Musculoskeletal, Skin, and Connective Tissue Flashcards
What does the Lipoxygenase pathway yield?
Leukotrienes
What is LTB4?
A neutrophil chemotactic agent
What do LTC4, D4, and E4 function in?
Bronchoconstriction, vasoconstriction, contraction of smooth muscle, and ↑ vascular permeability
What does PGI2 do?
Inhibit platelet aggregation and promotes
vasodilation. It also ↓ bronchial tone and ↓ uterine tone.
What do corticosteroids do?
Block protein synthesis and inhibit Phospholipase A2 (so membrane lipids don’t turn into Arachidonic Acid)
What does Zileuton do?
Inhibits Lipoxygenase so Arachidonic acid doesn’t turn into Hydroperoxides (HPETEs)
What do Zafirlukast and Montelukast do?
Leukotriene receptor agonsists. They ↑ bronchial tone.
What do NSAIDS, aspirin, acetaminophen, COX-2 inhibitors do?
Inhibit Cyclooxygenase (COX-1, COX-2) so Arachidonic acid doesn’t turn into Endoperoxides (PGG2, PGH2).
What do Prostaglandins (PGE2 and PGF2a) do?
↑ uterine tone and ↓ bronchial tone
What does Thromboxane (TXA2) do?
↑ platelet aggregation
↑ vascular tone
↑ bronchial tone
What is the mechanism of Aspirin?
Irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) by covalent acetylation, which ↓ synthesis of both thromboxane A2 (TXA2) and prostaglandins. ↑ bleeding time until new platelets are produced (∼ 7 days). No effect on PT, PTT. A type of NSAID.
What is the clinical use of Aspirin?
Low dose (< 300 mg/day): ↓ platelet aggregation. Intermediate dose (300–2400 mg/day): antipyretic and analgesic. High dose (2400–4000 mg/day): anti-inflammatory.
What is the toxicity of Aspirin?
Gastric ulceration, tinnitus (CN VIII). Chronic use can lead to acute renal failure, interstitial nephritis, and upper GI bleeding. Risk of Reye syndrome in children treated with aspirin for viral infection. Also stimulates respiratory centers, causing hyperventilation and respiratory alkalosis.
What are the NSAIDs?
Ibuprofen, naproxen, indomethacin, ketorolac, diclofenac
What is the mechanism of NSAIDs?
Reversibly inhibit cyclooxygenase (both COX-1 and COX-2). Block PG synthesis.
What is the clinical use of NSAIDs?
Antipyretic, analgesic, anti-inflammatory. Indomethacin is used to close a PDA.
What is the toxicity of NSAIDs?
Interstitial nephritis, gastric ulcer (PGs protect gastric mucosa), renal ischemia (PGs vasodilate afferent arteriole).
What is the mechanism of COX-2 inhibitors (celecoxib)?
Reversibly inhibit specifically the cyclooxygenase (COX) isoform 2, which is found in inflammatory cells and vascular endothelium and mediates inflammation and pain; spares COX-1, which helps maintain the gastric mucosa. Thus, should not have the corrosive effects of other NSAIDs on the GI lining. Spares platelet function as TXA2 production is dependent on COX-1.
What is the clinical use of COX-2 inhibitors (celecoxib)?
Rheumatoid arthritis and osteoarthritis; patients with gastritis or ulcers.
What is the toxicity of COX-2 inhibitors (celecoxib)?
↑ risk of thrombosis. Sulfa allergy.
What is the mechanism of Acetaminophen?
Reversibly inhibits cyclooxygenase, mostly in CNS. Inactivated peripherally.
What is the clinical use of Acetaminophen?
Antipyretic, analgesic, but not anti-inflammatory. Used instead of aspirin to avoid Reye syndrome in children with viral infection.
What is the toxicity of Acetaminophen?
Overdose produces hepatic necrosis; acetaminophen metabolite (NAPQI) depletes glutathione and forms toxic tissue adducts in liver. N-acetylcysteine is antidote—regenerates glutathione.
What are the Bisphosphonates?
Alendronate, other -dronates.
