NonOpioid Analgesia Flashcards
Describe the major mechanism of action of NSAIDS
Inhibit the biosynthesis of prostaglandins by preventing the substrate arachidonic acid from binding to the cyclooxygenase enzyme active site.
According to Dr. C’s PowerPoint, which nonopioids are centrally acting?
Clonidine
Dex
Ketamine
Magnesium
What forms does the COX enzyme exist in?
COX-1 isoenzyme
COX-2 isoenzyme
Name three functions of COX-1 Isoenzyme?
-Maintenance of normal renal function in the kidneys
-Mucosal protection in the GI tract
-Production of proaggregatory thromboxane A2 in the platelets
What is the only COX-2 selective inhibitor available?
Celecoxib (Celebrex)
COX-2 expression can be induced by? Leading to?
Inflammatory mediators in many tissues, therefore, plays a role in the mediation of pain, inflammation, and fever.
What are the benefits of coxibs (cox-2 selective inhibitors)?
Improved quality of analgesia
Reduced incidence of GI side effects
No platelet inhibition
All NSAIDs are weakly basic or weakly acidic?
Weakly acidic
How long does GI absorption of NSAIDS take
within 15-30 minutes
What organ metabolizes most NSAIDs?
Liver
How are NSAIDs excreted?
into urine or bile
How does reduced renal function affect NSAIDs?
Prolongs half-life, the dose should be lowered proportionally in patients with impaired kidney function
Moderate to severe liver disease impairs NSAID metabolism, increasing the potential for?
Toxicity
Is the volume of distribution of NSAIDs high or low?
Low. 0.1-0.3L/kg, suggesting minimal tissue binding.
Why does Celecoxib (Celebrex) not impact platelet function?
Celecoxib is a COX-2 Selective inhibitor. There is no COX-2 isoenzyme in platelets.
What patient population is contraindicated to give nonselective NSAIDs to?
GI Gastric Sleeve, Roux-N-Y surgeries due to the risk of ulcers, perforation, and bleeding.
It’s generally recommended that patients with GI risk factors should be treated with COX-2–selective agents or non-selective NSAIDs with GI protective co-therapy.
Risk factors for NSAID-associated GI complications include:
High NSAID dose, older age, H. Pylori infection, anticoagulants, corticosteroids, concomitant low-dose aspirin use
Why do COX-2 inhibitors have a higher risk of cardiac side effects?
Imbalance Between Prostacyclin (PGI₂) and Thromboxane A₂ (TXA₂). COX-2 inhibits prostacylin, leaving procoag thromboxane a2 predominating.
List some possible cardiac side effects of NSAIDS
hypertension, prothrombotic effect (more likely with coxibs)
List some possible respiratory side effects of NSAIDs
Nasal Polyps, Dyspnea, bronchospasm, and angioedema, may exacerbate asthma
Are hypersensitivities to NSAIDs rare or common? What patient population experiences reactions more?
Rare.
If they occur, they are more common in people with nasal polyps or asthma
More than ____% of NSAIDs are bound to albumin after absorption.
90%!
(Influencing their distribution and drug-drug interaction.)
List 2 possible renal side effects of NSAIDs
Renal insufficiency
Sodium/Fluid Retention
Describe the MOA of Alpha 2 Agonists
Stimulates alpha 2 receptors in brainstem. Reducing catecholamine release therefore a reduction in sympathetic outflow.
What are some adverse reactions associated with alpha 2 agonists
Dex: Bradycardia - common
- Hypotension - common
Clonidine: Dry mouth
-Sedation
-Bradycardia
-Sexual dysfunction
-Withdrawal syndrome and potentially life threatening rebound hypertension
-Prolonged sedation (especially in the elderly)
Describe the MOA of gabapentinoids
reduction of the axon excitability
Gabapentin interacts with cortical neurons at delta subunits of calcium channels
Where do peripheral analgesics act at?
The sensory input level by blocking the impulse to the brain
Why can peripherally administered medications lead to lower systemic levels and fewer adverse systemic effects?
Peripherally administered drugs can potentially optimize drug concentrations at the site of pain origin
Nociceptive, inflammatory, and neuropathic pain depend to some degree on peripheral activation of?
Primary sensory afferent neurons
Name five inflammatory mediators that analgesics try to target
Prostanoids
Bradykinin
Adenosine Triphosphate
Histamine
Serotonin
True or False: Combinations of agents that act via different mechanisms may be particularly useful.
True
NSAIDs have 3 shared properties. What are they?
Analgesia, Anti-Inflammatory, and Antipyretic
What does NSAIDs stand for?
Nonsteroidal anti-inflammatory drugs
Ketorolac (Toradol) is dosed at?
15-30mg IV or IM q6 hours
(some literature, there is no increase in the efficacy of 30mg)
Pediatric dosing of Ketorolac (Toradol)
0.5mg/kg up to 15mg q6 hours
What is the elimination half-life of Ketorolac (Toradol)?
2.5-8.5 hours
What doses are available for Celecoxib (Celebrex)?
100-200mg
What is the elimination half-life of Celecoxib (Celebrex)
11-16 hours
What is the leading cause of acute liver failure in the US?
Acetaminophen
About half are due to unintentional overdoses
How does acetaminophen damage the liver?
Results from one of the acetaminophen metabolites, N-acetyl-p-benzoquinone imine (NAPQI). NAPQI depletes liver antioxidant glutathione and directly damages liver cells.
What is the treatment/antidote to acetaminophen toxicity?
Acetylcysteine. It acts as a precursor for glutathione and can neutralize NAPQI directly.
