Multiple Sclerosis and RA Pharmacotherapy Dr. Covert EXAM 3 Flashcards
What are the primary complications of MS?
immune cells that attack axons
-Visual disturbance
-Gait or motor disturbance
-Sexual dysfunction
-Speech disturbances
-Cognitive decline
-Bowel/ bladder dysfunction
Secondary:
-UTIs from bladder dysfunction
-Decubitus ulcers/osteomyelitis
-Osteoporosis
-Depression
-poor nutrition
What is considered an acute exacerbation in MS?
neurologic disturbance lasting >24h
treat if:
-localized to optic nerve, spinal cord, brain stem
-ADL becomes limited
-continued worsening over 2 weeks
Which drug is used in an acute exacerbation in MS?
high dose steroids
Methylprednisone 500 mg - 1g PO/IV for 3-10d
-reduces edema in the area of demyelination
-shortens the duration of exacerbation and increases the time between next exacerbation
What should be monitored when using high-dose steroids?
-Blood glucose
-BP
-mood swings
-infections
Which drugs are used for relapsing forms of MS (baseline -> flare -> back to baseline)? Are they first or second gen? More or less potent?
-β-Interferons
-Glatiramer acetate (Copaxone, Glatopa)
-they are 1st gens
-less potent
-more frequent injections
Which of the second gens are indicated for patients who have the progressive form (PPMS) of MS?
!!!
-Ocrelizumab (Ocrevus)
PPMS: Primary Progressive MS
also used for RRMS
What should be monitored when using Ocrelizumab?
-Hep B screening
-infusion reaction, wait until 1h after infusion
-infections
-malignancies
-some cases of PML (check if JC virus is negative)
-avoid co-administering live and live-attenuated vaccines
What is Natalizumab used for? What should be checked before using it?
!
-2nd Gen used for relapsing MS
-check JC virus antibodies prior to use and every 6 months during therapy
BBW: PML
Which of the 2nd gen injectables is very potent and is reserved for patients who failed 2 other drugs?
What is the BBW?
Alemtuzumab (Lemtrada)
BBW: serious/fatal immune reaction
Oral immunosuppressive agents can only be used for which type of MS?
Relapsing-remittent MS (RRMS)
What is the unique side effect and monitoring point of Sphingosine 1 phosphate receptor modulators? Be able to identify them.
-they all end in -imod (Fingolimod (Gilenya) Ponesimod (Ponvory) Ozanimod (Zeposia)
-Cardiovascular side effects (hypertension, hypotension, edema)
-avoid in patients with heart block, QTc > 500ms, on antiarrhythmics, ischemic or HF events
-some CYP interactions
Ponesimod has fewer contraindications
Which of the oral agents has the least side effects, contraindications, and monitoring points?
Dimethyl Fumarate (Tecfidera)
Based on the guidelines which drugs are preferred for mild to moderated RRMS?
1st gens injectables:
-Interferon-β: Avonex, Rebif, Betaseron, Extavia, Plegridy
-Glatiramer acetate
oral agents:
-Sphingosine phosphate receptor modulator
(-imod)
-Teriflunomide, Dimethyl Fumarate
Based on the guidelines which drugs are preferred for severe or rapidly progressing MS?
2nd Gen:
-Ocrelizumab
-Natalizumab
-Alemtuzumab
same for secondary progressive MS (SPMS)
Which drugs may be considered for Spasticity?
drugs +/- physical therapy
muscle spasm, muscle tightness
-Baclofen
-Tizanidine (alpha-2, rebound HTN)
-Tiagabine
-Gabapentin (neuropathy)
-Botulinum Toxin
-Dalfampridine (walking-related issues)
less evidence:
-BZD
-Dantrolene
What is the drug class of Dalfampridine and what is it used for?
!!
-specific CCB
-used for spasticity, gait issues related to MS
Which drugs are used for Hyper-reflexic bladder in MS patients?
Anticholinergics
TCAs
Which drugs are used for Hypo-reflexic bladder in MS patients?
-patients may self-catheterize
-cholinergic agents like bethanechol
-watch out for UTIs (bc they use the bathroom frequently)
-Know how to treat a UTI !!!
more common than hyper-reflexic
Which drugs are used for constipation in MS patients?
fiber
laxatives
enemas
Which drugs are used for fatigue in MS patients?
not going to ask on the exam
Stimulants
-Amantadine
-methylphenidate
-dextroamphetamine
-modafinil
-armodafinil
Which drugs are used for cognitive decline in MS patients?
not going to ask on the exam?
-Stimulants
-Acetylcholinesterase inhibitors
Which drugs are used for Pseudobulbar palsy in MS patients?
not going to ask on the exam?
dextromethorphan + quinidine (Nuedexta)
TV is a 24 yo F with no significant PMH who was recently diagnosed with RRMS who is admitted with an acute flare.
She has not yet been started on any therapy for her disease.
Start IV methylprednisone 500 mg daily IV to treat the acute exacerbation
What are common symptoms of Rheumatic arthritis?
-Joint pain/stiffness/deformity -> symmetrical joint symptoms (both knees affected)
-Fatigue
-Weakness
-Fever
-Extra-articular involvement
-Joint warmth, tenderness, swelling
-Rheumatoid nodules
What labs indicate Rheumatic arthritis?
!!!
-Rheumatoid factor (elevated in RA)
-Elevated ESR/CRP (elevated in inflammatory processes)
-Joint fluid aspiration with WBCs, crystals
-Anemia
Which joints are impacted in Rheumatic Arthritis, and how is it different from OA?
Hands and feet -> caused by an autoimmune reaction
-patients often present with system symptoms: fatigue, fever, weight loss, anemia, morning pain >30 mins after waking up
in OA: more knees, hips, neck, lower back
-> caused by overuse
What are non-pharmacological therapy options for RA?
