L12- Arthritis

Question 1

What are the two types of arthritis?

Answer 1

• Osteoarthritis

* Rheumatoid arthritis

Question 2

What is the structure of a healthy joint?

Answer 2

• Synovial membrane allowed smooth functioning and contains few cells
• Bone is rounded
• Cartilage present

Question 3

What is the structure of a rheumatoid arthritis joint?

Answer 3

• Growth of synovial membrane which invades the bone

* Worn down cartilage and narrowed joint space

Question 4

What is rheumatoid arthritis?

Answer 4

• Inflammatory condition affecting joints
• They become painful, stiff and swollen
• Primarily a synovitis, leads to joint destruction and systemic lesions
• Can be autoimmune

Question 5

What is osteoarthritis?

Answer 5

• Affects a large percentage of people over 60
• Progressive and disabling
• Cartilage cells change and it thins, loses elasticity and starts to split
• Loses normal functioning
• Bone loses shape and thickens at the ends to produce bony spurs

Question 6

How is the management of RA carried out?

Answer 6

• Unknown aetiology so management directed towards relief of symptoms
• Conservation and restoration of function in affected joints
• Suppression of active progressive disease

Question 7

What are the mediators of arthritis?

Answer 7

KEY: TNFa produced by inflammatory cellsa round joint

• IL1,IL6,IL8,IL17 pro inflammatory cytokines
• IL10 anti inflammatory

Question 8

What are NSAIDs?

Answer 8

Non-steroidal anti-inflammatory drugs e.g aspirin
• Most widely prescribed
• Analgesic
• Anti-inflammatory

Question 9

What is the mechanism of action of NSAIDs?

Answer 9

• Inhibit the COX enzyme to prevent prostaglandin production
• By time dependent irreversible inactivation (aspirin, indomethacin) or by reversible competitive inhibition (ibuprofen, meloxicam)

Question 10

What are the different NSAIDs?

Answer 10

• Salicylates- aspirin
• Acetic acids- indomethacin, didofenac= potent with adverse side fx
• Proprionic acids- ibuprofen, naproxen= common, less potent and less adverse side fx
• Oxicoms- prioxicam, phenylebutazone
• Fenamates- meclofenamate
• Paracetamol (acetaminophen)- not anti-inflammatory

Question 11

What is the difference between COX1 and COX2?

Answer 11

COX1 found in most cells and involved in normal homeostasis
COX2 released by inflammatory cells by inflammatory stimuli, to produce prostaglandins at inflammatory sites
COX2 must be inhibited more than COX1

Question 12

What are non-selective COX inhibitors?

Answer 12

• Indomethacin
• Ibuprofen
• Aspirin
Side effects on gut and kidney

Question 13

What are COX2 selective inhibitors?

Answer 13

• Celecoxib
• Meloxicam
• Rofecoxib

Question 14

What are DMARDs?

Answer 14

Disease modifying anti-rheumatic drugs
Slow acting
Second line (all have side effects)

Question 15

What are examples of DMARDs?

Answer 15

• Methotroxate
• Gold salts
• Anti malarials
• Pencillamine

Question 16

What are the glucocorticoids used?

Answer 16

• Hydrocortisone
• Dexamethasone
• Prednisolone

Question 17

What are the advantages of glucocorticoids?

Answer 17

• Several anti-inflammatory activities- inhibit cytokines, down regulate adhesion molecules
• Inhibition of enzyme induction (COX, NOS)

Question 18

What are the disadvantages of glucocorticoids?

Answer 18

• Immune suppression so increased risk of infection
• Osteoporosis
• Adrenal atrophy

Question 19

What is methotroxate?

Answer 19

• Folate antagonist
• Used as anti-metabolite in cancer chemotherapy but may act via other mechanisms for anti-inflammatory effect
• Disease modifying agent for RA treatment

Question 20

What is an established therapy for arthritis?

Answer 20

Inhibition of TNF-a

Question 21

What drugs inhibit TNF-a?

Answer 21

• Anti-TNF antibodies= infliximab, adalimumab
• Soluble TNF receptor construct= etanercept
Used when other DMARDs have failed

Question 22

What are the emerging drug approaches?

Answer 22

• Cytokines- IL1 antibodies, IL6 and IL17 blockers

* Cell based- rituximab removes B cels, abatacept inhibits T cells