1.5 Myasthenia Gravis

Pathophysiology of Myasthenia Gravis:

The pathophysiology involves an immune-mediated attack on acetylcholine receptors (AChRs) at the neuromuscular junction, which is the synapse between a motor neuron and a muscle fiber. The body’s immune system produces antibodies against AChRs, leading to receptor degradation and a reduction in the number of available receptors. These antibodies bind to the acetylcholine receptors on the muscle cell membrane, blocking the binding of acetylcholine (ACh) and impairing muscle contraction.

In a healthy neuromuscular junction, ACh is released from the motor neuron and binds to AChRs on the muscle cell, causing muscle contraction. In myasthenia gravis, the binding of antibodies to AChRs disrupts this process, resulting in muscle weakness and fatigue. Additionally, these antibodies can activate the complement system, leading to further destruction of the postsynaptic membrane and loss of AChRs. This immune response leads to a significant reduction in the efficiency of neuromuscular transmission, causing the characteristic symptoms of the disease.

Mechanism of Action of Drugs Used to Treat Myasthenia Gravis:

To manage myasthenia gravis, several pharmacological treatments are employed. Acetylcholinesterase inhibitors, such as pyridostigmine and neostigmine, are commonly used. These drugs inhibit the enzyme acetylcholinesterase, which breaks down acetylcholine in the synaptic cleft. By inhibiting this enzyme, acetylcholinesterase inhibitors increase the concentration of acetylcholine at the neuromuscular junction, enhancing neuromuscular transmission and improving muscle contraction.

Immunosuppressants like prednisone, azathioprine, and mycophenolate mofetil are also used to treat myasthenia gravis. These drugs suppress the immune response, reducing the production of antibodies against AChRs. By decreasing antibody production, these medications slow the progression of the disease and improve muscle strength. Additionally, intravenous immunoglobulin (IVIG) therapy is believed to modulate the immune system by providing a large number of antibodies that can alter the immune response, reducing the level of pathogenic antibodies in the blood and temporarily improving muscle strength.

Plasmapheresis is another treatment option, involving the removal of plasma from the blood and its replacement with a plasma substitute. This process effectively removes the antibodies against AChRs from circulation, providing temporary relief of symptoms and improved muscle strength. Monoclonal antibodies, such as rituximab and eculizumab, target specific components of the immune system. Rituximab targets CD20 on B cells, reducing their number and antibody production, while eculizumab inhibits the complement system. These treatments decrease autoimmune activity against AChRs, improving muscle strength and reducing disease activity.

These various treatments aim to enhance neuromuscular transmission, reduce the autoimmune attack on acetylcholine receptors, and manage the symptoms of myasthenia gravis, ultimately improving the quality of life for patients.