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825 > RA - Nonbiologic Drugs > Flashcards

RA - Nonbiologic Drugs Flashcards

1
Q

NSAIDs

A
  • Used for symptomatic relief
  • Use at antiinflammatory doses
  • Opioids are also an option
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2
Q

Oral Prednisone

A
  • Used for symptom relief
  • <10 mg per day
  • Mild to moderate: 1-3 months
  • Moderate to severe: 3-6 months
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3
Q

Intraarticular Injections

A
  • Used for symptom relief
  • Glucocorticoids
  • No more frequently than every 3 months
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4
Q

Methotrexate

A
  • Trexall (oral), Otrexup (IM)
  • 1st line DMARD
  • Used for moderate to severe RA
  • Different MoA and indications based on dose
  • Use folic acid supplementation to help offset MTX toxicities without impacting therapeutic efficacy for RA
  • Onset of action: 3-6 weeks
  • Causes significant reduction in CV mortality
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5
Q

Methotrexate ADME

A
  • A: oral is variable, IM is complete
  • D: slow penetration into 3rd space fluids, slow exit. Stored in tissues for long periods (liver and kidney), adjust for dosing for renal impairment
  • M: Oral has partial metabolism by intestinal flora
  • E: dose and route dependent, IV: urine, half life 3-15 hours
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6
Q

Methotrexate High Dose

A
  • Indication: cancer

- MoA: inhibits DHFR at high doses which produces purines and pyrimidines for DNA synthesis

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7
Q

Methotrexate Low Dose

A
  • Indication: RA
  • MoA: MTX polyglutamates which inhibits AICAR T-ase enzyme causing an accumulation of adenosine. Adenosine binding to adenosine receptors is broading anti-inflammatory
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8
Q

Methotrexate Box Warnings

A
  • Bone marrow suppression
  • Hepatotoxicity
  • Renal impairment
  • Secondary malignancy
  • Dermatologic toxicity
  • Opportunistic infections
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9
Q

Methotrexate Monitoring

A
  • LFTs
  • CBC
  • Creatinine
  • Albumin
  • Bilirubin
  • Hep B/C serology if warranted
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10
Q

Hydroxychloroquine

A
  • Plaquenil
  • Antimalarial used for RA off-label
  • Use for mild disease or in combination
  • Weaker DMARD than other 1st line
  • Relatively fast onset: 2-6 months
  • ADE: retinopathy (retinal toxicity)
  • Monitoring: ophthalmologic exam
  • CI: significant visual, hepatic, or renal impairment
  • Dose: 200 mg BID
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11
Q

Plaquenil Other ADEs

A
  • GI: N/V, diarrhea (take with food)
  • Dermatology: pruritis, rash, alopecia, increased skin pigmentation
  • Neurologic: HA, insomnia, and vertigo
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12
Q

Plaquenil MoA and ADME

A

-MoA: Inhibits immune cell trafficking and impair complement-dependent Ag-Ab interctions, MAY diminish Ag presentation to T cells and reduce immune response to self-proteins

  • A: oral (~70%)
  • M: hepatic
  • E: urine, half life ~40 days
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13
Q

Sulfasalazine

A
  • Azulfidine
  • Onset: >4 weeks
  • Treatment of mild disease or in combination
  • Decreased absorption with iron or when antibiotics eradicate colonic bacteria
  • Dose: 500 mg BID, increase to 1g BID
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14
Q

Salfasalazine MoA and ADME

A

-MoA: antiinflammatory that cleaves into 5-ASA and sulfonamide in colon, 5-ASA may reduce loval chemical mediators of inflammatory response

  • A: oral <15% of parent drug, peaks 6-10 hours
  • M: 1st by colonic microflora, then by acetylation
  • E: Urine, half life ~8-15 hours
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15
Q

Sulfasalazine ADE and Monitoring

A

ADE

  • GI effects
  • Leukopenia
  • Anemia
  • Yellow-orange discoloration of skin/urine

Monitoring

  • CBC
  • Creatinine
  • LFTs
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16
Q

Leflunomide

A
  • Arava
  • Similar to SSZ and MTX
  • Usually used in combination or to replace MTX
  • Onset: 1-3 months
  • Pregnancy category X
  • Dose: 100 mg daily for 3 days, then 10-20 mg daily
17
Q

Leflunomide MoA and ADME

A

-MoA: prodrug, hepatic metabolism to active teriflunomide, inhibits pyrimidine synthesis (anti-inflammatory and anti-proliferative)

  • A: Oral, time to peak 6-12 hours
  • M: hepatic, enterohepatic recirculation is LONG (15-18 day half life)
  • E: Feces/urine
18
Q

Leflunomide Warnings and Monitoring

A

Box Warnings

  • Hepatotoxicity
  • Embryofetal toxicity

Monitoring

  • Pregnancy test
  • CBC
  • LFTs (ALT)
19
Q

JAK Inhibitors

A
  • Tofacitinib (Xeljanz) - 5 mg PO BID
  • Baricitinib (Olumiant) - 2 mg PO QD
  • Indication: moderate to severe RA with inadequate response to Anti-TNF
  • DON’T USE WITH BIOLOGIC DMARDS OR STRONG IMMUNOSUPPRESANTS

Onset: weeks to months

20
Q

JAK Inhibitor MoA and ADME

A

-MoA: inhibits JAK enzymes which reduces cytokine-mediated gene expression, circulating NK cells, serum IgG, IgM, and IgA, CRP

  • A: oral (ER also available)
  • M: hepatic, substrate of CYP3A4
  • E: urine, half life elimination 5-10 hours
21
Q

JAK Inhibitor Warnings and Monitoring

A

Box Warnings

  • Serious infection**
  • Malignancy**
  • Neutropenia
  • Anemia
  • Increased LDL/HDL

Monitoring

  • Lymphocyte
  • Neutrophil/platelet counts
  • Infection
  • Lipids
  • Hemoglobin
  • LFTs
22
Q

Other JAK Inhibitor Concerns

A
  • Bone marrow suppression
  • GI perforation
  • Hepatotoxicity
  • Lipid abnormalities

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