Date post: | 23-Dec-2015 |
Category: |
Documents |
Upload: | wilfred-bryan |
View: | 213 times |
Download: | 0 times |
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Chapter 23
Drugs for Multiple Sclerosis
2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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.
3Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Multiple Sclerosis (MS)
Primary pathology of MS Inflammation mechanism Initiation of the autoimmune process After an acute attack Myelin sheaths of peripheral neurons
4Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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.
5Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Subtypes of MS
Relapsing-remitting MS Secondary progressive MS Primary progressive MS Progressive-relapsing MS
6Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
7Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Diagnostic Tools for MS
Diagnosis of MS Diagnostic criteria: 1965, 2001, 2005, 2010 MRI CSF testing Visual evoked potential (VEP)
8Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Fig. 23-1. Symptom patterns that define the four subtypes of MS.
9Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Drug Therapy for MS
Disease-modifying therapy Not a cure, but a delay and a decrease in intensity
and frequency Immunomodulators and immunosuppressants
10Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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)
11Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
12Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
13Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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)
14Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
15Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
16Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
17Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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)
18Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Disease-Modifying Drugs II: Immunosuppressants
Only one approved by the FDA: mitoxantrone More toxic than immunomodulators Produce greater suppression of immune
function
19Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
20Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
21Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Symptom Management
Bladder dysfunction Bowel dysfunction Fatigue Depression Spasticity Sexual dysfunction Neuropathic pain Ataxia and tremor Cognitive dysfunction Dizziness and vertigo