Post on 08-Jun-2020
Access Denied: Living with Multiple Sclerosis
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Reproduction in whole or in part without permission is prohibited.
Page 1
Access Denied:
Living with Multiple Sclerosis
Thomas A. Woods, DHSc., M. Ed., PA-C
Associate Professor, Department of Physician Assistant Sciences
Saint Francis University
Peter A. Kreckel, BS Pharm
Adjunct Assistant Professor of Pharmacology
Saint Francis University
PharmCon is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing
pharmacy education
Legal Disclaimer: The material presented here does not necessarily reflect the views of Pharmaceutical Education Consultants
(PharmCon) or the companies that support educational programming. A qualified healthcare professional should always be
consulted before using any therapeutic product discussed. Participants should verify all information and data before treating patients or employing any therapies described in this educational activity.
This program has been
supported by an educational
grant from Bayer Healthcare
Access Denied:
Living with Multiple Sclerosis
This program has been supported by an educational grant from Bayer Healthcare
Accreditation:
Pharmacists: 0798-0000-10-053-L01-P
Pharmacy Technicians: 0798-0000-10-053-L01-T
CE Credits: 1 contact hour
Target Audience: Pharmacists & Technicians
Program Overview:
This program will assist pharmacists in understanding facets of the debilitating effects MS has on its
patients, and the challenges of treating and counseling its victims. It will also enhance their knowledge of
available options for those patients under these conditions. The program includes information on
pharmacologic treatments, patient counseling and a question and answer period.
Objectives:
• Summarize recent developments in understanding the etiology, pathophysiology, and impact of multiple
sclerosis
• Review currently available treatments strategies for relapsing-remitting multiple sclerosis, including
dosing and administration and efficacy and safety of treatments.
• Identify unique challenges and opportunities for educating and counseling patients who are suffering from
multiple sclerosis.
Access Denied:
Living with Multiple Sclerosis
PharmCon is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing
pharmacy education
Legal Disclaimer: The material presented here does not necessarily reflect the views of Pharmaceutical Education Consultants (PharmCon) or the companies
that support educational programming. A qualified healthcare professional should always be consulted before using any therapeutic product discussed.
Participants should verify all information and data before treating patients or employing any therapies described in this educational activity.
This program has been
supported by an educational
grant from Bayer Healthcare
Speaker: Dr. Woods received his Doctor of Health Science in December 2003 from Nova Southeastern University, Fort
Lauderdale, Florida, and his BS in Physician Assistant Science from Saint Francis College, Loretto, PA in August 1997.
He is currently an Associate Professor, Department of Physician Assistant Sciences Saint Francis University, where he
is the Clinical Medicine HIV/AIDS Unit designer and instructor. He has earned several teaching awards and has
presented numerous presentations as a keynote speaker, in addition to having authored several publications.
Peter A. Kreckel R.Ph. is a graduate of the University of Pittsburgh, Bachelor of Science in Pharmacy, Magna Cum
Laude, Class of 1981. He served as the President of the Pharmacy School Class of 1981 for 3 years, and President of
the Pharmacy School Student Council for 2 years. During this time he received the Upjohn Achievement Award for
leadership and academic achievement. In addition to managing a retail pharmacy, pharmacist Kreckel is an Adjunct
Assistant Professor of Pharmacology, Department of Physicians Assistant Sciences, St. Francis University. His
assignments include teaching a HIV pharmacotherapy course for Physician Assistant students, currently doing their
clinical rotations, that are pursuing a Masters of Medical Science Degree from St. Francis University.
Speaker Disclosure: Dr. Woods and Mr. Kreckel have no actual or potential conflicts of interest in relation
to this program.
Educational Objective #1
1. Summarize the recent developments in
understanding the etiology, pathophysiology
and impact of multiple sclerosis.
Access Denied: Living with Multiple Sclerosis
© 2010 Pharmaceutical Education Consultants, Inc. unless otherwise noted. All rights reserved.
Reproduction in whole or in part without permission is prohibited.
