Ch 23 Drugs for Multiple Sclerosis

Question 1

MS is a chronic inflammatory autoimmune disorder that
damages the _____. Because of demyelination, axonal conduction is slowed or blocked, giving rise to a host of sensory, motor, and cognitive deficits. When inflammation subsides, some degree of recovery occurs, at least in the early stage of the disease.

Answer 1

myelin sheath of neurons in the CNS

Question 2

In addition to stripping off myelin, inflammation may injure the underlying ___.

Answer 2

axon and may also injure nearby oligodendrocytes, the cells that make CNS myelin

Question 3

What causes MS?

Answer 3

There is general agreement that MS develops in genetically vulnerable people following exposure to an environmental or microbial factor that initiates autoimmune activity.

Question 4

There are four subtypes of MS:

Answer 4

relapsing-remitting (the most common form),
secondary progressive,
primary progressive, and
progressive-relapsing.

Question 5

In patients with MS, drugs are employed to __(3)__. We have no drugs to cure MS.

Answer 5

(1) modify the disease process,
(2) treat acute relapses, and
(3) manage symptoms

Question 6

Disease-modifying drugs can decrease the __(4)__. In addition, they may prevent permanent damage to axons.

Answer 6

frequency and severity of relapses,
reduce development of brain lesions,
decrease future disability, and
help maintain quality of life

Question 7

There are two main groups of disease-modifying drugs:

__(2)__.

Answer 7

immunomodulators and immunosuppressants

Question 8

The ___—are safer than mitoxantrone (the only FDA-approved immunosuppressant for MS), and hence are generally preferred.

Answer 8

immunomodulators

interferon beta, dimethyl fumarate, glatiramer acetate, natalizumab, fingolimod, and teriflunomide

Question 9

All patients with ___ should receive an immunomodulator—interferon beta, dimethyl fumarate, glatiramer acetate, natalizumab, fingolimod, or teriflunomide—beginning as soon as possible after diagnosis and continuing indefinitely.

Answer 9

relapsing-remitting MS

Question 10

Interferon beta and glatiramer are administered by ____ and dimethyl fumarate, fingolimod, and teriflunomide are administered ___. Natalizumab is administered by ___.

Answer 10

selfinjection (IM or subQ)
PO
IV infusion in a specialized center

Question 11

Interferon beta is generally well tolerated, although side

effects—__(4)_—are relatively common.

Answer 11

flu-like reactions, liver injury, myelosuppression,

injection-site reactions

Question 12

The most common side effect of dimethyl fumarate is ___; the most serious adverse effect is ___.

Answer 12

flushing,

lymphopenia, with a resulting increase in the risk of infections

Question 13

Dimethyl fumarate can decrease the body’s response to

___.

Answer 13

live virus vaccines (patients should not receive live virus

vaccines when taking this drug)

Question 14

Glatiramer is less well tolerated than interferon beta, and

requires ___.

Answer 14

more frequent injections

Question 15

The most common side effects of glatiramer are ___, and the most disturbing side effect is brief but severe ___ after the injection. Unlike interferon beta, glatiramer
does not cause flu-like symptoms or myelosuppression.

Answer 15

injection site reactions (pain, erythema, pruritus, induration);
chest pain

Question 16

___ binds with sphingosine 1-phosphate receptors on lymphocytes, and thereby keeps them sequestered in lymph nodes. As a result, fewer lymphocytes enter the brain, and hence axonal damage from inflammation is reduced.

Answer 16

Fingolimod (as fingolimod phosphate)

Question 17

Although effective, fingolimod can cause a host of ___..

Answer 17

adverse effects

e.g., bradycardia, infection, macular edema, liver injury, fetal harm

Question 18

Natalizumab can cause progressive multifocal leukoencephalopathy (PML), a severe CNS infection caused by reactivation of the JC virus. To reduce the risk of PML, natalizumab must __(3)__.

Answer 18

NOT be combined with other immunosuppressant drugs, must NOT be given to patients with HIV/AIDS and other conditions that compromise cell-mediated immunity, and must be used in accord with the TOUCH Prescribing Program

Question 19

___ has a very long half-life of approximately

2.5 to 3 weeks and may be detectable in the serum as long as 2 years after cessation of therapy.

Answer 19

Teriflunomide

Question 20

Teriflunomide can cause serious ___

Answer 20

birth defects if taken by pregnant women, and birth defects may occur if a woman is impregnated by a man who is taking teriflunomide.

Question 21

Patients taking teriflunomide should not take___
as this combination has resulted in conditions that have
been fatal.

Answer 21

leflunomide

Question 22

Patients taking teriflunomide should avoid ___.

Answer 22

live virus vaccines

Question 23

___ is the only immunosuppressant currently

approved for MS.

Answer 23

Mitoxantrone

Question 24

Mitoxantrone suppresses immune function more strongly

than the immunomodulators, but is also more toxic. Accordingly, the drug is generally reserved for patients who ___

Answer 24

who are unresponsive to, or intolerant of, an immunomodulator.

Question 25

In patients with MS,___ suppresses production

of immune system cells and thereby decreases autoimmune destruction of myelin.

Answer 25

mitoxantrone

Question 26

The major side effects of mitoxantrone are __(3)__.

Answer 26

myelosuppression, cardiotoxicity, and fetal injury

Question 27

The risk of cardiotoxicity from mitoxantrone increases

significantly if the lifetime cumulative dose exceeds ___.

Answer 27

140 mg/m2, and hence the total dose should not exceed this amount

Question 28

A short course of high-dose ___ is the preferred treatment for an acute MS relapse. Intravenous gamma globulin is an option.

Answer 28

IV glucocorticoids (e.g., methylprednisolone)