NonOpioid Analgesia

Question 1

Describe the major mechanism of action of NSAIDS

Answer 1

Inhibit the biosynthesis of prostaglandins by preventing the substrate arachidonic acid from binding to the cyclooxygenase enzyme active site.

Question 2

According to Dr. C’s PowerPoint, which nonopioids are centrally acting?

Answer 2

Clonidine
Dex
Ketamine
Magnesium

Question 3

What forms does the COX enzyme exist in?

Answer 3

COX-1 isoenzyme
COX-2 isoenzyme

Question 4

Name three functions of COX-1 Isoenzyme?

Answer 4

-Maintenance of normal renal function in the kidneys
-Mucosal protection in the GI tract
-Production of proaggregatory thromboxane A2 in the platelets

Question 5

What is the only COX-2 selective inhibitor available?

Answer 5

Celecoxib (Celebrex)

Question 6

COX-2 expression can be induced by? Leading to?

Answer 6

Inflammatory mediators in many tissues, therefore, plays a role in the mediation of pain, inflammation, and fever.

Question 7

What are the benefits of coxibs (cox-2 selective inhibitors)?

Answer 7

Improved quality of analgesia
Reduced incidence of GI side effects
No platelet inhibition

Question 8

All NSAIDs are weakly basic or weakly acidic?

Answer 8

Weakly acidic

Question 9

How long does GI absorption of NSAIDS take

Answer 9

within 15-30 minutes

Question 10

What organ metabolizes most NSAIDs?

Answer 10

Liver

Question 11

How are NSAIDs excreted?

Answer 11

into urine or bile

Question 12

How does reduced renal function affect NSAIDs?

Answer 12

Prolongs half-life, the dose should be lowered proportionally in patients with impaired kidney function

Question 13

Moderate to severe liver disease impairs NSAID metabolism, increasing the potential for?

Answer 13

Toxicity

Question 14

Is the volume of distribution of NSAIDs high or low?

Answer 14

Low. 0.1-0.3L/kg, suggesting minimal tissue binding.

Question 15

Why does Celecoxib (Celebrex) not impact platelet function?

Answer 15

Celecoxib is a COX-2 Selective inhibitor. There is no COX-2 isoenzyme in platelets.

Question 16

What patient population is contraindicated to give nonselective NSAIDs to?

Answer 16

GI Gastric Sleeve, Roux-N-Y surgeries due to the risk of ulcers, perforation, and bleeding.

Question 17

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:

Answer 17

High NSAID dose, older age, H. Pylori infection, anticoagulants, corticosteroids, concomitant low-dose aspirin use

Question 18

Why do COX-2 inhibitors have a higher risk of cardiac side effects?

Answer 18

Imbalance Between Prostacyclin (PGI₂) and Thromboxane A₂ (TXA₂). COX-2 inhibits prostacylin, leaving procoag thromboxane a2 predominating.

Question 19

List some possible cardiac side effects of NSAIDS

Answer 19

hypertension, prothrombotic effect (more likely with coxibs)

Question 20

List some possible respiratory side effects of NSAIDs

Answer 20

Nasal Polyps, Dyspnea, bronchospasm, and angioedema, may exacerbate asthma

Question 21

Are hypersensitivities to NSAIDs rare or common? What patient population experiences reactions more?

Answer 21

Rare.
If they occur, they are more common in people with nasal polyps or asthma

Question 22

More than ____% of NSAIDs are bound to albumin after absorption.

Answer 22

90%!
(Influencing their distribution and drug-drug interaction.)

Question 23

List 2 possible renal side effects of NSAIDs

Answer 23

Renal insufficiency
Sodium/Fluid Retention

Question 24

Describe the MOA of Alpha 2 Agonists

Answer 24

Stimulates alpha 2 receptors in brainstem. Reducing catecholamine release therefore a reduction in sympathetic outflow.

Question 25

What are some adverse reactions associated with alpha 2 agonists

Answer 25

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)

Question 26

Describe the MOA of gabapentinoids

Answer 26

reduction of the axon excitability Gabapentin interacts with cortical neurons at delta subunits of calcium channels

Question 27

Where do peripheral analgesics act at?

Answer 27

The sensory input level by blocking the impulse to the brain

Question 28

Why can peripherally administered medications lead to lower systemic levels and fewer adverse systemic effects?

