Myasthenia Gravis

• Affected groups


  • Women in their 20s and 30s
  • Men in their 60s and 70s
• Autoimmune condition


  Can wake up feeling fine but as day progresses feel weaker and weaker and gets worse
• Autoimmune condition


  • Esp with jobs that require repetitive movements
  • Can affect eyes as well as skeletal muscle
  • No evidence why it happens like that
• Normal muscle contraction


  1. Motor neurones release neurotransmitters acetylcholine

  2. Acetylcholine binds to nicotinic acetylcholine receptors

  3. Signal activated causes chain reaction to happen

  4. Muscle starts to contract
• Myasthenia gravis


  • A type 2 hypersensitivity reaction
  • Causes cytotoxic injury
  • Body mistakes its own cells as foreign
  • Results in cell lysis/cell death
  • B cells create autoimmune antibodies
  • Autoimmune antibodies bind to nicotinic acetylcholine receptors
  • Acetylcholine can't bind
  • Muscle isn't able to respond to CNS and contract
• Autoimmune antibody effects


  1. Activate classical complement pathway

  2. Involves small family of proteins that work via an enzyme cascade

  3. Usually work off bacterial infections

  4. Activation results in inflammation, destruction of host cells

  5. Reduction of acetylcholine receptors on the surface
• Normal neuromuscular junction


  Surface has enough receptors for neurotransmitters to bind to
• Autoimmune effects on neuromuscular junction

  • Receptors are destroyed, fewer receptors on the surface
  • Fewer neurotransmitters can bind
• Muscle specific tyrosine kinase antibodies (MUSK)


  • Minority of patients with MG can produce this type of harmful antibody
  • Instead of working on the surface of the muscle, they go inside the muscle cells and attack from inside rather than targeting receptors on the surface
• Myasthenic crisis


  • Life threatening
  • Decreased function of breathing muscles
  • Not able to breathe as normally as you possibly can
• There are medications to help reduce mortality in myasthenic crisis
• Treatments to enhance neuromuscular transmission

  • Acetylcholinesterase inhibitors
  • Neostigmine
  • Pyridostigmine
  • Immunosuppressant therapy
  • Corticosteroids
  • Azathioprine
  • Methotrexate
  • Ciclosporin
• Acetylcholinesterase inhibitors


  • Enhance neuromuscular transmission in voluntary and involuntary muscle in myasthenia gravis
  • Excessive dosage can impair neuromuscular transmission and precipitate cholinergic crises by causing a depolarising block
  • Hard to distinguish from worsening myasthenic state
• Side effects of acetylcholinesterase inhibitors

  • Increased sweating
  • Increased salivary and gastric secretions
  • Increased gastro-intestinal and uterine motility
  • Bradycardia
• Atropine sulfate


  Antagonises the parasympathetic effects of acetylcholinesterase inhibitors
• Drugs used in myasthenia gravis

  • Anticholinesterases (first line in ocular myasthenia gravis, used as adjunct to immunosuppressant therapy for generalised myasthenia gravis)
  • Corticosteroids (if anticholinesterases don't control completely)
  • Immunosuppressant therapy (azathioprine to reduce production of autoimmune antibodies)
• Anticholinesterases


  We don't want acetylcholine to break down, want as much as possible so can bind to the receptors
• Neostigmine


  • Produces a therapeutic effect for up to 4 hours
  • Helps to increase concentration of acetylcholine at the neuromuscular junction
  • Pronounced muscarinic action
  • Can require an antimuscarinic drug to be administered at the same time
  • In severe disease may be given every 2 hours
  • Max daily dose 180mg
  • Excess can cause impairment of neuromuscular transmission, precipitating cholinergic crisis by causing depolarising block
• Pyridostigmine bromide


  • Less powerful and slower in action than neostigmine
  • Longer duration of action
  • Preferable to neostigmine due to smoother action and less frequency of dosage
  • Preferred in patients whose muscles are weak on waking
  • Mild GI side effects but an antimuscarinic may be required
  • Less pronounced side effects compared to neostigmine
• Immunosuppressant therapy for neuromuscular disorders

  • Corticosteroids (established treatment for myasthenia gravis, commonly given on alternative days, all patients should receive osteoporosis prophylaxis, prednisolone commonly used)
  • Azathioprine (usually started at same time as corticosteroid, allows lower maintenance dose of corticosteroid to be used)
  • Ciclosporin
  • Methotrexate
  • Mycophenolate mofetil (used if patient not tolerable to steroids or azathioprine)
• Drugs to be used with caution in myasthenia gravis

  • Antibiotics (tetracyclines, macrolides, fluoroquinolones)
  • Antimalarials (hydroxychloroquine)
  • Beta blockers (atenolol, carvedilol, propranolol, sotalol)
  • Neurological drugs (lithium, risperidone, phenytoin, sulpride)