DMARDs and Biologics

Question 1

What does DMARDs stand for?

Answer 1

Disease-Modifying Anti-Rheumatic Drugs

Question 2

Prednisone

Answer 2

Glucocorticoid – “bridge” agent”

Question 3

Is methotrexate a DMARD or biologic?

Answer 3

First-choice DMARD

Question 4

DMARD vs Biologic

Answer 4

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

Question 5

Methotrexate pharmacokinetics

Answer 5

Oral/SC
Administered once/week

Question 6

Methotrexate structure

Answer 6

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

Question 7

Methotrexate main mechanism

Answer 7

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

Question 8

Methotrexate mechanism summary

Answer 8

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

Question 9

Methotrexate side effects

Answer 9

• folate deficiency
• teratogenic (used as abortifacient with misoprotosol)

Question 10

Methotrexate elimination

Answer 10

Kidneys (renal insufficiency = major contraindication)

Question 11

Hydroxychloroquine pharmacokinetics

Answer 11

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

Question 12

hydroxychloroquine side effects

Answer 12

• retinal damage
• hypoglycemia

Question 13

can you use hydroxychloroquine while pregnant?

Answer 13

yes – secreted into breast milk but safe

Question 14

hydroxychloroquine precautions

Answer 14

psoriasis, porphyria, liver damage, alcoholism

Question 15

sulfasalazine pharmacokinetics

Answer 15

• oral, daily
• metabolized in gut to salicylate + sulfapyridine

Question 16

sulfasalazine side effects

Answer 16

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

Question 17

triple drug therapy

Answer 17

methotrexate (MTX), hydroxychloroquine, sulfasalazine

Question 18

leflunomide MOA

Answer 18

• inhibits pyrimidine synthesis
• inhibits tyrosine kinases at higher doses

Question 19

leflunomide overall effects

Answer 19

• inhibits T-cell proliferation
• reduces B-cell antibody production

Question 20

leflunomide pharmacokinetics

Answer 20

• oral, daily
• prodrug
  -long half-life

Question 21

what is leflunomide converted to?

Answer 21

teriflunomide

Question 22

why does leflunomide have a long half life?

Answer 22

entero-hepatic circulation

Question 23

leflunomide side effects

Answer 23

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

Question 24

minocycline MOA

Answer 24

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

Question 25

minocycline pharmacokinetics

Answer 25

oral, effective for use in early disease progression

Question 26

minocycline side effects

Answer 26

dizziness, hyperpigmentation

Question 27

Traditional DMARDs (5)

Answer 27

- methotrexate - hydroxychloroquine - sulfasalazine - leflunomide - minocycline

Question 28

Biologics (5)

Answer 28

- etanercept - infliximab - adalimumbab - abatacept - rituximab

Question 29

all biologics are more effective when combined with ______

Answer 29

methotrexate (MTX)

Question 30

shared side effects of biologics

Answer 30

- increased infection risk - blood dyscrasias - increased cancer incidence - GI probs, headache, skin rash, sinusitis, cough

Question 31

anti-TNF biologics (3)

Answer 31

- etanercept - infliximab - adalimumab

Question 32

T and B cell targeted biologics (2)

Answer 32

- abatacept - rituximab

Question 33

what do tumor necrosis factors (TNFs) do?

Answer 33

cytokine, promote inflammation and joint

Question 34

etanercept MOA

Answer 34

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

Question 35

etanercept pharmacokinetics

Answer 35

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

Question 36

etanercept side effects

Answer 36

- headaches, sinusitis, allergic reactions - PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) - box warning for lymphomas

Question 37

infliximab MOA

Answer 37

- monoclonal antibody against TNF - mouse-human chimera (xi)

Question 38

infliximab pharmacokinetics

Answer 38

- IV 4-8 weeks - always with MTX or other t-DMARDs

Question 39

infliximab side effects

Answer 39

- similar to etanercept - hypotension (don't use in heart failure patients)

Question 40

adalimumab MOA

Answer 40

- anti-TNF monoclonal antibodies like infliximab - fully human protein

Question 41

adalimumab pharmacokinetics

Answer 41

- injected SC 2x/month

Question 42

adalimumab side effects

Answer 42

- demyelination so contraindicated in demyelinating diseases like MS

Question 43

abatacept MOA

Answer 43

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

Question 44

abatacept pharmacokinetics

Answer 44

- peptide drug, injected SC weekly or IV monthly - moderate to severe RA not responsive to other DMARDs - LAST RESORT

Question 45

abatacept side effects

Answer 45

- serious infections - infusion reactions, bronchospasm, angioedema, hypotension - should NOT be combined with TNF inhibitiors - should NOT be used in patients with COPD

Question 46

rituximab MOA

Answer 46

anti-CD20 monoclonal antibody = B cell inhibitor

Question 47

rituximab pharmacokinetics

Answer 47

IV, combo with MTX, not with TNF inhibitors

Question 48

rituximab side effects

Answer 48

infection risks, infusion reactions, PML