antiarthritics

Question 1

Hydroxychloroquine Sulfate (Plaquenil)

Answer 1

Nonbiologic Disease Modifying Antirheumatic Drugs (DMARDs)

half-life: 6-7 days! long!

deposits in tissues (eyes)–>irreversible ocular toxicity
retinopathy

fetal uveal tissue (CI in preg.)

may use in combo with corticosteroids and salicylates

Question 2

Methotrexate (Trexall, Rheumatrex)

Answer 2

non-bio DMARD

• see immune lecture
  v. common, cheap

Question 3

Sulfasalazine (Azulfidine)

Answer 3

non-bio DMARD

split in intestine–>5-ASA*(active) and SP (danger)
SP–>acetyl-SP: slow or fast metabolizers–>slow metabs @ risk for adverse events

affin. for CT, immunosuppr.
* reversible* neutropenia (vs. hydroxchloraquine)

Question 4

Leflunomide (Arava®)

Answer 4

non-bio DMARD

inhibits dihydroorotate dehydrogenase (pyrimidine biosyn.)
antiproliferative,
anti-inflamm, tx for RA

6-12 hr onset, 2wk half life!!!

hepatotoxicity- black box (FDA warning)

not used in pregnancy

Question 5

Etanercept

Answer 5

bio DMARD
TNF inhibitor

dimeric fusion protein: human rec. P75 attached to Fc of IgG–>attaches TNF-a or B and inhibits their binding to TNF receptors

risks: infections, sepsis and malignancies
tx: RA, JRA

can use in combo with methotrexate

Question 6

Infliximab (Remicade)

Answer 6

bio DMARD
TNF inhibitor

chimera: human Fc IgG, murine variable region-binds TNF-a (NOT TNF-B)

half life about 9.5 days

tox: hypersn to murine portion
immunosuppr: TB, fungal infections, OIs
infusion-rel. reactions: dev. human anti-chimeric Abs (HACAs)

tx: RA, Crohn’s
used in combo with methotrexate

Question 7

Anakinra

Answer 7

bio DMARD
non-TNF inhibitor
IL-1 receptor antagonist

Question 8

non-bio DMARDs already know

Answer 8

Azathioprine (Imuran®)

Cyclosporine (Sandimmune, Neoral)

Question 9

arthritis

Answer 9

assoc. with spondylitis
degen. joint disease
assoc. with infection

Question 10

initial tx??

then move on to ??

Answer 10

aspirin, salicylates, NSAIDs (if do not tolerate/respond to salicylates)

disease‐modifying antirheumatic drugs (DMARDs)

Question 11

use ?? for flares

Answer 11

glucocorticoids, don’t want to use chronically

prednisone, prednisolone

Question 12

ASA dosage

Answer 12

3 gs/day
3-6 for significant anti-inflam.
GI intolerance

Question 13

NSAIDs

Answer 13

same affects as ASA

*indomethacin: less GI complaints

Question 14

combo therapy of DMARDs

Answer 14

synergistic
reduce resistance and toxicity
*agent of choice det. by pt and physician

Question 15

70-80% of individuals w. RA show…

Answer 15

RF
B‐cells that secrete immunoglobulins, including the autoantibody rheumatoid factor, which can be identified in 80% of affected individuals.

Question 16

inflammatory mediators present in RA

Answer 16

complement cleavage products, leukotrienes, prostaglandins, histamine, serotonin, proteases, platelet‐activating factor and cytokines (TNF‐), IL‐1, IL‐6, etc)

neutrophils–>lysosomal enz. TOI, AA cascade products

Question 17

progressive RA therapy

Answer 17

a. Reduce pain, swelling and inflammation
b. Maintain joint mobility and range of motion
c. Prevent deformity
d. Retard disease progression

Question 18

start pt w. education, PT, OT…then

Answer 18

salicylates (ASA) and NSAIDS

Question 19

use ??? btw 1st and 2nd line agents

Answer 19

low-dose corticosteroids

“bridge”

Question 20

DMARDs

Answer 20

2nd line
slow onset, more toxic
agent det. by Dr., pt
consider: convenience, monitoring, costs, time of onset, adverse effects

Question 21

early RA (

Answer 21

mild:
DMARD monotherapy: methotrexate/Cl on its own

mod or high:
DMARD combo
+/- TNF inhibitor

Question 22

established RA (>6 mos)

Answer 22

mild:
DMARD combo

mod or high:
DMARD combo
+ TNF inhibitor OR
+ non-TNF inhibitor

Question 23

JRA tx: ASA ?

Answer 23

concern for Reyes w. ASA

Question 24

JRA tx: NSAIDs?

Answer 24

use Tolmetin and Naproxen

Question 25

JRA tx: DMARDs?

Answer 25

use methotrexate
gen. well-tolerated

sulfasalazine
hydroxychloroquine (but ocular toxicity!)

Question 26

JRA tx: if DMARDs fail

Answer 26

bio. agents: TNF inhibitors

Etanercept

Question 27

JRA tx: corticosteroids

Answer 27

NO
potential adverse reactions, including growth retardation and problems associated with withdrawal

can use inj. 3-4/yr

Question 28

OA

Answer 28

not systemic, typically 1 joint: cartilage

most common

Question 29

OA tx

Answer 29

Acetaminophen
then NSAIDs: Ibuprofen, naproxen, COX-2 inhib.

NOT ketorolac or mefenamic acid
-don’t work

intermittent corticosteroid intra-art. injections

Question 30

OA initial tx

Answer 30

exercise, wl, PT

Question 31

OA tx after NSAIDs

Answer 31

glucosamine and chondroitin: controversial

Question 32

OA tx after glucosamine and chondroitin

Answer 32

opioids
then corticosteroid injection
hyaluronic injection

Question 33

OA last resort

Answer 33

joint replacement

Question 34

other major sulfasalazine adverse effects

Answer 34

anorexia, ha, N/V, GI distress (reversible)

along with rev. neutropenia