Diagnosis & Management of a Patient with Myasthenia Gravis
Question:
Patient presents with signs & symptoms of progressive ptosis, dysphagia, weakness and slurred speech over last few weeks.
1. Deduce the most probable Diagnosis
2. Name test is used to diagnose it
3. Explain how the test is conducted
4. Describe the management of this patient?
5. Differentiate the toxicity of drug treatment from drug failure?
6. Classify drugs used to treat this condition
Answers:
1.Diagnosis: Myasthenia Gravis
This is an autoimmune disease in which antibodies are produced against the nicotinic receptors at the neuromuscular junction. Therefore synaptic transmission at the neuromuscular junction is severely impaired.
The patient complains of severe muscular weakness worsened by even slight physical exertion. Ptosis reflects the muscle weakness. Respiratory muscles may even be affected causing respiratory embarrassment.
2.Test to Diagnose: Tensilon Test (Edrophonium Test)
3. How to conduct: Give Edrophonium IV- an effective acetylcholinesterase inhibitor – will reduce the muscle weakness by blocking the enzymatic effect ofacetylcholinesterase enzymes, prolonging the presence of acetylcholine in the synaptic cleft. If improvement occurs on administration the diagnosis of myasthenia gravis is confirmed.
Edrophonium is preferred over other reversible acetylcholinesterase inhibitors because of its ultra-short duration of action, so that even if does not improve the condition, its adverse effects will only be for a short duration (about 10 minutes).
4. Management:
Reversible anticholinestrases are used to treat this condition because they increase the duration and intensity of action of acetylcholine at the synaptic cleft.
Neostigmine is preferred over physostigmine because:
- Neostigmine has both direct as well as in direct action at the neuromuscular junction & thus more effective
- Neostigmine has less/minimal CNS adverse effects as it doesnt cross BBB that readily, due to its polar nature
Other quaternary amines like Pyridostigmine or Ambenonium may be given; these have longer duration of action
Atropine may also given to decrease disturbing muscarinic actions of these drugs like increased frequency of urination, diarrhea etc
Other Drugs: See classification below
5. How to differentiate cholinergic crisis from Myasthenic crisis:
a) During the treatment of myasthenia gravis with neostigmine, muscle weakness may suddenly occur
b) In case of MYASTHENIC CRISIS, the dose of neostigmine is insufficient —-muscle weakness occurs
c) In case of CHOLINERGIC CRISIS, the dose of neostigmine is excess—-muscle weakness occurs (Due to persistent depolarization, there is depolarization block causing skeletal muscle weakness)
d) Edrophonium is given to differentiate and plan further action/treatment:
• If improvement occurs—Myasthenic crisis, so increase dose of neostigmine
• If condition worsens–Cholinergic Crisis, so decrease dose of neostigmine
Treatment of Myasthenia Gravis
A. Pharmacological Treatment
- Anticholinestrases
Neostigmine Pyridostigmine
Ambenonium Physostigmine
- Immunosuppressants
a) Corticosteroids
Prednisone Methylprednisolone
b) Other Immunosuppressants
Azathioprine Cyclosporine
Mycophenolate Mofetil Methotrexate
Cyclophosphamide Rituximab
c) Immunoglobulin
Immune Intravenous Globulin G (IVIG)
B. Plasma Exchange (Plasmapheresis)
C. Thymectomy
(From my book Nauman’s Textbook of Pharmacology)
For more details and other useful information on Pharmacology
Read ‘Nauman’s Textbook of Pharmacology’ (3rd Edition)
For comprehensive classification of drugs:
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‘Learning Pharmacology from Nauman’s MCQS’