Podcast
Questions and Answers
What is the primary pathological process underlying motor symptoms in Parkinson's disease (PD)?
What is the primary pathological process underlying motor symptoms in Parkinson's disease (PD)?
- Degeneration of neurons in the substantia nigra leading to dopamine deficiency. (correct)
- Formation of amyloid plaques in the cerebellum.
- Overstimulation of acetylcholine receptors in the motor cortex.
- Excessive production of dopamine in the basal ganglia.
Why are foods high in tyramine a concern for patients treated with MAO-B inhibitors for Parkinson's disease?
Why are foods high in tyramine a concern for patients treated with MAO-B inhibitors for Parkinson's disease?
- MAO-B inhibitors, at higher doses, can inhibit MAO-A, reducing tyramine metabolism and causing a hypertensive crisis. (correct)
- Tyramine can cause a build-up of dopamine, leading to dopamine toxicity.
- Tyramine interferes with the absorption of levodopa, reducing its effectiveness.
- Tyramine directly inhibits MAO-B, negating the therapeutic effect of the medication.
Which of the following is a significant risk factor for developing Alzheimer's disease (AD)?
Which of the following is a significant risk factor for developing Alzheimer's disease (AD)?
- Diet rich in antioxidants.
- Advanced age. (correct)
- Low cholesterol levels.
- High levels of physical activity.
What are the key neuropathological hallmarks of Alzheimer's disease?
What are the key neuropathological hallmarks of Alzheimer's disease?
What is the initial recommended pharmacological treatment for a patient presenting with mild symptoms of Alzheimer's disease?
What is the initial recommended pharmacological treatment for a patient presenting with mild symptoms of Alzheimer's disease?
A 70-year-old male is newly diagnosed with Parkinson's disease. Which of the following symptoms is considered a motor symptom?
A 70-year-old male is newly diagnosed with Parkinson's disease. Which of the following symptoms is considered a motor symptom?
A patient with Parkinson's disease who is being treated with Selegiline decides to start eating a diet very high in tyramine. What potential adverse effect could occur?
A patient with Parkinson's disease who is being treated with Selegiline decides to start eating a diet very high in tyramine. What potential adverse effect could occur?
Which pathophysiological change is most closely associated with the cognitive decline seen in Alzheimer's disease?
Which pathophysiological change is most closely associated with the cognitive decline seen in Alzheimer's disease?
An 82-year-old female with a history of Alzheimer's disease is brought in by her daughter. The daughter states that the patient has been on donepezil for two years. The patient's memory and ability to do daily tasks has progressively declined. What medication is recommended to add to the current treatment plan?
An 82-year-old female with a history of Alzheimer's disease is brought in by her daughter. The daughter states that the patient has been on donepezil for two years. The patient's memory and ability to do daily tasks has progressively declined. What medication is recommended to add to the current treatment plan?
What is the most common initial symptom in early-stage Alzheimer's disease?
What is the most common initial symptom in early-stage Alzheimer's disease?
Which of the following medications used in Parkinson's disease directly stimulates dopamine receptors?
Which of the following medications used in Parkinson's disease directly stimulates dopamine receptors?
What is the primary mechanism of action of carbidopa in the treatment of Parkinson's disease?
What is the primary mechanism of action of carbidopa in the treatment of Parkinson's disease?
A patient with Parkinson's disease experiences 'wearing-off' phenomenon despite optimal levodopa therapy. Which of the following medication classes can be added to prolong the effect of levodopa?
A patient with Parkinson's disease experiences 'wearing-off' phenomenon despite optimal levodopa therapy. Which of the following medication classes can be added to prolong the effect of levodopa?
What is the most likely mechanism by which memantine helps manage symptoms of Alzheimer's disease?
What is the most likely mechanism by which memantine helps manage symptoms of Alzheimer's disease?
Which of the following is a risk factor that may increase the likelihood of developing late-onset Alzheimer's disease?
Which of the following is a risk factor that may increase the likelihood of developing late-onset Alzheimer's disease?
