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Musculoskeletal/rheum > Pharm DMARDs > Flashcards

Pharm DMARDs Flashcards

1
Q

MTX MOA

A

In RA: inhibits AICAR transformylase, leads to buildup of adenosine, which is anti-inflammatory (inhibits IL1, TNF, IFN, increases IL4, inhibits release of histamine from basophils and chemotaxis of PMNs)

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2
Q

MTX AEs

A

Blood: myelosuppression, increased risk of infection/bleed.
Cancer: malignant lymphoma.
Derm: severe/fatal derm rxns
GI: GI tox in patients with PUD/ulcerative colitis (esp with concurrent NSAIDs)

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3
Q

MTX contraindications/cautions

A

CIs: pregnancy (cat X), breastfeeding, pre-existing BM suppression/HIV, vaccination.
Caution: renal failure. adjust dose as needed

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4
Q

MTX elimination route

A

Renal (tubular secretion). In renal failure, hydration & alkalinization to help with clearance and renal protection. Competetion for secretion from weak acids, probenicid.

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5
Q

MTX monitoring

A

CBC/diff, LFTs, BUN/Cr, serum uric acid

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6
Q

Sulfasalazine MOA

A

Metabolized to sulfapyridine & mesalamine. Mesalamine (aka 5-aminosalicylic acid) inhibits PG and LT synthesis (anti-inflammatory effect)

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7
Q

Sulfasalazine AEs

A

Blood dyscrasias (potentially fatal)

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8
Q

Sulfasalazine elim.

A

Different for different metabolites
Sulfapyridine: acetylation (genetics plays a role) and hepatic elim.
Mesalamine: renal elim

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9
Q

Sulfasalazine CIs/cautions

A

CI: allergy (sulfa drugs, aspirin, 5-aminosalicylate)
Caution: renal failure (adjust dose)

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10
Q

Sulfasalazine indications

A

Patients who have failed therapy with salicylates or other NSAIDs

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11
Q

Sulfasalazine monitoring

A

CBC with diff, LFTs, BUN/Cr, urinalysis

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12
Q

Leflunomide MOA

A

Metab. to A77 1726, which then inhibits dihydroorotate dehydrogenase. DHODH is a mitochondrial enzyme involved in de novo pyrimidine synthesis. Causes cell cycle arrest of B and T cells (cytostatic, NOT cytotoxic). Decreases Ig production.

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13
Q

Leflunomide AEs

A

hepatic tox. with chronic use

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14
Q

Leflunomide CIs/cautions

A

CI: preexisting immunosuppression, uncontrolled infection, bone marrow dysplasia
Caution: alchoholics/heavy EtOH use (can lead to hepatic toxicity)

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15
Q

Leflunomide elim.

A

A77 1726: elim. in feces, causes a uricosuric effect.

Also elim. via glucuronide conjugates and other metabolites.

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16
Q

Hydroxychloroquine MOA

A

Increases pH of vacuoles, lysosomes, Golgi, interferes with post-translation protein modification. Ultimately, interferes with Ag processes/presentation, which decreases immune response to autoantigens.

17
Q

Hydroxychloroquine AEs

A

Eye: corneal opacities, retinopathy, keratopathy
Liver: drug accumulates (liver tox in hepatic disease or alcoholism)
Blood: blood dyscrasias
CNS: ototoxicity, polyneuritis, seizures, neuromyopathy

18
Q

Hydroxychloroquine monitoring

A

CBC with diff, ophthal. exam

19
Q

Hydroxychloroquine elim.

A

Partial hepatic metabolism, then extensive/slow renal elim.

20
Q

Abatacept: admin route, structure/MOA

A

IV/SC
Fusion protein: CTLA4 + IgG1 Fc
Binds to CD80/86 on B cells, prevents CD80/86 from activating CD28 on T cells (thus prevents costimulatory signal to T cells, prevents T cell activation)

21
Q

Adalimumab: admin route, structure/MOA

A

SC
Human anti-TNF mAb
Binds TNF, prevents it interacting with p55 and p75 TNF receptors on cell surfaces

22
Q

Anakinra: admin route, structure/MOA

A

SC
Recombinant IL-1 receptor antagonist
Competitively inhibits IL-1α and IL-1β binding to IL-1R1 (IL-1 type 1 rec.)

23
Q

Certolizumab: admin route, stucture/MOA

A

SC
Fab frag. of humanized anti-TNF Ab
Binds/neutralizes soluble and transmembrane TNFα

24
Q

Etanercept: admin route, structure/MOA

A

SC
Ligand-binding portion of p75 TNF receptor + IgG Fc (p75:Ig = 2:1)
Binds/inactivates TNF, but does not affect serum TNF concentrations or production

25
Q

Golimumab: admin route, structure/MOA

A

SC
Human anti-TNFα Ab
Binds/neutralizes transmembrane and soluble TNF

26
Q

Infliximab: admin route, structure/MOA

A

IV
Chimeric (mouse/human) IgG1k mAb (anti-TNFα)
Binds/neutralizes transmembrane and soluble TNF

27
Q

Rituximab: admin route, structure/MOA

A

IV
Chimeric (mouse/human) IgG1k mAb: anti-CD20
Binds to CD20 on B cells, kills them in 3 ways: induction of apoptosis, antibody-dependent cellular cytotoxicity, complement-mediated cytotoxicity.
Can make drug-resistant B-cell lymphoma sensitive to cytotoxic therapy

28
Q

Tocilizumab: admin route, structure/MOA

A

IV
Humanized anti-IL-6-receptor mAb
Binds soluble (in serum and synovial fluid) and membrane-bound IL-6 receptor, inhibits its signalling.

Musculoskeletal/rheum (2 decks)

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