💊Pharmacology for Nurses Unit 10 – Myasthenia Gravis & Alzheimer's Medications

What's the Deal?

• Myasthenia gravis (MG) is an autoimmune neuromuscular disorder that causes weakness and fatigue in voluntary muscles
• Occurs when the immune system mistakenly attacks and destroys acetylcholine receptors (AChRs) at the neuromuscular junction
• Leads to impaired communication between nerves and muscles, resulting in muscle weakness and fatigue
• Symptoms can vary in severity and may fluctuate over time, often worsening with activity and improving with rest
• Common symptoms include drooping eyelids (ptosis), double vision (diplopia), difficulty speaking (dysarthria), and trouble swallowing (dysphagia)
• MG can affect individuals of any age but is most commonly diagnosed in women under 40 and men over 60
• Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and changes in behavior and personality
• AD is the most common cause of dementia, accounting for 60-80% of all dementia cases

Key Players

• Acetylcholine (ACh): a neurotransmitter responsible for transmitting signals from nerves to muscles at the neuromuscular junction
• Acetylcholine receptors (AChRs): proteins on the surface of muscle cells that bind to ACh, allowing the muscle to contract
• Autoantibodies: antibodies produced by the immune system that mistakenly target and destroy the body's own tissues, such as AChRs in MG
• Thymus gland: an organ located in the chest that plays a role in the development of the immune system; abnormalities in the thymus (hyperplasia or tumors) are associated with MG
• Beta-amyloid plaques: abnormal accumulations of beta-amyloid protein fragments that build up between nerve cells (neurons) in the brain, contributing to the development of AD
• Neurofibrillary tangles: abnormal accumulations of tau protein inside neurons that disrupt their function and contribute to the progression of AD
• Cholinergic neurons: nerve cells in the brain that use ACh as their primary neurotransmitter; these neurons are particularly affected in AD

How It Works

• In MG, the immune system produces autoantibodies that target and destroy AChRs at the neuromuscular junction
  • This reduces the number of available AChRs, impairing the transmission of signals from nerves to muscles
  • As a result, muscles become weak and fatigued, leading to the characteristic symptoms of MG
• The exact cause of MG is unknown, but genetic and environmental factors may play a role in triggering the autoimmune response
• In AD, the accumulation of beta-amyloid plaques and neurofibrillary tangles in the brain leads to the dysfunction and death of neurons
  • Beta-amyloid plaques form when beta-amyloid protein fragments clump together, disrupting communication between neurons and triggering inflammation
  • Neurofibrillary tangles form when tau protein becomes abnormally phosphorylated and aggregates inside neurons, interfering with their normal function
• The loss of cholinergic neurons in AD contributes to cognitive decline and memory loss, as ACh is essential for learning and memory processes
• The exact cause of AD is not fully understood, but a combination of genetic, lifestyle, and environmental factors is thought to contribute to its development

Spotting the Signs

• MG symptoms may include:
  • Drooping eyelids (ptosis)
  • Double vision (diplopia)
  • Difficulty speaking (dysarthria) or swallowing (dysphagia)
  • Weakness in the arms and legs, particularly in proximal muscles (those closest to the body)
  • Fatigue that worsens with activity and improves with rest
• Symptoms of MG can vary in severity and may fluctuate over time
• AD symptoms typically develop gradually and worsen over time, progressing through mild, moderate, and severe stages
• Early signs of AD may include:
  • Difficulty remembering recent events or conversations
  • Trouble finding the right words or following conversations
  • Misplacing items or getting lost in familiar places
  • Changes in mood, behavior, or personality
• As AD progresses, symptoms may include:
  • Significant memory loss, including forgetting important events, names, and faces
  • Difficulty performing familiar tasks or learning new information
  • Confusion about time, place, or people
  • Impaired judgment and decision-making
  • Withdrawal from social activities or hobbies