A patient with moderate Alzheimer's disease is on donepezil, but their cognitive decline continues. They now exhibit increased agitation and personality changes. What is the next step in managing this patient's symptoms?
A patient with moderate Alzheimer's disease is on donepezil, but their cognitive decline continues. They now exhibit increased agitation and personality changes. What is the next step in managing this patient's symptoms?
A patient with Parkinson's disease experiences increased constipation. Which of the following non-pharmacological interventions is most appropriate?
A patient with Parkinson's disease experiences increased constipation. Which of the following non-pharmacological interventions is most appropriate?
Which of the following is the primary role of acetylcholine in the pathophysiology of Alzheimer's disease?
Which of the following is the primary role of acetylcholine in the pathophysiology of Alzheimer's disease?
Which of the following is a common non-motor symptom of Parkinson's disease that can significantly impact a patient's quality of life?
Which of the following is a common non-motor symptom of Parkinson's disease that can significantly impact a patient's quality of life?
What is the rationale for caution when prescribing anticholinergic medications to manage urinary issues in a patient with Parkinson's disease who also has cognitive impairment and dementia?
What is the rationale for caution when prescribing anticholinergic medications to manage urinary issues in a patient with Parkinson's disease who also has cognitive impairment and dementia?
In the pathophysiology of Parkinson's disease, the loss of dopaminergic neurons leads to an imbalance with which other neurotransmitter?
In the pathophysiology of Parkinson's disease, the loss of dopaminergic neurons leads to an imbalance with which other neurotransmitter?
An elderly patient with Parkinson's disease begins experiencing hallucinations. What is the most appropriate initial step in managing this symptom?
An elderly patient with Parkinson's disease begins experiencing hallucinations. What is the most appropriate initial step in managing this symptom?
A patient with moderate Alzheimer's disease taking donepezil is experiencing significant nausea. What is a recommended strategy to manage this side effect?
A patient with moderate Alzheimer's disease taking donepezil is experiencing significant nausea. What is a recommended strategy to manage this side effect?
A patient with Parkinson's disease is on levodopa/carbidopa and reports frequent, uncontrolled involuntary movements. Which medication might be added to help manage these dyskinesias?
A patient with Parkinson's disease is on levodopa/carbidopa and reports frequent, uncontrolled involuntary movements. Which medication might be added to help manage these dyskinesias?
A patient with Alzheimer's disease is prescribed donepezil. What is a key consideration when monitoring this patient for adverse effects?
A patient with Alzheimer's disease is prescribed donepezil. What is a key consideration when monitoring this patient for adverse effects?
What is the primary mechanism of action of levodopa in treating Parkinson's disease?
What is the primary mechanism of action of levodopa in treating Parkinson's disease?
What are common early symptoms of Alzheimer's disease?
What are common early symptoms of Alzheimer's disease?
A patient taking levodopa for Parkinson's disease is counseled to avoid high-protein meals. Why is this important?
A patient taking levodopa for Parkinson's disease is counseled to avoid high-protein meals. Why is this important?
A 75-year-old patient is diagnosed with mild Alzheimer's disease, and the physician decides to start her on a cholinesterase inhibitor. Which of the following should be discussed with the patient and her family regarding the expectations of this treatment?
A 75-year-old patient is diagnosed with mild Alzheimer's disease, and the physician decides to start her on a cholinesterase inhibitor. Which of the following should be discussed with the patient and her family regarding the expectations of this treatment?
A patient with Alzheimer's disease is prescribed memantine. Which of the following conditions would warrant caution or dose adjustment?
A patient with Alzheimer's disease is prescribed memantine. Which of the following conditions would warrant caution or dose adjustment?
A 68-year-old male with Parkinson's disease develops significant postural instability leading to frequent falls. What should be implemented to manage this specific symptom?
A 68-year-old male with Parkinson's disease develops significant postural instability leading to frequent falls. What should be implemented to manage this specific symptom?
What are the key differences between Lewy Bodies and Alzheimer's β-amyloid plaques?
What are the key differences between Lewy Bodies and Alzheimer's β-amyloid plaques?
