Arthritis Flashcards
What is a common side effect of cyclophosphamide treatment?
Haemorrhagic cystitis - this is caused by the metabolite acrolein and the effect can be reduced by increasing fluid intake.
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…
Gastric ulcer - as a COX-2 selective inhibitor, it reduces inflammation but does not block mucus production in the stomach.
Methotrexate is a cytotoxic drug used to treat rheumatoid arthritis. Its mechanism of action involves a reduction in the synthesis of..
Folic acid - this is essential in DNA synthesis - as a result it has an immunosuppressant effect.
What is the proposed mechanism for the gastric bleeding associated with use of NSAIDs?
Inhibition of COX-1 - this isoform of COX is responsible for protecting the lining of the stomach by increasing mucus secretion.
Where does Osteoarthritis occur?
In the bone and is related to wear and tear.
Where does Rheumatoid arthritis occur?
Tends to affect small joints first, such as in hands and feet but can affect any connective tissues
Why does Rheumatoid arthritis occur?
Because antibodies are aimed towards normal proteins in the connective tissue of joints, with the result that pro-inflammatory chemicals called cytokines are released.
What type of joints does Osteoarthritis occur in?
Synovial joints.
What do PGD2/ PGI2 cause?
Vasodilation.
What does PGE2 cause?
vasodilation, pyrogenic + (under certain conds.) anti-inflammatory effects.
Prostaglandins cause what increased reaction in histamine and bradykinin?
- Increased permeability of venules → oedema
- Increased sensitivity of C fibres (PAIN!)
What does a Antipyretic drug do?
Inhibits actions of Prostaglandin on hypothalamus.
What does an Analgesic drug do in arthritis?
- reduce sensitivity of neurons to bradykinin
- effective against pain of muscular/ skeletal origin
What does an Anti-inflammatory drug do in arthritis?
Reduces vasodilation and decrease permeability of venules.
What are the Problems with NSAIDs ?
- 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
Why might NSAIDs be a problem in arthritis?
Many inhibit COX1 as well as COX2.
Why is COX1 needed?
It does not stop the production of gastric mucus, which means there is less chance of developing a gastric ulcer.
What is Meloxicam ?
COX-2 inhibitor (It does not target COX1) and concentrates on the synovial fluid.
Name 2 COX2 inhibitors…
.Celecoxib and etoricoxib
What are the main side effects of .celecoxib and etoricoxib?
Headache, dizziness, skin rash, peripheral oedema.
What is Misoprostol ?
A synthetic prostaglandin
Why is Misoprostol given?
It is given alongside NSAIDs to preserve mucous lining of GI tract and protect against ulceration.
Side effects of Misoprostol?
Diarrhoea (can be severe) and vaginal bleeding .
Drugs used to treat osteoarthritis ….
- 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)
What does Strontium ranelate do?
- promotes osteoblast differentiation/ inhibits osteoclast activity*
- reduces pain*
- Indicated for prevention of fractures in severe osteoporosis
What are the drugs used to treat pain in Rheumatoid arthritis ?
NSAIDs/ opioid analgesics and Glucocorticoids
what drugs are used to limit joint damage in Rheumatoid arthritis?
- Immunosuppressants
- Disease Modifying Antirheumatic Drugs (DMARDS)
- Anticytokines
Where are glucocorticoids produced naturally in the body?
In the adrenal glands.
Glucocorticoids can be used in the short term to…
To manage flare-ups (rapidly reduce inflammation) in patients with recent-onset or established disease.
What are the two main types of action of adrenal steroids?
Glucocorticoid:
- metabolic effects
- anti-inflammatory
- immunosuppressive
Mineralocorticoid:
- water & electrolyte balance
Name 2 naturally occurring types of steroids?
Hydrocortisone/ corticosterone:
- show both (MC + GC) activities
Aldosterone:
- mineralocorticoid only
Name 2 drugs that have both gluco-/ mineralocortiocoid activity…
Prednisolone and prednisone
Name 4 drugs that have glucocorticoid activity…
Dexamethasone, betamethasone, beclomethasone and budesonide.
Name a drug that has mainly mineralocorticoid activity…
Fludrocortisone
Name a short-acting (1 -12 hrs ) steroid…
Cortisone/ hydrocortisone:
Twice daily cream or intra-articular injection.
Name an Intermediate-acting (12 – 36 hrs) steroid…
Prednisolone:
Daily oral or intra-articular injection
Name a long-acting (36 – 55 hrs) steroid…
Dexamethasone:
Intra-articular injection every 3 - 21 days
What are the general problems with using Immunosuppressants in people with Rheumatoid arthritis?
- Increase risk of infection
- Increase risk of cancer