Answer 28

Peripherally administered drugs can potentially optimize drug concentrations at the site of pain origin

Question 29

Nociceptive, inflammatory, and neuropathic pain depend to some degree on peripheral activation of?

Answer 29

Primary sensory afferent neurons

Question 30

Name five inflammatory mediators that analgesics try to target

Answer 30

Prostanoids Bradykinin Adenosine Triphosphate Histamine Serotonin

Question 31

True or False: Combinations of agents that act via different mechanisms may be particularly useful.

Answer 31

True

Question 32

NSAIDs have 3 shared properties. What are they?

Answer 32

Analgesia, Anti-Inflammatory, and Antipyretic

Question 33

What does NSAIDs stand for?

Answer 33

Nonsteroidal anti-inflammatory drugs

Question 34

Ketorolac (Toradol) is dosed at?

Answer 34

15-30mg IV or IM q6 hours (some literature, there is no increase in the efficacy of 30mg)

Question 35

Pediatric dosing of Ketorolac (Toradol)

Answer 35

0.5mg/kg up to 15mg q6 hours

Question 36

What is the elimination half-life of Ketorolac (Toradol)?

Answer 36

2.5-8.5 hours

Question 37

What doses are available for Celecoxib (Celebrex)?

Answer 37

100-200mg

Question 38

What is the elimination half-life of Celecoxib (Celebrex)

Answer 38

11-16 hours

Question 39

What is the leading cause of acute liver failure in the US?

Answer 39

Acetaminophen About half are due to unintentional overdoses

Question 40

How does acetaminophen damage the liver?

Answer 40

Results from one of the acetaminophen metabolites, N-acetyl-p-benzoquinone imine (NAPQI). NAPQI depletes liver antioxidant glutathione and directly damages liver cells.

Question 41

What is the treatment/antidote to acetaminophen toxicity?

Answer 41

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.

Question 42

Conventional dosing of acetaminophen is?

Answer 42

325-650mg every 4-6 hours.

Question 43

The total daily dose of acetaminophen should not exceed?

Answer 43

Most now say 3,000mg daily. (used to be 4,000)

Question 44

How is the oral bioavailability of acetaminophen? Poor or Good?

Answer 44

excellent

Question 45

What drug is included in IV Tylenol (OFIRMEV)?

Answer 45

Mannitol 3,850mgs, almost 4 grams, in each 100mL bottle.

Question 46

Dosing of IV Tylenol (OFIRMEV) for patients <50kg?

Answer 46

15mg/kg

Question 47

Which steroids have the most powerful anti-inflammatory characteristics?

Answer 47

Glucocorticoids

Question 48

What are Mineralcorticoids?

Answer 48

Adrenal cortical steroid hormones that have a greater effect on water and electrolyte imbalance.

Question 49

The main endogenous hormone is?

Answer 49

Aldosterone

Question 50

Corticosteroids are a subgroup of compounds known as?

Answer 50

Adrenocorticoids that are naturally secreted from the adrenal gland

Question 51

How does use of corticosteroids influence opioid use?

Answer 51

There is evidence supporting their use for post-op recovery, minimizing opioid doses and, therefore, side effects

Question 52

What is the effect of adding dexamethasone to anesthetic blocks?

Answer 52

Has been found to prolong local anesthetic block duration

Question 53

What is the dosing for Dexamethasone (Decadron) for PONV prophylaxis?

Answer 53

4-8mg

Question 54

What is the dosing for Dexamethasone (Decadron) for pain management?

Answer 54

0.1-0.2mg/kg Some cap dose at 10mg to minimize side effects, others cap at 20mg.

Question 55

How much more potent is Dexamethasone (Decadron) compared to natural human cortisol?

Answer 55

~25-26 more potent (~6 times more potent than prednisone)

Question 56

Duration of action of Dexamethasone (Decadron)?

Answer 56

36-54 hours

Question 57

The half-life of Dexamethasone (Decadron)?

Answer 57

3.5-5 hours

Question 58

What are a few potential side effects of corticosteroids?

Answer 58

Hyperglycemia Delayed wound healing osteoporosis (remember short term verse long term SEs)

Question 59

How do systemic local anesthetics, such as Lidocaine, work?