A 60 yo patient is prescribed pramipexole for her Parkinson's Disease. What are two of the most important counseling points the pharmacist must counsel the patient?
A 60 yo patient is prescribed pramipexole for her Parkinson's Disease. What are two of the most important counseling points the pharmacist must counsel the patient?
A patient has been experiencing memory loss, confusion, and difficulty with problem-solving but has Alzheimer's Disease listed in her record from previous appointments. To start medication, aside from her updated cognitive assessment, which of the following findings would lead you to believe that his symptoms can no longer be managed with Donepezil, alone?
A patient has been experiencing memory loss, confusion, and difficulty with problem-solving but has Alzheimer's Disease listed in her record from previous appointments. To start medication, aside from her updated cognitive assessment, which of the following findings would lead you to believe that his symptoms can no longer be managed with Donepezil, alone?
Two women, of the same age, are being assessed for possible Alzheimer's disease risks. Both have a Parent that suffered from the disease but one has a sedentary lifestyle and has low folic acid while the other exercises and eats healthy. Which of the following factors makes one more likely to develop Alzheimer's based on the information presented?
Two women, of the same age, are being assessed for possible Alzheimer's disease risks. Both have a Parent that suffered from the disease but one has a sedentary lifestyle and has low folic acid while the other exercises and eats healthy. Which of the following factors makes one more likely to develop Alzheimer's based on the information presented?
How does the disruption of transmission in the brain's striatum contribute to the motor symptoms observed in Parkinson's disease?
How does the disruption of transmission in the brain's striatum contribute to the motor symptoms observed in Parkinson's disease?
A patient with Alzheimer's disease begins experiencing hallucinations and agitation. Which medication should be added to their treatment plan?
A patient with Alzheimer's disease begins experiencing hallucinations and agitation. Which medication should be added to their treatment plan?
Which of the following medications is least likely to cause orthostatic hypotension in geriatric patients?
Which of the following medications is least likely to cause orthostatic hypotension in geriatric patients?
What is the primary mechanism of action of pramipexole in treating Parkinson's Disease?
What is the primary mechanism of action of pramipexole in treating Parkinson's Disease?
A patient taking pramipexole reports a sudden increase in gambling urges. What is the most appropriate course of action?
A patient taking pramipexole reports a sudden increase in gambling urges. What is the most appropriate course of action?
Which of the following drug interactions should be closely monitored when a patient is prescribed pramipexole?
Which of the following drug interactions should be closely monitored when a patient is prescribed pramipexole?
Amantadine is used in Parkinson's disease primarily for what purpose?
Amantadine is used in Parkinson's disease primarily for what purpose?
A patient taking amantadine reports developing a mottled skin rash on their legs. Which adverse effect is this most likely?
A patient taking amantadine reports developing a mottled skin rash on their legs. Which adverse effect is this most likely?
What significant drug interaction should be monitored when prescribing amantadine?
What significant drug interaction should be monitored when prescribing amantadine?
What is the most significant consideration regarding renal function when prescribing amantadine?
What is the most significant consideration regarding renal function when prescribing amantadine?
When counseling a patient who is starting Levodopa, what should you include?
When counseling a patient who is starting Levodopa, what should you include?
What is the rationale for combining carbidopa with levodopa in the treatment of Parkinson's disease?
What is the rationale for combining carbidopa with levodopa in the treatment of Parkinson's disease?
A patient on levodopa/carbidopa develops uncontrolled, involuntary movements after several years of treatment. What is the likely cause?
A patient on levodopa/carbidopa develops uncontrolled, involuntary movements after several years of treatment. What is the likely cause?
What should patients taking levodopa be educated about when considering their diet?
What should patients taking levodopa be educated about when considering their diet?
What is the primary mechanism of action of Donepezil in treating Alzheimer's disease?
What is the primary mechanism of action of Donepezil in treating Alzheimer's disease?
A patient taking donepezil experiences frequent nausea and vomiting. What is the best course of action?
A patient taking donepezil experiences frequent nausea and vomiting. What is the best course of action?
