and lipids, needs consideration
• Be aware of polypharmacy
• Recognize that fluctuations in ability are real, impacting body image, predictable function, independence, and confidence
• Address unpredictability, frustration, and loss
• Balance therapeutic benefits against side effects

Alzheimer's Disease (AD)

• AD is the second most common degenerative central nervous system disease, characterized by structural damage to the brain
• There is a progressive loss of brain function, including memory loss, confusion, and dementia
• Mainly affects people over the age of 50
• Symptoms include impaired memory and judgment, confusion, and disorientation
• There is currently no cure

Goals of AD Therapy

• Slow memory loss and dementia symptoms
• Improve activities of daily living
• Improve behavior and cognition

Cholinesterase Inhibitors

• Prevents the breakdown of acetylcholine and enhance transmission in cholinergic neurons
• Slow the progression of AD
• Example: donepezil (Aricept)
• Side effects include headache, dizziness, insomnia, nausea, diarrhea, vomiting, muscle cramps, anorexia, abdominal pain, hepatotoxicity, renal toxicity, bradycardia, heart block, and extreme weight loss

Donepezil (Aricept)

• Mechanism of action: prevents the breakdown of acetylcholine to enhance transmission in neurons
• Primary use is to slow the progression of the disease
• Adverse effects include nausea/vomiting, dizziness and headache, abnormal dreams, irritability, and darkened urine
• A long half-life permits once-daily dosing
• Administer the medication prior to bedtime
• It is most effective when given on a regular schedule
• Long-term use is needed to assess benefits

Memantine (Namenda)

• Approved for the treatment of moderate to severe AD
• Reduces abnormally high levels of glutamate
• May have a protective function in reducing neuronal calcium overload
• Can cause constipation and other gastrointestinal issues
• CNS effects include dizziness, headache, and confusion
• Interacts with OTC calcium carbonate