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PHAR358 > Multiple Sclerosis > Flashcards

Multiple Sclerosis Flashcards

1
Q

What is MS?

A

chronic disease of the CNS
-hits the brain and spinal cord

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2
Q

Which sex is impacted by MS the most?

A

women ~ 3:1
-males tend to have a more severe course

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3
Q

What is the leading cause of non-traumatic disability in young adults?

A

MS

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4
Q

Describe the pathophysiology of MS.

A

inflammation <–> demyelination <–> axonal degeneration in the CNS

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5
Q

Describe the distribution of MS.

A

highest prevalence in North America
-less sunlight = less vit D??
-3rd world countries = poor health care = under identified??

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6
Q

Describe the etiology of MS.

A

immunological
genetic
-not entirely, one twin may develop while the other may not
environmental
-nothing identified as causative
infectious
-Epstein Barr = 32x more likely to develop MS
etiology is unknown, interplay of genetics + triggers

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7
Q

What are some of the many potential symptoms of MS?

A

numbness, tingling
vision problems
dizziness
cognitive dysfunction
depression
fatigue
muscle spasms
weakness
walking difficulty
pain
bladder dysfunction
bowel dysfunction
unique:
-Lhermitte’s Sign
-Uhtohoff’s Phenomena
-MS Hug

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8
Q

What are the different types of MS?

A

relapsing-remitting
-most common type
-fine –> episode –> repeat
primary progressive
-no episodes
-continual increasing disability over time
secondary progressive
-not returning to baseline, permanent disability
-most ppl with relapsing-remitting develop this type
clinically isolated syndrome
-episode of sx and then never having another attack

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9
Q

What is key to recognize regarding inflammation and the different types of MS?

A

inflammation is high during active relapses but inflammation actually decreases with time
-many drugs work on inflammation, over time they may have nothing to work on

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10
Q

How is progression measured in MS?

A

Expanded Disability Status Scale
-focuses mainly on mobility
-doesnt capture cognition or upper limb mobility

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11
Q

What is the EDSS score that signifies the person with MS can no longer mobilize?

A

6
-we dont know how drugs work on people with a score of 6 or higher

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12
Q

What is the non-pharmacological management of MS?

A

exercise
-old thoughts were take it easy = no longer the case
diet
-just overall healthy eating
complementary/alternative medicine

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13
Q

What are the 3 approaches to pharmacological management of MS?

A

treat acute relapses
treat/manage symptoms
prevent disease activity and progression

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14
Q

What is an MS relapse?

A

new or worsening symptoms
lasts 24 hours or longer
absence of fever (infection) or other causes
separated from previous relapse by 30 days or more

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15
Q

What is the treatment for an MS relapse?

A

high-dose steroids
-methylprednisolone 500-1000 mg IV x 3-5 days
-oral prednisone 1250 mg = 1000 mg IV MP

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16
Q

What is the therapy for a MS relapse non-responsive to high dose steroids?

A

may consider plasma exchange

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17
Q

True or false: all MS relapses are treated

A

false

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18
Q

Differentiate primary and secondary fatigue.

A

primary - caused by MS
-more energy needed because of damaged CNS
secondary - caused because of living with MS
-depression, pain, spasms, sleep disturbances

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19
Q

What is the non-pharm management for fatigue?

A

OT/PT
-helping focus where to use energy
sleep hygiene
avoid excessive heat
exercise and diet

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20
Q

What are the pharmacological options for fatigue?

A

amantadine
-insomnia
modafinil
-HA, insomnia, SJS, fetal abnormalities
methylphenidate
-insomnia, anxiety, dizziness
these dont work very well, limited evidence

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21
Q

What are the non-pharm options for gait?

A

OT/PT
bracing/walking aids
exercise

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22
Q

What is the pharmacological option for gait in MS?

A

fampridine
-indicated to increase walking speed (?benefit)

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23
Q

What are the adverse effects of fampridine?

A

UTI
insomnia
headache
dizziness
seizure risk (dose-dependent)

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24
Q

Can fampridine be used in pregnancy?

A

pregnancy and breastfeeding risk unknown

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25
Q

What are the non-pharmacological options for spasticity in MS?

A

exercise
stretching

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26
Q

What are the pharmacological options for spasticity in MS?

A

baclofen 5-10 mg TID
-GI issues, drowsiness
gabapentin 900 mg TID
-drowsiness, nausea, blurred vision
botulinum toxins q3-6 mo
-pain, bruising

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27
Q

Which cannabis product is used in MS?

A

Sativex
-indicated as add-on treatment of spasticity and pain in MS
-lack of evidence for use in any other MS symptoms

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28
Q

What are the potential ADRs of Sativex?

A

dizziness
blurred vision
tachycardia
falls
fatigue
long-term cognition effects

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29
Q

What are the current challenges with cannabis in MS?