Which of the following medications would most likely interact with Donepezil, reducing its therapeutic effects?
Which of the following medications would most likely interact with Donepezil, reducing its therapeutic effects?
What side effect should be closely monitored in patients taking donepezil, especially considering its implications for older adults?
What side effect should be closely monitored in patients taking donepezil, especially considering its implications for older adults?
What is the primary mechanism of action of memantine in the treatment of Alzheimer's disease?
What is the primary mechanism of action of memantine in the treatment of Alzheimer's disease?
What is the primary indication for memantine use in Alzheimer's disease?
What is the primary indication for memantine use in Alzheimer's disease?
A patient with Alzheimer's disease who is taking Memantine also has renal impairment. Which action is most appropriate?
A patient with Alzheimer's disease who is taking Memantine also has renal impairment. Which action is most appropriate?
What is an established adverse effect of Memantine?
What is an established adverse effect of Memantine?
What is a key difference between the mechanism of action of donepezil and memantine in treating Alzheimer's disease?
What is a key difference between the mechanism of action of donepezil and memantine in treating Alzheimer's disease?
When should levodopa/carbidopa be initiated in a patient with Parkinson's disease?
When should levodopa/carbidopa be initiated in a patient with Parkinson's disease?
What strategy can be implemented to reduce 'off' times experienced by patients on Levodopa/Carbidopa?
What strategy can be implemented to reduce 'off' times experienced by patients on Levodopa/Carbidopa?
Which medication is used to mitigate drug-induced dyskinesias due to Levodopa?
Which medication is used to mitigate drug-induced dyskinesias due to Levodopa?
In which of the following patients taking levodopa/carbidopa would caution be warranted?
In which of the following patients taking levodopa/carbidopa would caution be warranted?
Why might neuropsychiatric symptoms emerge in patients with Alzheimer's Disease?
Why might neuropsychiatric symptoms emerge in patients with Alzheimer's Disease?
Which combination of medications are implemented for patients with moderate-severe alzheimer's disease progression?
Which combination of medications are implemented for patients with moderate-severe alzheimer's disease progression?
What is the recommendation for cognitive therapy among patients with cognitive impairment and dementia caused by parkinson's disease?
What is the recommendation for cognitive therapy among patients with cognitive impairment and dementia caused by parkinson's disease?
A patient with Parkinson's disease reports urinary issues. What is a possible medication-related cause that should first be assessed?
A patient with Parkinson's disease reports urinary issues. What is a possible medication-related cause that should first be assessed?
A patient taking Pramipexole should be counselled regarding all side effects, except:
A patient taking Pramipexole should be counselled regarding all side effects, except:
Which class of medication has shown to be effective for anxiety and depression caused by Parkinson's Disease?
Which class of medication has shown to be effective for anxiety and depression caused by Parkinson's Disease?
Which of the following is not a known adverse effect of Levodopa?
Which of the following is not a known adverse effect of Levodopa?
Which Alzheimer's Disease medication is also used for Drug-Induced Extrapyramidal Symptoms (EPS)?
Which Alzheimer's Disease medication is also used for Drug-Induced Extrapyramidal Symptoms (EPS)?
Hallucinations are a common side effect among the medications, so it must be considered for which?
Hallucinations are a common side effect among the medications, so it must be considered for which?
At higher doses, what may MAO-B inhibitors also inhibit?
At higher doses, what may MAO-B inhibitors also inhibit?
If discontinuation is warranted, which medication cannot be withdrawn quickly?
If discontinuation is warranted, which medication cannot be withdrawn quickly?
What is the generic name for Aricept?
What is the generic name for Aricept?
Which medication elevates ACh in the periphery too = bronchoconstriction, more selective for the brain?
Which medication elevates ACh in the periphery too = bronchoconstriction, more selective for the brain?
Bradycardia is a side effect for which medication?
Bradycardia is a side effect for which medication?
Flashcards
Levodopa: Mechanism of Action
Levodopa: Mechanism of Action
A precursor to dopamine that crosses the blood-brain barrier and is converted into dopamine to increase dopaminergic activity in the brain.
