Pharmacology of agents used for the treatment of common joint problems Flashcards
What are the three key inflammatory mediators targeted by anti-inflammatory drugs?
Eicosanoids (e.g., prostaglandins, thromboxanes)
Biological oxidants
Cytokines
🧠 Mnemonic: “Eat Bright Carrots” (Eicosanoids, Biological oxidants, Cytokines).
Which COX isoform is primarily involved in inflammatory prostaglandin synthesis?
COX-2 (cyclooxygenase-2).
🖼️ Dominant in inflammation; NSAIDs inhibit COX-2 to reduce pain/swelling.
Explain the mechanism of action of NSAIDs in treating inflammation.
NSAIDs block COX-2, inhibiting prostaglandin/thromboxane synthesis. This reduces:
Vasodilation
Vascular permeability
Pain signaling
Leukocyte migration
🧠 “No COX-2 → No PGs → No Inflammation!”
What initiates the inflammatory process?
Cellular damage from stimuli like infection, physical stress, autoimmune reactions, or chemicals. This activates transcription factors (e.g., NF-κB) that trigger inflammatory mediator release.
What are common adverse effects of NSAIDs?
GI ulcers/bleeding (reduced protective PGs)
Kidney damage (impaired renal blood flow)
Increased cardiovascular risk (e.g., with COX-2 inhibitors)
Allergic reactions (e.g., aspirin-induced asthma)
Contraindications for NSAID use?
Peptic ulcer disease
Severe kidney/liver disease
Aspirin allergy (avoid salicylates)
Pregnancy (3rd trimester: risk of premature ductus arteriosus closure)
Indications for NSAIDs in joint disorders?
Osteoarthritis pain
Rheumatoid arthritis inflammation
Acute gout flares
Ankylosing spondylitis
Trade vs. generic names of NSAIDs: Examples?
Ibuprofen: Advil, Motrin
Celecoxib: Celebrex
Aspirin: Bayer, Ecotrin
Naproxen: Aleve
What are the three classifications of NSAIDs based on COX selectivity?
Non-selective COX-1/COX-2 inhibitors (e.g., ibuprofen, diclofenac)
Selective COX-2 inhibitors (e.g., celecoxib, rofecoxib)
Salicylates (e.g., aspirin).
Why do COX-2 inhibitors cause fewer gastrointestinal (GI) adverse effects than non-selective NSAIDs?
COX-2 inhibitors spare COX-1, which maintains protective prostaglandins (PGE₂) in the stomach lining.
🧠 “COX-2 spares COX-1 → Happy Stomach!”
Explain the mechanism of diclofenac-induced gastric ulceration and how to mitigate it.
Cause: Diclofenac inhibits COX-1, reducing PGE₂ (protects gastric mucosa).
Prevention: Combine with omeprazole (PPI) or misoprostol (PG analog) to reduce acid/ulcer risk.
Why is ibuprofen not recommended with aspirin for cardioprotection?
Ibuprofen competes with aspirin for COX-1 binding, blocking aspirin’s irreversible antiplatelet effect.
🧠 “Ibuprofen blocks aspirin’s heart shield!”
Adverse renal effects of NSAIDs (e.g., COX-2 inhibitors)?
Reduced renal blood flow (inhibits vasodilatory PGs).
Sodium retention → hypertension.
Risk of acute kidney injury (especially in volume-depleted patients).
Key uses of indomethacin?
Acute gout (rapid pain/inflammation relief).
Rheumatoid arthritis.
🖼️ High potency but limited by frequent side effects (e.g., headache, GI issues).
Why is aspirin contraindicated in gout?
Aspirin impairs uric acid excretion by inhibiting renal tubular secretion, worsening hyperuricemia.
Advantages and disadvantages of celecoxib (COX-2 inhibitor)?
Advantages: Fewer GI ulcers, no antiplatelet effect (safer for bleeding risk).
Disadvantages: No cardioprotection, expensive, risk of hypertension/edema.
What makes acetaminophen different from other NSAIDs?
Weak anti-inflammatory activity.
No COX inhibition in peripheral tissues (works centrally).
Safe for GI but risky in overdose (hepatotoxicity).
How does aspirin’s antiplatelet effect last 8–10 days?
Aspirin irreversibly inhibits COX-1 in platelets. Platelets lack nuclei to regenerate COX.
Formulations of NSAIDs?
Oral (tablets, capsules).
Topical (diclofenac gel).
Injectable (ketorolac).
Suppository (indomethacin).
Trade vs. generic names:
Celecoxib
Ibuprofen
Diclofenac
Celecoxib → Celebrex
Ibuprofen → Advil, Motrin
Diclofenac → Voltaren
What are rheumatic diseases?
Chronic inflammatory disorders (e.g., rheumatoid arthritis, systemic lupus erythematosus) characterized by immune-mediated tissue damage and increased phagocyte activity.
What are the primary goals of rheumatic disease management?
Relieve pain/symptoms.
Arrest disease progression.
Maintain mobility/quality of life.
🧠 “Relieve, Arrest, Maintain!”
Therapeutic strategies for rheumatic diseases?
Symptom control: NSAIDs, corticosteroids.
Disease modification: DMARDs (e.g., methotrexate, TNF-α inhibitors).
🖼️ NSAIDs = quick relief; DMARDs = long-term control.
What are DMARDs?
Disease-Modifying Antirheumatic Drugs (e.g., methotrexate, sulfasalazine) that slow/stop immune-mediated joint damage (no direct anti-inflammatory/analgesic effects).
