Duan: Corticosteroids and DMARDs

Question 1

What are the goals of RA therapy?

Answer 1

control inflammation

slow progression/rate of joint damage

Question 2

Drugs that treat pain and inflammation but do not limit joint damage

Answer 2

NSAIDs

corticosteroids

Question 3

Drugs that help control disease and limit joint damage

Answer 3

DMARDs

disease modifying anti-rheumatic drugs

Question 4

What are some of the downsides to NSAID therapy?

Answer 4

doesn't affect disease progression
GI toxicity is common
renal complications may occur
hepatic dysfuntion
CNS toxicity w high dose

Question 5

include thesteroid hormoneseither produced in theadrenal cortexofvertebrates, or synthetic analogues of these hormones. They are involved in a wide range of physiological processes, includingstress response, immune response, and regulation of inflammation, carbohydrate metabolism, proteincatabolism, bloodelectrolytelevels, and behavior.

Answer 5

corticosteroids

Question 6

control carbohydrate, fat and protein metabolism, and are anti-inflammatory by preventing phospholipidrelease, decreasing eosinophilaction and a number of other mechanisms.

Answer 6

glucocorticoids

Question 7

How do corticosteroids work?

Answer 7

they are steroids that actually enter the target cell and bind to transcription factor receptors within the cytosol; the receptor-steroid complex translocates to the nucleus and regulates the synthesis of specific proteins, like TNF-alpha, IL-1, IL-2, etc

Question 8

Corticosteroids act on (blank) to reduce inflammation by inhibiting the induction of (blank) expression

Answer 8

phospholipase A2; COX-2

Question 9

These are two corticosteroids frequently used in RA therapy

Answer 9

prednisone

dexamethasone

Question 10

Compare prednisone and dexamethasone in terms of route of administration, anti-inflammatory potency, and duration of action

Answer 10

prednisone: oral, potency of 4, lasts 3-4 hours
dexamethasone: oral, injectible or topical, potency of 30, lasts 36-54 hours

Question 11

Adverse effects of chronic use of glucocorticoids?

Answer 11

suppresses HPA axis
Cushing's syndrome
moon face, buffalo hump
diabetes mellitus
CNS effects
impaired wound healing
musculoskeletal
cardio
gastric ulcers
growth inhibition in children

Question 12

What are some pros in using glucocorticoids in RA?

Answer 12

anti-inflammatory and immunosuppressive
can be used to bridge gap b/w initiation of DMARD therapy and onset of action
intra-articular injections can be used for individual joint flares and is the major benefit in RA

Question 13

What are some downsides in using glucocorticoids in RA?

Answer 13

doesn’t affect disease progression
tapering/discontinuation often unsuccessful
low doses result in skin thinning, ecchymoses, and Cushingoid appearance
can cause steroid-induced osteopenia

Question 14

How do DMARDs differ from NSAIDs and corticosteroids?

Answer 14

they retard or halt the underlying progression of disease, so they limit the amount of joint damage that occurs

**lack anti-inflammatory and analgesic effects of NSAIDs and corticoids

Question 15

What are biologic DMARDs? Like what do they do?

Answer 15

they are genetically engineered antibodies and proteins; Block the activity of immunostimulatory cytokines and other cell-signaling molecules.

**examples include TNF-alpha blockers and drugs that target IL-1 and IL-6

Question 16

This DMARD is a purine synthesis inhibitor; prevents leukocyte proliferation

Answer 16

azathioprine

Question 17

This DMARD is a calcineurin inhibitor

Answer 17

ciclosporin

Question 18

This DMARD is a pyrimidine synthesis inhibitor

Answer 18

Leflunomide

Question 19

This DMARD is a purine metabolism inhibitor

Answer 19

methotrexate

Question 20

What is the recommended dose for methotrexate?

Answer 20

7.5-20mg/wk

**moderate toxicity level

Question 21

First-line drug of choice for treating RA

Answer 21

methotrexate

Question 22

How does methotrexate work?

