19 - Musculoskeletal

Question 1

Difference between rheumatoid arthritis and osteoarthritis?
- Which symmetry and laterality of them

Answer 1

Rhuematoid is swollen and inflammed synovial membrane whilst osteo is thinned cartillage causing bone rubbing.

Rheumatoid arthritis more bilateral and symmetrical

Question 2

3 effects of NSAIDs?

Answer 2

Arachidonate –(Cyclo-oxygenase)–> PG cyclo endoperoxides
- Anti-inflammatory (decrease prostacyclin, PGE2)
- Analgesic (less prostaglandin sensitisation from pain receptors) (anti-pain)
- Antipyretic (less prostaglandin release from IL-1) (anti-fever)

Question 3

Describe cyclooygenase enzymes
- How do drugs specify which enzyme to target?

Answer 3

COX-1 is a housekeeping enzyme focused on tissue homeostasis such as prostaglandin synthesis which normally inhibits acid secretion and protects mucosa. Inhibition of this can cause peptic ulcer.
COX-2 is induced by inflammatory cells and makes prostanoid mediators of inflammation.
- By using larger drugs which can fit into the wider chanel of COX-2 but not the smaller channel of COX1.

Question 4

Adverse drug reactions of NSAIDs? (7 total)

Answer 4

• Upper GI erosions, ulcers, bleeding… (ibuprofen is safest but sitll 2x more likely)
• Renal impairment in elderly (reduce dose and time if possible)
• Skin reactions
• Liver disorders, be mindful of.
• Bone marrow depression in some ppl
• Bronchospasm in asthmatics
• Cardiovascular risk (naproxen safest)

Question 5

1) What are DMARDs?
2) How do they work?

Answer 5

1) Disease modifying anti-rheumatic drugs
2) Target specific cells in autoimmunity.
E.g.
- Glucocorticosteroids target macrophages
- Immunosuppresants like methotrexate target CD4 T cells

Question 6

How to Tx rheumatoid arthritis?

Answer 6

NSAIDs alone not enouggh since it only limits pain and inflammation. You need drugs to prevent deformities caused by rheumatoid arthritis.

NSAID and atleast one DMARD since DMARD takes time to work. May even give low dose corticosteroid treatment. When in remission, regular NSAIDs and corticosteroids not needed.

Question 7

Ocular side effects of NSAIDs?
Ocular side effects of DMARDs?

Answer 7

• Increases bleeding e.g. Subconj. haemorrhage
• Methotrexate often related to folate deficiency (since it’s a folic acid antagonist)

Question 8

List 2 drugs that affect bone metabolism

Answer 8

Biphosphates and Selective Estrogen Receptor Modulators (SERMs)

Question 9

How do biphosphates work?
- Side effects?
- Ocular side effects?

Answer 9

Biphosphates are similar to our natural pyrophosphate and so it’s incorporated into bone. When osteoblasts eats it, it dies and oestoblasts come over and fix damage. This will also inhibit oestoclast recruitment.

• Atypical fractures likely due to stopping natural cycle of bone replacement w/ healthier bones
• Inflammation of anterior eye. Rare conditions of optic neuritis, orbital/periorbital edema.

Question 10

1) SERMs work how?
2) ADRs?
3) Examples of SERMs?

Answer 10

1) Agonist for estrogen receptors in bone and CV system. Increases osteoblast activity and reduces osteoclast action.
2) Hot flushes, leg crampes, venous thromboembolism.
3)
- Tamoxifen
- Raloxifene