Chapter 74 - NSAIDs and Acetaminophen Flashcards
How do cyclooxygenase inhibitors work?
inhibit COX, the enzyme that converts arachidonic acid into prostanoids
What does COX regulate?
-stomach: promote PGE2 and PGI2 synthesis that protect mucosa
-promote inflammation and sensitize receptors to pain
-stimulate platelet aggregation
-causes vasodilation via prostacyclin
-vasodilation in kidneys
-mediates fever and contributes to pain perception
-promotes uterine contractions
What is the benefit of inhibiting COX-1?
protect against MI and stroke
Drugs that inhibit COX-1 can cause:
-gastric ulcers
-bleeding
-renal impairment
What are the beneficial effects of COX-2 inhibition?
-suppress inflammation
-alleviate pain and fever
-protect against colorectal cancer
What are things that drugs that inhibit COX-2 can cause?
-renal impairment
-promotion of MI and stroke
What are COX inhibitors used for?
-suppressing inflammation
-pain relief
-fever reduction
NSAIDs are a class of __________
COX inhibitors
What are some NSAIDs?
-aspirin (ASA)
-celecoxib
-ibuprofen (advil)
-naproxen
-diclofenac
-ketoprofen
-flurbiprofen
-indomethacin
-ketorolac
-menfenamic acid
What are the classes of COX inhibitors?
-anti-inflammatory - NSAIDs
-not anti-inflammatory - acetaminophen (tylenol)
1st Gen NSAIDs inhibit COX ___
1 and 2
What are 1st gen NSAIDs used to treat?
-inflammatory disorders
-pain
-fever
How does ASA act?
non-selectively inhibits COX
Does ASA pass membranes?
yes all including fetal tissue and CNS
What are the uses of ASA?
-analgesic
-antipyretic
-anti inflammatory
-suppresses platelet aggregation
-cancer prevention
What are the adverse effects of ASA?
-GI effects
-bleeding
-renal impairment
-tinnitus
-sweating
-headache
-dizziness
-pregnancy - anemia, hemorrhage, prolong labour
-hypersensitivity
What does ASA interact with?
-anticoagulants
-glucocorticoids
-alcohol
-ibuprofen
-ACEIs
-ARBs
ASAs should not be used in people with…
-bleeding disorders
-peptic ulcer disease
How are non-ASA 1st gen NSAIDs different:
-fewer Gi, renal, hemorrhagic effects
-have reversible inhibition
-don’t protect against MI and strok
What are non-ASA 1st gen NSAIDs used for?
-rheumatoid arthritis
-osteoarthritis
-pain conditions
What kind of drug is ibuprofen?
1st gen NSAID
How does ibuprofen act?
COX inhibition and antiinflammatory, analgesic, antipyretic actions
What is ibuprofen used for?
-fever
-mild to moderate pain
-arthritis
What are the adverse effects of ibuprofen?
-GI upset
-risk of GI bleed
-confusion in elderly
-allergic rxn
-fluid retention
What is a safety risk for 1st gen NSAIDs?
-risk of GI bleeding: esp with hx of ulcer, multiple NSAID use, anticoagulant, SSRI, steroid, > 60 yoa, hx of heart disease
How do 2nd gen NSAIDs compare?
-just as effective
-lower risk of GI side effects
-can impair renal function
-may cause HTN and edema
-increased risk of MI and stroke
-work mainly on COX 2
What drug class is Celecoxib?
a 2nd gen COX 2 inhibitor
Why is Celecoxib the last choice drug for pain?
CV effects
What is celecoxib used for?
-osteoarthritis
-rheumatoid arthritis
-acute pain
What are the adverse effects of celecoxib?
-dyspepsia
-abdominal pain
-sulfa allergy
-CV events
What is acetaminophen (tylenol) used for?
-analgesic
-antipyretic
-no anti inflammatory or antirheumatic action
-not associated with Reye’s syndrome
How does acetaminophen act?
inhibits prostaglandin synthesis in CNS (not periphery)
What does acetaminophen interact with?
ALCOHOL and warfarin
How is acetaminophen metabolized?
-major pathway is conjugation to nontoxic metabolites
-minor pathway via CYP450 to toxic metabolite then to non-toxic metabolite via glutathione
What are the adverse effects of acetaminophen?
-few at normal doses***
-Stevens-Johnson syndrome
-Toxic epidermal necrolysis
-hepatotoxicity (OD or liver failure)
What are the signs and symptoms of hepatic necrosis?
-N&V
-diarrhea
-sweating
-abdominal pain
What is the treatment for acetaminophen OD?
acetylcysteine via IV or oral - converts toxic metabolits to non-toxic form
