NSAIDS Flashcards
What are the properties of NSAIDs?
Analgesic, Anti-inflammatory, Anti-pyretic
Used to treat pain and inflammation, surgical procedures, inflammatory diseases, osteoarthritis, rheumatoid arthritis, migraine, dysmenorrhea, myalgia, and dental pain.
From what natural source were NSAIDs originally derived?
Bark of the willow tree, Salix alba
These plants contain derivatives of salicylic acid and were used to treat pain and fever.
When were the first alkaloids of NSAIDs chemically synthesized?
1860 with commercial production by 1874
Claims of being able to ‘cure’ rheumatic disorders first published in 1876.
What is the mechanism of action of NSAIDs?
Inhibition of the enzyme cyclo-oxygenase (COX)
This prevents the synthesis of prostaglandins.
What are the two isoforms of COX identified in the late 1980s and early 1990s?
COX-1 and COX-2
COX-2 is induced by cellular cytokines in localized areas of injury.
What is the primary role of COX-1?
Responsible for maintaining homeostasis
Expressed in low levels in many tissues including lung, liver, spleen, kidney, and stomach.
What is the primary effect of conventional NSAIDs on COX-1 and COX-2?
Non-specific inhibitors of both isoforms
This provides analgesia and anti-inflammatory action but affects platelet function and gastric mucosa protection.
What distinguishes newer COX-2 inhibitors from conventional NSAIDs?
They spare the COX-1 isoform
This is thought to provide a more favorable side effect profile.
What is nociception?
Detection of extremes of temperature, painful mechanical stimuli, and noxious chemical stimuli by primary afferent neurons
These neurons terminate in the dorsal horn of the spinal cord.
What triggers the production of prostaglandins?
Inflammatory process via COX
Prostaglandins increase the sensitivity of nociceptive neurons to various stimuli.
What happens to arachidonate in the inflammatory response?
It is oxidized by COX to PGG2, then to PGH2
Prostaglandins and thromboxanes are produced from PGH2.
List the tissues where COX-1 is distributed.
- GI tract
- Platelet
- Kidney
- Most other tissues
COX-1 plays a role in homeostatic functions.
List the locations where COX-2 is distributed.
- Inflammatory cells
- Female reproductive tract
- Brain
- Kidney
- Cancer cells
COX-2 is induced by cytokines such as interleukin-1.
What are competitive, reversible inhibitors of NSAIDs?
Ibuprofen
Other types include time-dependent inhibitors and mixed kinetic inhibitors.
What type of inhibitor is aspirin classified as?
Irreversible inhibitor
Aspirin permanently inhibits COX activity.
What is the primary route of excretion for NSAIDs?
Renal
Metabolism varies greatly among different NSAIDs.
What are some common COX-2 inhibitors?
- Celecoxib (Celebrex)
- Rofecoxib (Vioxx)
- Valdecoxib (Bextra)
These differ in physical properties and have limited aqueous solubility.
What are the risks associated with NSAID use?
- Increased bleeding risks
- Renal injury
- Cardiovascular effects
COX-2 inhibitors have less interaction with anticoagulants but still carry risks.
What is the maximum dose of ketorolac for patients under 65 years of age?
120 mg/24 hours
Ketorolac use should be limited to 5 days due to risks of GI ulceration and bleeding.
What is the analgesic dose of aspirin?
3 grams per day
Cardioprotective doses are much lower (81-325 mg per day).
What is the contraindication for acetaminophen in terms of dosage?
No more than 4 grams per day
This is to prevent hepatotoxicity associated with glutathione depletion.
What is the route of administration for IV acetaminophen (Ofirmev)?
1000 mg given as a 15 minute infusion
This is one of the newer agents in pain management.
What type of pain is contraindicated for the use of ibuprofen IV (Caldolor)?
Peri-operative pain in the setting of coronary artery bypass graft surgery
Similar contraindications apply to diclofenac IV (Dyloject).
What should be monitored in patients taking NSAIDs?
History of hypersensitivity, bleeding complications, GI disease, renal and hepatic impairment
Special caution should be taken for elderly patients and those on multiple medications.
