copyright © 2013, 2010 by saunders, an imprint of elsevier inc. chapter 23 drugs for multiple...

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.


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

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

Relapsing-remitting MS Secondary progressive MS Primary progressive MS Progressive-relapsing 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

Diagnosis of MS Diagnostic criteria: 1965, 2001, 2005, 2010 MRI CSF testing Visual evoked potential (VEP)


Fig. 23-1. Symptom patterns that define the four subtypes of MS.


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 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 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 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

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 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 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

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)

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

Only one approved by the FDA: mitoxantrone More toxic than immunomodulators Produce greater suppression of immune

function


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


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

Bladder dysfunction Bowel dysfunction Fatigue Depression Spasticity Sexual dysfunction Neuropathic pain Ataxia and tremor Cognitive dysfunction Dizziness and vertigo

copyright © 2013, 2010 by saunders, an imprint of elsevier inc. chapter 23 drugs for multiple...

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ms disease

unknown ms

symptoms of ms symptoms

subtypes of ms relapsing

multiple sclerosis ms

immunosuppressants slide

multiple sclerosis slide