-Rest (but not too much)
-OT or physical therapy
-weight loss
-Surgery (replacement of affected joints)
What is the first-line pharmacologic therapy option?
DMARD
Disease-Modifying- Anti-Rheumatic Drug
for symptomatic relief:
NSAIDs
Corticosteroids
Which DMRADS are tried first in patients with RA?
!!!
Non-Biologics (oral agents) DMARDs
-Methotrexate !!!
-Hydroxychloroquine !!!
tend to be less effective:
-Leflunomide
-Sulfasalazine
What are the treatment options for RA if patients fail non-biologics?
Biologics:
TNF-α Inhibitors (ACEIG)
-Adalimumab
-Certolizumab
-Etanercept
-Infliximab
-Golimumab
IL-1 Antagonist
-Anakinra
IL-6 Antagonists
-Tocilizumab, Sarilumab
-Rituximab (CD-20)
JAK inhibitors (inib)
-Tofacitinib, Baricitinib, Upadacitinib
What is the unique side effect of Hydroxychloroquine?
!!!
-Occular toxicities (retinopathy, need eye exams) !!
-GI
-dermatologic toxicity
What is the brand name for Hydroxychloroquine?
Plaquenil
When might Methotrexate be contraindicated?
-Pregnancy
-Liver disease (causes cirrhosis)
-PO route preferred, causes less toxicity
ADE:
Teratogenic
-cirrhosis
-diarrhea
-anemia
-leukopenia
-neutropenia
Recognize the TNF-α Inhibitors.
!!!
ACEIG
MOA: reduced immune cell migration
-Adalimumab
-Certolizumab - avoid in HF
-Etanercept - avoid in HF
-Infliximab - IV - infusion reaction - avoid in HF !!!
-Golimumab
-increased risk for infection
-screen for TB
-increased risk for cancer (lymphomas)
-avoid live vaccines
Name the IL-6 Antagonists. What is the MOA?
-Tocilizumab (Actemra)
-Sarilumab (Kevzara)
MOA: reduction in cytokine and acute phase reactants
Name the IL-1 Antagonist.
Anakinra
Name the CD-20 inhibitor. Name the brand name.
Rituximab (Rituxan)
Name the JAK inhibitors.
They are the only ____ biologics.
What are the unique side effects?
inib
-Tofacitinib (Xaljanz)
-Baricitinib (Olumiant)
-Upadacitinib (Rinvoq)
the only oral biologics
-major cardiovascular events !!!
-thrombosis !!!
also: hepatotoxic, malignancies, infections
What is the definition of RA remission?
FYI
-1 or less tender joint
-1 or less swollen joint
-CRP of 1 or less
How long should an RA patient be on their meds before switching to another drug?
!!!
at least 3 months
A patient was recently diagnosed (< 6 months) with RA and has high disease activity, complaining about pain in hands and feet. Which drug would you start with?
How would you start if they had low disease activity?
Start with non-biologic
high disease activity: Methotrexate
low disease activity: HQ (alternative: Sulfasalazine, then Mtx, then Leflunomide)
treat for at least 3 months
What side effects to expect from HQ and Mtx?
REMINDER
HQ: ocular toxicity
Mtx:
-cirrhosis
-Teratogenic
-diarrhea
-anemia
-leukopenia
-neutropenia
A patient was started on Mtx 1 month ago due to high-disease activity of RA. He is still complaining about the pain. What do you recommend?
They should stay on Mtx for at least 3 months
-add steroids for short-term use until Mtx fully works
A patient was started on Mtx 5 months ago, and still complains about severe pain from RA. What is the next step of drug treatment based on the guidelines?
What if they started on HQ?
- may add HQ to the Mtx
- may add TNF-α Inhibitor (ACEIG)
- may start mono TNF-α Inhibitor
- add a IL-1, IL-6, Rituximab or JAK inhibitor
- start mono IL-1, IL-6, Rituximab or JAK inhibitor
-> may bridge with short-term steroid
if they started on HQ -> add Mtx switch to Mtx
What would be the approach to treat RA patients who failed a TNF-α Inhibitor after 3 months?
try different TNF inhibitors and non-TNF inhibitors
but avoid combining them due to side effects
may combine TNFα Inhibitor with Mtx or non-TNF with Mtx
What is the approach for RA patients in remission with a combination of a biologic and non-biologic drug?
For example: Adalimumab + Mtx
- taper the non-biologic (Mtx)
- keep the biologic (Adalimumab)
the non-biologic is the less effective one, don’t d/c all RA therapy
What drug class does Etanercept belong to?
RA
TNF-inhibitor
What drug class does Tocilizumab belong to?
RA
IL-6
What drug class does Baricitinib belong to? What administration route?
RA
JAK inhibitor (inib)
JAKs are PO
-watch for thrombosis (DVT, PE)
What drug class do Golimumab, Humira and Sarilumab belong to?
RA
Humira, Adalimumab: TNF inhibitor
Golimumab: TNF inhibitor
Sarilumab: IL-6
What drug class does Alemtuzumab (Lemtrada) belong to?
MS
Second Gen injectable
What drug class does Ozanimod (Zeposia) belong to?
MS
Oral agent
What drug class does Glatiramer acetate (Copaxone) belong to?
MS
1st gen injectable
T-lymphocyte suppressor
Which type of drug is Dimethyl Fumarate (Tecfidera)?
MS
oral agent for MS
What drug class does Avonex belong to?
MS
First-Gen injectable
Interferon-β
What type of drugs are Natalizumab (Tysabri) and
Teriflunomide (Aubagio)?
MS
Natalizumab: 2nd gen injectable (integrin receptor antagonist)
Teriflunomide (Aubagio): oral agent for MS
