Question

A 26-year-old gymnastics instructor presents with complaints of muscle weakness in her face that comes and goes, but has been getting worse over the past two months. Most notably, she complains that her "jaw gets tired" as she chews and that swallowing has become difficult. She also notes diplopia ("double vision") which seems to come on late in the evening, particularly after reading for a few minutes. At work, it has become increasingly difficult to "spot" her gymnasts during acrobatic moves because of upper arm weakness.

On physical examination, she has notable ptosis ("drooping") of both eyelids after repeated blinking exercises. When smiling, she appears to be snarling. Electromyographic testing revealed progressive weakness and decreased amplitude of contraction of the distal arm muscles upon repeated mild shocks (5 shocks per second) of the ulnar and median nerves. Both her symptoms and electromyographic findings were reversed within 40 seconds of intravenous administration of edrophonium (Tensilon), an acetylcholinesterase inhibitor (i.e. an "anticholinesterase"). Blood testing revealed high levels of an anti-acetylcholine receptor antibody in her plasma, and a diagnosis of myasthenia gravis was made.

Jill was treated with pyridostigmine bromide, which is a long-acting anticholinesterase drug, and was also started on prednisone, which is a corticosteroid drug. She also underwent occasional plasmapheresis when her symptoms became especially severe. She was given a prescription of atropine as needed to reduce the nausea, abdominal cramps, diarrhea, and excessive salivation she experienced as side effects of the anticholinesterase drug.

Questions (1pt each)

1. Why are nausea, abdominal cramps, diarrhea, and excessive salivation all side effects of the anticholinesterase drug she is taking?

2. Why is atropine beneficial in treating the gastrointestinal side effects mentioned in question #2?

3. Why does repetitive nerve stimulation result in decreased amplitude of the muscle contractions?

4. What is plasmapheresis and why must Jill undergo plasmapheresis when her symptoms become especially severe?

5. Jill's doctor advises her that she is at increased risk for respiratory failure. Why?

Answer 1

Anticholinesterases act by inhibiting the enzyme acetylcholinesterse ( which degrades acetylcholine ) thus increasing the availability of acetycholine and prolonging the action of Ach .
In parasympatetic system ,Ach is the principal neurotransmitter hence it is also known as cholinergic nervous system .

1)Cholinergic system stimulates the secretion of glands and results in increased salivation,lacrimation and sweating .
Also it increases the peristalsis in Gastrointestinal tract and relaxation of sphincters causing Abdominal cramps and diarrhea .Nausea is because of Hydrochloric acid secretion in stomach .

2) Atropine is anticholinergic drugs hence decreasing the actions of Ach on muscaranic receptors .In gastrointestinal tract it decreases the motility,tone and secretions hence beneficial in Gastrointestinal side effects

3)Repetitive nerve stimulation (RNS) is an effective way to fatigue the NMJ which will result slowly in acetylcholine depletion. These studies are abnormal in more than 60% of myasthenic patients. A decremental response on RNS is the electrical correlate of clinical muscle fatigue and weakness in myasthenic pateints means that with repeated stimulation no vesicles are left to release acetycholine and hence the contraction is decreased with every Rapid nerve stimulation .

4.)Plasmapheresis (plasma exchange PLEX) is plamsa compartment of blood is exchanged with substitute plasma and thereby removing circulating humoral factors (ie, anti-AChR antibodies and immune complexes) from the circulation. It is used for myasthenia crisis management. Like IVIg, plasmapheresis is generally reserved for myasthenic crisis and refractory cases. Improvement seen in few days, but it does not last for more than 2 months.
Plasmapheresis is an effective therapy for MG and is often the initial treatment of choice in myasthenic crisis given for 2 weeks .

5)She is at increased risk of respiratory failure because slowly Repiratory muscles weakness occur in myasthnia pateints durjng myasthenia crisis resulting in respiratory failure and is the most common cause of death .