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Drugs And Disease > Arthritis > Flashcards

Flashcards in Arthritis Deck (17):
1

What is arthritis?

A common inflammatory disease, caused by a combination of genetic, environmental and hormonal factors. It decreases your quality of life.

2

Tell me some facts about arthritis.

40% people over 65 have arthritis
Affects 1% popn (1:3, males:females)
Expensive medical costs

3

What is osteoarthritis?

progressive and disabling disease
people over 60
not so painful
cartilage cells change, thins, lose elasticity and start to split...lose smooth functioning...bonce loses shape and thickens at the end producing bony spurs

4

What is rheumatoid arthritis?

25-50yrs, children? 1:3, M:F
Autoimmune, genetic, bacterial, viral?
Affects joints, painful and stiff and imflammed (swelling).
Primarily a synovitis (thick, inflammed synovial membrane) but leads to joint destruction and systemic lesions.

5

What are the principlesof managing rheumatoid arthritis?

Relieve symptoms, conserve and restore joint function, supress active pregressive disease, reduce mortality

6

What mediators are involved in arthritis?

TNF-alpha, IL1, IL6, IL8, IL10, IL17, and PGE2

7

Describe the mechanism of action of NSAIDs.

Inhibit COX and therefore inhibit PG production too (except paracetamol)
There are 2 central mechanisms...
1) time dependant irreversible inactivation
- aspirin and indomethacin
2) reversible competitive inhibition
- ibuprofen and meloxicam

8

Where is COX-1 found?

most cells, constitutive expressed, maintains homeostasis, Gi tract - maintains BF
TxA2 - platelet aggregation
PGI2 - inhibit platelet aggregation

9

Where is COX 2 found?

Induced inflammatory cells by inflammatory stimuli
Releases high levels of PG.

10

Name NSAIDs that are nonselective

Aspirin, Ibuprofen and Indomethacin

11

Name NSAIDs COX-2 selective

Celecoxib, rofecoxib, meloxicam
BUT have cardiac effects...x2 risk of MI

12

Disease Modifying Anti-Rheumatic Drugs:
SLow acting acnti rheumatic drugs - expain

2nd line therapies...
Methotrexate - folate antag, antimetabolite in cancer chemo, most widely used, best used with NSAIDs
Gold salts
Antimalaria - chloroquine
Suplhasalasine
Penicllinamine

13

Disease Modifying Anti-Rheumatic Drugs:
Immunosupressives

Steroids, cyclosporins (toxic)

14

What are the pros and cons of using corticosteroids or glucocorticoids?

Pros:
Inhibit AA release
Cytokine inhibition
Down reg adhesion molecules
inhibit COX, iNOS induction

CONS:
osteoporosis
increase risk of infection
adrenal atrophy

Also inhibit t-lymph proliferation adn induce apoptosis.

15

Actions of TNF-alpha?

cytokine release (inc IL-1), decrease surface, TNF receptor, increase soluble TNF receptors, ingiogensis, MHC class 1and2, adhesion molecule expression, cehmokine release, tissue damage, metalloproetinase, PGE2 production

16

What 'biologic' drugs are there?

Anti TNF antibodies...infiximab and adalimumab
Soluble TNF receptor contruct
Etanercept

17

What other drug treatments are in the pipeline for treating arthritis?

Cytokine receptor antagonist (IL-1,6,17)
B cell removers
Rituximab - removes antibodies producing B cells (WBC)