A

dosage/ratio unknown
type of cannabinoid(s) to use
varying quality/quantity if street cannabis
finding cannabis “naive” study participants

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30
Q

What are the potential benefits of disease-modifying therapies?

A

attempt to slow the inflammatory process
decrease frequency and severity of relapses
decrease lesions on MRI
reduce accumulation of neurological impairment and disability over time (?)

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31
Q

When is it best to start disease-modifying therapies?

A

earlier is better

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32
Q

Which DMTs are injectable?

A

interferon beta-1b
glatiramer acetate
interferon beta-1a
peginterferon beta-1a
oftatumumab

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33
Q

Which DMTs are oral?

A

fingolimod
dimethyl fumarate
teriflunomide
cladribine
siponimod
ozanimod
ponesimod

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34
Q

Which DMTs are infused?

A

natalizumab
alemtuzumab
ocrelizumab
rituximab

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35
Q

What are the two main MOAs of DMTs?

A

immunomodulator
immunosuppressant

36
Q

Which DMTs are examples of immunomodulators?

A

interferon-beta
glatiramer acetate

37
Q

Which DMTs are examples of immunosuppressants?

A

dimethyl fumarate
teriflunomide
fingolimod
siponimod
ozanimod
ponesimod
natalizumab
ocrelizumab
ofatumumab
alemtuzumab
cladribine

38
Q

What is PML?

A

progressive multifocal leukoencephalopathy
-rare, but often fatal
-opportunistic infection by JC virus
-destroys the cells that produce myelin

39
Q

What is the cure for PML?

A

no cure - “fix” the reason for immune suppression
-stop meds (plasma exchange if needed)

40
Q

Which DMTs is PML seen most often with?

A

natalizumab (highest risk)
dimethyl fumarate
fingolimod
ocrelizumab

41
Q

What increases the risk for PML?

A

JCV +
prior immunosuppressant
> 2 yrs use (natalizumab)

42
Q

How frequently are the injectable DMTs given?

A

interferon beta 1b: SC EOD
interferon beta 1a: IM weekly or SC 3/week
peginterferon beta 1a: SC q2/52
glatiramer acetate: SC OD or SC 3/week
ofatumumab: week 1-3 SC weekly then SC q 4 wks

43
Q

What are the monitoring parameters for interferon DMTs?

A

CBC and LFT every 6 months or prn
same monitoring parameters for ofatumumab

44
Q

What are the common adverse reactions for interferon DMTs?

A

injection site reactions
flu-like symptoms
hepatotoxicity
lymphopenia

45
Q

What are the adverse reactions of glatiramer acetate?

A

injection site reactions
post injection systemic reactions
lipoatrophy*

46
Q

What are the monitoring parameters for glatiramer acetate?

A

no monitoring required but watch for lipoatrophy

47
Q

What are the adverse reactions of ofatumumab?

A

injection site reactions
URTI
headache
potential for serious infections (HBV reactivation)
PML occurred with higher doses when used for chronic lymphocytic leukemia

48
Q

How frequently are the oral DMTs dosed?

A

teriflunomide: OD
dimethyl fumarate: BID
fingolimod: OD
siponimod: OD
ozanimod: OD
cladribine: OD for 4 or 5 days beginning each of first 2 months of years 1 and 2 of treatment

49
Q

Which oral DMTs are potential teratogens?

A

teriflunomide (M & F)
fingolimod (2-3 month washout)
siponimod (washout 10 days)
ozanimod (2-3 month washout)
cladribine (M & F)

50
Q

What are the adverse reactions of teriflunomide?

A

diarrhea/nausea
hair thinning
hepatotoxicity
peripheral neuropathy
headache

51
Q

What are the adverse reactions of dimethyl fumarate?

A

flushing
GI intolerance (nausea/diarrhea)
lymphopenia*
PML (rare)

52
Q

What are the adverse reactions of fingolimod?

A

bradycardia/atrioventricular conduction slowing (prolonged QT)
macular edema
herpes simplex infections
HTN
hepatotoxicity
PML (rare)

53
Q

What are the adverse reactions of siponimod?

A

HTN
bradycardia
headache, dizziness
lymphopenia
diarrhea/nausea
pain in hands and feet (and/or swelling)

54
Q

What are the adverse reactions of ozanimod?

A

infections (URTI, nasopharyngitis, UTI)
bradycardia (temporary)
HTN
lymphopenia

55
Q

What are the adverse reactions of cladribine?

A

nausea
headache
thinning hair
flu-like symptoms
increased infections (vaginal, shingles, oral herpes)

56
Q

What are the monitoring parameters for teriflunomide?

A

baseline pregnancy test
baseline TB test
CBC
LFT monthly x 6/12 then q 6/12

57
Q

What needs to be reinforced with teriflunomide?

A

contraception
-up to 2 years post-drug or rapid elimination protocol

58
Q

What are the monitoring parameters for dimethyl fumarate?

