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Clinical Pharmacology Exam 3 > Inflammatory Arthritis > Flashcards

Inflammatory Arthritis Flashcards

1
Q

Disease Modifying Anti-Rheum Drugs (DMARDs): Use, timeline, what is used for bridge?

A
  • Used early to prevent irreversible damage, minimize toxicities ass. with NSAIDs and corticosteroids
  • No immediate analgesic effects, controls symptoms over time to delay/stop progression
  • NSAIDs used to bridge pain relief
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2
Q

Non-Biologic DMARDs: when to initiate therapy, what to start on

A
  • Initiate therapy within 3 months
  • Start MTX or leflunomide
  • Milder RA: hydroxychloroquine or sulfasalazine
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3
Q

Biologic DMARDs: reserved for who, what do they start on

A
  • Reserved for pts who don’t respond well to non-biologic DMARDs OR have mod-severe dz
  • Used alone or combo with non-bio DMARDs
  • Most pts start a TNF inhibitor
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4
Q

Step-up approach

A
  • Initiate 1 non-biologic DMARD, add others if needed
  • Bridge NSAIDs or corticosteroids
  • Intra-articular steroids are an underused tx option
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5
Q

Step-down approach

A
  • Can work faster, initiate 2-3 DMARDs, then step down when/if remission occurs
  • NSAIDs or corticosteroids
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6
Q

Two common regimens

A
  • Triple therapy: MTX + sulfasalazine + hydroxychloroquine

- Biologic therapy: MTX (or leflunomide) + TNF-alpha inhibitor

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7
Q

When there is an acute flare in a patient with RA or psoriatic arthritis, what must you rule out? Explain symptom presentation

A
  • Rule out acute infectious arthritis (usually Staph aureus)
  • Symptoms may be more subtle as pt is on immunosuppressants
  • Pts should report fever, malaise, etc (increased risk of infection)
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8
Q

Leading cause of death in RA pts

A

CAD

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9
Q

What is the main goal of therapy in pts with inflammatory arthritis?

A

Hit em hard and fast

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10
Q

How far in advance should live viral vaccines should be given prior to DMARD therapy?

A

1 month

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11
Q

Methotrexate MOA, clinical indications

A
  • MOA: Folate antimetabolite that inhibits DNA synthesis

- Uses: various tumors, RA, psoriasis/psoriatic arthritis

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12
Q

What should you supplement 24 hours after MTX dose to decrease ADRs?

A

Folate (5mg)

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13
Q

MTX clinical pearls

A
  • Anchor drug for RA
  • Takes 3-6 weeks to kick in
  • Hold for sick pts in hospital due to aplastic crisis
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14
Q

MTX and pregnancy; how long should men and women wait before attempting to conceive?

A
  • Teratogenic and abortifacient (need condom + something)
  • Men should wait at least 3 months
  • Women at least 6 months
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15
Q

MTX - bone marrow suppression reversed with? Who should we not give it to? Abstain from what?

A
  • Leukovorin
  • Don’t give to pts with eGFR <30mL/min
  • Abstain from ETOH
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16
Q

MTX Drug Interactions

A
  • Anti-folate drugs (TMP-SMX)
  • Drugs that decrease renal function (NSAIDs) increase risk of toxicity)
  • PPIs increase concentration of MTX -> increase risk of toxicity
  • Other immunosuppressants
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17
Q

MTX ADRs

A
  • Stomatitis
  • GI intolerance
  • Bone marrow suppressant (RA ass with lymphoma)
  • LFT abnormalities -> hepatitis -> liver fibrosis***
  • MTX lung
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18
Q

Leflunomide MOA, clinical indication

A
  • Immunomodulatory agent that inhibits pyrimidine synthesis

- Use: main role for pt who responded to MTX but got toxicity from it

19
Q

Leflunomide precautions

A
  • Carcinogenic and teratogenic (CI during pregnancy)

- Take cholestyramine to bind/eliminate drug

20
Q

Leflunomide ADRs

A
  • Diarrhea***
  • Reversible alopecia
  • Bone marrow suppression
  • LFT abnormalities
21
Q

Hydroxychloroquine MOA, clinical indications, pregnancy?

