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35 Cards in this Set
- Front
- Back
NSAIDS: Mechanisms of therapeutic action
1) Antiinflammatory |
1) Inhibits synthesis of PGs which leads to increased blood flow, permeability, and WBC recruitment (COX 2 most important here). NSAIDS reduce acute inflammation via COX but reduction of chronic inflammation not completely explained
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NSAIDS: Mechanisms of therapeutic action
2) Antipyretic |
2) Reduce production of PGE 2 which acts in preoptic hypothalamus to increase body temperature. Individuals without fever are not affected by NSAIDS
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NSAIDS: Mechanisms of therapeutic action
3) Analgesia |
3) Inhibit production of PG's which both sensitize pain receptors withing PNS as well as modulating perception of pain within the CNS. Mostly effective on low to moderate pain of integument structures. Not good for visceral pain.
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Aspirin: Low dose for thrombosis prevention
1) Mechanism of action |
1) Irreversible COX inhibitor. COX 1 - inhibition --> TXA decrease (TXA is potent platelet aggregator released by platelets) and COX -2 --> PG synthesis inhibitor (potent antiplatelet aggregator released by endothelial cells.) Endothelial cells can make new protein while platelets cannot, so --> increased ratio of PG: TXA --> prolonged anti platelet aggregation effect
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Aspirin: Low dose for thrombosis prevention
2) Recommended dosing? Why? 3) What to take for pain? Why? |
2) Low dose selectively inhibits COX-1 more than COX-2 --> greater PG:TXA ratio
3) Many other NSAIDs, like ibuprofin interfere with aspirins access to COX-1. So some recommendations are: acetaminophen, or coxib (which does not act at COX-1) -increase aspirin to antiinflammatory dose -take aspirin 2hrs before NSAID but 6-8 hrs after previous NSAID b/c while aspirin is irreversible other NSAIDs are reversible |
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NSAIDS: dysmenorrhea
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PG --> uterine muscle contraction. Overproduction in uterus can --> bad cramping. ibufrofin, naproxen and NSAIDs other than aspiring are commonly used to treat pain
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NSAIDs: Bartter's Syndrome
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From overproduction of renal PGs. All but aspirin work
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NSAIDs: Patent ductus arteriosis
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PGs keep ductus open. NSAIDs are sometimes administered to neonates to close ductus. Conversely near term mothers must be careful about NSAID use.
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NSAID: Acute Gouty Arthritis
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can be used to treat gouty attacks, mechanism unclear
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NSAIDs: Familial Adenomatous Polypsis (FAP) and colorectal cancer
1) Hypotheses? Cox involvement? Other mediators? |
NSAID use has been found to decrease colon cancer especially in pts with FAP. They are found to decreased polyp formation. Mechanism: COX-2 inhibition b/c COX-2 is often induced in neoplastic tissue.
2) Regulation of gene expression outside COX inhibition: Found that PPARd (a member of ligand dependent activators of transcription) receptor expression is depressed in cells expressing APC (tumor suppressor). Sulindac was found to suppress PPAR via route other than COX inhibition |
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NSAIDs: Gastric lesions
1) Mechanisms of harm? 2) Where? |
1) a) direct irritation of mucosa, especially aspirin b/c most are acidic
b) Inhibition of PGI2 and PGE2 --> decreased EP3 activation. EP3 typically reduces gastric acid secretion c) mucus production decreased -bicarbonate production decreased -mucosal proliferation decreased -there is a loss of maintenance of normal endothelial integrity which normally participates in cytoprotection and HCO3 production 2) Throughout GI |
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Misoprostal
1) What is it? 2) Function? Mechanism 3) Down falls |
1) PGE1 analog
2) Reduces NSAID induced duodenal and gastric ulcers 3) Causes diarrhea in 30% patients |
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Strategies to minimize NSAID GI effects
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-use acetominophen instead
-use of COX-2 selective NSAIDs -substitution of salsalid for other salicylates -prophylaxis of ulcers with proton pump inhibitors -Misoprostol or high dose H2 blockers (misoprostol are more effective than H2 blockers) |
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NSAIDs: Renal complications
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Patients with decreased renal function should not be given NSAIDs. Although PGs normally play small role in blood flow to kidney, in many clinical settings PGs are required to maintain sufficient blood flow to kidney. (via angiotensin, to increase SNS, to NE, to AVP, to PG up). Can lead to renal failure
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NSAIDs: Common indicators of NSAID induces renal failure (sxs)
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-oliguria
-hyperkalemia out of proportion to renal failure -low fractional excretion of sodium |
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Aspirin sensitivity
1) In who? 2) Sxs 3) Sequelae? |
1) 8-25% middle aged pts. with asthma, nasal polyps, or chronic urticaria
2) runny nose, bronchial asthma, hypotension, and shock (death) 3) x-reactivity of NSAIDs |
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NSAIDs: Bronchoconstriction
1) Who? 2) Mechanisms? |
1) 10% asthmatics
2)a) PGE2 loss, via COX inhibition. PGE2 maintains dilator substances in bloodstream. b) Substrate switching of 5-lipooxygenase to production of LTC and D4 --> bronchoconstriction |
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NSAIDs: Prolonged bleeding time
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Inhibit platelet aggregation so typically advised against for pts undergoing surgery. However, found to reduce MI, thrombosis, stroke, renal failure, and bowel infarction post surgery.
