Musculoskeletal, Skin, and CT Flashcards
Aspirin (acetylsalicylic acid) / ASA
Irreversible inhibitor of cyclooxygenase (COX1 AND COX2) via covalent acetylation
Decreases synthesis of both thromboxane A2 (TXA2) and prostaglandins
Type of NSAID
How does aspirin irreversibly inhibit COX 1 and 2?
Covalent acetylation
How does aspirin affect bleeding time, PT, and PTT?
Increased bleeding time until new platelets are produced (7 days)
No effect on PT, PTT
Clinical use for low, intermediate, and high doses of aspirin
Low dose (
Aspirin toxicity
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 for viral infection
Stimulates respiratory centers = hyperventilation and respiratory alkalosis
What syndrome can children get if given aspirin? What is one case in which you should give aspirin to children?
Reye syndrome (fulminant hepatic necrosis and encephalopathy)
Kawasaki syndrome (IVIG and aspirin)
NSAIDs
Ibuprofen Naproxen Indomethacin Ketorolac Diclofenac
Ibuprofen, Naproxen, Indomethacin, Ketorolac, Diclofenac
Mechanism?
Uses?
Reversibly inhibit COX1 and COX2 = block prostaglandin synthesis
Uses = antipyretic, analgesic, anti-inflammatory
Indomethacin used to close a PDA
NSAIDs
Toxicity?
Interstitial NEPHRITIS Gastric ulcer (PGs protect gastric mucosa) Renal ischemia (PGs vasodilate afferent arteriole)
Which NSAID can be used to close a PDA?
Indomethacin
Prostaglandin E2 used to keep open
COX2 inhibitor
Mechanism?
Celecoxib
Reversibly inhibit specifically COX 2 isoform = found in inflammatory cells and vascular endothelium; mediates inflammation and pain
Spares COX 1 = helps maintain gastric mucosa
Benefit = does not have corrosive effects of other NSAIDs on the GI lining; spares platelet function as TXA2 production is dependent on COX1
Celecoxib
Uses?
Toxicity?
Selective COX2 inhibitor
Uses = rheumatoid arthritis and osteoarthritis; patients with gastritis or ulcers
Toxicity = increased risk of thrombosis; sulfa allergy
Acetaminophen / APAP
Mechanism?
Uses?
Reversibly inhibits COX, mostly in CNS
Inactivated peripherally
Antipyretic, analgesic, NOT anti-inflammatory
Used instead of ASA to avoid Reye syndrome in children with viral infection
Does acetaminophen have anti-inflammatory effects?
NO
Acetaminophen toxicity?
LIVER Overdose = hepatic necrosis Acetaminophen metabolite (NAPQI) depletes glutathione and forms toxic tissue adducts in liver
Antidote = N-acetylcysteine (regenerates glutathione)
Antidote for acetaminophen overdose?
N-acetylcysteine
Regenerates glutathione
Bisphosphonates
Mechansim?
Alendronate
“-dronate”
Pyrophosphate analogs
Bind hydroxyapatite in bone, inhibiting osteoclast activity
Alendronate
Uses?
Toxicity?
Bisphosphonate
Uses = osteoporosis, hypercalcemia, Paget disease of bone
Toxicity = corrosive esophagitis (take with water and remain upright for 30 min); osteonecrosis of jaw
Chronic gout drugs (preventive)
3; “AFP”
Allopurinol
Febuxostat
Probenecid
Allopurinol - gout prevention
Mechanism?
Uses?
Xanthine oxidase inhibitor
Decreases conversion of xanthine to uric acid
Used in lymphoma/leukemia to prevent tumor lysis-associated urate nephropathy
Increases concentrations of azathioprine and 6-MP (both normally metabolized by xanthine oxidase)
Should salicylates be used in the long term/preventative treatment of gout?
NO = all but highest doses depress uric acid clearance
Even high doses (5-6g/day) have only minor uricosuric activity
Febuxostat
Gout prevention
Inhibits xanthine oxidase
Probenecid
Gout prevention
Inhibits reabsorption of uric acid in PCT (also inhibits secretion of penicillin)
High dose salicylates have similar effect but only MINOR (don’t use for prevention)
Acute gout drugs (3)
NSAIDs = naproxen, indomethacin
Glucocorticoids = oral or intraarticular
Colchicine
Colchicine
Mechanism?
Side effects?
Binds and stabilizes tubulin to inhibit microtubules polymerization = impairs leukocyte chemotaxis and degranulation
Acute and prophylactic value
GI side effects
Which gout drug has both acute and prophylactic value?
Colchicine
Binds and stabilizes tubulin to inhibit microtubules polymerization = impairs leukocyte chemotaxis and degranulation
List the breakdown pathway from purines to uric acid
Diet/nucleic acids –> purines –> hypoxanthine –[XO]–> xanthine –[XO]–> plasma uric acid
Uric acid then either excreted in urine or deposited as urate crystals in joints (gout)
TNF-a inhibitors (3; “AEI”)
Etanercept
Inflixamab
Adalimumab
All predispose to infection, including reactivation of latent TB = TNF blockade prevents activation of macrophages and destruction of phagocytosed microbes
How do TNF-a inhibitors predispose to infection? What type of infection is commonly reactivated?
TNF blockade prevents activation of macrophages and destruction of phagocytosed microbes
Reactivation of latent TB can be seen
Etanercept
Mechanism?
Uses?
Fusion protein (receptor for TNF-a + IgG1 Fc) = produced by recombinant DNA "EtanerCEPT is a TNF decoy reCEPTor"
Uses = RA, psoriasis, ankylosing spondylitis
Infliximab, Adalimumab
Mechanism?
Uses?
Anti-TNF-a monoclonal antibody
Uses = IBD, RA, ankylosing spondylitis, psoriasis