Treatment Gameplan

• Treatment for MG aims to improve muscle strength, reduce symptoms, and prevent complications
• Cholinesterase inhibitors (pyridostigmine) are the first-line treatment for MG
  • These medications increase the availability of ACh at the neuromuscular junction, enhancing muscle strength
• Immunosuppressants (prednisone, azathioprine, mycophenolate mofetil) may be used to suppress the immune system and reduce the production of autoantibodies
• Plasmapheresis and intravenous immunoglobulin (IVIG) can be used for short-term symptom control in severe cases or before surgery
• Thymectomy (surgical removal of the thymus gland) may be recommended for patients with thymic abnormalities
• Treatment for AD focuses on managing symptoms, slowing disease progression, and providing support for patients and caregivers
• Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are used to increase ACh levels in the brain, temporarily improving cognitive function
• Memantine, an NMDA receptor antagonist, may be used in moderate to severe AD to help slow cognitive decline
• Non-pharmacological interventions, such as cognitive stimulation, exercise, and social engagement, can help maintain cognitive function and quality of life

Meds to Know

• Pyridostigmine (Mestinon): a cholinesterase inhibitor used as the first-line treatment for MG
  • Increases the availability of ACh at the neuromuscular junction, improving muscle strength
  • Side effects may include diarrhea, abdominal cramps, and increased secretions
• Prednisone: an immunosuppressant corticosteroid used to reduce inflammation and suppress the immune system in MG
  • Helps decrease the production of autoantibodies targeting AChRs
  • Side effects may include weight gain, mood changes, and increased risk of infections
• Azathioprine (Imuran) and mycophenolate mofetil (CellCept): immunosuppressants used as steroid-sparing agents in MG
  • Help maintain symptom control while reducing the need for high-dose corticosteroids
  • Side effects may include gastrointestinal disturbances, increased risk of infections, and liver function abnormalities
• Donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne): cholinesterase inhibitors used to treat mild to moderate AD
  • Increase ACh levels in the brain, temporarily improving cognitive function and reducing symptoms
  • Side effects may include nausea, vomiting, diarrhea, and loss of appetite
• Memantine (Namenda): an NMDA receptor antagonist used to treat moderate to severe AD
  • Helps slow cognitive decline by regulating glutamate activity in the brain
  • Side effects may include dizziness, headache, and constipation

Nursing Know-How

• Assess patients with MG for signs of respiratory distress, such as difficulty breathing or swallowing, and monitor vital signs closely
• Encourage patients to take frequent rest periods and conserve energy during activities
• Educate patients and caregivers about the importance of medication adherence and proper administration techniques
• Monitor for side effects of medications and report any adverse reactions to the healthcare team
• Assist patients with AD in maintaining a safe and familiar environment to reduce confusion and agitation
• Encourage patients to engage in cognitive stimulation activities, such as puzzles, games, and reminiscence therapy
• Provide support and education to caregivers, emphasizing the importance of self-care and stress management
• Collaborate with the interdisciplinary team to develop individualized care plans that address the unique needs of each patient

Watch Out For

• Myasthenic crisis: a life-threatening complication of MG characterized by severe weakness of the respiratory muscles
  • Requires prompt recognition and management, including respiratory support and intensive care
• Cholinergic crisis: an overdose of cholinesterase inhibitors, leading to excessive ACh activity and symptoms such as muscle weakness, sweating, and bradycardia
  • Treated by discontinuing the medication and providing supportive care
• Adverse reactions to immunosuppressants, such as increased risk of infections, liver or kidney dysfunction, and bone marrow suppression
• Behavioral and psychological symptoms of dementia (BPSD) in AD, such as agitation, aggression, and wandering
  • May require non-pharmacological interventions and careful use of antipsychotic medications when necessary
• Caregiver burnout and stress, which can negatively impact the well-being of both the caregiver and the patient with AD
  • Encourage caregivers to seek support, respite care, and resources to manage the challenges of caregiving