July 23, 2008
Pharmacologic Management of Multiple Sclerosis
By Blasier, Mary Gail
Key Words: Multiple sclerosis, central nervous system, disease modifying therapies, quality of life. Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS), which is composed of the brain, optic nerves, and spinal cord (Graham, 2009). It is thought to be an autoimmune disorder that afflicts approximately 400,000 Americans in early to middle adulthood (ages 20 to 40) (National Multiple Sclerosis Society [NMSS], 2008). About 200 people are newly diagnosed each week. Worldwide, MS is believed to affect about 2.5 million (NMSS, 2008). Women are affected twice as often as men, and Caucasians are affected more often than Hispanics, Blacks, or Asians (Graham, 2009). The disease is more prevalent in the colder climates of North America and Europe. If someone is born in a high-risk area for MS and moves to a low-risk area after age 15, that person still carries the risk of the area of origin (Graham, 2009).ETIOLOGY AND PATHOPHYSIOLOGY
Susceptibility may be determined by genetic and environmental factors, as well as triggers, such as the Epstein-Barr virus. MS is characterized by chronic inflammation and destruction of the myelin sheath of neurons in the CNS. The myelin sheath is essential for the normal conduction of nerve impulses. Patches of myelin deteriorate at irregular intervals along the nerve axon, causing slowing of nerve conduction. Axonal destruction also occurs in MS (Graham, 2009).
Precipitating factors can precede the onset of an exacerbation of MS, such as infection, physical injury, emotional stress, pregnancy, and fatigue (Graham, 2009). Signs and symptoms of MS most commonly include weakness and/or sensory symptoms involving a limb, visual difficulties, and gait and coordination abnormalities. Sensory symptoms may include "pins and needles" in a limb. Optic neuritis can result in blurring or misting of vision. Initial symptoms present as follows:
* Sensory loss - 37%.
* Optic neuritis - 36%.
* Weakness - 35%.
* Paresthesias - 24%.
* Diplopia - 15%.
* Ataxia - 11%.
* Bladder dysfunction - 4%.
Physical examination may be difficult in terms of diagnosis due to the widespread nature of the symptoms; delayed diagnosis is common. MRI is abnormal in over 95% of patients (NMSS, 2008).
MS has four clinical patterns of presentation, making the onset insidious or dramatic (Graham, 2009). The pattern of presentation determines the treatment. The four presentation patterns are:
* Relapsing-remitting MS is characterized by recurrent attacks of neurologic dysfunction with or without recovery.
* Secondary progressive MS presents with a relapsing-remitting pattern but evolves to be progressive.
* Primary progressive - Gradual progression of disability from onset.
* Progressive-relapsing - Rare; begins with progressive but relapses can occur.
The chronic nature of this disease creates serious quality-of- life issues over a lifetime. Fifteen years after diagnosis, 20% of patients have no functional limitation, 70% are limited or unable to perform major activities of daily living, and 75% are not employed (Hauser & Goode, 2004). Bladder and bowel dysfunction, vision loss, weakness, loss of coordination, fatigue, and/or depression are the primary problems experienced by most patients (Graham, 2009). Detrusor hyperreflexia is seen in 60% of patients, and about one- third of patients with detrusor hyperreflexia have vesicosphincter dyssynergia (Hauser & Goode, 2004; Siroky, Oates, & Babayan, 2004). About 20% of patients have detrusor areflexia.
Treatment generally falls into one of three categories: 1) treatment of acute relapses, 2) treatment aimed at disease management, and 3) treatment of symptoms (Graham, 2009).
Acute relapses that produce functional impairment may be treated with a short course of intravenous or oral corticosteroids to decrease inflammation and suppress the immune system. This regimen speeds recovery and may modestly improve the degree of recovery. The most common drug for acute relapses is methylprednisolone. Other immunosuppressive agents may be used for more severe exacerbations (Graham, 2009).
The FDA has approved several disease modifying therapies (DMT) to treat MS (see Table 1). Unfortunately, these drugs do not cure MS or make the patient feel better while taking them. However, DMTs slow the progression of the disease to provide long-term benefits for patients. People who start treatment early and continue with treatment have better outcomes. The actions of DMTs include:
* Decrease the frequency and severity of clinical attacks.
* Decrease the accumulation of lesions found in the brain and spinal cord.
* Slow the onset of disabilities (Graham, 2008; NMSS, 2008).
