DMARDs

Question 1

Define DMARDs

Answer 1

Disease Modifying : used both to control symptoms and to slow/stop the progression of the disease
Anti-Rheumatic: Used for Rheumatoid Arthritis and other chronic inflammatory diseases as well

Question 2

Rheumatoid Arthritis (RA) can cause:

Answer 2

diabetes

Question 3

Autoimmune define:

Answer 3

The immune system attacks healthy cells in the body—> persistent inflammation (mostly in the joints) = joint damage

Question 4

List some differences in a healthy joint compared to arthritic joint

Answer 4

increased number of inflammatory cells (i.e. B-cell, T-cells, macrophages etc)
Increases level of inflammatory mediators (TNFalpha, IL-1,IL-6)

Question 5

csDMARDs

Answer 5

conventional synthetic DMARDS

Question 6

bDMARDs

Answer 6

biological DMARDS

Question 7

EXAMPLE of commonly used csDMARD

Answer 7

Methotrexate

Question 8

MECHANISM of action for csDMARDs

Answer 8

NON-SPECIFIC

Question 9

mechanism of Methotrexate

Answer 9

• inhibits dihydrofolate reductase (involved in folate metabolism)= no DNA/RNA synthesis= inhibits cell proliferation/death
• inhibits the enzyme AICAR transformylase (ATIC) = increased levels of AICAR
  overall less inflammation because decreased levels of inflammatory cells

Question 10

Adenosine receptor is what type of receptor?

Answer 10

G protein coupled receptor

Question 11

cons of csDMARDs

Answer 11

require regular monitoring
takes time for their effects ( 7 months)

Question 12

Advantages of bDMARDs

Answer 12

Highly specific in their mechanism of action
High efficacy (relief symptoms + slow/stop progression of the disease)

Question 13

Biological DMARDs define + characteristics

Answer 13

• Medicinal products derived from a living organism
  -Mostly proteins
  -Most manufactured using recombinant DNA technology

Question 14

Most biologics are manufactured using?

Answer 14

recombinant DNA technology

Question 15

csDMARDS define:

Answer 15

small synthetic molecules
-originally developed to treat cancer

Question 16

csDMARDs also used to treat?

Answer 16

Psoriasis, Crohn’s disease

Question 17

Biologics vs Conventional drugs

Answer 17

-Manufacturing process highly complex and difficult to replicate but csDMARDs its easy to replicate (chemical synthesis)
-biologics are large molecules conventional drugs are small molecules
-Biologics are more unstable and sensitive to external conditions but conventional are stable

Question 18

how might biologics work?

Answer 18

B cells depletion
Inhibition of T-cell activation
Cytokine Inhibition : TNF-alpha/ IL inhibitors

Question 19

Examples of TNF- alpha inhibitors

Answer 19

Adalimumab,Infliximab

Question 20

TNF-alpha define

Answer 20

key pro-inflammatory cytokine
produced predominantly by macrophages

Question 21

How might biologics TARGET PRO-INFLAMMATORY CYTOKINES?

Answer 21

-anti TNF-alpha therapy
-inhibit other cytokines (ANTI: IL-1, IL-6 THERAPIES )

Question 22

IL-1, IL-6 define

Answer 22

pro-inflammatory cytokines with a central role in the activation of an inflammatory response

Question 23

Anakinra

Answer 23

recombinant antagonist of the IL-1 receptor

Question 24

Canakinumab

Answer 24

Antibody that binds to IL-1: (SELECTIVELY BLOCKING)

Question 25

Examples of anti IL-1 therapies

Answer 25

Anakira Canakinumab

Question 26

Tocilizumab

Answer 26

an antibody that binds to IL-6 receptors (blocking)

Question 27

Rituximab

Answer 27

antibody specific for CD20, which is expressed on B cells

Question 28

Biologic that decreases B cells

Answer 28

Rituximab

Question 29

Mechanism of action for rituximab

Answer 29

targets CD20 on B cells CDC- complement-dependent cytotoxicity and ADCC :antibody-dependent cell-mediated cytotoxicity lead to apoptosis=promotes cell lysis B-CELL DEPLETION

Question 30

Abatacept

Answer 30

inhibits the "second signal" required for T-cell activation prevents co-stimulation prevents activation of T-cells

Question 31

Disadvantages of DMARDs

Answer 31

side effects: increased susceptibility to infection, increased risk of malignancy Mode of administration: IV, subcutaneous Manufactured using a living organism= manufacturing process highly complex and difficult to replicate Unstable (storage conditions very important!) High price

Question 32

side effects of biological DMARDs

Answer 32

increased susceptibility to infection, increased risk of malignancy