Transcription
Hello everybody. In this video, we'll talk about multiple sclerosis medications. First, I will talk about the pathophysiology of multiple sclerosis.
MS is a progressive, chronic autoimmune disease. Here we have the neuron, and it is protected by the myelin sheath. In MS, T cells will recognize myelin as foreign and will attack it, causing a demyelination of the neuron. Now, the signals that should have been transmitted to the area that the nerve supply will not be transmitted properly.
Let's go back to the T cells. T cell action will start the inflammatory process. It will allow more T cells to come in from the blood-brain barrier, and cytokines like interleukin-1, interleukin-2, and TNF will be released. These cytokines will dilate the blood vessels in the blood-brain barriers and attract B-cells and macrophages as part of the inflammatory process.
Now, for the symptoms. Since it's a fixed transmission of signals, we would expect coordination issues, sensory problems, and cognitive issues. We have four types of multiple sclerosis. First, the relapsing-remitting, which is the most common type, where the patient will have relapse phases followed by remission phases. Then we have secondary progressive, which is the same as the first one but in a progressive manner. Then we have primary progressive, which is always progressive, and then we have a progressive-relapsing. It's progressive but with a relapsing phase.
Now let's talk about the treatment options. We have disease-modifying agents and symptomatic medications. First, disease-modifying agents are indicated to decrease relapse rates or, in some cases, prevent disability. The major targets of these medications are to modify the immune response through the inhibition of white blood cell-mediated inflammatory process that eventually leads to myelin sheath damage.
First medications we have are the interferon beta 1a and beta-1b. They suppress production of the pro-inflammatory cytokines and reduce the inflammatory cell migration of the T-cells across the blood-brain barrier. Adverse effects include depression, local injection site reaction, increased hepatic enzymes, and flu-like symptoms.
Second, we have glatiramer, which is a synthetic polypeptide that resembles myelin protein and may act as a trap for T-cell attacks. Side effects include injection site reaction that happens with more than 90 percent and other systemic reactions like chest tightness, flushing, and dyspnea.
Third, we have fingolimod, which is an oral drug that alters lymphocyte migration by inhibiting the S1P receptor, resulting in fewer lymphocytes in the CNS. Fingolimod may cause first-dose bradycardia and is associated with increased risk of infection and macular edema.
Fourth, we have teriflunomide, which is an oral pyrimidine synthesis inhibitor that leads to a lower concentration of active lymphocytes in the CNS. Side effects include elevated liver enzymes, and it is pregnancy category X.
The fifth agent is the dimethyl fumarate. It promotes anti-inflammatory and cytoprotective activity. It is an oral agent that alters cellular response to oxidative stress to reduce disease progression. Flushing and abdominal pain are the most common adverse effects.
Sixth, we have natalizumab. The "zumab" suffix reminds us of the monoclonal antibodies. So yes, it's the first monoclonal antibody developed specifically for treatment of multiple sclerosis. It is for patients who have failed first-line therapies. Its mechanism of action is it inhibits migration of T-cells across the blood-brain barrier. Other adverse effects include headache, UTI, respiratory tract infection, depression, abdominal pain, but the most serious side effect of them all is the PML, or the progressive multifocal leukoencephalopathy, which is a disease that causes demyelination similar to MS.
Seventh agents we have are the mitoxantrone, which is a cytotoxic and anthracycline analog that kills T cells and may also be used for multiple sclerosis. Adverse effects will logically include leukopenia since it decreases T cells and cardiotoxicity since anthracycline is known to cause cardiotoxicity. Also, it causes alopecia and UTI.
Now we have other monoclonal antibodies like ofatumumab, ocrelizumab, and alemtuzumab. Ofatumumab will target CD52, which is highly expressed on the lymphocytes, T and B cells, resulting in decreased levels of these cells. Side effects will of course include infections like UTI, URI, herpesviral infections. For ocrelizumab, its mechanism of action is it modulates interleukin-2 mediated activation of lymphocytes through binding to CD25. Side effects include rash, high ALT, and pharyngitis. For alemtuzumab, it binds to CD20, which is a cell surface antigen present on the pre-B and mature B lymphocytes, resulting in antibody-dependent cellular cytotoxicity. Side effects will include autoimmune restrictive infection, depression, and back pain.
Okay, now we've finished from the disease-modifying agents and we'll go to the symptomatic treatments. First, for spasticity, we can use muscle relaxants like baclofen or tizanidine. For baclofen, it can cause somnolence and confusion that improve with time. Tizanidine, it can cause extreme sedation.
For bladder dysfunction, like having the symptoms of urgency and frequency, we can use one of these anticholinergics or one of these antimuscarinics. And side effects can be dry mouth or constipation.
For bowel function, like having the symptoms of constipation or diarrhea. For diarrhea, we can use a high-fiber diet, and for constipation, we can use laxatives and stool softeners.
For neurogenic pain, like having the symptoms of numbness and tingling, the medication can be gabapentin and pregabalin.
For tremors, we can use beta-blockers like propranolol or benzodiazepines like clonazepam.
For cognitive dysfunction, like having reduced attention, reduced short-term memory, or reduced verbal fluency, we can use donepezil, which is an acetylcholine esterase inhibitor that is used with Alzheimer's disease patients.
Last, for depression, we can use one of the SSRIs or TCAs.
And that's the end of this video. Please do forget to subscribe, share, and like.