DMARDS

Question 1

Methotrexate

Answer 1

Immunosuppressant DMARD

1st line treatment for RA (adenosine signalling) (also anti cancer drug @ high dose- DHFR antagonist). Onset 6-8wks (rapid) 12.5-15mg once/wk up to 20mg first 3 months. Max is 30mg. Oral or s.c.

Effects - Generate ROS, Decrease adhesion molecules, inhibit pro-inflammatory cytokines

SE - hepatic cirrhosis, interstitial pneumonitis, myelosuppression

Question 2

Sulfasalazine

Answer 2

Immunosuppressant DMARD - Prodrug with anti-inflammatory activity that inhibits T cell proliferation and B cell activation. The metabolite produced acts as NSAID

INHIBITOR OF NFKB

“Triple therapy” with MTX and hydroxychloroquine for RA that doesn’t respond to MTX alone
2-3g/day 2X

Takes 6wks to see effect

SE- hypersensitivity and allergy to sulfa meds, NSAID S.E, photosensitivity, discolouration of uring/skin to orange, hypoglycemia

Question 3

Leflunomide

Answer 3

Immunosuppressant DMARD

Prodrug converted to teriflunomide inhibits dihydroorotate dehydrogenase (inhibits pyrimidine synthesis in T CELLS)

Question 4

Azathioprine

Answer 4

Immunosuppressant DMARD

Prodrug converted to 6-MP by TPMT that inhibits purine synthesis in T and B lymphocytes

Question 5

Cyclosporine

Answer 5

Immunosuppressant DMARD

Question 6

Hydroxychloroquine/chloroquine

Answer 6

Antimalarial DMARD

Used for RA when there is MILD non-erosive disease

Low toxicity and efficacy - inhibits T cell proliferation, leukocyte chemotaxis & IL1 production

ONLY DMARD THAT DOES NOT INREASE RISK OF SEVERE INFECTIONS but does cause retinopathy***

Question 7

Aurothioglucose, auranofin

Answer 7

Gold Compounds DMARD - Last resort

Aurothioglucose - intramuscular
Auranofin - oral and slower onset 3-4mths

SE - nephrotoxicity, pruritis, ulceration of mouth tongue and throat

Question 8

Penicillamine

Answer 8

DMARD

Question 9

Etanercept

Answer 9

Biological - Anti -TNFalpha

Fusion protein has a piece of the receptor ligand binding domain bound to IgG and acts as a DECOY receptor for TNF (a and B)

SE (opportunistic infections, malignancy, congestive HF, demyelination, injection rxn, lupus like disease, congenital heart defects)

Question 10

Infliximab

Answer 10

Biological - Anti -TNFalpha

Used for RA chrons psoriasis, psoriatic arthritis

Binds soluble and transmembrane TNF and prevents it binding receptor

SE- opportunistic infections, esp mycobacterium tuberculosis with this drug and AntiTNF - SE (opportunistic infections, malignancy, congestive HF, demyelination, injection rxn, lupus like disease, congenital heart defects)

Question 11

Adalimumab

Answer 11

Biological - Anti -TNFalpha

First fully human mAB. Binds TNFa and blocks it binding receptor

Used for RA, psoriatic arthritis, IBD

SE (opportunistic infections, malignancy, congestive HF, demyelination, injection rxn, lupus like disease, congenital heart defects)

Question 12

Anakinra

Answer 12

Biological - IL1 receptor antagonist

Binds receptors

For RA when other drugs fail

Question 13

Certolizumab

Answer 13

Biological - Anti -TNFalpha

Question 14

Golimumab

Answer 14

Biological - Anti -TNFalpha

Question 15

Tocilizumab

Answer 15

Biological - IL6 antagonist

Binds soluble and membrane bound IL6 receptors. Note - IL6 is proinflammatory

Reserved for resistant RA

Question 16

rituximab

Answer 16

Biological - Anti - CD20

On B cells (does NOT affect plasma B cells bc they are CD20negative)

Used for B cell lymphoma and MS and RA (when given with MTX)

Question 17

Abatacept

Answer 17

Biological - T cell co-stimulatory inhibitor

Fusion protein CTLA4 piece from T cell with IgG. It will bind CD80 on APC and prevent the APC from binding CTLA4 and co-stimulating the T cell to respond

Question 18

Ocrelizumab

Answer 18

Biological - Anti - CD20

This one is fully humanized (vs rituximab)

Used for MS