Page 2
http://worriedlebanese.files.wordpress.com/2010/01/masquerade-trifaccia-dipinta-mask.jpg,
http://www.istockphoto.com/file_thumbview_approve/4580797/2/istockphoto_4580797-mardi-gras-masquerade-party-masks.jpg
M.S. = Masquerade
Pathophysiology of M.S.
• Chronic inflammatory condition of the CNS
which causes demyelination
• The infiltration of T cells, B cells,
macrophages, and activated microglia
demyelinate and cause inflammatory
reactions, which are characteristic of M.S.
lesions (Cudrici et al., 2006)
Epidemiology
A Unknown
B Autoimmune
C Viral Theory
D Geographical Gradient
E Combined Theory » Hauser and Goodin
http://foreclosurenv.files.wordpress.com/2010/03/800px-world_map_with_equator.jpg
http://images.free-extras.com/pics/n/no_kissing-1441.jpg
http://www.cap.nsw.edu.au/bb_site_intro/stage1_Modules/WWS-stage1/images/sun.gif
Access Denied: Living with Multiple Sclerosis
© 2010 Pharmaceutical Education Consultants, Inc. unless otherwise noted. All rights reserved.
Reproduction in whole or in part without permission is prohibited.
Page 3
Epidemiology
• Major cause of disability in young adults
• Predominant age 16-40
• F>M 3 fold more common in females
• 2.5 million patients world wide with M.S.
• 400,000+ patients with M.S. in USA
• http://www.munnkykrunchers.com/images/Logos/MS%20WALK_logo_ENG
_2%20col_horizontal.jpg
Four Clinical Types of MS
Relapsing/Remitting
– Accounts for 85% of MS cases
– Characterized by discrete attacks that
generally evolve over days to weeks with
recovery over the ensuing weeks to months.
If ambulation is impaired – may not improve.
– B/t attacks patients become neurologically
stable
Symptoms & Signs
** Diagnose early!!**
http://www.shirleymclennan.com/wp-
content/uploads/2008/02/house-for-sale-sign.jpg
Symptoms
A Vision changes
B Sensory changes
C Ataxia
D Vertigo
E Urinary Disturbance
Detrusor hyperreflexia – frequency
Detrousor Sphincter Dyssynergia - retention
Access Denied: Living with Multiple Sclerosis
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Reproduction in whole or in part without permission is prohibited.
Page 4
Symptoms
F Mental Disturbance
G Fatigue
Worse after activity
Physical Exam Manifestations
What is causing this visual distortion?
http://www.mult-sclerosis.org/optic_neuritis.jpg
Physical Exam Manifestations
Optic neuritis
http://www.mult-sclerosis.org/optic_neuritis.jpg
What condition is being demonstrated by this
evaluation of eye movements?
• http://en.acade
mic.ru/pictures
/enwiki/73/Internuclear_ophth
almoplegia.jpg
Access Denied: Living with Multiple Sclerosis
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Reproduction in whole or in part without permission is prohibited.
Page 5
Internuclear ophthalmoplegia
• http://en.acade
mic.ru/pictures
/enwiki/73/Internuclear_ophth
almoplegia.jpghttp://www.wrongdiagnosis.com/bookimages/5/4404.1.jpg
Signs
• Spasticity
• Mood changes
• Cognitive changes
• Weakness of limbs• Exercise induced
Hauser & Goodin, 2008
http://buckeyepsych.files.wordpress.com/2009/11/multiple-sclerosis.png
https://hvelink.saintlukeshealthsystem.org/library/healthguide/en-
us/images/media/medical/hw/h9991221.jpg
Access Denied: Living with Multiple Sclerosis
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Reproduction in whole or in part without permission is prohibited.
Page 6
Educational Objective #3
Patient Education
1 Maintain activity but avoid overwork and fatigue
2 Rest during periods of acute relapses
Fever worsens symptoms
3 PT maintain ROM and strength to avoid contractures
4 Course of the disease is highly variable and unpredictable
counseling to avoid sense of hopelessness
5 Support groups for patient and family
Smith, 2009
Explanation of M.S.
