MS Flashcards
What are the two major theories as to who MS occurs?
- Microbial: Virus directly attacks myelin or oligodendrocytes which in turn stimulates an immune response; Supportive evidence: increased IgG synthesis in CNS and Ab levels to certain viruses (HHV-6)
- Autoimmune: Body recognizes myelin or oligodendrocytes as foreign and begins to attack; Inflammatory cascade is initiated
What is the main type of drug used to treat acute exacerbations of MS?
Corticosteroids:
- IV Solumedrol
- Oral Prednisone
- shorten duration of episode
- does not alter progression of disease, no LT benefites
Help to prevent relapse and progression; Initiate ASAP following diagnosis; Therapy should be continued indefinitely unless Clear lack of benefit, Intolerable side effects, or New clinical suggest otherwise
Disease modifying agents
a common virus that is harmless in most people;Can cause a rare and serious brain infection (progressive multifocal leukoencephalopathy [PML]) in some patients who have weakened immune systems
John Cunningham (JC) virus
Symptoms may include: progressive weakness on one side of the body, clumsiness, vision problems, confusion, and changes in thinking, personality, memory, and orientation; Can lead to severe disability or death.
PML
- damage to white matter
What is the major downfall of disease modifying drugs for MS?
Very expensive; Monthly cost:
- Aubagio - $4,757.19
- Avonex - $5,058.19
- Betaseron - $5,809.69
- Copaxone - $6,000.09
- Extavia - $5,589.99
- Gilenya - $4790.19
- Rebif - $5,304.49
- Tecfidera - $5,320.09
- Tysabri - $5,629.49
What are the different disease modifying agents for MS
- Avonex and Rebif (Interferon β1-A)
- Betaseron and Extavia (Interferon β1-B)
- Copaxone (Glatiramer Acetate)
Disease modifying agent MOA: Naturally occurring cytokines with immunomodulating activities that reduce the inflammatory process - Antiviral properties
Interferons
Disease modifying agent MOA: Mimics the antigenic effects of myelin basic protein so that the binding of MBP peptides to T-cells is inhibited
Induced anti-inflammatory lymphocytes
Copaxone
What are the ADRs of Betaseron?
- Flu-like Sx (premedicate with Ibuprofen/APAP (Tylenol))
- Pain, redness at injection site
- SOB
- Tachycardia
- Leukopenia, Neutropenia, Increased LFT’s
- Depression
- Neutralizing antibodies
- avonex and rebid have similar ADRs, but no incr in depression
What does it mean when someone develops neutralizing antibodies to a disease modifying agent?
Neutralizes the drug after its injected – so getting same amt of drug but only certain amt is having effect
- typically appears btwn 6-15 mos into therapy
- Betaseron>Rebif>Avonex
- can’t switch to different interferon; antibodies have cross-over
What are ADRs of Copaxone?
- injection site pain
- Neutralizing antibodies?
- 10-15% of patients have chest tightness and flushing that resolves within 20 minutes
What are ADRs of extavia?
- Flu like symptoms – pretreat with analgesics or antipyretics on treatment days.
- Liver injury (severe is rare)
- allergic reactions
- depression
- CHD and cardiomyopathy
- leukopenia
- injection site necrosis, pain, rash
- myalgia
Alternative treatment for MS:
SAM blocker, white cells must bind adhesion molecules to cross arterial blood vessels and enter the brain; Originally withdrawn from the market due to leukoencephalopathy, also anaphylaxis and neutralizing Ab formation; Now back on the market, Dosed IV every 4 weeks
Tysabri (natalizumab)
Alternative treatment for MS: Chemotherapy agent
For secondary progressive MS – slows progression; Dosed IV every 3 monthss; Cardiomyopathy – has maximal lifetime dose** (LVEF must be assessed prior to therapy; Left ventricular ejection fraction); May cause hair loss and leukopenia
Novatrone (mitoxantrone)
