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Pharmacology > DMARDs and Biologics > Flashcards

DMARDs and Biologics Flashcards

1
Q

What does DMARDs stand for?

A

Disease-Modifying Anti-Rheumatic Drugs

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2
Q

Prednisone

A

Glucocorticoid – “bridge” agent”

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3
Q

Is methotrexate a DMARD or biologic?

A

First-choice DMARD

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4
Q

DMARD vs Biologic

A

DMARD: small, oral, broad immuno-toxic mechanism
Biologic: large, parenteral (inject), target specific signaling molecules

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5
Q

Methotrexate pharmacokinetics

A

Oral/SC
Administered once/week

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6
Q

Methotrexate structure

A

folic acid analog, enters cells via folate transporters, poly-glutamated inside cells (traps active drug in cell and prolongs action)

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7
Q

Methotrexate main mechanism

A
  1. inhibits enzyme AICAR transformylase
  2. this inhibits purine synthesis
  3. this increases adenosine
  4. adenosine reverses inflammation
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8
Q

Methotrexate mechanism summary

A

decreases purine and pyrimidine synthesis (decrease cell proliferation)
increases adenosine (decrease inflammation)

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9
Q

Methotrexate side effects

A
  • folate deficiency
  • teratogenic (used as abortifacient with misoprotosol)
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10
Q

Methotrexate elimination

A

Kidneys (renal insufficiency = major contraindication)

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11
Q

Hydroxychloroquine pharmacokinetics

A
  • oral, taken daily
  • slow onset, very long half-life (45 days)
  • SKIN = RESERVOIR
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12
Q

hydroxychloroquine side effects

A
  • retinal damage
  • hypoglycemia
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13
Q

can you use hydroxychloroquine while pregnant?

A

yes – secreted into breast milk but safe

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14
Q

hydroxychloroquine precautions

A

psoriasis, porphyria, liver damage, alcoholism

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15
Q

sulfasalazine pharmacokinetics

A
  • oral, daily
  • metabolized in gut to salicylate + sulfapyridine
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16
Q

sulfasalazine side effects

A
  • blood dyscrasias
  • reduce folate absorption
  • don’t use if sulfa/celebrex allergy
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17
Q

triple drug therapy

A

methotrexate (MTX), hydroxychloroquine, sulfasalazine

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18
Q

leflunomide MOA

A
  • inhibits pyrimidine synthesis
  • inhibits tyrosine kinases at higher doses
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19
Q

leflunomide overall effects

A
  • inhibits T-cell proliferation
  • reduces B-cell antibody production
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20
Q

leflunomide pharmacokinetics

A
  • oral, daily
  • prodrug
    -long half-life
21
Q

what is leflunomide converted to?

A

teriflunomide

22
Q

why does leflunomide have a long half life?

A

entero-hepatic circulation

23
Q

leflunomide side effects

A
  • diarrhea, alopecia
  • carcinogenic/teratogenic (cholestyramine washout prior to stopping BC) DON’T USE PREGNANT
  • inhibits CYP450s
24
Q

minocycline MOA

A
  • tetracycline antibiotic
  • inhibits matrix metallo-porteinases including collagenase
  • decrease collagen degradation
25
Q

minocycline pharmacokinetics

A

oral, effective for use in early disease progression

26
Q

minocycline side effects

A

dizziness, hyperpigmentation

27
Q

Traditional DMARDs (5)

A
  • methotrexate
  • hydroxychloroquine
  • sulfasalazine
  • leflunomide
  • minocycline
28
Q

Biologics (5)

A
  • etanercept
  • infliximab
  • adalimumbab
  • abatacept
  • rituximab
29
Q

all biologics are more effective when combined with ______

A

methotrexate (MTX)

30
Q

shared side effects of biologics

A
  • increased infection risk
  • blood dyscrasias
  • increased cancer incidence
  • GI probs, headache, skin rash, sinusitis, cough
31
Q

anti-TNF biologics (3)

A
  • etanercept
  • infliximab
  • adalimumab
32
Q

T and B cell targeted biologics (2)

A
  • abatacept
  • rituximab
33
Q

what do tumor necrosis factors (TNFs) do?

A

cytokine, promote inflammation and joint

34
Q

etanercept MOA

A

p75 unit binds to and prevents TNF from binding to its cell receptor

35
Q

etanercept pharmacokinetics

A
  • protein, injected SC weekly
  • shortest duration of all anti-TNF
  • usually used with MTX
36
Q

etanercept side effects

A
  • headaches, sinusitis, allergic reactions
  • PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)
  • box warning for lymphomas
37
Q

infliximab MOA

A
  • monoclonal antibody against TNF
  • mouse-human chimera (xi)
38
Q

infliximab pharmacokinetics

A
  • IV 4-8 weeks
  • always with MTX or other t-DMARDs
39
Q

infliximab side effects

A
  • similar to etanercept
  • hypotension (don’t use in heart failure patients)
40
Q

adalimumab MOA

A
  • anti-TNF monoclonal antibodies like infliximab
  • fully human protein
41
Q

adalimumab pharmacokinetics

A
  • injected SC 2x/month
42
Q

adalimumab side effects

A
  • demyelination so contraindicated in demyelinating diseases like MS
43
Q

abatacept MOA

A

CTLA-4 analog = CD28 receptor antagonist = T-cell activation inhibitor

44
Q

abatacept pharmacokinetics

A
  • peptide drug, injected SC weekly or IV monthly
  • moderate to severe RA not responsive to other DMARDs
  • LAST RESORT
45
Q

abatacept side effects

A
  • serious infections
  • infusion reactions, bronchospasm, angioedema, hypotension
  • should NOT be combined with TNF inhibitiors
  • should NOT be used in patients with COPD
46
Q

rituximab MOA

A

anti-CD20 monoclonal antibody = B cell inhibitor

47
Q

rituximab pharmacokinetics

A

IV, combo with MTX, not with TNF inhibitors

48
Q

rituximab side effects

A

infection risks, infusion reactions, PML

Pharmacology (2 decks)

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