Levodopa: Indication/Use
Levodopa: Indication/Use
Primary treatment for Parkinson's disease and parkinsonism; may be used with carbidopa.
Levodopa: Adverse Effects
Levodopa: Adverse Effects
Dyskinesias, nausea, hypotension, hallucinations, and the wearing-off phenomenon.
Levodopa: Contraindications
Levodopa: Contraindications
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Levodopa: Interactions
Levodopa: Interactions
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Levodopa: Patient Education
Levodopa: Patient Education
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Carbidopa: Mechanism of Action
Carbidopa: Mechanism of Action
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Carbidopa: Indication/Use
Carbidopa: Indication/Use
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Carbidopa: Adverse Effects
Carbidopa: Adverse Effects
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Carbidopa: Contraindications
Carbidopa: Contraindications
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Carbidopa: Interactions
Carbidopa: Interactions
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Pramipexole: Mechanism of Action
Pramipexole: Mechanism of Action
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Pramipexole: Indication/Use
Pramipexole: Indication/Use
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Pramipexole: Adverse Effects
Pramipexole: Adverse Effects
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Pramipexole: Contraindications
Pramipexole: Contraindications
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Pramipexole: Interactions
Pramipexole: Interactions
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Amantadine: Mechanism of Action
Amantadine: Mechanism of Action
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Amantadine: Indication/Use
Amantadine: Indication/Use
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Amantadine: Adverse Effects
Amantadine: Adverse Effects
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Amantadine: Contraindications
Amantadine: Contraindications
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Amantadine: Interactions
Amantadine: Interactions
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Donepezil: Mechanism of Action
Donepezil: Mechanism of Action
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Donepezil: Indication/Use
Donepezil: Indication/Use
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Donepezil: Adverse Effects
Donepezil: Adverse Effects
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Donepezil: Precautions
Donepezil: Precautions
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Donepezil: Interactions
Donepezil: Interactions
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Memantine: Mechanism of Action
Memantine: Mechanism of Action
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Memantine: Indication/Use
Memantine: Indication/Use
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Memantine: Adverse Effects
Memantine: Adverse Effects
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Memantine: Contraindications
Memantine: Contraindications
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Memantine: Interactions
Memantine: Interactions
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Parkinson's: Management
Parkinson's: Management
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Parkinson's: Hallucinations
Parkinson's: Hallucinations
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Alzheimer's: Management (Moderate-Severe)
Alzheimer's: Management (Moderate-Severe)
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Levodopa: Class
Levodopa: Class
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Carbidopa: Class
Carbidopa: Class
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Levodopa/Carbidopa: Monitoring
Levodopa/Carbidopa: Monitoring
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Pramipexole: Class
Pramipexole: Class
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Amantadine: Class
Amantadine: Class
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Donepezil: Class
Donepezil: Class
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Donepezil: Monitoring
Donepezil: Monitoring
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Memantine: Class
Memantine: Class
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Study Notes
Parkinson's Disease Overview
- Parkinson's Disease (PD) affects roughly 1% of adults over 60.
- Primary risk factor is age, other risk factors include genetics, environmental exposures (pesticides, heavy metals), and male sex.
- Motor symptoms include resting tremor, bradykinesia, rigidity, postural instability.
- Non-motor symptoms include depression, sleep disturbances, and fatigue.
- Autonomic dysfunctions include constipation, urinary retention, and incontinence.
- Complications involves dyskinesias from long-term levodopa use, falls, fractures from instability, and dementia in later stages.
- Aspiration pneumonia is a leading cause of death in advanced PD.
Parkinson's Disease Pathophysiology
- Motor symptoms arise from damage to the extrapyramidal system, which regulates movement.
- Normal movement relies on a balance between dopamine (inhibitory) and acetylcholine (excitatory).
- PD involves the degeneration of neurons in the substantia nigra that supply dopamine to the striatum, leading to dopamine deficiency.
- 70-80% of dopamine-producing neurons are lost before clinical symptoms appear.
