What does the Lipoxygenase pathway yield?
What is LTB4?
Neutrophil chemotatic agent
What do LTC4, D4 & E4 function in?
Bronchoconstriction, vasoconstriction, contraction of sm & inc vascular permeability
What do PGI2 do?
Inhibits platelet aggregation & promotes vasodilation
What is the MOA of aspirin?
Irreversibly inhibits COX-1 & COX-2 by acetylation, which dec synthesis of both thromboxane A2 (TXA2) & PG. Inc bleeding time. Nof affect on PT, PTT. Type of NSAID
Clinical use of aspirin
Low dose: (
Indermediate dose (300-2400 mg/day) antipyretic & analgesic
High dose (2400-4000 mg/day) anti-inflam
What can aspirin toxicity cause?
Tinnitus (CN VIII)
Chronic use can l/t acute renal failure, intersitial nephritis, & upper GI bleeding
Risk of Reye's synd in children tx w/ apsirin for viral infection
Stim resp centers, causing hyperventilation & resp alkalosis
What are examples of NSAIDs?
What is the MOA of NSAIDs?
Reversibly inhibits COX 1 & 2 & blocks PG synthesis
What are the clinical uses of NSAIDs?
Indomethacin is used to close a PDA
What can NSAID toxicity cause?
Gastric ulcer (PG's protect gastric mucosa)
Renal ischemia (PG vasodilate afferent arteriole)
What is the MOA of COX-2 inhibitors (celecoxib)?
Reversibly inhibit specifically the COX isoform 2, which is found in inflam cells & vascular endothelium & mediates inflam & pain. Spares COX-1 & TXA2
What is the clinical use of COX-2 inhibitors?
Rheumatoid arthritis & osteoarthritis; pts w/ gastritis or ulcers
What can COX-2 inhibitor toxicity cause?
Inc risk of thrombosis; sulfa allergy
What is the MOA of Acetaminophen?
Reversibly inhibits COX, mostly in CNS. Inactivated peripherally
What are the clinical uses of Acetaminophen?
Analgesic but not anti-inflam
Used instead of aspirin to avoid Reye's synd in children w/ viral infection
What can Acetaminophen toxicity cause?
Overdose produces hepatic necrosis; acetaminophen metabolite depletes gluthione & forms toxic tissue adducts in liver. N-acetylcysteine is antidote-regenerates glutathione.
What is an example of a bisophosphonates?
Alendronate, other -dronates
What is the MOA of Bisphosphates?
Pyrophosphate analogs; bind hydroxyapatite in bone, inhibiting osteoclast activity
What are the clinical uses of Bisphosphonates?
Paget's dz of bone
What can Bisphosphonate toxicity cause?
Corrosive esophagitis, osteonecrosis of the jaw
What are the chronic gout drugs?
What are the Acute gout drugs?
NSAIDs (naproxen, indomethacin)
Glucocorticoids (oral or intraarticular)
What is the MOA of Allopurinol?
Inhibits xanthine oxidase, dec conversation of xanthine to uric acid
What is Allopurinol used for?
Lymphoma & leukemia to prevent tumor lysis- assoc w/ urate nephropathy
What can Allopurinol inc conc of?
Azathioprine & 6-MP (both normally metabolized by xanthine oxidase)
What can you not give Allopurinol w/?
Don't give w/ salicylates; all but the highest doses depress uric acid clearance. Even high doses (5-6g/day) have only minor uriosuric activity
What is the MOA of Febuxostat?
Inhibits xanthine oxidase
What is the MOA of Probenecid?
Inhibits reabsorption of uric acid in PCT (also inhibits sec of penecillin)
What is the MOA of Colchine?
Binds & stabilizes tubulin to inhibit polymerization, impairing leukocyte chemotaxis & degranulation
What are the TNF-alpha inhibitors?
What can all TNF-alpha inhibitors cause?
Predispose to infection including reactivation of latent TB since TNF blockade prevents activation of macro & destruction of phagocytosed microbes
What is the MOA of Etanercept?
Fusion protein (recptor for TNF-alpha + IgG1 Fc), produced by recombiant DNA
What are the clinical uses of Etanercept?
What is the MOA of Infliximab & Adalimumab?
Anti-TNF-alpha monoclonal Ab
What are the clinical uses of Infliximab & adalimumab?
How do you treat Osteoporosis?
What is osteoporosis prophylaxis?
adequate Ca & Vit D throughout life
What drugs are contraindicated in osteoporosis?