Pharmacology Block B (2)

Front 1

What antibodies are in RA are against

Back 1

IgG-Fc

Citrullinated proteins

Collagen type II

Front 2

How do you get T cell activation

Back 2

Apc present antigen to CD4 cells move to Th0 naive t cell then move into Th2 lineage

Front 3

How to get the B cell to make antibodies

Back 3

Apc present to CD4 cell then to Th0 then Th2 lineage which produces IL-4 to help mature B cell then to antibodies

Front 4

How do Th1 cause inflammation

Back 4

Produce IFNy and TNFa

Front 5

How does Th17 move to inflammation

Back 5

Produce Il-17

Front 6

Th1 lineage deals with what

Back 6

Viral infection

Front 7

What does th2 lineage fight against

Back 7

extracellular pathogen

Asthma is a Th2 response

Front 8

What role does B cells play

Back 8

Important role in antibody production and in activating T crlls through antigen presentation

Front 9

How is complement activated

Back 9

Through antigen/antibody/c1 complex)

Front 10

What is rankl and what does it do

Back 10

Its a ligand that stimulates osteoclast which is bone erosion

Front 11

What do cytokines fo to the fibroblast

Back 11

Activate the synovial fibroblast so they proliferate, then release MMP(matrix metalproteases) they dissolve matrix

Front 12

What do fibroblasts do

Back 12

Replace cartilage lose of function then and replacing it with something that isnt functional

Front 13

Name cellular events in RA

Back 13

Inflammation occurs- inc blood flow to joint, leakiness and swelling::Increased expression of adhesion molecules and influx of white blood cells into the joint

T and b cells and macrophages

Macrophages activate to produce 2 major cytokines TNFa and IL-1b

Stumulate to induce COX-2 and increase PGEs(pain and more inflammation)

Stimulated to release chemo-attractants and attract more cells to joint

Front 14

What does TNFa do

Back 14

Stimulates synoviocytes (fibroblast like cells in the joint)

Front 15

What do tnfα and IL-1β do

Back 15

Stimulates the Sinoviocytes to proliferate

As a ressult the cartilage gets replaced with fibroblasts non-functional – disaster

Front 16

What does il-17 stimulate

Back 16

Macrophages and synoviocytes in the joint to release cytokines such as IL-6

Front 17

Th17 cells produce what

Back 17

RANKL molecule which interacts with the receptor RANK

cause the activation of osteoclasts- they destroy bone

Bone is broken down, further destruction and damage to the joint

Front 18

Cells in the joint release what and what does this do

Back 18

IL-3, GM-CSF and G-CSF

These molecules tell the bone marrow to make more of leukocytes

Leucocytes are directed into inflamed joint synovium

Front 19

Joint destruction involves what

Back 19

Slow growth of synovial tissue onto the articular surface( no sponginess just grating)

Sustained release of PGs and LTs

Pain and oedema

Fused joint

Front 20

Delays in treatment of RA can result in what

Back 20

Long term joint damage

Front 21

What can early intensive treatment of RA do

Back 21

Increase chances of halting or slowing disease progression

Front 22

What drugs can treat RA

Back 22

NSAIDs

DMARDs

Glucocorticoids

Front 23

Name some NSAIDs

Back 23

Asprin, indomethacin, ibuprofen, diclofenac

Front 24

What do NSAIDs block at

Back 24

COX

Front 25

Whats the 2 forms cox exists as

Back 25

COX-1 and COX-2

Front 26

What is the characteristics for COX-1

Back 26

constitutive

Involved in normal physiology e.g g.i tract, lungs, kidneys, vascular endothelium, platelets

Front 27

Cox-2 characteristics

Back 27

Inducible

Induced in inflammed tissue

Front 28

What are classical NSAIDS

Back 28

non selective binding both COX-1 and COX-2 with most showing some moderate or marked preference for COX-1

Front 29

Whats some COX-2 selective inhibitors

Back 29

Celecoxib, refecoxib and eterocoxib

Front 30

What does asprin trigger

Back 30

Formation of lipoxins- asprin triggered lipoxin (ATL) and resolvins via COX-2

Front 31

Asprin acetylating COX-2 dors what

Back 31

Acetylated COX-2 converts eicosapentanoic(EPA) to 18R-HEPE which is then converted by 5-LOX to resolvin E1

Front 32

Indomethacin and diclofenac inhibit what

Back 32

Degradation of resolvins/lipoxins

Front 33

Whats the therapeutic effects of NSAIDS

Back 33

reduce pain

Reduce inflammation-pain, vasodilation, increased vascular permeability-swelling reduced

Reduce morning joint stiffness

Antipyretic

Effectively reduce symptoms but do not modify underlying disease process

Front 34

Where are the adverse effects of using NSAIDS

Back 34

Gi tract

Kidney

Lung

Cardiovascular system

Front 35

What is asprin-induced asthma

Back 35

Common

High cross-reactivity (up to 100%) with other NSAIDs

Push pathway towards the production of leukotrienes

Front 36

Cox-2 inhibitors have what

Back 36

Therapeutic action of NSAIDs but without gi adverse effects

Front 37

When should COX-2 inhibitors be cautiously used

Back 37

In patients with pre existing peptic ulcer disease

Front 38

When is COX-2 inhibitors a problem

Back 38

Increased cardiovascular mortality

Front 39

What are the cardiovascular effects of NSAIDs

Back 39

Increased risk of MI

Increased risk of stroke

Varies among compounds

Relative potency for COX-1 verus cox-2?? Not COX-2 related

Front 40

What happen with Merck and Vioxx

Back 40

Vioxx was a COX-2 inhibitor

Kept all data about CV Problems quiet

Responsible for 1000 of deaths in the US