Myasthenia gravis (MG) is a chronic autoimmune disorder of the postsynaptic membrane at the neuromuscular junction (NMJ) in skeletal muscle. Circulating antibodies against the nicotinic acetylcholine receptor (achr) and associated proteins impair neuromuscular transmission

1. DRUGS USED IN
MYASTHENIA GRAVIS
BY
SUDHARSAN.M
SECOND PHARM.D(18-19)
KARPAGAM COLLEGE OF PHARMA
COIMBATORE

2. • MYASTHENIA GRAVIS" LITERALLY MEANS
"GRAVE MUSCLE WEAKNESS, = கடுமையான தமை
பலவ ீ
னம்
• Myasthenia gravis (MG) is a chronic autoimmune disorder of
the postsynaptic membrane at the neuromuscular junction
(NMJ) in skeletal muscle. Circulating antibodies against the
nicotinic acetylcholine receptor (achr) and associated proteins
impair neuromuscular transmission

5. ETIOLOGY
The etiology for the synthesis of autoimmune antibodies remains
unclear, although certain genotypes, particularly linked to the human
leukocyte antigen (HLA) complex, may be more susceptible.
several papers have reported SINGLE NUCLEAR
POLYMORPHISMS in a wide variety of genes in different
populations of patients with MG. also, the THYMUS may be
involved.
MG is associated with THYMIC FOLLICULAR HYPERPLASIA
or THYMOMA in 70% and 10% patients, respectively.

6. PATHOPHYSIOLOGY
• MG is an AUTOIMMUNE SYNAPTOPATHY .The disorder occurs
when the immune system malfunctions and generates antibodies that
attack the body's tissues. The antibodies in MG attack a normal human
protein, the nicotinic acetylcholine receptor, or a related protein
called musk a muscle-specific kinase other less frequent antibodies are
found against LRP4, agrin and titin proteins.
• Human leukocyte antigen (HLA) haplotypes are associated with
increased susceptibility to myasthenia gravis and other autoimmune
disorders. Relatives of MG patients have a higher percentage of other
immune disorders

8. MYASTHENIA GRAVIS FOUNDATION
OF AMERICA CLINICAL
CLASSIFICATION
Class Description
I
Any eye muscle weakness,
possible PTOSIS no other evidence of
muscle weakness elsewhere
II
Eye muscle weakness of any severity,
mild weakness of other muscles
IIa Predominantly limb or axial muscles
IIb
Predominantly bulbar and/or respiratory
muscles
III
Eye muscle weakness of any severity,
moderate weakness of other muscles
IIIa Predominantly limb or axial muscles
IIIb
Predominantly bulbar and/or respiratory
muscles
IV
Eye muscle weakness of any severity,
severe weakness of other muscles
IVa Predominantly limb or axial muscles
IVb
Predominantly bulbar and/or respiratory
muscles

11. DIAGNOSIS
PHYSICAL EXAMINATION
• During a physical examination to check for MG, a doctor might
ask the person to perform repetitive movements. For instance, the
doctor may ask one to look at a fixed point for 30 seconds and to
relax the muscles of the forehead.
• This is done because a person with MG and PTOSIS of the eyes
might be involuntarily using the forehead muscles to compensate
for the weakness in the eyelids.
• The clinical examiner might also try to elicit the "curtain sign" in
a patient by holding one of the person's eyes open, which in the
case of MG will lead the other eye to close

12. BLOOD TESTS
• One test is for antibodies against the acetylcholine
receptor; the test has a reasonable sensitivity of 80–
96%, but in ocular myasthenia, the sensitivity falls
to 50%.
• A proportion of the patients without antibodies
against the acetylcholine receptor have antibodies
against the musk protein
• In specific situations, testing is performed
for lambert-eaton syndrome

13. ELECTRODIAGNOSTICS
• Muscle fibers of people with MG are easily fatigued, which the repetitive
nerve stimulation test can help diagnose
• A thin needle electrode is inserted into different areas of a particular
muscle to record the action potentials from several samplings of different
individual muscle fibers.
• Two muscle fibers belonging to the same motor unit are identified, and the
temporal variability in their firing patterns is measured.
• Frequency and proportion of particular abnormal action potential patterns,
called "jitter" and "blocking", are diagnostic.
• Jitter refers to the abnormal variation in the time interval between action
potentials of adjacent muscle fibers in the same motor unit.
• Blocking refers to the failure of nerve impulses to elicit action potentials in
adjacent muscle fibers of the same motor unit.

15. ICE TEST
• Applying ice for two to five minutes to the muscles
reportedly has a sensitivity and specificity of 76.9% and
98.3%, respectively, for the identification of MG.
• Acetylcholinesterase is thought to be inhibited at the lower
temperature, and this is the basis for this diagnostic test.
• This generally is performed on the eyelids when a ptosis is
present, and is deemed positive if a ≥2 mm rise in the eyelid
occurs after the ice is removed.

