NSAIDs Flashcards
What are the three purposes of NSAIDs?
Anti-inflammatory, Anti-pyretic, and Analgesic
What enzyme is typically present/induced during inflammation?
COX-2
How does Acetylsalicylic Acid effect platelets and endothelium?
Inhibits platelets ability to produce Thromboxane (TXA2) for the lifetime of the platelet since it doesn’t have the ability to produce new protein. Endothelium is inhibited from making PGI2, which is inflammation prostaglandin.
What are unique effects of Aspirin?
Uricosuric Effect, low dose prevents uric acid excretion, high dose increases excretion of uric acid. Not related to prostaglandins.
CNS Effects - tinnitus, depression, confusion
Respiratory acidosis
What is important regarding ASA overdose and dose dependent metabolism?
If enough ASA is taken it can saturate the enzymes metabolizing, which then causes excretion to be Zero Order Kinetics. Half-Life goes from 2-3 hours to 15-30 hours in overdose.
What happens during an NSAID hypersensativity reaction?
Due to COX being inhibited all the extra arachodonic acid shunts to leukotrienes, which cause bronchoconstriction and chemotaxis to the airway. Typically patients have respiratory related symptoms.
How can you remedy the adverse effects of NSAIDs on the stomach lining?
NSAIDs prevent production of protective PGs, so if there are adverse GI effects, Misoprostol can be taken as a supplement protective PGs.
What is a contraindication of giving NSAIDs to a patient regarding kidneys?
If the patient has diseased state kidneys, NSAIDs can decrease blood flow and retain water/sodium, essentially making their symptoms worse.
What patient population do you have to consider renal toxicity?
Elderly and Diseased State individuals.
Can NSAIDs cross the placental barrier, if so what are effects?
Yes. Can cause premature closure of the ductus arteriosis, prolonged gestation/labor, and increased chance of hemorrhage.
How can NSAIDs help with a nonpregnant uterus?
NSAIDs can inhibit PG production, which typically cause contraction during menstruation, and can help with pain.
What are the Propionic derviatives and their benefits?
Ibuprofen and Naproxen, reversible COX inhibitors that are less harsh on the stomach lining. Naproxen has longer half life for longer effects and Ibuprofen is short acting for acute inflammation.
What do you worry about if giving a child aspirin?
Reye’s Syndrome. Developed usually after the child had a viral illness causing encephalopathy and liver degradation. 6-11 year olds.
What is Indomethacin typically used for?
Treatment of Gout. Not used for fever reduction/pain. More common adverse reactions.
What drug is used as an alternative to opoid therapy?
Ketorolac. Should only be used short term less than 5 days.
What NSAID is a prodrug and what does it do?
Nabumetone. More selective for COX-2 compared to COX1 and has minimal adverse side effects.
What NSAID has a long half-life and is used to treat RA and Osteoartritis?
Piroxicam. Long Half-life of 50 hours, but metabolized by CYP2C9, chance for adverse reactions.
How does Sulfsalazine work and what is it used for?
Sulfasalazine works independent of COX. Is converted to active form in the GI tract by resident bacteria and exerts a local anti-inflammatory effect. Used primarily for Acute Ulcerative Colitis.
If not related to COX how does Sulfasalazine work?
Azo-link prevents absorption in GI. Bacteria cleave it into active form preventing production of IL-1, TNFa, and transciption of NFkB. High adverse reaction rate due to Sulfa moiety.
What do you have to be cautious of with Celecoxib?
If the patient has history of GI bleeding, Celebrex will actually increase the chance of GI bleeding. Increased risk of CV events.
Also metabolized by CYP2C9, so can interfere with other drugs.
How does Celecoxib work?
Selective competitve COX-2 Inhibitor
What kind of patients would Acetaminophen be ideal for?
Used for analgesic and fever. Also should be used with patients with kidney disease.
How does Acetaminophen work?
Inhibits COX peroxidase mechanism, but Acetaminophen is NOT Anti-inflammatory. Maybe more selective for brain COX?
What is the major mechanism of metabolism for Acetaminophen?
Glucuronidation and Sulfation
How is Acetaminophen become toxic?
The minor metabolism pathway is by Cytchromes (CYP2E1), which creates NAPQI highly reactive metabolite, that causes local damage in the liver. NAPQI must be broken down by glutathione to be excreted and neutralized.