- Progressive loss of dopaminergic neurons in the substantia nigra (part of basal ganglia) leads to dopamine deficiency
- Neurotoxic fibrils known as Lewy bodies accumulate and are visible on autopsy, serving as a characteristic of PD.
Parkinson's Disease Management: Medications
- Treatments aim to balance dopamine and acetylcholine levels in the brain.
- Dopamine Replacement involves Levodopa (with Carbidopa), a dopamine precursor.
- Dopamine Agonists directly stimulate dopamine receptors, like Pramipexole
- MAO-B Inhibitors include Selegiline, which slows the breakdown of dopamine.
- COMT Inhibitors includes Entacapone, which prolongs the effect of levodopa.
- NMDA Receptor Modulators includes Amantadine, which enhances dopamine release and reduces dyskinesias.
- Anticholinergics (for Tremor) includes Benztropine, which reduces excess acetylcholine activity.
MAO-B Inhibitors and Tyramine Interaction
- Selegiline & Rasagiline: inhibit monoamine oxidase-B (MAO-B), slowing breakdown of dopamine
- MAO-B inhibitors are recommended for mild symptoms of PD.
- At higher doses, MAO-B inhibitors may also inhibit MAO-A, leading to reduced tyramine metabolism
- Tyramine, found in aged cheeses, cured meats, and fermented foods, causes norepinephrine release
- Normally, MAO enzymes break down excess norepinephrine.
- Inhibition of MAO-A leads to excess norepinephrine, potentially causing a hypertensive crisis.
Levodopa
- Levodopa is a precursor to dopamine that crosses the blood-brain barrier and increases dopaminergic activity in the brain
- Primarily used to treat Parkinson's disease and parkinsonism.
- May be used with carbidopa for better efficacy
- Adverse effects include dyskinesias, nausea, hypotension, and hallucinations.
- Can also lead to a "wearing-off" phenomenon over time.
- Contraindications include narrow-angle glaucoma and a history of melanoma or skin lesions.
- Caution is advised for patients with cardiovascular disease, psychosis, and liver disease.
- Interacts with antipsychotics (block dopamine), iron salts (decrease absorption), and MAO inhibitors (hypertensive crisis).
- Patients should take levodopa with food to reduce nausea and avoid high-protein meals.
- It is important not to stop the medication suddenly to avoid withdrawal symptoms.
Carbidopa
- Carbidopa inhibits peripheral decarboxylation of levodopa.
- Carbidopa is used with levodopa for Parkinson’s disease.
- Side effects include nausea, orthostatic hypotension, dyskinesias, and hallucinations.
- Contraindications involve non-selective MAO inhibitors and narrow-angle glaucoma.
- Interacts with iron salts and vitamin B6, decreasing levodopa's effect.
Pramipexole
- Pramipexole is a dopamine agonist that stimulates dopamine receptors in the brain.
- It is used for Parkinson’s disease and restless legs syndrome (RLS).
- Side effects include drowsiness, orthostatic hypotension, nausea, and impulse control disorders.
- Contraindications include history of psychotic disorders.
- Interacts with antipsychotics and CYP450 inhibitors.
Amantadine
- Amantadine increases dopamine release and blocks NMDA receptors.
- It is used for Parkinson’s disease and drug-induced extrapyramidal symptoms (EPS).
- Side effects include dizziness, livedo reticularis, peripheral edema, and hallucinations.
- Dosage adjustments are required for patients with renal impairment.
- Interacts with anticholinergics and antihypertensives.
Parkinson's Disease Management: Strategies
- For mild symptoms, a MAO-B inhibitor provides symptomatic benefit.
- For severe symptoms, start with either levodopa (+ carbidopa) or a dopamine agonist like pramipexole.
- Levodopa use is more effective but carries a higher risk of disabling dyskinesias with long-term use.
- Drug induced dyskinesias (involuntary movements), amantadine can help
- Motor fluctuations can be reduced with dopamine agonists, COMT inhibitors, and MAO-B inhibitors.
- "Off" times equal loss of symptom relief.