Reflections from patients with
the condition
http://www.youtube.com/watch?v=DvaJ9py-vOc
Peter A. Kreckel, BS Pharm
Adjunct Assistant Professor of Pharmacology
Saint Francis University, Loretto PA
Access Denied:
Living with Multiple Sclerosis
Pharmacologic Intervention
Management of
most common
symptoms
Spasticity
40-70%
Tremor
75%
Pain
Neurogenic
80%
Bladder
disorders
80-96%
Fatigue
80-97%
Bowel
complaints
80%
Mood
disorders
50%
Management
of “flare ups”
Access Denied: Living with Multiple Sclerosis
© 2010 Pharmaceutical Education Consultants, Inc. unless otherwise noted. All rights reserved.
Reproduction in whole or in part without permission is prohibited.
Page 7
Slowing Progression of MS
• Disease modifying drugs
– Interferons
• Interferon beta-1a (Avonex®),(Rebif®)
• Interferon beta-1b (Extavia, Betaseron)
– Immunomodulators
• glatiramer (Copaxone)
• mitoxantrone (Novantrone)
• natalizumab (Tysabri)
Management of Spasticity
• Benzodiazepines (Valium®)– Most useful for night time spasms
– Caution: dependency & sedation
• Baclofen (Lioresal®)– Drowsiness, dizziness
– Caution: patients with seizure disorder. Gradually withdraw
• Tizanidine (Zanaflex®)– Sedation and dry mouth
– Caution: hypotension
Management of Pain
• Gabapentin (Neurontin®): minimal drug interactions. Good for pins/needles sensation
• Carbamazepine (Tegretol®): potent CYP4503A4 inducer. Caution with Asian patients. Good for TMJ
• Tricyclic Antidepressants (Elavil®): May help with extremity pain. Watch for anticholinergic side effects
Management of Pain
• Pregabalin (Lyrica®): better tolerated than gabapentin Lower doses used
• Duloxetine (Cymbalta®): for episodic or continual pain from nerves
• NSAIDs (Motrin® others): drug of choice for musculoskeletal pain
Access Denied: Living with Multiple Sclerosis
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Reproduction in whole or in part without permission is prohibited.
Page 8
Management of Fatigue
• Methylphenidate (Ritalin®)- may give early in morning or early afternoon depending on time of onset of fatigue. Dose: 10-20mg/day
• Amantadine (Symmetrel®)- dose 100mg-200mg given early in the day /or early afternoon
• Fluoxetine (Prozac®) –may be helpful if depression is a component of fatigue. Dose:20-80mg daily
Management of Mood Disorders
• SSRI: fluoxetine (Prozac)
Might help combat fatigue
• TCA: amitriptyline(Elavil) anticholinergic
effects may also help control bladder
incontinence
• SNRI: venlafaxine (Effexor) & duloxetine
(Cymbalta) may also help manage neuropathic
pain
Management of Tremor
• Propranolol (Inderal): most
efficacious for limb and hand
tremor. (60-800mg/day in divided doses)
• Primidone (Mysoline): efficacious for limb
tremor. (62.5-750mg/day)
• Clonazepam (small benefit- watch sedation)
• Gabapentin: conflicting data for tremor
Management of Bladder Disorders
• Urinary antispasmotics (anticholinergics)
may cause dry mouth, increase fluid intake
and worsen problem
Tolterodine (Detrol LA)
Oxybutnin (Ditropan)
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Reproduction in whole or in part without permission is prohibited.
Page 9
Management of Bowel Complaints
• Stool softeners: docusate
• Bulking agents (psyllium,
methylcellulose) add water &
bulk to stool. Metamucil/Citrucel
• Stimulants: less likely to produce
loose stool (incontinence)
Watch anticholinergics!!!
Management of “Flare-ups”
• Methylprednisolone (Solu-Medrol): 500-
1000mg IV for 3-5 days --THEN:
• Prednisone Taper : 60mg daily for 3 days,
50mg daily for 3 days. 40mg daily for 3 days.
30mg daily for 3 days. 20 mg daily for 3 days.
