Introduction
Myasthenia gravis (MG) is an autoimmune disorder that affects the neuromuscular junction and causes fluctuating weakness of voluntary muscles. The condition is due to antibodies that attack nicotinic acetylcholine receptors at the motor end plate, reducing neuromuscular transmission. Understanding its drug therapy is important for clinical practice, especially in emergency and long-term management.
Etiology and Mechanism
In most patients, the body produces IgG antibodies against nicotinic acetylcholine (ACh) receptors. About 90% of MG patients show elevated anti-ACh receptor antibody levels. These antibodies destroy or block the receptors, reducing the number of functional receptors available for muscle activation.
This leads to:
- Reduced end-plate potential
- Failure to trigger action potential
- Weak, easily fatigable skeletal muscles
Abnormal thymus gland is seen in around 75% of MG cases, suggesting a strong immune origin.
Clinical Symptoms
Symptoms usually worsen with activity and improve with rest. Early signs often appear in fast-moving muscles.
- Ptosis (drooping eyelids)
- Diplopia (double vision)
- Difficulty in speaking (slurred speech)
- Difficulty in swallowing
- Weakness of arms and legs
- Severe cases involve respiratory muscle weakness
Importantly, the weakness is not associated with pain.
Drug Treatment of Myasthenia Gravis
The primary goal of therapy is to improve neuromuscular transmission by increasing acetylcholine levels or reducing antibody formation.
1. Anticholinesterase Drugs (First-line Therapy)
These drugs inhibit acetylcholinesterase, thereby increasing ACh concentration at the neuromuscular junction. They improve muscle strength but do not treat the underlying autoimmune cause.
a) Neostigmine
- Oral dose: 15–30 mg/day in divided doses
- Injectable: 0.5–2.5 mg IM or SC
- Dose is increased gradually until muscle strength improves
b) Pyridostigmine
- Preferred in long-term treatment due to longer action
- Oral dose: 60 mg, three times daily
- Sustained-release tablets may be given at bedtime
c) Ambenonium
- Oral dose: 2.5–5 mg every 6 hours
Note
Long-acting anticholinesterases like organophosphates are not used because of dangerous toxicity.
Titration and Crisis Management
Patients may show fluctuations between too little drug (myasthenic crisis) and too much drug (cholinergic crisis). Both present with muscle weakness, so correct identification is essential.
Edrophonium Test (Tensilon Test)
- Injection of 2 mg IV Edrophonium is given
If weakness improves: the problem is due to under-treatment → increase anticholinesterase dose.
If weakness worsens: the patient is in cholinergic crisis due to over-treatment → reduce the dose.
Immunosuppressive Therapy
Because MG is autoimmune, drugs that reduce antibody formation are used as add-on therapy.
1. Glucocorticoids
- Prednisolone improves symptoms by suppressing immune response
2. Immunosuppressants
- Azathioprine
- Cyclosporine
- Mycophenolate mofetil (in some regimens)
Other Treatment Approaches
1. Thymectomy
Recommended in younger patients or those with thymoma. Many patients show long-term remission after thymus removal.
2. Plasmapheresis
Removes circulating antibodies from the blood. Useful in severe cases or before major surgery.
3. Intravenous Immunoglobulin (IVIG)
Provides rapid improvement in acute MG exacerbations.
Drugs That Worsen Myasthenia Gravis
Some drugs aggravate symptoms and must be avoided or used cautiously:
- Aminoglycoside antibiotics (gentamicin, amikacin)
- Beta-blockers
- Magnesium salts
- Quinine and quinidine
- Neuromuscular blockers
Detailed Notes:
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