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Chapter 23. Drugs for Multiple Sclerosis. Multiple Sclerosis (MS). Chronic, inflammatory, autoimmune disorder that damages the myelin sheath of neurons in the CNS Exact cause is unknown MS causes a wide variety of sensory and motor deficits

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chapter 23

Chapter 23

Drugs for Multiple Sclerosis

multiple sclerosis ms
Multiple Sclerosis (MS)
  • Chronic, inflammatory, autoimmune disorder that damages the myelin sheath of neurons in the CNS
  • Exact cause is unknown
  • MS causes a wide variety of sensory and motor deficits
  • Most patients experience periods of acute clinical exacerbations (relapses) alternating with periods of complete or partial recovery (remissions)
  • Over time, symptoms usually grow progressively worse.
multiple sclerosis ms1
Multiple Sclerosis (MS)
  • Primary pathology of MS
  • Inflammation mechanism
  • Initiation of the autoimmune process
  • After an acute attack
  • Myelin sheaths of peripheral neurons
drug therapy for ms
Drug Therapy for MS
  • 1993: dramatic change occurred
    • First disease-modifying agent approved
  • Now disease progression can be slowed, frequency and intensity of relapses decreased, and permanent neurologic loss delayed
  • Early treatment increases the chances of significantly improving prognosis.
subtypes of ms
Subtypes of MS
  • Relapsing-remitting MS
  • Secondary progressive MS
  • Primary progressive MS
  • Progressive-relapsing MS
signs and symptoms of ms
Signs and Symptoms of MS
  • Symptoms vary depending on where CNS demyelination occurs and the size of the region of demyelination.
    • Paresthesias
    • Muscle or motor problems
    • Visual impairment
    • Bladder and bowel symptoms
    • Sexual dysfunction
    • Disabling fatigue
    • Emotional lability
    • Depression
diagnostic tools for ms
Diagnostic Tools for MS
  • Diagnosis of MS
  • Diagnostic criteria: 1965, 2001, 2005, 2010
  • MRI
  • CSF testing
  • Visual evoked potential (VEP)
drug therapy for ms1
Drug Therapy for MS
  • Disease-modifying therapy
    • Not a cure, but a delay and a decrease in intensity and frequency
    • Immunomodulators and immunosuppressants
drug therapy for ms2
Drug Therapy for MS
  • Relapsing-remitting MS
    • This type benefits the most from therapy.
    • Treatment should begin as soon as diagnosed and should continue indefinitely.
    • All patients (regardless of age) should receive immunomodulators.
      • Interferon beta-1a (Avonex)
      • Interferon beta-1a (Rebif)
      • Interferon beta-1b (Betaseron)
      • Glatiramer acetate (Copaxone)
      • Natalizumab (Tysabril)
drug therapy for ms3
Drug Therapy for MS
  • Secondary progressive MS
    • Interferon beta
    • Mitoxantrone
  • Primary progressive MS
    • No drugs have shown effectiveness
    • Promising studies (methotrexate, azathioprine, cyclophosphamide)
  • Progressive-relapsing MS
    • Mitoxantrone
drug therapy for ms4
Drug Therapy for MS
  • Treating an acute episode (relapse)
    • Short course of high-dose IV glucocorticoid
    • IV gamma globulin
  • Drug therapy of symptoms
    • All four subtypes have the same symptoms
disease modifying drugs i immunomodulators
Disease-Modifying Drugs I: Immunomodulators
  • Seven immunomodulators currently available
  • Four preparation of interferon beta
  • All except natalizumab are recommended as first-line therapy for all patients with relapsing-remitting MS and for those with secondary progressive MS who are experiencing acute exacerbations.
  • Decrease relapse rate about 30%
  • Self-injected (except for fingolimod)
interferon beta
Interferon Beta
  • Interferon is a naturally occurring glycoprotein with antiviral, antiproliferative, and immunomodulatory actions.
  • Therapeutic use
    • Reduces the frequency and severity of attacks
    • Reduces the number and size of MRI-detectable lesions
    • Delays progression of disability
interferon beta1
Interferon Beta
  • Adverse effects and drug interactions
    • Flu-like reactions
    • Hepatotoxicity
    • Myelosuppression
    • Injection-site reactions
    • Depression
    • Drug interactions
  • Preparation, dosage, and administration
    • Dispensed as single-use syringes and vials
glatiramer acetate
Glatiramer Acetate
  • Therapeutic use
    • For long-term therapy of relapsing-remitting MS
  • Description and mechanism
    • Protects myelin by inhibiting immune response to myelin basic protein
  • Adverse effects
    • Well tolerated
natalizumab tysabril
Natalizumab (Tysabril)
  • Introduced in 2004 and withdrawn a few months later owing to three reports of progressive multifocal leukoencephalopathy (severe brain infection)
  • Reintroduced in 2006 with protective restrictions on who can prescribe, dispense, administer, receive it
  • Therapeutic uses – MS and Crohn’s disease
  • Prevents circulating leukocytes from leaving the vasculature
  • Adverse effects – generally well tolerated (headache, fatigue, abdominal discomfort, arthralgia, depression, diarrhea, gastroenteritis, UTI, lower respiratory tract infection)
disease modifying drugs ii immunosuppressants
Disease-Modifying Drugs II: Immunosuppressants
  • Only one approved by the FDA: mitoxantrone
  • More toxic than immunomodulators
  • Produce greater suppression of immune function
mitoxantrone
Mitoxantrone
  • Therapeutic use
    • Decreases neurologic disability and clinical relapses
  • Mechanism of action
    • Binds with DNA and inhibits topoisomerase
  • Adverse effects and drug interactions
    • Myelosuppression
    • Cardiotoxicity
    • Fetal harm
    • Reversible hair loss, injury to GI mucosa, nausea/vomiting, amenorrhea, allergy symptoms, blue-green tint to urine, skin, and sclera
mitoxantrone1
Mitoxantrone
  • Monitoring summary
    • Perform complete blood counts at baseline and before each dose
    • Perform liver function tests at baseline and before each dose
    • Perform a pregnancy test before each dose
    • Determine left ventricular ejection fraction (LVEF)
      • Before the first dose
      • Before all doses once cumulative dose has been reached
      • Whenever signs of congestive heart failure (CHF) develop
symptom management
Symptom Management
  • Bladder dysfunction
  • Bowel dysfunction
  • Fatigue
  • Depression
  • Spasticity
  • Sexual dysfunction
  • Neuropathic pain
  • Ataxia and tremor
  • Cognitive dysfunction
  • Dizziness and vertigo
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