MYASTHENIA GRAVIS Flashcards
What is myasthenia gravis?
It is an autoimmune disease that is characterised with autoantibodies binding to the nicotinic acetylcholine receptors at the neuromuscular junction (NMJ) thereby causing weakness in the skeletal muscle as no action potential in the skeletal muscle.
What are the symptoms of myasthenia gravis?
It starts with ocular symptoms and it involves;
- Drooping eyelids (ptosis)
- Diplopia (double vision)
- Restricted eye movement
It can also present with symptoms like
-shortness of breath (this can be intense and cause myasthenia crisis where you are unable to breath because the diaphragm is a skeletal muscle and since there is no action potential it becomes difficult to breath. About 20% of patients may need a ventilator.
-Weakness
- slurred speech
-diffculty swallowing.
- lack of facial expression
What are the tests that can be done to diagnose myasthenia gravis?
-ice test( ice is put on the muscle and as it cools it the function improves)
- blood test for autoantibodies
- neurophysiology to test for action potential.
- edrophonium test which involves giving a short acting drug edrophonium and if the symptoms increase then it is diagnostic.
- CAT scan to rule out thymoma.
What are the treatment options for myasthenia gravis?
First line is acetylcholinesterase inhibitors.
Immunosuppressants (steroids, other immunosuppressants like azathioprine)
Intravenous immunoglobin
Surgery to remove thymus (thymectomy)
What is the pathophysiology of myasthenia gravis?
In normal situations, the body releases acetylcholine from the presynaptic neuron at the nmj when ca2+ binds the vesicles. Acetylcholine when released binds to the nicotinic acetylcholine receptors on the post synaptic neur. on which then opens up the Na+ channel and allows Na+ to move in causing depolarisation and action potential which leads to the contraction of the skeletal muscle. In myasthenia gravis the body makes autoantibodies which binds to the receptors and prevents the acetylcholine from binding thereby resulting in no contraction or less in the skeletal muscle
Where in the body can acetylcholine be found?
-skeletal muscle (via muscarinic receptors)
-parasympathetic synapse (via nicotinic receptors)
- Sweat glands
- autonomic ganglion
Why do we give acetylcholinesterase inhibitor to a patient who suffers from myasthenia gravis?
Acetylcholinesterase is an enzyme that breaks down acetylcholine to choline and acetate and thereby terminating the signal at the skeletal muscle at the nmj, also there is another cholinesterase which is butyl esterase which is found in other parts of the body. In normal situations where acetylcholine can bind to the receptors with no impedance, this is a good thing but in myasthenia gravis where acetylcholine cannot bind to the receptor, we want more in the synapse to allow more of the contraction of the skeletal muscle. Hence giving acetylcholinesterase inhibitors will prevent the enzyme from breaking down acetylcholine leaving more in the synapse for its action.
What are the types of acetylcholinerase inhibitors?
- Short acting; edrophonium
- medium acting; eg pyridostigmine , neostigmine
- Long acting; malathion, novichock, sarin
What are the effects of cholinesterase inhibitors?
- At the neuromuscular junction and the drugs more specific are neostigmine and pyridostigmine. It increases the twitch tension.
- At the parasympathetic synapses and the drugs more specific are physostigmine and organophosphates it causes a decrease in heart rate (bradycardia) , dilation of the blood vessels via the release of NO{cardiovascular) , constriction of the bronchioles, contraction of the gut, contraction of the bladder{smooth muscles}, contraction of the pupils and increases secretion at the glands and the sweat glands.
They also have central effects if they can cross the blood brain barrier and the effects include; - improved cognition (therapeutics)
- convulsions, unconsciousness, respiratory failure (toxicity)
How can you manage myasthenia gravis?
- Avoid disease triggers
- Symptomatic treatment to produce- minimal symptoms + minimal drug side effects.
- immunosuppressant drugs.
- immunomodulatory treatments (includes treatments like plasma exchanges immunoglobulin and potentially surgery)
What are the triggers of myasthenia gravis?
- infection
- stress and trauma
- thyroid dysfunction
- withdrawal of acetylcholinesterase inhibitors.
- rapid introduction or increase of corticosteroids.
- Anaemia
- Electrolyte imbalances
- Medicines (always check co-prescription)
All patients with myasthenia gravis should receive annual flu and pneumococcal vaccines to minimise the risk of getting the infection.
What are the symptomatic treatment of myasthenia gravis?
- Oral acetylcholinesterase inhibitor; pyridostigmine (neostigmine is not mostly used) and the dose is normally 15mg QDS with food and this is to reduce the GI effects, assess cholinergic site effects and the maintenance dose is 60mg four to six times a day.
What are the adverse effects of acetylcholinesterase?
It normally depends on the dose and it is predictable.
- Nicotinic effects: muscle and abdominal cramps.
- Muscarinic: gut hypermotility (cramps and diarrhoea), increased sweating, salivations, lacrimation (crying), hypotension, bradycardia, miosis, urinary incontinence, increased bronchial secretions and tachypnoea.
What is cholinergic crisis?
It is the result of excessive acetylcholinesterase inhibitor which causes weakness and is hard to distinguish from worsening MG, however with the doses that are prescribed, it is unlikely to cause it.
How do you manage the side effects of myasthenia gravis?
-taking with food can mitigate GI side effects.
- co-prescribing oral anti-cholinergic drugs ( that have little or no effect on nicotinic receptors ie do not produce weakness eg; glycopyrrolate, propantheline.
- Diarrhoea can be controlled using loperamide.
