NSAIDs Flashcards
What is the MOA of NSAIDs?
cyclooxygenase (COX) inhibitors
prevent binding of arachidonic acid to cox enzyme
inhibits the biosynthesis of prostaglandins (pain
causing)
What are some common effects of NSAIDs?
common analgesic, anti-inflammatory, and antipyretic effects
Which drugs most likely work on 1st order neuron?
NSAIDs
How do NSAIDs affect COX inhibitors?
they are either non-selective or Cox-2 selective (viox)
Cox 1 isoenzymes are involved in physiologic functions
maintenance of renal function
mucosal protection of the GI tract (more prone to developing ulcers)
production of thromboxane A2 (released by platelets to attract other platelets)
Cox 2 isoenzymes are
expression induced by inflammatory mediators
role in: mediation of pain, inflammation, & fever
Cox 2 isoenzymes are things we
want to block
What is a drug we can give that is Cox 2 selective?
celebrix but this comes with its own cardiac issues
non-selective nsaids are rarely used in the periop setting b/c of
GI toxicity and platelet dysfunction
What is a consideration of NSAIDs with bone healing?
bone healing is delayed with NSAIDs but safe in the setting of primary bone healing
What is the dose of toradol (ketorolac) and what is a consideration to not giving it?
15 mg IV or IM Q6h
do not give in patients with reduced renal function
What are some considerations with Celebrex?
have less GI toxicity since it is a Cox 2 selective inhibitor but does have cardiovascular risks
What is the dosing of celebrex and when might we give it?
part of ERAS surgery
400 mg PO preop
200 mg BID x 5 days postop
NSAIDs are acids or bases?
weak acids (like propofol and barbiturates)
What kind of distribution to NSAIDs have?
low Vd (.1-.3 L/kg)
Additional important pharmacokinetics of NSAIDs?
plasma half-life is variable
increased protein binding
GI absorption occurs rapidly
How are NSAIDs metabolized and excreted?
liver metabolizes most NSAIDs
eliminated primarily by renal and biliary excretion
How do NSAIDs affect platelet function?
primarily through Cox-1
What are risk factors for increased GI complications?
elderly, hx of previous ulcer, H. pylori infection, concomitant use of aspirin, anticoagulants, or corticosteroids
Aspirin is a derivative of
salicylic acid
How is aspirin metabolizied?
plasma esterases, erythrocytes, and liver
What is aspirin used for?
general analgesic & “irreversible” platelet inhibitor
What is aspirin toxicity related to?
drug acidity and prostaglandin inhibition
What are s/s of aspirin overdose?
N/V, abdominal pain, hearing impairment, CNS depression, higher doses can result in metabolic acidosis, renal failure, CNS changes (agitation, confusion, coma), and hyperventilation with respiratory alkalosis
Urine alkalinization increases salicylate elimination
What is the dose of acetaminophen?
325-650 mg Q4-6h (total not to exceed 4,000 mg/24 hrs, 2000 for chronic alcholocis)
1000 mg Q6 Ofirmev IV
What are indications to give tylenol?
has analgesic and antipyretic properties
What is the mechanism of action of acetaminophen?
central analgesic effect through: activation of serotonergic pathways
antagonism of NMDA, substance P, and nitric oxide pathways
No anti-inflammatory actions
How is tylenol metabolized?
in the liver
leading cause of acute liver failure in US chronic usage <2g not associated with liver damage
Why does liver damage result with tylenol?
active metabolite N-acetyl-p-benzoquinoneimine leads to liver failure by depleting glutathione, a natural antioxidant
How do you treat tylenol OD?
aimed at removing acetaminophen (charcoal) and replacing glutathione (aceylcystein administration)
What is the structure of Gabapentin?
Gabapentin is a structural analogue of gamma-aminobutyric acid (GABA)- it acts on voltage-dependent Ca channels by inhibiting glutamate
What are the uses of gabapentin?
approved as an anticonvulsant medication
demonstrated efficacy in neuropathic pain
used in ERAS protocols- effective in reducing immediate postop pain and opioid consumption
can cause acute resp. depression in PACU
Describe the absorption of Gabapentin?
limited to a small part of the duodenum and can be impaired by antacids
has minimal protein binding and excreted without significant metabolism
What is the dosing of gabapentin?
Preop 1200 mg 1-2 h. before surgery
600 mg Q8 x 14 days
What are the side effects of gabapentin?
sedation, dizziness, HA, and visual disturbances
What is the pH of lidocaine?
slightly above that of physiologic pH, it is a weak base
When is IV lidocaine used?
as part of a multimodal pain management plan to supplement general anesthesia
What is the mechanism of action of lidocaine?
unknown; may involve sodium channels; block priming of polymorphonuclear granulocytes
How is lidocaine metabolized?
undergoes first pass extraction in the lungs (like propofol) and is metabolized in the liver (prolonged in pts under general anesthesia)
What is the dosing of lidocaine?
1.5 mg/kg bolus dose (IBW)
1-2 mg/kg/hour infusion
What surgical procedures are lidocaine indicated for?
reduces pain and speeds up return of bowel function in laparoscopic cases
decreases pain, improves functional outcomes in prostatectomy, thoracic, and major spine cases
What is a concern with lidocaine?
accumulation is a concern but at doses given during ERAS protocols serum levels are well below toxicity
monitoring at risk patients is advised
What is the mechanism of action of magnesium sulfate?
analgesic properties related to: regulation of Ca influx into cells, antagonism of NMDA receptors in CNS
What is the dosing of magnesium sulfate?
30-50 mg/kg bolus
10 mg/kg/h infusion
What are side effects of magnesium sulfate?
bradycardia and hypotension
prolongs muscle relaxant
shows a decrease in opioid consumption and pain
What is the mechanism of action of capsaicin?
transient receptor potential vanilloid (TRPV1) channel agonist
activation releases high-intensity impulses and release substance P (overload and release substance P so there’s nothing else to release)
What is capsacin?
the major pungent ingredient of chili peppers and botanicals
applied topically for neuralgia and neuropathies
What is the dosing for ketamine?
0.5-1 mg/kg prior to surgical incision
What are side effects of ketamine?
psychomimetic (give them versed)
dizziness, blurred vision, n/v
What is the mechanism of action of ketamine?
NMDA antagonist modulates central sensitization
induced by incision and tissue damage
role in preventing opioid-induced hyperalgesia
What is the mechanism of action of dexmedtominidine?
selective alpha-2 agonist
blunts central sympathetic response via acting on the locus cereleus
What is the dosing for dexmedetomindine?
0.5-2 mcg/kg
What are side effects of dexmedetomindine?
Hypotension & bradycardia
Peripherally acting opioids can
reduce plasma extravasation, vasodilation, proinflammatory neuropeptides, immune mediators, and tissue destruction
Peripheral opioids have a role in
arthroplasty and inflammatory bowel disease
