Anesthesia Adjuncts

Question 1

Volume of distribution: half life

Answer 1

Inversely proportional

*bigger Vd–>longer t1/2 (same rate of clearance)

Question 2

Mechanism of opioids

Answer 2

• All opioid receptors couple to G proteins; binding of an agonist to an opioid receptor causes membrane hyper polarization
• Acute opioid effects are mediated by inhibition of adenylyl cyclase (reductions in intracellular cAMP) and activation of phospholipase C
• Inhibit voltage-gated calcium channels and activate inwardly rectifying potassium channels (increase K and decrease Ca conductance)–>decrease release of neurotransmitters

Question 3

Opioid Receptors

Answer 3

Mu 1: supraspinal analgesia, muscle rigidity, euphoria, miosis, bradycardia
Mu 2: resp depression, constipation, sedation
Kappa: spinal analgesia, stops shivering, sedation, miosis
Delta: resp depression (maybe), constipation
Sigma: hallucinations/dysphoria

Question 4

Opioid side effects

Answer 4

• interruption of sympathetic tone
• parasympathetic-like effects
• decrease preload

Question 5

Meperidine unique effects

Answer 5

• decreases myocardial contractility
• atropine like structure (increase HR, mydriasis)
• histamine release (like morphine)–>decreased SVR and preload

Question 6

Opioid effects on respiratory system

Answer 6

• increased apnea threshold
• increase PaCO2 (acidosis)
• shifts CO2 response curve downward and to the right
• decreases hypoxic drive
• decreases A-a gradient and P/F ratios (but only at extremely high PaCO2s, especially at low FiO2s)

Question 7

Which two properties of opioids is resistant to tolerance?

Answer 7

Constipation and myosis

Question 8

Which opioids inhibit serotonin reuptake?

Answer 8

• meperidine
• methadone
• tramadol

Question 9

How does sufentanil compare to fentanyl?

Answer 9

Sufentanil

• more potent
• greater tendency to depress ventilation and cause bradycardia
• context sensitive half time increases to a lesser extent w/long infusions (>2hrs)

Question 10

Benzodiazepine receptor and effect

Answer 10

• Alpha subunit of GABA-A receptor (sedative, anxiolytic, hypnotic, amnestic, anticonvulsant) in cerebral cortex
• Gamma subunit of GABA-A receptor in the spinal cord (muscle relaxation)
• Enhanced chloride conductivity across (into cell) the membrane leading to hyperpolarization and reduced excitability of post-synaptic neurons in cerebral cortex
• changes the Nernst potential- the potential difference between EC and IC side of cell

Question 11

Baclofen receptor and location in body

Answer 11

GABA-B receptor found in CNS and ANS

Question 12

Dexmedetomidine

• side effects at high doses
• compared to clonidine
• effect of discontinuation

Answer 12

• at high doses, cross reactivity with alpha-1 receptor (HTN w/baroreceptor mediated bradycardia)
• more selective for alpha-2 receptor than clonidine
• discontinuation of prolonged use can lead to rebound HTN (like clonidine)

Question 13

Dextromethorphan

Answer 13

• primarily used as antitussive agent
• NMDA antagonist (like ketamine and methadone- local anesthetic)
• local anesthetic effects
• SSRI qualities- like methadone (so should be used w/MAOIs)

Question 14

Prolonged exposure to opioids and hyperalgesia

Answer 14

• fewer opiod receptors: down regulation and internalization of opioid receptors, leading to less membrane hyper polarization (of pain fibers/pathways)
• reduced response of opioid receptors: “decoupling” of secondary messaging systems (G-proteins)
• down-regulation of glutamate receptors in the spinal cord leading to wind up(opioids also have weak NMDA agonistic properties)

Question 15

NMDA antagonists

Answer 15

• ketamine
• dextromethorphan
• methadone

Question 16

Methylnaltrexone

Answer 16

Peripheral opioid antagonist that cannot pass the BBB

-used for reversal of GI side effects of opioids

Question 17

Opioid side effects

Answer 17

GI: decrease motility, gastric secretions, and pancreatic secretions; decreased LES tone and increased GERD; increased sphincter of Oddi; increased amylase and lipase
CNS: directly stimulate CTZ, decreased sympathetic outflow
Airway: decreased cough reflex
Respiratory: decreased CO2 responsiveness, increased OSA sxs
CV: histamine release (morphine, meperidine)
MSK: muscle rigidity

Question 18

Opioid elimination half-life

• short
• intermediate
• long

Answer 18

• short: remifentanil (10min)
• intermediate: morphine<fentanyl
• long: methadone (34 hrs)

Question 19

Elimination half-life and duration of action: fentanyl v morphine

Answer 19

• fentanyl has longer elimination half-life but shorter duration of action
• fentanyl is very lipophilic and distributes from central compartment to muscle and fat, thus terminating its effects (large volume of distribution)

Question 20

Relative potency of opioids:

• meperidine
• morphine
• alfentanil
• fentanyl
• remifentanil
• sufentanil

Answer 20

Meperidine: 0.1
Morphine: 1.0
Alfentanil: 10
Fentanyl: 100
Remifentanil: 300
Sufentanil: 1,000

Question 21

Largest patient factor that prolongs opioid clearance

Answer 21

Advanced age

-morphine half-life almost doubles in the elderly

Question 22

Partial opioid agonists

Answer 22

Nalbuphine and butorphanol

• less resp depression
• very sedating
• less GI effects (esp butorphanol)
• precipitate withdrawal sxs in dependent patients (nalbuphine)

Question 23

Efficacious applications of 0.04 mg naloxone

Answer 23

• N/V
• sedation
• pruritus (including neuraxial opioids)