Answer 22

blocks dihydrofolate reductase

Question 23

This is a COX and lipoxygenase inhibitor

Answer 23

Sulfasalazine

Question 24

What is one negative effect of azathioprine to be aware of?

Answer 24

high risk for severe leukopenia and/or thrombocytopenia

Question 25

This DMARD blocks phagocytosis; it requires a long course to determine its effectiveness; Toxicities: skin lesions, stomatitis, oral ulcerations, glomerulonephritis, nephrosis, thrombocytopenia, agranulocytosis

Answer 25

Gold Auranofin

Question 26

Inhibits de novo pyrimidine biosynthesis through the inhibition of the mitochondrial enzyme dihydroorotate dehydrogenase.
Laboratory studies have demonstrated that it has effects on stimulated T cells.

Answer 26

Leflunomide

Question 27

What kind of biological DMARD are the following?

Etanercept (Enbrel)
Infliximab (Remicade)
Adalimumab (Humira)

Answer 27

TNF-alpha blockers

Question 28

This biological DMARD is an anti-CD20 B cell antibody

Answer 28

rituximab

Question 29

What kind of biological DMARD is the following?

anakinra

Answer 29

block IL-1

Question 30

A dimeric fusion protein consisting of the extracellular ligand-binding portion of the human tumor necrosis factor receptor (TNFR) linked to the Fc portion of human IgG1
Binds to TNFalpha and prevents its interaction with the TNF receptor

Answer 30

Etanercept

Question 31

Chimeric, mouse/human IgG1 monoclonal antibody that binds to TNFalpha with high affinity and specificity
Neutralizes the biological activity of TNFα by binding with high affinity to the soluble and transmembrane forms of TNFα and inhibits binding of TNFα with its receptors.

Answer 31

Infliximab

Question 32

Recombinant human IgG1 monoclonal antibody specific for human TNF, and the first product consisting entirely of human peptide sequences.
Binds specifically to TNF- and blocks its interaction with the p55 and p75 cell surface receptors.

Answer 32

adalimumab

Question 33

T/F: Combining two biologic DMARDs in early RA has superior efficacy compared to single-DMARD regimens

Answer 33

False; combining up to 3 DMARDs is only shown to be more effective than monotherapy in patients with advanced disease and LONGSTANDING RA

Question 34

Which are better, biologic or oral DMARDs?

Answer 34

biologic!!!

**greater symptom response

Question 35

T/F: In patients with longstanding active RA, combining up to three oral DMARDs (MTX, sulfasalazine, and hydroxychloroquine) produces greater improvements in disease activity than one or two oral DMARDs.

Answer 35

True!!!

Question 36

In patients with inadequate disease control, biologic DMARDs used in combination with (blank) offer greater relief than monotherapy with either

Answer 36

methotrexate

Question 37

For patients with EARLY RA who have not previously been treated with oral DMARDs, combining oral DMARDs (sulfasalazine and MTX) improves symptom response, radiographic progression, or functional capacity more than monotherapy.

Answer 37

False!!!

Question 38

DMARDs should be initiated (blank) in active RA
DMARDs may be limited by their (blank) profiles
DMARD combination treatment is indicated as X + (blank)
(blank) DMARDs are indicated when oral DMARDs are not successful
Biologic DMARDs + Methotrexate appears to be superior to oral DMARD alone in (blank) disease.

Answer 38

early; toxicity; MTX; biologic; advanced

Question 39

Adding (blank) to treatment with oral DMARDs improves function and may limit radiographic progression, although there is evidence that the combination increases the risks of adverse effects.

Answer 39

prednisone

Question 40

Is one class of DMARD, oral vs biologic, favored in terms of toxicity or tolerability?

Answer 40

no; DMARDs of both classes are associated with well-known adverse effects (toxicity of oral DMARDs, serious infections with biologic DMARDs), but the comparative risks are not known.
Overall tolerability is similar between DMARDs of both classes.