Activated charcoal - can decrease absorption if administered shortly after ingestion of overdose.
Conventional dosing of acetaminophen is?
325-650mg every 4-6 hours.
The total daily dose of acetaminophen should not exceed?
Most now say 3,000mg daily. (used to be 4,000)
How is the oral bioavailability of acetaminophen? Poor or Good?
excellent
What drug is included in IV Tylenol (OFIRMEV)?
Mannitol
3,850mgs, almost 4 grams, in each 100mL bottle.
Dosing of IV Tylenol (OFIRMEV) for patients <50kg?
15mg/kg
Which steroids have the most powerful anti-inflammatory characteristics?
Glucocorticoids
What are Mineralcorticoids?
Adrenal cortical steroid hormones that have a greater effect on water and electrolyte imbalance.
The main endogenous hormone is?
Aldosterone
Corticosteroids are a subgroup of compounds known as?
Adrenocorticoids that are naturally secreted from the adrenal gland
How does use of corticosteroids influence opioid use?
There is evidence supporting their use for post-op recovery, minimizing opioid doses and, therefore, side effects
What is the effect of adding dexamethasone to anesthetic blocks?
Has been found to prolong local anesthetic block duration
What is the dosing for Dexamethasone (Decadron) for PONV prophylaxis?
4-8mg
What is the dosing for Dexamethasone (Decadron) for pain management?
0.1-0.2mg/kg
Some cap dose at 10mg to minimize side effects, others cap at 20mg.
How much more potent is Dexamethasone (Decadron) compared to natural human cortisol?
~25-26 more potent
(~6 times more potent than prednisone)
Duration of action of Dexamethasone (Decadron)?
36-54 hours
The half-life of Dexamethasone (Decadron)?
3.5-5 hours
What are a few potential side effects of corticosteroids?
Hyperglycemia
Delayed wound healing
osteoporosis
(remember short term verse long term SEs)
How do systemic local anesthetics, such as Lidocaine, work?
Produces analgesia by suppressing sodium channels in neurons that respond to noxious stimuli, thereby preventing nerve conduction and pain transmission.
What effect does systemic lidocaine have on MAC of volatile anesthetics?
Decrease in MAC
What is the dosing of IV Lidocaine for bolus and continuous infusion for pain management?
Bolus: 100mg or 1-2mg/kg
Infusion: 0.5-2mg/kg/hour
What is the onset of IV Lidocaine?
45-90 seconds
What is the half-life of IV lidocaine?
Initial (Distribution) 7-30 minutes
(why Dr. C says to turn drip off 30 min before end of case)
Terminal (Elimination): 1.5-2 hours
What are the two Gabapentinoids we commonly see?
Gabapentin (Neurontin)
Pregabalin (Lyrica)
Both Gabapentin (Neurontin) and Pregabalin (Lyrica) bind to?
Alpha 2 delta subunits of the voltage-gated calcium channels in the CNS
Gabapentin (Neurontin) is an effective analgesic particularly for what kind of pain?
Diabetic neuropathy, post-herpetic neuralgia, and neuropathic pain
What is the dosing of Gabapentin that can reduce opioid administration?
300-900mg PO (commonly administered in preop)
smaller doses in the elderly - can be very sedating
How does Pregabalin (Lyrica) provide analgesia
reduces hyper-excitability of dorsal horn neurons
What is the dose of Pregabalin (Lyrica) for analgesia
150-600mg/day in 2-3 doses
Dosing for Clonidine epidural administration
75-150mcg
Dosing for Clonidine intrathecal administration
30-65mcg
What is Clonidine’s MOA?
Selective partial Alpha-2 Receptor Agonist
(Ultimately limits Norepi release, decreasing overall sympathetic outflow)
Neuraxially administered opioids and alpha 2 agonists exhibit?
Synergism
The addition of clonidine to opioids for postoperative analgesia as a continuous epidural infusion reduces opioid requirements by what %?
20-60%
Neuraxial clonidine is indicated for the treatment of intractable pain in ______ patients unresponsive to max opioid doses.
Cancer patients
How will Dexmedetomidine (Precedex) effect MAC levels?
Will reduce MAC requirements
A dose of ____ mcg of intrathecal Precedex is equipotent to _____ mcg of clonidine
3mcg precedex =
30mcg clonidine intrathetcal
Epidural Dexmedetomidine (Precedex) exhibits:
-Synergism with local anesthetics
-Increasing the density of a motor block
-Prolonging the duration of both sensory and motor block
-Improves postop analgesia
What is the IV bolus dosing and continuous infusion dosing for Dexmedetomidine (Precedex)?
Bolus: 4-10mcg/mL
Infusion: 0.2-0.8mcg/kg/hr
What is the bolus and infusion doses of IV Ketamine?
Bolus: small incremental boluses. 0.1-0.5 mg/kg. Up to 0.5mg/kg.
Infusion: 10-25mg/hr
Time onset for IV Ketamine
30-60 seconds
Time to onset for IM Ketamine
2-4 minutes
Mechanism of action of Ketamine (Ketalar)
noncompetitive antagonism of N- methyl-D-aspartate (NMDA) receptors. Blocks influx of calcium, resulting in a decrease in glutamate release.
Magnesium works best in conjunction with which medication to produce analgesia?
Ketamine
What is Magnesium’s MOA for analgesia?
NMDA antagonist.
What is the bolus and continuous infusion dosing for Magnesium?
Bolus/Loading: 30-50mg/kg (usually give 1-2g IVPB) for adults
Infusion: 6-20mg/kg/h
Side effects of Magnesium Sulfate
Hypotension
Diarrhea
