irreversibly inhibits COX by covalent acetylation; this decreases synthesis of TXA2 and prostaglandins
Decreased synthesis of TXA2 and prostaglandins leads to…
increased bleeding time until new platelets are produced (7 days).
Low dose Aspirin (
decreased platelet aggregation
Intermediate dose (300-2400) Aspirin use
antipyretic and analgesic
High dose (2400-4000) Aspirin use
gastric ulceration and tinnitus
Chronic use of Aspirin leads to…
acute renal failure, interstitial nephritis and upper GI bleeding.
Aspirin can also stimulate respiratory centers leading to…
hyperventilation and respiratory alkalosis.
an NSAID used to close a PDA.
NSAIDs cause gastric ulcer bc…
prostaglandins protect the gastric mucosa.
NSAIDs cause… renal ischemia bc…
PGs vasodilate the afferent arteriole.
a COX-2 inhibitor
COX-2 is found in…
inflammatory cells and vascular endothelium. It mediates inflammation and pain.
COX1 which helps maintain the gastric mucosa. And spares platelet fxn because TXA2 production is dependent on COX1.
Use of Celecoxib
RA and osteoarthritis; pts with gastritis or ulcers
Toxicity of Celecoxib
-increased risk of thrombosis -sulfa allergy
reversibly inhibits COX, mostly in CNS; inactivated peripherally
Use of acetaminophne
antipyretic, analgesic, but not anti-inflammatory; use instead of aspirin to avoid Reye
Toxicity of Acetaminophen
hepatic necrosis - a metabolite (NAPQI) depletes glutathione and forms toxci tissue adducts in liver
Antidote to Acetaminophen induced Hepatotoxicity is…
N-acetylcysteine - it regenerates glutathione
Bisphosphonates (Aledronate) MOA
pyrophosphate analogs; binds hydroxyapatite in bone, inhibiting osteoclast activity
Use of Bisphosphonates
-osteoporosis -hypercalcemia -Paget disease of bone
Toxcity of Bisphosphonates
-corrosive esophagitis -osteonecrosis of the jaw
Allopurinol acts by…
inhibiting xanthine oxidase, which decreases the conversion of xanthine to uric acid.
Additional use of Allopurinol
in lymphoma and leukemia to prevent tumor lysis-associated urate nephropathy
Chronic gout drugs
-Allopurinol -Febuxostat -Probenecid
inhibits xanthine oxidase
inhibits reabsorption of uric acid in the PCT
Acute gout drugs
-NSAIDs (naproxen, indomethacin) -Glucocorticoids -Colchicine -TNF-alpha inhibitors (Etanercept, Infliximab, Adalimumab)
Colchicine acts by…
binding and stabilizing tubulin to inhibit microtuble polymerization, impairing leukocyte chemotaxis and degrunlation
Etanercept is a…
fusion protein (TNF-alpha inhibitor) used in RA, psoriasis, ankylosing spodylits and gout.
Infliximab/Adalimumab is an…
anti-TNFalpha monoclonal antibody used for IBD, RA, ankylosing spondylitis, psoriasis and gout