Immunosuppressive Therapies for Auto-immune MSK Diseases

Question 1

What drugs are used to relieve symptoms in MSK disease?

Answer 1

NSAIDs

analgesics

gluccocorticoids

Question 2

What is the benefit of treating the underlying pathophysiology in MSK diseases?

Answer 2

potential to relieve symptoms, bu talso halt progression and prevent disability

since they work on physiologic mechanisms, may affect other biologic processes, adversely or beneficially

newer (knowledge of pathophysiology recent)

potentially more complex, costly, less time tested

Question 3

What is the use of NSAIDS in arthritis?

Answer 3

reduce pain

relieve inflammation

useful in inflammatory and non inflammatory arthritis

Question 4

What is the use of corticosteroids in arthritis treatment?

Answer 4

REALLY reduce pain, relieve inflammation

symptom reliever in inflammatory arthritis, intra-articular symptom reliever in non-inflammatory arthritis

Question 5

What is the use of analgesics in arthritis treatment?

Answer 5

relieve discomfort

must be for chronic use, so tolerance, dependence, and habituation are potential issues with narcotics

Question 6

What are the nonpharmacologic therapies for arthritis?

Answer 6

patient and family education

physical therapy

occupational therapy

Question 7

What are the pharmacologic therapies for arthritis?

Answer 7

NSAIDs

glucocorticoids joint injections

low-dose systemic steroids

initiate DMARD therapy

Question 8

What are the cahracteristics of DMARDs?

Answer 8

inhibit structural damage (radiographic bone erosion and joint space narrowing, cartilage loss) in rheumatoid arthritis

all are also anti-inflammatory, but not through prostaglandin pathways

therefore used in other conditions of joint inflammation (Lupus, spondyloarthropathies)

mostly discovered by accident

Question 9

methotrexate

Answer 9

increases adenosine at inflammatory sites and thereby diminishes leukocyte accumulation

Question 10

hydroxychloroquine (HCQ)

Answer 10

decreases toll-like receptor activation

Question 11

leflunomide (LEF)

Answer 11

inhibits mitochondrial enzyme dihydroorotate dehydrogenase (an enzyme involved in de novo pyrimidine synthesis)

Question 12

sulfasalazine (SSZ)

Answer 12

because sulfasalazine and its metabolite 5-ASA are poorly absorbed into the bloodstream, it is surprising that the drug is effective against symptoms outside of the intestine

Question 13

What are the commonly used immunosuppresive drugs?

Answer 13

azathioprine

cyclosporin and calcineurin inhibitors

mycophenolate

Question 14

azathioprine

Answer 14

prevent transplant organ rejection

active metabolite is methyl-thioinosine monophosphate (meTIMP)

a purine synthesis inhibitor that works by blocking the enzyme amidophosphoribosyltransferase

T and B lymphocytes are very sensitive to this inhibition

Question 15

cyclosporin and calcineurin inhibitors

Answer 15

ciclosporin binds to the cytosolic protein cyclophilin (immunophilin) of lymphocytes, especially T cells

this complex of ciclosporin and cyclophilin inhibits calcineurin, which, under normal circumstances, is responsible for activating and transcription of interleukin 2

ciclosporin prevents the dephosphorylation of NF-AT by binding to cyclophilin

it also inhibits lymphokine production and interleukin release

leads to reduced function of effector T-cells

Question 16

mycophenolate

Answer 16

derived from the fungus Penicillium stoloniferum or in P. echinulatum

mycophenolate mofetil is metabolised in the liver to the active moiety mycophenolic acid

inhibits inosine monophosphate dehydrogenase, the enzyme that controls the rate of synthesis of guanine monophosphate in the de novo pathway of purine synthesis used in the proliferation of B and T lymphocytes