Chapter 9 anti-inflammatory and immunomodulating agents - rheumatoid arthritis (RA) drugs

Question 1

NSAIDs

Answer 1

block COX1 + 2
* reduces prostaglandin synthesis
* essential for inflammation + platelet stickiness – GI bleed is a SE
* PPI (omepraozle/prilosec) can be used to counter GI toxicity

Question 2

COX 2 inhibitors (celecoxib [celebrex])

Answer 2

only COX2, which reduces inflammation (COX1 – more responsible for GI)
* better for pts that need chronic NSAID relief from inflammation

Question 3

Prednisone
Methylprednisone (medrol)
triamcinolone

corticosteroids

Answer 3

• reduce inflammation by suppressing fx of immune cells
• as a result, infection risk inc

effects
* osteoporosis — reduce the body’s ability to absorb calcium and increase how fast bone is broken down. (take vitamin D and ca++ supplements along with bisphosphonates [alendronate — osteoporosis + also used to treat Paget’s disease of bone (a condition in which the bones are soft and weak and may be deformed, painful, or easily broken).]
* HTN – verstimulation of the mineralocorticoid receptor, resulting in sodium retention in the kidney.
* weight gain + inc blood sugar — cause the liver to release more glucose. stop glucose being absorbed from the blood by the muscle and fat cells.
* avascular bone necrosis
* cataracts (cloudy area in lens of eye)

PO or by IV (or, such as triamcinolone, injinected into joint and has reduced systemic toxicity

Question 4

Methotrexate (rheumatrex, trexall)

Disease modifying anti-rhematic drugs (DMARDs) - slow joint damage

Answer 4

• lower doses — cancer tx
• reduce inflammation + joint pain by suppressing proliferation of immune cells via inhibition of dihydrofolate reductase (enzyme needed for folic acid metabolism)
• 1st line DMARD – often effective and well tolerated for long periods of time

onset 4-6 weeks

effects
* rare — hepatic cirrhosis, interstitial pneumonitis (large group of diseases that cause scarring (fibrosis) of the lungs), severe myelosuppression (also known as bone marrow suppression, is a decrease in bone marrow activity that results in reduced production of blood cell)
* common – liver injury, fatigue, headache

TO relieve those side effects => co administration of leucovorin [5-formyl derivative of folic acid] (leucovorin is FDA indicated after high dose methotrexate therapy in osteosarcoma to decrease the toxic effects of methotrexate or counter the toxic effects of folate antagonists.)

Question 5

hydroxychloroquine

Disease modifying anti-rhematic drugs (DMARDs) - slow joint damage

Answer 5

• antimalarial drug
• unknown mech — reduce pain and inflammation of joint disease in RA
• typically… used with sulfasalazine and methotrexate in TRIPLE therapy
• 2-4 month response and considered to have failed if no response by 6 months

effects
* serious eye toxicities (rare)
* evaluate for retinopathies prior to starting this drug
*

Question 6

sufasalazine (azulfidine)

Disease modifying anti-rhematic drugs (DMARDs) - slow joint damage

Answer 6

• mechanism unknown
• ususally used with methotrexate and hydroxychloroquine
• sulfa drug hypersensitivity occurs in some

////
effects
* GI distress — use enteric coated tablets

contra
* screen for G6PD (glucose-6-phosphate dehydrogenease) deficiency before starting to avoid hemolysis in these kind of pts

Question 7

leflunomide (arava)

Disease modifying anti-rhematic drugs (DMARDs) - slow joint damage

Answer 7

• mech unknown
• alternative to methotrexate
• monitor liver enzymes

contra
* pregnant women

Question 8

etanercept (enbrel)
infliximab (remicade)
adalimumab (humira)
certolizumab pegol (cimzia)
golimumab (simponi)

Disease modifying anti-rhematic drugs (DMARDs) - slow joint damage

Answer 8

• tumor necrosis factor (TNF) inhibitors
• All are monocolonal antibodies, except etanercept (fusion protein made from TNF receptor and Fc domain of an immunoglobulin)
• injection for administration

effects:
sx relief is 2-4 weeks
* increased risk of opportunistic infections (tuberculosis, fungal infections)
* reactivation of hep b
* risk inc some cancers

Question 9

abatacept (orencia)

Disease modifying anti-rhematic drugs (DMARDs) - slow joint damage

Answer 9

t-cell costimulatory blockers

• t cells require CD3 stimulation + co-stimulation through CD28 or other costimulatory receptors to become fully activated
• activated t cells contribute to RA joint damage… this drug binds to CD28 which blocks co-stimulation

Question 10

rituximab (rituxan)

Disease modifying anti-rhematic drugs (DMARDs) - slow joint damage

Answer 10

b cell depletion

• this drug is an antibody that binds to CD20 => which coats B cells
• this binding depletes b cells (which is causing the RA)
• for some who failed with TNF inhibitors (have like 5 drugs?)

effects
* infusion reaction (immune sys recognize antibody as foreign)
* infection risk
* hep b reactivation

Question 11

tocilizumab (actemra)
sarilumab (kevzara)

Disease modifying anti-rhematic drugs (DMARDs) - slow joint damage

Answer 11

interleukin-6 (IL6) inhibitors

• IL-6 is a pro inflammatory cytokine produced by immune cells
• monoclonal antibodies that bind these IL-6 l/t reduced RA joint dmg

effect
* infection risk
* thrombocytopenia
* liver toxicity
* neutropenia
* elevated lipids

Question 12

anakinra (kineret)

Disease modifying anti-rhematic drugs (DMARDs) - slow joint damage

Answer 12

interleukin-1 (IL1) inhibitors

• IL1 – proinflammatory cytookine produced by immune cells
• monoclonal AB’s bind to them to reduce RA join damage

effects
* injection site rxn
* increased infection risk

Question 13

tofacitinib (xelijanz)
baricitinib (olumiant)

Disease modifying anti-rhematic drugs (DMARDs) - slow joint damage

Answer 13

janus kinase (JAK) inhibitor

• JAK/STAT pathway induces transcription of genes that are involved in inflammation
• JAK inhibitors used in RA patients that have failed TNF inhibitors (about 5?)

effects
* fatal infections (TB, bacterial, fungal, viral)
* increased risk of cancer