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NSAIDs: Prolongation of gestation
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PGs E and F are uterotropic, so inhibition --> failure to deliver
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Aspirin and salicylates: NFkB hypothesis
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-Evidence supports idea that these drugs may inhibit IkB kinase activation that normally would phosphorylate inhibitor of NFkB, IkB, allow for NFkBs activation
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Salsalate
1) Drug class 2) Mechanism of action 3) Toxicity |
1) Salicylic acid
2) Reversible inhibitor of COX 3) Less GI toxicity than aspirin |
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Reye's Syndrome
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Do not use aspirin in children because can lead to fatty deposition in liver and encephalopathy. May be due to viral infection
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Acetominophen
1) Drug class 2) Sites of action/effects 3) Uses 4) Toxicity |
1) NSAID
2) Weak Cox inhibition --> other action, mostly antipyretic and analgesic, not antiinflammatory 3) When aspiring counterindicated (peptic ulcer, or prolonged bleeding bad) 4) Metabolite depletes glutathione and then binds liver enzymes --> inactivation and hepatic toxity, txt with n-acetylcytein b/c repletes glutathione levels |
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n-acetylcystein
1) What is it used for |
1) Acetominophen hepatotoxicity b/c repletes glutathione levels
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Celecoxib
1) Drug class 2) Mechanism 3) Possible problems |
1) NSAID
2) Selective Cox 2 inhibitor 3) Since TXA production not inhibited may lead to thrombosis. |
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Diflusinol
1) Drug class 2) Mechanism/use |
1)NSAID
2) reversible nonselective cox inhibitor, used as analgesic |
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ibuproben
1) Uses 2) Similar spectrum to what other drug |
1) RA, osteoarthritis, analgesia, temper, patent ductus, dysmenorrhea
2) naproxen |
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naproxen
1) Uses 2) similar use spectrum to what other drug |
1) RA, osteoarthritis, analgesia, temper, patent ductus, dysmenorrhea
2) ibuprofen |
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Indomethacin
1) Drug class 2) Uses 3) Toxicity |
Indocin
1) non-selective Cox inhibitor 2) RA, acute gouty arthritis, ankylosing spondylitis, patent ductus arteriosis, prevent preterm labor 3) CNS-Hd ache, dizziness, confusion, depression, psychosis, hallucinations GI effects and platelet effects |
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Ketorolac
1)Mechanism 2)Use 3)Administration 4) alternative to what 5) Toxicity |
1) Non-selective Cox inhibition
2) Analgesic only, post op 3) IV or IM, or orally <5days 4) Meperidine, and morphine 5) No resp depression, tolerance or withdrawal sxs. some GI and renal toxicity |
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Mesalamine
1) Drug class 2) Administration 3) F, use |
1) NSAID, salicylate
2) Oral 3) Not absorbed from GI, used for IBS |
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Rofecoxib
1) Drug class 2) Mechanism 3) Use |
Vioxx
1) NSAID 2) Selective Cox 2 inhibitor 3) No longer on market, b/c very selective for Cox 2 and led to thrombotic events |
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Sodium salicylate
1) Drug class 2) Mechanism |
1) NSAID
2) Reversible Cox inhibition, also evidence for inhibition of NFkB via inhibition of IkB kinase |
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Sulfasalazine
1) Drug class 2) Use |
1) NSAID, salicylate
2) IBS b/c not absorbed from gut but inhibits Cox |
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Sulindac
1) Drug class 2) Mechanism 3) Use 4) Met, excretion, t1/2 5) Toxicity |
1) NSAID
2) COX inhibition plus inhibition of PPARd 3) osteoarthritis, RA, acute gouty arthritis, ankylosing spondylitis 4) Prodrug, eneterohepatic circulation --> 12-16 hr duration 5) Little GI toxicity, but otherwise the same as other NSAIDs |