10mg daily for 3 days. Then STOP.
INTERACTIVE QUESTION
Can you name an immunosuppressant drug that is the drug of choice for DMARD (disease modifying anti- rheumatic drug) therapy?
This drug is also included in many MS regimens.
Type your
answer in
the CHAT
BOX!
Oligodendrocyte???
• Oligodendrocytes: CNS cells that are responsible for producing a fatty protein, called myelin, which insulates axons, the long extensions of nerve cells (neurons). Myelinated axons transmit nerve signals much faster than unmyelinated ones,similar to the insulation on an electric wire. Each oligodendrocyte can supply myelin for several axons and each axon can be supplied by several oligodendrocytes. Oligodendrocytes wrap the myelin around the axons in thin sheets like rolled up paper.
• Schwann cells makes a slightly different kind of myelin in the peripheral nervous system.
Access Denied: Living with Multiple Sclerosis
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Reproduction in whole or in part without permission is prohibited.
Page 10
http://blustein.tripod.com/Olig
odendrocytes/08-zoom.jpg
Interferon beta-1a
Avonex®/ Rebif®• Avonex: 30mcg/week IM
• Rebif: 22- 44mcg 3 times a week SC
• Interferon Side Effects– Flu like illness-sweating, fever, chills,
myalgia may be decreased by Tylenol or NSAIDS
– Watch for injection site necrosis. Rotate sites!
– Thrombocytopenia, potential liver damage
– AVONEX: MUST keep refrigerated. (Prefilled syringes stable for 7 days at controlled room temperature)
– Rebif: room temperature storage up to 30 days, if refrigeration is unavailable.
Interferon Beta-1b
Betaseron®• Dose: 0.3mg SC every other day
• Patient education:– Watch for depression
– Potential abortifacient
– Flu like illness-sweating, fever, chills, myalgia may be decreased by Tylenol or NSAIDS
– Watch for injection site necrosis. Rotate sites!
– Thrombocytopenia, potential liver damage
– BETASERON can be stored at room temperature for longer than 30 days. After reconstitution, if not used immediately, the product should be refrigerated and used within 3 hours.
Immunomodulator:
Glatiramer acetate (Copaxone®)
• Mechanism: random mixture of 4 amino acids (L-alanine,
L-glutamic acid, L-lysine & L-tyrosine) which is
antigenically similar to myelin basic protein
• Thought to suppress T-lymphocytes specific for myelin
antigen. Because it is similar to myelin basic protein,
Copaxone may also act as a sort of decoy, diverting an
autoimmune response against myelin.
Access Denied: Living with Multiple Sclerosis
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Reproduction in whole or in part without permission is prohibited.
Page 11
Glatiramer acetate
(Copaxone®) • Dose: 20mg SC daily
• Precautions: anaphylaxis,
transient chest pain
• Post Injection reactions: flushing, chest pains palpitations, anxiety, throat constriction. Skin necrosis at injection site
• Does NOT produce neutralizing antibodies (like interferons can induce)
• PHARMACY MUST keep refrigerated-However, excursions from recommended storage conditions (59F to 86F) for up to one month have been shown to have no adverse impact on the product
Natalizumab
(Tysabri®)
Mechanism: selective adhesion molecule inhibitor. It binds to T cells and prevents them from migrating across the walls of blood vessels. Believed that such migration causes inflammation and the resulting damage to nerve fibers that produces MS symptoms
• Adults: 300 mg IV infusion given over 1 hour every 4 weeks
• 627 patients studied: 67% remained relapse-free over 24 months while 41% of 315 patients who received placebo remained relapse-free
• TOUCH certified clinic: Tysabri Outreach: Unified Commitment to Health (TOUCH)
– To monitor risk of PML (progressive multifocal leukoencephalopathy) and other adverse advents. There is no treatment, and PML nearly always is fatal.
• May be combined with Avonex® (interferon beta-1a)
Natalizumab
(Tysabri®) Mitoxantrone
(Novantrone®)
• Mechanism: has been shown in vitro to
inhibit B cell, T cell, and macrophage
proliferation and impair antigen
presentation, as well as the secretion of
interferon gamma, TNFα, and IL-2.
