Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disorder characterized by fluctuating skeletal muscle weakness that worsens with activity and improves with rest. The cornerstone of symptomatic treatment in myasthenia gravis is the use of anticholinesterase (cholinergic) drugs.
The most important drugs in this category are Edrophonium, Neostigmine, and Pyridostigmine. These agents are essential not only for treatment but also for diagnosis and crisis differentiation, making them high-yield exam topics.
Therapeutic and Pharmacologic Class
These drugs are classified as:
- Antimyasthenic agents
- Anticholinesterase drugs
- Indirect-acting cholinergic agonists
They increase the availability of acetylcholine at the neuromuscular junction.
Pathophysiology of Myasthenia Gravis (Quick Review)
In myasthenia gravis:
- Autoantibodies destroy or block nicotinic acetylcholine receptors
- Fewer functional receptors are available
- Normal acetylcholine release is insufficient to trigger muscle contraction
- Result → muscle weakness and fatigability
Anticholinesterase drugs do not cure the disease, but they improve neuromuscular transmission.
Mechanism of Action (Core Concept)
Edrophonium, neostigmine, and pyridostigmine work by:
- Inhibiting acetylcholinesterase
- Preventing breakdown of acetylcholine
- Increasing acetylcholine concentration in the synaptic cleft
- Enhancing stimulation of remaining nicotinic receptors
- Improving muscle contraction and strength
Result: temporary improvement in muscle strength
Edrophonium
Edrophonium is a short-acting anticholinesterase drug.
Key Feature
- Very rapid onset
- Very short duration of action
Clinical Uses
Edrophonium is mainly used for:
- Diagnosis of myasthenia gravis (historically – Tensilon test)
- Differentiation between myasthenic crisis and cholinergic crisis
- Assessing adequacy of anticholinesterase therapy
Diagnostic Logic (High-Yield)
- If muscle strength improves → Myasthenic crisis
- If muscle strength worsens → Cholinergic crisis
Note: The Tensilon test is now rarely used, but it remains important for exams.
Neostigmine
Neostigmine is an intermediate-acting anticholinesterase drug.
Mechanism
- Inhibits acetylcholinesterase
- Increases acetylcholine at neuromuscular junction
Therapeutic Uses
Neostigmine is used for:
- Treatment of myasthenia gravis
- Reversal of non-depolarizing neuromuscular blockers
- Postoperative urinary retention
- Postoperative ileus
Key Point
Neostigmine has more muscarinic side effects than pyridostigmine.
Pyridostigmine
Pyridostigmine is the drug of choice for long-term management of myasthenia gravis.
Why Pyridostigmine Is Preferred
- Longer duration of action
- Better tolerated
- Suitable for chronic use
- Available as sustained-release (SR) formulation
Therapeutic Uses
Pyridostigmine is used for:
- Long-term symptomatic treatment of myasthenia gravis
- Maintenance therapy to improve muscle strength
Most patients with MG require lifelong pyridostigmine therapy.
Adverse Reactions and Side Effects
Because these drugs increase acetylcholine, side effects are cholinergic.
Central Nervous System
- Dizziness
- Weakness
- Dysphasia, dysphonia
- Seizures (severe cases)
Eye, Ear, Nose, Throat (EENT)
- Diplopia
- Lacrimation
- Miosis
Respiratory
- Bronchospasm
- Increased bronchial secretions
Cardiovascular
- Bradycardia
- Hypotension
Gastrointestinal
- Abdominal cramps
- Diarrhea
- Dysphagia
- Excess salivation
- Nausea and vomiting
Genitourinary
- Urinary frequency
- Incontinence
Dermatologic & Musculoskeletal
- Sweating
- Rashes
- Muscle fasciculations
Cholinergic Crisis vs Myasthenic Crisis (VERY HIGH-YIELD)
Cholinergic Crisis
Cause:
Excess anticholinesterase drugFeatures:
Increased weaknessSLUDGE symptoms
- Salivation
- Lacrimation
- Urination
- Diarrhea
- GI distress
- Emesis
Management:
- Stop anticholinesterase
- Give Atropine (anticholinergic)
Myasthenic Crisis
Cause:
Insufficient medication or disease worseningFeatures:
- Severe muscle weakness
- Respiratory distress
- No excessive secretions
Management:
- Increase anticholinesterase dose
- Ventilatory support if needed
Nursing and Patient-Care Teaching
Patients should be taught to:
- Take medication exactly on time
- Wear a Medic-Alert bracelet
- Understand that treatment is lifelong
- Space activities to avoid fatigue
- Recognize early signs of crisis
- Never self-adjust dosage
Monitoring and Safety (“Make the Connection”)
Healthcare providers should:
- Monitor respiratory function
- Assess muscle strength regularly
- Watch for cholinergic symptoms
- Administer drugs exactly as ordered
- Keep atropine available for toxicity
Contraindications and Precautions
Use cautiously in patients with:
- Asthma or COPD
- Bradycardia
- GI obstruction
- Urinary obstruction
Nursing Diagnosis (Exam-Relevant)
Common nursing diagnoses include:
- Risk for activity intolerance
- Fatigue
- Ineffective breathing pattern
- Risk for aspiration
High-Yield Exam Points
1. Pyridostigmine is the drug of choice for long-term MG treatment.
2. Edrophonium is used for diagnosis and crisis differentiation.
3. These drugs work by inhibiting acetylcholinesterase.
4. Cholinergic crisis shows SLUDGE symptoms.
5. Atropine treats cholinergic toxicity, not muscle weakness.
Simple Mnemonic for Recall
“END-P for Myasthenia”
E – Edrophonium (diagnosis)
N – Neostigmine (treatment + reversal)
D – Diagnose crisis
P – Pyridostigmine (preferred long-term)
FAQs on Myasthenia Gravis Drugs
Which drug is best for long-term myasthenia gravis?
Pyridostigmine is the preferred long-term drug.
Why do these drugs improve muscle strength?
They increase acetylcholine availability at the neuromuscular junction.
What is the most dangerous complication of therapy?
Cholinergic crisis due to drug overdose.
How is cholinergic crisis treated?
By stopping the drug and giving atropine.
Is treatment for myasthenia gravis lifelong?
Yes, most patients require lifelong therapy.
