Arthritis

Question 1

What is a common side effect of cyclophosphamide treatment?

Answer 1

Haemorrhagic cystitis - this is caused by the metabolite acrolein and the effect can be reduced by increasing fluid intake.

Question 2

Celecoxib is a COX-2 selective inhibitor with potentially serious side effects. Compared to non-selective NSAIDs, celecoxib is thought to have a reduced risk of causing…

Answer 2

Gastric ulcer - as a COX-2 selective inhibitor, it reduces inflammation but does not block mucus production in the stomach.

Question 3

Methotrexate is a cytotoxic drug used to treat rheumatoid arthritis. Its mechanism of action involves a reduction in the synthesis of..

Answer 3

Folic acid - this is essential in DNA synthesis - as a result it has an immunosuppressant effect.

Question 4

What is the proposed mechanism for the gastric bleeding associated with use of NSAIDs?

Answer 4

Inhibition of COX-1 - this isoform of COX is responsible for protecting the lining of the stomach by increasing mucus secretion.

Question 5

Where does Osteoarthritis occur?

Answer 5

In the bone and is related to wear and tear.

Question 6

Where does Rheumatoid arthritis occur?

Answer 6

Tends to affect small joints first, such as in hands and feet but can affect any connective tissues

Question 7

Why does Rheumatoid arthritis occur?

Answer 7

Because antibodies are aimed towards normal proteins in the connective tissue of joints, with the result that pro-inflammatory chemicals called cytokines are released.

Question 8

What type of joints does Osteoarthritis occur in?

Answer 8

Synovial joints.

Question 9

What do PGD2/ PGI2 cause?

Answer 9

Vasodilation.

Question 10

What does PGE2 cause?

Answer 10

vasodilation, pyrogenic + (under certain conds.) anti-inflammatory effects.

Question 11

Prostaglandins cause what increased reaction in histamine and bradykinin?

Answer 11

• Increased permeability of venules → oedema

- Increased sensitivity of C fibres (PAIN!)

Question 12

What does a Antipyretic drug do?

Answer 12

Inhibits actions of Prostaglandin on hypothalamus.

Question 13

What does an Analgesic drug do in arthritis?

Answer 13

• reduce sensitivity of neurons to bradykinin

- effective against pain of muscular/ skeletal origin

Question 14

What does an Anti-inflammatory drug do in arthritis?

Answer 14

Reduces vasodilation and decrease permeability of venules.

Question 15

What are the Problems with NSAIDs ?

Answer 15

• Risk of gastric ulcers
• Impair coagulation
• Use with caution in elderly (GI bleeding can be serious/ fatal)
• Risk of CV events in patients with cardiac disease/ hypertension
• May induce asthma attack, angioedema, urticaria or rhinitis

Question 16

Why might NSAIDs be a problem in arthritis?

Answer 16

Many inhibit COX1 as well as COX2.

Question 17

Why is COX1 needed?

Answer 17

It does not stop the production of gastric mucus, which means there is less chance of developing a gastric ulcer.

Question 18

What is Meloxicam ?

Answer 18

COX-2 inhibitor (It does not target COX1) and concentrates on the synovial fluid.

Question 19

Name 2 COX2 inhibitors…

Answer 19

.Celecoxib and etoricoxib

Question 20

What are the main side effects of .celecoxib and etoricoxib?

Answer 20

Headache, dizziness, skin rash, peripheral oedema.

Question 21

What is Misoprostol ?

Answer 21

A synthetic prostaglandin

Question 22

Why is Misoprostol given?

Answer 22

It is given alongside NSAIDs to preserve mucous lining of GI tract and protect against ulceration.

Question 23

Side effects of Misoprostol?

Answer 23

Diarrhoea (can be severe) and vaginal bleeding .

Question 24

Drugs used to treat osteoarthritis ….

Answer 24

• Paracetamol – regular dosing ± oral NSAID (with PPI*)
• Topical NSAID or capsaicin (esp knee/ hand)
• Opioid analgesic – for further relief
• Intra-articular corticosteroid injection → temporary benefit
• Joint replacement surgery (hip, knee, ankle)

Question 25

What does Strontium ranelate do?

Answer 25

• promotes osteoblast differentiation/ inhibits osteoclast activity*
• reduces pain*
• Indicated for prevention of fractures in severe osteoporosis

Question 26

What are the drugs used to treat pain in Rheumatoid arthritis ?

Answer 26

NSAIDs/ opioid analgesics and Glucocorticoids

Question 27

what drugs are used to limit joint damage in Rheumatoid arthritis?

Answer 27

• Immunosuppressants
• Disease Modifying Antirheumatic Drugs (DMARDS)
• Anticytokines

Question 28

Where are glucocorticoids produced naturally in the body?

Answer 28

In the adrenal glands.

Question 29

Glucocorticoids can be used in the short term to…

Answer 29

To manage flare-ups (rapidly reduce inflammation) in patients with recent-onset or established disease.

Question 30

What are the two main types of action of adrenal steroids?

Answer 30

Glucocorticoid:

• metabolic effects
• anti-inflammatory
• immunosuppressive

Mineralocorticoid:
- water & electrolyte balance

Question 31

Name 2 naturally occurring types of steroids?

Answer 31

Hydrocortisone/ corticosterone:
- show both (MC + GC) activities

Aldosterone:
- mineralocorticoid only

Question 32

Name 2 drugs that have both gluco-/ mineralocortiocoid activity…

Answer 32

Prednisolone and prednisone

Question 33

Name 4 drugs that have glucocorticoid activity…

Answer 33

Dexamethasone, betamethasone, beclomethasone and budesonide.

Question 34

Name a drug that has mainly mineralocorticoid activity…

Answer 34

Fludrocortisone

Question 35

Name a short-acting (1 -12 hrs ) steroid…

Answer 35

Cortisone/ hydrocortisone:

Twice daily cream or intra-articular injection.

Question 36

Name an Intermediate-acting (12 – 36 hrs) steroid…

Answer 36

Prednisolone:

Daily oral or intra-articular injection

Question 37

Name a long-acting (36 – 55 hrs) steroid…

Answer 37

Dexamethasone:

Intra-articular injection every 3 - 21 days

Question 38

What are the general problems with using Immunosuppressants in people with Rheumatoid arthritis?

Answer 38

• Increase risk of infection

- Increase risk of cancer