Anesthesia Adjuncts Flashcards
Volume of distribution: half life
Inversely proportional
*bigger Vd–>longer t1/2 (same rate of clearance)
Mechanism of opioids
- 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
Opioid Receptors
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
Opioid side effects
- interruption of sympathetic tone
- parasympathetic-like effects
- decrease preload
Meperidine unique effects
- decreases myocardial contractility
- atropine like structure (increase HR, mydriasis)
- histamine release (like morphine)–>decreased SVR and preload
Opioid effects on respiratory system
- 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)
Which two properties of opioids is resistant to tolerance?
Constipation and myosis
Which opioids inhibit serotonin reuptake?
- meperidine
- methadone
- tramadol
How does sufentanil compare to fentanyl?
Sufentanil
- more potent
- greater tendency to depress ventilation and cause bradycardia
- context sensitive half time increases to a lesser extent w/long infusions (>2hrs)
Benzodiazepine receptor and effect
- 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
Baclofen receptor and location in body
GABA-B receptor found in CNS and ANS
Dexmedetomidine
- side effects at high doses
- compared to clonidine
- effect of discontinuation
- 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)
Dextromethorphan
- 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)
Prolonged exposure to opioids and hyperalgesia
- 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)
NMDA antagonists
- ketamine
- dextromethorphan
- methadone
Methylnaltrexone
Peripheral opioid antagonist that cannot pass the BBB
-used for reversal of GI side effects of opioids
Opioid side effects
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
Opioid elimination half-life
- short
- intermediate
- long
- short: remifentanil (10min)
- intermediate: morphine<fentanyl
- long: methadone (34 hrs)
Elimination half-life and duration of action: fentanyl v morphine
- 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)
Relative potency of opioids:
- meperidine
- morphine
- alfentanil
- fentanyl
- remifentanil
- sufentanil
Meperidine: 0.1 Morphine: 1.0 Alfentanil: 10 Fentanyl: 100 Remifentanil: 300 Sufentanil: 1,000
Largest patient factor that prolongs opioid clearance
Advanced age
-morphine half-life almost doubles in the elderly
Partial opioid agonists
Nalbuphine and butorphanol
- less resp depression
- very sedating
- less GI effects (esp butorphanol)
- precipitate withdrawal sxs in dependent patients (nalbuphine)
Efficacious applications of 0.04 mg naloxone
- N/V
- sedation
- pruritus (including neuraxial opioids)