A
  • MOA: inhibits movement of neutrophils and chemotaxis of eosinophils
  • Uses: SLE, RA
  • Safe in pregnancy
22
Q

Hydroxychloroquine monitoring, contraindications

A
  • Monitoring: Ophtho exam baseline and q3-12 months after 5 years of therapy
  • Anyone with hx of retinal or visual field abnormalities
23
Q

Hydroxychloroquine ADRs

A
  • Watch QT issues
  • Hemolysis in G6PD deficiency pts
  • Ophthalmic ADRs (blurred vision, retinal damage)
24
Q

Sulfasalazine MOA, clinical indications, pregnancy?

A
  • MOA: interferes with secretion by inhibiting prostaglandin synthesis
  • Uses: RA (with MTX and hydroxychloroquine in triple therapy), IBD
  • Safe in pregnancy
25
Q

Sulfasalazine ADRs

A
  • Common: GI intolerance, sulfa rash**
  • Serious rxns rare: hepatitis, bone marrow suppression
  • Other: lupus-like syndrome, hemolysis in G6PD deficiency pts (get a quant G6 prior to initiation)
26
Q

JAK inhibitors

A
  • Tofacitinib
  • Baricitinib
  • Upadacitinib
27
Q

JAK Inhibitors MOA

A

-Janus kinase inhibitor -> JAK signaling is a critical step in hematopoiesis and immune activation

28
Q

JAK inhibitors clinical pearls including who you should save it for, pregnancy, and pt ed

A
  • Oral biologic DMARDs*
  • Save for severe RA
  • Pregnancy: use effective contraception while taking and for at least 4 weeks after last dose
  • Pt ed: call if fever, rash, etc
29
Q

JAK Inhibitors Drug Interactions

A

Should not be co-administered with other biologic agents or potent immunosuppressive drugs (Azathioprine or cyclosporine)

30
Q

JAK Inhibitor ADR to know for exam

A

-Thromboembolic dz** (consider in DDX of VTE, AMI, thrombotic CVA eval)

31
Q

Azathioprine and Cyclosporine Uses

A

-Pts with refractory RA or systemic involvement such as rheumatoid vasculitis

32
Q

TNF inhibitors (first and second line)

A
  • First line: Infliximab, Etanercept, Adalimumab

- Second line: Certolizumab, Golimumab

33
Q

TNF inhibitors MOA, clinical indications

A
  • Pro-inflammatory cytokine that binds TNF and blocks its activity
  • Uses: moderate to severe RA**, others include psoriatic arthritis, IBD, ankylosing spondylitis, systemic JIA
34
Q

What TNF inhibitor is not effective for tx of IBD?

A

Etanercept

35
Q

TNF inhibitors plus what has synergistic beneficial effects?

A

MTX

36
Q

What other things must be done prior to TNF inhibitor usage?

A
  • Appropriate vaccinations
  • Appropriate CA screenings
  • TST or IGRA before starting therapy, yearly after
  • Serologic testing for HIV/HBV/HCV
37
Q

Precautions with TNF inhibitors

A
  • Hx of CA or CNS demyelinating disorders like MS

- Can cause or worsen CHF

38
Q

TNF inhibitor ADRs

A
  • Common: injection site rxns, infusion rxns, URTIs, GI intolerance
  • Serious: drug-induced lupus, bone marrow suppression, demyelinating disorders, increased risk of malignancies (lymphoma)
  • Other serious: serious bacterial infections, TB reactivation or dissemination, invasive or disseminated fungal infections (histoplasmosis)
39
Q

Is there any affect on overall mortality rates associated with opportunistic infections while using TNF inhibitors?

A

No

40
Q

What other biologic DMARD has been approved for giant cell arteritis and systemic JIA?

A

IL-6 receptor antagonist (Tocilizumab)

41
Q

Moderate to severe psoriatic arthritis, step 1 and 2? Other options?

A
  • Step 1: MTX or leflunomide
  • Step 2: TNF-alpha inhibitors
  • Others: oral PDE4 inhibitors, IL-17A antagonists (Secukinumab), IL-12/23 antagonists (Ustekinumab), abatacept, JAK inhibitors
42
Q

Presentation of systemic JIA

A
  • Daily high fever
  • Evanescent MP rash
  • Inflammatory polyarthritis
  • Complication includes macrophage activation syndrome
43
Q

Mild-mod tx and mod/severe tx of sJIA

A
  • Mild to mod: NSAID, Systemic glucocorticoid, or both

- Mod to severe: traditional DMARD used (MTX or TNF-inhibitors)

44
Q

What type of toxicity is an important cause of morbidity in the sJIA pts?

A

Glucocorticoid toxicity

Clinical Pharmacology Exam 3 (19 decks)

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