Parkinson's Disease Management: Non-Motor Symptoms
- Cognitive impairment and dementia are managed with medications like Donepezil or Rivastigmine and cognitive therapy.
- Depression and anxiety are treated with Amitriptyline or SSRIs, coupled with cognitive-behavioral therapy (CBT).
- Sleep disturbances are addressed with Melatonin for insomnia or Modafinil for excessive daytime sleepiness.
- Excessive Daytime Sleepiness: Modafinil, adjusting dopaminergic meds
- Autonomic dysfunctions are managed with increased salt/fluid intake or fludrocortisone for orthostatic hypotension.
- Constipation is relieved with a high-fiber diet, stool softeners, or polyethylene glycol (PEG).
- Urinary issues are managed with anticholinergics for urgency or scheduled voiding.
- Psychosis and hallucinations are treated with medication adjustments or Pimavanserin
Alzheimer's Disease Overview
- Alzheimer's Disease is characterized by memory loss, impaired thinking, neuropsychiatric symptoms, and inability to perform ADLs.
- Affects more than 5.5 million in the U.S.
- Onset age is 65+.
- Genetics (family history)
- Other risk factors include being female, history of head injury, low education, production of apoE4, low folic acid, and sedentary lifestyle.
- Early stage involves short-term memory loss adn Mild confusion & disorientation.
- Moderate stage involves impaired reasoning and Personality/behavioral changes.
- Late stage involves severe cognitive decline and loss of motor function.
Alzheimer's Disease Pathophysiology
- Alzheimer's Disease involves progressive neurodegeneration from abnormal protein accumulation and neuronal loss in the hippocampus and cerebral cortex.
- Key features are β-Amyloid Plaques, which disrupt synaptic function and trigger neuroinflammation as well as hyperphosphorylated tau protein forming tangles inside neurons.
Alzheimer's Disease Pathophysiology in Detail
- Neuroinflammation and oxidative stress exacerbate neuron damage and synaptic dysfunction.
- Neuronal loss leads to brain atrophy/shrinkage, particularly in the hippocampus and cerebral cortex.
- Loss of cholinergic neurons leads to memory and cognitive decline.
Alzheimer's Disease Management
- Mild symptoms are first managed with cholinesterase inhibitors.
- For moderate-severe symptoms, combine a cholinesterase inhibitor with memantine.
- Discontinue medications if benefits are no longer obtained or risks outweigh benefits.
- Evaluate patients 2-4 weeks after a medication change or status change and every 3-6 months if stable.
Cholinesterase Inhibitors (Donepezil, Rivastigmine, Galantamine)
- Acetylcholinesterase inhibitors increase acetylcholine availability in the brain.
- Enhanced transmission by cholinergic neurons that haven’t been destroyed can help those affected by Alzheimer's
- They treat Alzheimer’s disease but do not cure or stop disease progression.
- Not all patients benefit, and improvements may be modest & short-lasting
- Side effects include N/V/D, dizziness, HA, and bradycardia.
- They can cause bronchoconstriction.
- Donepezil is more selective for the brain.
- Interactions involve anticholinergic drugs.
- Caution with COPD or asthma
Memantine
- Memantine is an NMDA receptor antagonist.
- It modulates glutamate (excitatory transmitter in CNS) activity to improve neuronal function and reduce excitotoxicity.
- Primarily treats moderate to severe Alzheimer’s.
- May slow decline in function or improve symptoms, but it doesn't affect the underlying disease mechanism.
- Well-tolerated, but there are some side effects of dizziness, headache, and confusion (5-7%).
- Rare side effects: SJS, cardio events (HTN, bradycardia, angina)
- Contraindications involve renal impairment.
- Memantine also interacts with other NMDA antagonists like amantadine or ketamine.
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Description
Overview of Parkinson's Disease (PD), its risk factors such as age and genetics, and the primary motor and non-motor symptoms. Covers autonomic dysfunctions and complications of long-term levodopa use. Discussion of the pathophysiology of PD, focusing on the degeneration of neurons in the substantia nigra.