Answer 59

Produces analgesia by suppressing sodium channels in neurons that respond to noxious stimuli, thereby preventing nerve conduction and pain transmission.

Question 60

What effect does systemic lidocaine have on MAC of volatile anesthetics?

Answer 60

Decrease in MAC

Question 61

What is the dosing of IV Lidocaine for bolus and continuous infusion for pain management?

Answer 61

Bolus: 100mg or 1-2mg/kg Infusion: 0.5-2mg/kg/hour

Question 62

What is the onset of IV Lidocaine?

Answer 62

45-90 seconds

Question 63

What is the half-life of IV lidocaine?

Answer 63

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

Question 64

What are the two Gabapentinoids we commonly see?

Answer 64

Gabapentin (Neurontin) Pregabalin (Lyrica)

Question 65

Both Gabapentin (Neurontin) and Pregabalin (Lyrica) bind to?

Answer 65

Alpha 2 delta subunits of the voltage-gated calcium channels in the CNS

Question 66

Gabapentin (Neurontin) is an effective analgesic particularly for what kind of pain?

Answer 66

Diabetic neuropathy, post-herpetic neuralgia, and neuropathic pain

Question 67

What is the dosing of Gabapentin that can reduce opioid administration?

Answer 67

300-900mg PO (commonly administered in preop) smaller doses in the elderly - can be very sedating

Question 68

How does Pregabalin (Lyrica) provide analgesia

Answer 68

reduces hyper-excitability of dorsal horn neurons

Question 69

What is the dose of Pregabalin (Lyrica) for analgesia

Answer 69

150-600mg/day in 2-3 doses

Question 70

Dosing for Clonidine epidural administration

Answer 70

75-150mcg

Question 71

Dosing for Clonidine intrathecal administration

Answer 71

30-65mcg

Question 72

What is Clonidine's MOA?

Answer 72

Selective partial Alpha-2 Receptor Agonist (Ultimately limits Norepi release, decreasing overall sympathetic outflow)

Question 73

Neuraxially administered opioids and alpha 2 agonists exhibit?

Answer 73

Synergism

Question 74

The addition of clonidine to opioids for postoperative analgesia as a continuous epidural infusion reduces opioid requirements by what %?

Answer 74

20-60%

Question 75

Neuraxial clonidine is indicated for the treatment of intractable pain in ______ patients unresponsive to max opioid doses.

Answer 75

Cancer patients

Question 76

How will Dexmedetomidine (Precedex) effect MAC levels?

Answer 76

Will reduce MAC requirements

Question 77

A dose of ____ mcg of intrathecal Precedex is equipotent to _____ mcg of clonidine

Answer 77

3mcg precedex = 30mcg clonidine intrathetcal

Question 78

Epidural Dexmedetomidine (Precedex) exhibits:

Answer 78

-Synergism with local anesthetics -Increasing the density of a motor block -Prolonging the duration of both sensory and motor block -Improves postop analgesia

Question 79

What is the IV bolus dosing and continuous infusion dosing for Dexmedetomidine (Precedex)?

Answer 79

Bolus: 4-10mcg/mL Infusion: 0.2-0.8mcg/kg/hr

Question 80

What is the bolus and infusion doses of IV Ketamine?

Answer 80

Bolus: small incremental boluses. 0.1-0.5 mg/kg. Up to 0.5mg/kg. Infusion: 10-25mg/hr

Question 81

Time onset for IV Ketamine

Answer 81

30-60 seconds

Question 82

Time to onset for IM Ketamine

Answer 82

2-4 minutes

Question 83

Mechanism of action of Ketamine (Ketalar)

Answer 83

noncompetitive antagonism of N- methyl-D-aspartate (NMDA) receptors. Blocks influx of calcium, resulting in a decrease in glutamate release.

Question 84

Magnesium works best in conjunction with which medication to produce analgesia?

Answer 84

Ketamine

Question 85

What is Magnesium's MOA for analgesia?

Answer 85

NMDA antagonist.

Question 86

What is the bolus and continuous infusion dosing for Magnesium?

Answer 86

Bolus/Loading: 30-50mg/kg (usually give 1-2g IVPB) for adults Infusion: 6-20mg/kg/h

Question 87

Side effects of Magnesium Sulfate

Answer 87

Hypotension Diarrhea