17. EDROPHONIUM TEST
• This test requires the intravenous administration
of edrophonium chloride or neostigmine, drugs that block
the breakdown of acetylcholine
by cholinesterase (acetylcholinesterase inhibitors).
• This test is no longer typically performed, as its use can
lead to life-threatening bradycardia (slow heart rate) which
requires immediate emergency attention

19. IMAGING
• A chest x-ray may identify widening of
the mediastinum suggestive of thymoma, but computed
tomography or magnetic resonance imaging (MRI) are
more sensitive ways to identify thymomas and are generally
done for this reason.
• MRI of the cranium and orbits may also be performed to
exclude compressive and inflammatory lesions of the
cranial nerves and ocular muscles.[37]

21. TREATMENT
Treatment is usually started with neostigmine 15 mg orally 6
hourly; dose and frequency is then adjusted to obtain optimum relief
from weakness however
Pyridostigmine is an alternative which Needs less frequent
dosing. Pyridostigmine is a relatively long-acting drug (when compared
to other cholinergic agonists), with a half-life around four hours with
relatively few side effects.
The steroid prednisone might also be used to achieve a better result, but
it can lead to the worsening of symptoms for 14 days and takes 6–8
weeks to achieve its maximal effectiveness.[44] due to the myriad
symptoms that steroid treatments can cause, it is not the preferred
method of treatment. Other immune suppressing medications may also
be used including rituximab.

22. • Several immunosuppressant options are available and
include low-dose corticosteroids, azathioprine, evidence
C mycophenolate, cyclosporine, and tacrolimus, or a
combination of corticosteroids and one of these agents.
• If the myasthenia is serious (myasthenic
crisis), plasmapheresis can be used to remove the putative
antibodies from the circulation. Also, intravenous
immunoglobulins (ivigs) can be used to bind the circulating
antibodies. Both of these treatments have relatively short-
lived benefits, typically measured in weeks, and often are
associated with high costs which make them prohibitive;
they are generally reserved for when MG requires
hospitalization

23. • Thymectomy may be performed in patients with mild,
moderate, or severe disease with thymoma (any age) or
without thymoma with achr antibodies (18 to <65 years
old). It is not yet completely clear at which stages of
myasthenia gravis, in which patients, and in what sequence
in relation to other therapies that thymectomy in
nonthymoma patients should be done.
• Onset of benefit is delayed, rarely seen within 6 months,
and requires follow-up of up to 2 to 5 years for
demonstrated efficacy
• It is generally accepted that the more complete the removal
of thymus, the higher the rate of remission in MG
symptoms.

24. An encapsulated thymoma (mixed
lymphocytic and epithelial type)

25. • Plasma exchange may be used for short-term
management of patients undergoing thymectomy to
avoid perioperative corticosteroids or other
immunosuppressive drugs.
• There is a rapid response with onset usually after 2
to 3 sessions. However, effects are temporary and
only last for a matter of weeks.
• Not all patients need to be treated with plasma
exchange, IVIG, or corticosteroids in order to
undergo thymectomy.

26. EMERGING TREATMENTS =
வளர்ந்து வரும் ைிகிச்மைகள்
• Amifampridine (3,4-diaminopyridine)
• The food and drug administration (FDA)
granted orphan drug designation to
amifampridine for the treatment of
myasthenia gravis (MG) in 2017.

27. METHOTREXATE
• A selective inhibitor of dihydrofolate reductase and
lymphocyte proliferation, methotrexate is used as
immunosuppressive medication for some autoimmune
diseases
• One phase II trial currently under way has set out to
determine if oral methotrexate is safe and effective for MG
patients who take prednisone.
• The results of a randomized controlled study of
methotrexate have been published and the primary end
point was not achieved.

28. BELIMUMAB
• B cell activating factor (BAFF), which promotes B cell
maturation and stimulation, has been reported to be
increased in serum and thymus of patients with myasthenia
gravis.
• Belimumab, a monoclonal antibody that binds to and
inhibits BAFF, has been approved as a therapy for patients
with systemic lupus erythematosus (SLE).
• A trial of belimumab in myasthenia gravis is currently
under way.

30. ETANERCEPT
• Tumor necrosis factor (tnf)-alpha is a
proinflammatory cytokine implicated in the disease
mechanism of MG. Etanercept, a soluble
recombinant TNF receptor fc, blocks tnf-alpha.
• A pilot open-label study showed improvement in
MG symptoms in 5 out of 8 patients who
completed the study.
• The drug was withdrawn in 2 patients due to
worsening of MG symptoms and in 1 patient due to
diffuse skin rash

32. EN101 ANTISENSE
OLIGONUCLEOTIDE
• In patients with MG, there is enhanced synthesis of
alternatively spliced isoform of acetylcholine (ach)
esterase, which inactivates ach before it binds to
the receptor (achr).
• EN101, an antisense oligonucleotide, suppresses
synthesis of the alternatively spliced isoform and
improves efficacy of achr activation.
• EN101 is undergoing clinical trials in humans.

33. STEM-CELL THERAPY
• Autologous hematopoietic stem-cell transplantation.
• There have been isolated reports of patients with
MG treated with stem-cell transplantation.
• There is an ongoing clinical trial but at this time this
should be considered as experimental therapy.

34. TARGET-SPECIFIC
IMMUNOSUPPRESSION
• Induction of immune tolerance by introduction of
achr or portion of sequence by tolerance-inducing
routes and t-cell vaccination, or depletion of achr-
specific B and T cells

35. REFERENCES
1. https://en.wikipedia.org/wiki/Myasthenia_gravis Myasthenia
gravis from wikipedia, the free encyclopedia.
2. https://bestpractice.bmj.com/ - Myasthenia gravis – BMJ Best
Practice
3. Chapter-7 ,cholinergic system and drugs ,2.myasthenia
gravis,pg.no 109, Kd-tripathi-essentials-of-medical-
pharmacologyunitedvrg-2013