2804NRS · Human Pathophysiology And Pharmacology 1
Musculoskeletal and Pain
The musculoskeletal system fails in two flavours — degenerative (wear of cartilage and bone) and inflammatory/autoimmune (the immune system attacking the joint) — and that split decides the drug. This chapter contrasts osteoarthritis (degenerative, asymmetric, local) with rheumatoid arthritis (autoimmune, symmetric, systemic), walks the four stages of bone healing and osteoporosis as an osteoclast-over-osteoblast imbalance, then turns to pain: the four steps of nociception (and where each analgesic acts), the headline COX pathway (why non-selective NSAIDs cause GI ulcers), and the three-step WHO analgesic ladder with opioids and their danger sign, respiratory depression. In 2804NRS this is Module 5 — examined by MCQ and short-answer, with the OA-vs-RA contrast and the COX/ladder pharmacology as the high-yield zones.
What this chapter covers
- 015.1 Two kinds of arthritis — OA vs RA
- 025.2 Bone healing (4 stages) & osteoporosis
- 035.3 Pain physiology — nociception (4 steps)
- 045.4 The COX pathway — how anti-inflammatories work
- 055.5 The WHO analgesic ladder & opioids
Why a non-selective NSAID causes GI ulcers
- +1The pathway: injured membranes release arachidonic acid, which COX enzymes convert to prostaglandins — the mediators of pain, fever and inflammation. NSAIDs block COX.
- +1Two isoenzymes: COX-2 is inducible and drives inflammation/pain (the target); COX-1 is constitutive 'housekeeping' — it makes protective gastric mucus, maintains renal blood flow and supports platelets.
- +1Non-selective NSAID: blocks BOTH COX-1 and COX-2, so it relieves pain but also removes COX-1's gastric protection → GI ulcers/bleeding and renal impairment.
- +1Coxib (COX-2 only): spares the stomach (COX-1 intact) but raises cardiovascular/thrombotic risk.
Key terms
- Osteoarthritis vs rheumatoid arthritis
- OA is degenerative (cartilage wear), asymmetric, in weight-bearing joints, local. RA is autoimmune/inflammatory, symmetric, hands and feet first, systemic (fever, malaise) — and is treated with disease-modifying drugs (DMARDs).
- Osteoporosis
- A metabolic bone disease of reduced density and mass: osteoclast resorption outpaces osteoblast formation. Loss of oestrogen at menopause unleashes osteoclasts — why postmenopausal women are most affected.
- Nociception
- The neural process that detects and signals a noxious stimulus, in four steps: transduction (NSAIDs act here), transmission (local anaesthetics), perception (opioids) and modulation (opioids and adjuvants).
- COX-1 vs COX-2
- COX-1 is constitutive/housekeeping (protects stomach lining, renal perfusion, platelets); COX-2 is inducible and drives inflammation, pain and fever. You want to block COX-2 and spare COX-1.
- WHO analgesic ladder
- A three-step approach matching drug to pain severity: Step 1 non-opioids (paracetamol, NSAIDs), Step 2 weak opioids (codeine), Step 3 strong opioids (morphine) — with non-opioids and adjuvants continued alongside at every step.
Musculoskeletal and Pain FAQ
How do I tell osteoarthritis from rheumatoid arthritis?
OA is degenerative, asymmetric and local — weight-bearing joints, worse with activity, bone spurs. RA is autoimmune, symmetric and systemic — hands and feet, morning stiffness over 30 minutes, fever/malaise. RA is treated with disease-modifying drugs (DMARDs) because the immune process can be switched off; OA management is symptomatic.
What are the four stages of bone healing?
Haematoma formation (a clot stabilises the site), fibrocartilaginous (soft) callus, ossified (bony) callus, and remodelling into strong lamellar bone. The process slows with age, poor circulation, infection and glucocorticoids.
Why does a non-selective NSAID cause stomach ulcers?
Because it blocks COX-1 as well as COX-2. COX-1 makes protective gastric mucus, maintains renal blood flow and supports platelets, so blocking it removes the stomach's protection → ulcers and bleeding. COX-2-selective coxibs spare the stomach but raise cardiovascular risk.
What is the most dangerous adverse effect of opioids?
Respiratory depression — monitor respiratory rate and sedation. Other effects include constipation (universal, give laxatives), nausea, tolerance and dependence. The reversal agent is naloxone.
Exam move
Treat OA-vs-RA as a guaranteed compare-and-contrast: degenerative/asymmetric/local vs autoimmune/symmetric/systemic, with DMARDs the RA-only clue. Learn the COX pathway as a diagram you can redraw — arachidonic acid → COX-1 (protective) vs COX-2 (inflammatory) — because the NSAID side-effect logic and the WHO ladder both hang off it. Memorise the four bone-healing stages in order, osteoporosis as osteoclast-over-osteoblast, and the opioid danger sign (respiratory depression).
