Non-Opioids Flashcards
Nonsteroidal anti inflammatory drugs (NSAIDs) are ___
cyclooxygenase COX inhibitors
cox inhibitors (aka NSAIDs)
prevent binding of arachidonic acid to cox enzyme and inhibit production of prostaglandins
where do NSAIDs act on the pain pathway
1st order neuron, do not act centrally
cox 1 isoenzyme
constitutively expressed (always on), maintenance of renal function, mucosal protection of GI tract, production of thromboxane A2
What does thromboxane A2 do?
released by plts. to attract more plts. (like axe body spray ;-) )
cox 2 isoenzyme
induced by inflammatory mediators, mediation of pain, inflammation, fever
toradol (ketorolac)
15 mg IV or IM q6h, don’t give with impaired renal function
celebrex (celecoxib)
cox 2 inhibitor, used in ortho surgery usually part of multimodal protocols, have less GI toxicity, increased CV risk
celebrex (celecoxib) dose
400 mg PO preop
200 mg BID x 5 days postop
PK of NSAIDs
WEAK ACIDS low Vd (.1-.3 L/kg) - good thing rapid GI absorption increased protein binding liver metabolizes most eliminated primarily by renal and biliary excretion
Side effects of NSAIDs
platelet function primarily thru cox 1
GI complications range- mild ulcer to perforation and bleeding (at risk: elderly, helicobacter pylori infection, hx of ulcer, concominant use of ASA, anticoags, or corticosteroids)
CV complications- increased risk of MI, HF, and HTN
Renal - changes to function including sodium excretion, tubular function, interstitial nephritis (at risk: CHF, already renal disease, hx diabetes, HTN, atherosclerosis, hypoalbuminemia)
Liver - liver failure, elevated transaminase levels
Risk of anaphylaxis with NSAIDS
allergic rhinitis + nasal polyps + asthma
NSAIDs drug interactions
increased bleeding with antiplatelet agents
ASA
rapidly metabolized by plasma esterases, erythrocytes and liver
uses: analgesic, irreversible platelet. inhibitor
ASA overdose
related to drug acidity and prostaglandin inhibition
symptoms: N/V, abd pain, hearing impairment, CNS depression
can lead to met. acidosis, renal failure
urine alkalinization increases salicylate elimination
Acetaminophen (tylenol)
analgesic and antipyretic- does have central effect thru activation of serotonergic pathways and antagonism of NMDA, substance p and nitric oxide pathways
no antiinflammatory actions
acetaminophen dosing
325-650 mg q4-6h (don’t exceed 4000mg/24hr or 2000mg in alcoholics)
ofirmev (IV) 1000 mg q6h
PK of acetaminophen
metabolized in liver
causes liver failure d/t damage from N-acetyl-p-benzoquinoneimine depleting glutathione
remove by use of charcoal and replace glutathione (acetylcysteine)
gabapentin
acts on voltage gated Ca2+ channels inhibiting glutamate
can be used as anticonvulsant
used in multimodal pain regimens
absorbed in duodenum and minimal protein binding and excreted with minimal metabolism
gabapentin dose and side effects
preop: 1200 mg 1-2hr before surgery
600 mg q8h x 14 days
side effects: sedation, dizziness, headache, visual disturbances
lidocaine
amide, weak base, pKa slightly above pH
MOA not certain (may involve Na+ channels, and block priming of polymorphonuclear granulocytes)
Lidocaine PK and dosing
first pass extraction in lungs, metabolized in liver (prolonged under GA)
dose: 1.5 mg/kg bolus, 1-2 mg/kg/hr infusion
not beneficial in all surgeries
magnesium sulfate
analgesic properties related to: Regulation of calcium influx into cell, antagonism of NMDA receptors in CNS
dose: 30-50 mg/kg bolus, 10 mg/kg/h infusion
side effects: bradycardia, hypotension
prolongs muscle relaxants, tends to sedate
capsaicin
transient receptor potential vanilloid (TRPV1) channel agonist (activation releases high intensity impulses and release of substance p)
applied topically for neuralgia
OTC: .025, .075, .25% creams/patch
ketamine
NMDA antagonist modulates central sensitization
base, less lipophilic than propofol, act centrally
dose: .5-1 mg/kg before incision
side effects: psychomimetic, dizziness, blurred vision, N/V
dexmedetomindine
selective alpha 2 agonist (blunts central sympathetic response)
dose: .5-2 mcg/kg
side effects: hypotension, bradycardia
peripherally acting opioids can reduce
plasma extravasation, vasodilation, proinflammatory neuropeptides, immune mediators and tissue destruction