Access Denied: Living with Multiple Sclerosis
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Reproduction in whole or in part without permission is prohibited.
Page 12
Mitoxantrone (Novantrone®)
• Dosage of Novantrone is 12
mg/m² given as a short
(approximately 5 to 15 minutes)
intravenous infusion every 3
months. Maximum cumulative
dose= 140 mg/m²
• Side effects: cardiac toxicity (need
frequent LVEF monitoring),
nausea, leukopenia, alopecia UTI
and URI
The Future?special thanks to Marissa Jacko
PA student Saint Francis University
Gilenia® (fingolimod)
• Fingolimod is an oral compound under evaluation for the treatment of multiple sclerosis.
• This drug is a sphingosine-1-phosphate-receptor modulator (S1P), which prevents the egression of lymphocytes from lymph nodes.
Watch for these 3
drugs:
1. fingolimod
2. dalfampridine
3. cladribine
Gilenia® (fingolimod)
• Side Effects:
o Increased liver-enzyme levels were found. After the drug was discontinued, the values returned to normal. Watch for bradycardia
o Macular edema was diagnosed in seven patients, all of whom were receiving 1.25mg Fingolimod. This issue resolved after discontinuation of the drug.
o Circulating lymphocytes were reduced, as anticipated based on the mechanism of action of Fingolimod.
Ampyra® (dalfampridine)
• Mechanism: potassium channel
blocker that is thought to increase
impulse conduction in nerve fibers.
• Use: to improve walking speed, NOT reduce relapses.
• About 27% see improvement, compared to placebo. Re-evaluate in 2 to 6 weeks to see if it's worth continuing.
• Side effects: increases seizure risk at higher doses (over 10mg BID). Avoid it in patients with prior seizures or impaired renal function.
• Cost $13,000/year and available through specialty pharmacies
Access Denied: Living with Multiple Sclerosis
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Reproduction in whole or in part without permission is prohibited.
Page 13
Leustatin® cladribine
• Mechanism: As a purine analog, it is a synthetic
anti-cancer agent that also suppresses the
immune system.
• Used for treatment of hairy cell leukemia
Hygiene Hypothesis
• National MS society testing the idea that infection with intestinal parasites may reduce immune attacks
• University of Nottingham protocol study: “Biological: live hookworm larvae 25 live hookworm will be applied to the arm and will infect transdermally. They will be eradicated after 48 weeks.”
Hookworm (Necator americanus)
Vitamin D
• M.S. incidence and prevalence increase with latitude, both north and south of the equator. The incidence of M.S. increases as distance from the equator increases.
• Hypothesis that deficiency of vitamin D may result in the formation of free radicals, which consequently, damages myelin.
• Furthermore, vitamin D is involved with stimulating transforming growth factor (TGF beta-1) and interleukin-4 production, which may suppress inflammatory T cell activity. Vitamin D may provide a preventative effect for those at risk of developing M.S.
References
Cudrici, C., Niculescu, T., Niculescu, F., Shin, M.L., & Rus, H. (2006). Oligodendrocyte cell
Death in pathogenesis of multiple sclerosis: Protection of oligodendrocytes from
apoptosis by complement. Journal of Rehabilitation Research & Development, 43,
123-132.
Hauser, S., Goodin, D., Multiple Sclerosis. Harrison’s Principles of Internal Medicine, 17th edition.
McGraw-Hill. 2008.
Smith, S., Multiple Sclerosis. The 5-Minute Clinical Consult. 17th ed. Wolters Kluwer Health,
Lippincott Williams & Wilkins. 2009.
Walton, B. (2008). Multiple sclerosis: A multi-faceted disease. ISNA (Indiana State Nurses
Association) Bulletin. Pp: 20-26.
Ascherio, A. & Munger, K. (2007). Environmental risk factors for multiple sclerosis. Part 1:
The role of infection. Annals of Neurology, 61, 288-299.