Three of the DMTs are classified as interferons: interferon beta- 1b (Betaseron(R)) and interferon beta-1a (Avonex(R) or Rebif(R)) (Graham, 2009; NMSS, 2008). Interferons are antiviral proteins produced by cells infected by a virus. These proteins are designed to inhibit the replication of virus cells. The interferon medications are injected subcutaneously (SQ) or intramuscularly (IM), with time frames that vary from every other day for Betaseron (SQ), once a week for Avonex (IM), and 3 times a week for Rebif (SQ). Side effects include fatigue, fever, allergic reactions, flu- like symptoms, injection site reactions, depression, and elevated liver enzymes (Graham, 2009).
Glatiramer acetate (Copaxone(R)) is an artificial protein that resembles the natural myelin protein that protects nerve fibers. It mimics the myelin basic protein and interrupts the inflammatory cascade to prevent damage to myelin (Graham, 2009; NMSS, 2008). Copaxone is given daily by subcutaneous injection. Because it is not an interferon, it does not produce side effects associated with interferons; however, vasodilation, anxiety, face flushing, chest tightness, and shortness of breath lasting less than 15 minutes have been reported.
Mitoxantrone HCI (Novantrone(R)) is an immune suppressing drug designed to slow down or turn off inflammatory cells that can cause damage to nerve cells (NMSS, 2008). Novantrone is given 4 times a year via intravenous (IV) infusion. The lifetime cumulative dose is limited to 140 mg/m2 (approximately 8 to 12 doses over 2 to 3 years) because of possible cardiac toxicity. The patient will show blue green urine 24 hours after dose, and he or she may be susceptible to infections, bone marrow decrease, nausea, fatigue, and liver or cardiac damage.
Natalizumab (Tysabri(R)) was approved by the FDA in 2006 and has been shown to be helpful in patients who have not had success with interferon drugs. This DMT drug is a recombinant monoclonal antibody that binds to alpha 4-integrin (NMSS, 2008). It is indicated as monotherapy for relapsing forms of MS to delay the accumulation of physical disability and reduce relapses. Before the patient can begin Tysabri, there must be a 2-week wash-out period if the patient has been treated with interferon drugs or Copaxone. Patients treated with Novantrone or other immunosuppressant medications should wait three months prior to starting Tysabri.
Tysabri is known to predispose patients to infection. Serious hypersensitivity (anaphylactic) reactions have occurred in less than 1% of patients. More common side effects may include dizziness, fever, rash, urticaria, rigors, nausea, flushing, hypotension, dyspnea, and chest pain. Nine percent of patients who experienced hypersensitivity reactions to Tysabri had detectable neutralizing antibodies to the drug. Administered by intravenous infusion monthly, it has been shown to be useful in patients who have not responded other interferon-type drugs (NMSS, 2008).
DMTs lessen the frequency of relapses, but other treatment forms are necessary to deal with symptom management. Additional symptomatic treatment may include clonazepam (Klonopin(R)) and propranolol (Inderal(R)) for ataxia and tremors; baclofen (Lioresal(R)), diazepam (Valium(R)), or tizanidine (Zanaflex(R)) for spasms; and anticonvulsants, such as gabapentin (Neurontin(R)), carbamazepine (Tegretol(R)), and phenytoin (Dilantin(R)), for pain (Graham, 2009). Bladder dysfunction can be managed with anticholinergics, such as oxybutynin (Ditropan(R)) and propantheline (Pro-Banthine(R)), initially (Graham, 2009).
Disease modifying treatments have meant improved quality of life for MS patients. As the disease progresses, the use of different drug classes to combat symptom flares and exacerbations varies. These drugs have side effects as well as benefits, complicating the lives of patients stricken with this chronic progressive disease.
Graham, P. (2009). Management of clients with degenerative neurologic disorders. In J. Black & J. Hawks (Eds.), Medical- surgical nursing: Clinical management for positive outcomes (8th ed., pp. 1909-1914). Philadelphia: Elsevier Saunders.
Hauser, S., & Goode, D. (2004). Multiple sclerosis and other demyelinating diseases. In D.L. Kasper, E. Braunwald, S. Hauser, D. Longo, J.L. Jameson, & A.S. Fauci (Eds). Harrison's principles of internal medicine (16th ed., pp. 2461-2465). New York: McGraw-Hill.
National Multiple Sclerosis Society (NMSS). About MS. (2008). Retrieved March 24, 2008, from http://www.nationalmssociety.org/ about-multiple-sclerosis/index.aspx
Siroky, M., Oates, R., & Babayan, R. (2004). Handbook of urology (3rd ed.). Philadelphia: Lippincott, Williams & Wilkins. Mary Gail Blasier, MSN, BSN, ANP, CUNP, is a Urologic Nurse Practitioner, Urology Department, Veterans' Administration Hospital, Ann Arbor, MI.
Copyright Anthony J. Jannetti, Inc. Jun 2008
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