A

CBC

59
Q

What are the monitoring parameters for fingolimod?

A

baseline LFT
baseline VZV status (vaccination if negative)
baseline ECG; further cardiac assessment if necessary
baseline ophthalmological assessment then at 3-4mo then prn
baseline pregnancy test
first dose cardiac observation for 6 hours

60
Q

What are the monitoring parameters for siponimod?

A

similar to fingolimod but no cardiac observation with first dose unless cardiac history
CBC and LFT

61
Q

What are the indications for siponimod?

A

SPMS and RRMS
-only drug that has an indication for SPMS

62
Q

What are the monitoring parameters for ozanimod?

A

similiar to siponimod
CBC and LFT

63
Q

What are the monitoring parameters for cladribine?

A

baseline pregnancy test
baseline VZV status
baseline CBC
monitor for TB infection
monitor for Hep B and C
CBCs

64
Q

What needs to be reinforced with cladribine?

A

contraception
-for 6 months after last dose

65
Q

How frequently are the infused DMTs dosed?

A

natalizumab: IV q 4/52
ocrelizumab: IV at week 0 and 2 then IV q 24 weeks
alemtuzumab: first course IV for 5 consecutive days then second course IV for 3 consecutive days at month 12 from initial course
rituximab: IV week 0 and 2 then q 6/12

66
Q

What are the adverse reactions of natalizumab?

A

hypersensitivity reactions
hepatotoxicity
headache
infections (UTI, LRTI)
joint pain
*PML (especially if used > 2 yrs)

67
Q

What are the adverse reactions of ocrelizumab?

A

infusion reactions (premedicate with IVMP and antihistamine 30-60 min prior to infusion)
increased risk of infections (LRTI, URTI, viral, conjunctivitis)
reactivation of HepB
depression and feelings of self harm
PML potential

68
Q

What are the adverse reactions of alemtuzumab?

A

infusion reactions (up to 2 h after infusion finished)
autoimmune thyroid disorders
immune thrombocytopenic purpura
glomerular nephropathies
increased risk of infections (UTI, URTI, viral)
increased risk of malignancy

69
Q

Which infused DMTs are potential teratogens?

A

ocrelizumab

70
Q

What are monitoring parameters for natalizumab?

A

baseline JCV status
baseline brain MRI
baseline CBC
baseline LFT
JCV status q 6-12 months
MRI brain q 6-12 months
LFT q 6 months
CBC
PML monitoring

71
Q

What are monitoring parameters for ocrelizumab?

A

hepatitis B screen (avoid ocrelizumab)

72
Q

What are the indications for ocrelizumab?

A

PPMS and RRMS
-only one indicated for PPMS

73
Q

How long should pregnancy be avoided after the last infusion of ocrelizumab?

A

avoid pregnancy for 6-12 months after last infusion

74
Q

How long do the adverse reactions of alemtuzumab need to be monitored?

A

up to 4 years after last dose
-especially autoimmune ADRs

75
Q

What are monitoring parameters for alemtuzumab?

A

baseline: CBC, SCr, LFT, TSH, VZV titer, HIV, hepatitis serology
baseline pregnancy test
baseline TB test
baseline skin exam to monitor for melanoma
baseline screening for HPV and cervical dysplasia

76
Q

How is rituximab used in MS?

A

used off-label in MS
-actually works really well in MS

77
Q

What does rituximab have the potential for?

A

PML

78
Q

What are factors to consider when choosing a DMT?

A

patient factors:
-age
-sex
-lifestyle factors
-pregnancy/breastfeeding
disease factors:
-disease course
-prognosis
-disease activity
induction vs escalation

79
Q

What are some important notes regarding pre-pregnancy and MS?

A

no effect of MS on fertility
dont routinely defer DMT
consider effect of exposure in males
pregnancy does not affect long-term disability outcomes
relapse risk during and after pregnancy

80
Q

What are some post-partum considerations in MS?

A

support breastfeeding alongside treatment considerations
methylprednisolone not CI in breastfeeding
increased of post-natal depression

81
Q

Does MS make a pregnancy automatically high-risk?

A

not automatically

82
Q

What are the 1st line injectable DMTs in pregnancy?

A

Copaxone/IFN-B preparations
-safe to continue until conception
-no evidence of harm to fetus
-if stopped, 3/12 to reach full efficacy post-partum
-benefits of breastfeeding on treatment outweigh risk

83
Q

Which DMTs are contraindicated in pregnancy?

A

teriflunomide
ocrelizumab
fingolimod
cladribine

84
Q

Describe vaccine use in MS patients.

A

inactivated vaccines = generally safe
live and live-attenuated = generally not recommended
-esp if taking DMT
wait until 4-6 weeks after relapse onset

85
Q

What is generally a good idea to do with MS patients and vaccines?

A

consider referring
-complex patients on complex drugs

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