Exam 1: General Opioids Flashcards
Opiates are:
Drugs derived from opium
Opioids are:
Any substance that binds to opioid receptors and produces agonist effect
Classes of opioids based on structure:
Phenanthrenes
Benzylisoquinolines
Classes of opioids based on production:
Naturally occuring
Semisynthetic
Synthetic
Groups of synthetic opioids:
Morphinan derivatives
Diphenyl derivatives
Benzomorphans
Phenylpiperidines
Examples of morphinan derivatives:
Levorphenol
Butorphenol
Example of dipheynl derivative:
Methadone
Structure and examples of benzomorphans:
Morphine + benzene rings
Phenazocine
Pentazocine
Examples of phenylpiperidines:
Meperidine Fentanyl Alfentanil Sufentanil Remifentanil
Classes of opioids based on action at receptor:
Agonist
Partial agonist
Mixed agonist/antagonist
Antagonist
Example of partial agonist:
Buprenorphine - regardless of dose, will not produce full mu receptor effects
Example of mixed agonist/antagonist:
Nalbuphine - agonist at kappa, antagonist at mu
Use of mixes agonist/antagonist:
Reverses respiratory depression while maintaining some analgesia
Example of antagonist:
Naloxone
Three endogenous opioid agonists:
Enkephalins
Endorphins
Dynorphins
Mu receptor subtypes:
Mu-1
Mu-2
Mu-3 (immune-related)
Location of mu receptors:
Brain and spinal cord, some in afferent neurons in periphery
Three ways opioid receptor activation causes ↓ neuronal activity:
- ↑ K+ conductance (hyperpolarization)
- ↓ Ca2+ conductance (↓ neurotransmitter/sub P release)
- ↓ cAMP
Opioids are (weak/strong acid/base):
Weak bases (except alfentanil, remifentanyl)
Effect of acidosis on opioid effect:
↑ ionization means less effective; higher doses will be needed
(but remember higher doses = ventilatory depression = worsening acidosis)
Opioids must be in this condition to diffuse from blood to target tissue:
Unionized and unbound
Alfentanil has rapid onset of action due to:
High % nonionized at physiologic pH
Morphine has slow onset of action due to:
Only 23% nonionized at physiologic pH
Effect of age on opioid PK/PD:
Neonates have ↓ elimination rate
Elderly are more sensitive
Effect of weight on opioid PK/PD:
Base dose on IBW
Effect of renal/hepatic failure on opioid PK/PD:
Can ↑ duration of action
Spinal analgesia effects produced by:
Receptor activation in spinal cord (substantia gelatinosa) and dorsal root ganglion
Supraspinal analgesia effects produced by:
Receptor activation in periaqueductal/periventricular gray and raphe nucleus
CNS effects of opioids:
Analgesia (duh) Euphoria Sedation/drowsiness Miosis (pinpoint pupils) Nausea (CRTZ-related) Modest ↓ ICP, CBF
Advantages of opioids in neuroanesthesia:
Hemodynamic stability
Cerebrovascular stability
CV effects of opioids:
Generally no impairment in cardiac function Bradycardia (dose dep't) Vasodilation ↓ BP, CO Histamine release
NMB with sympathomimetic effects and usefulness alongside opioids:
Pancuronium; SNS stimulation can offset opioid bradycardia
Meperidine-specific CV effects:
Tachycardia
Myocardial depression
Ventilatory effects of opioids:
Respiratory depression (dose dep’t)
↓ chest wall compliance
Constriction of pharyngeal, laryngeal muscles
↓ hypoxic ventilatory drive (need CO₂ to encourage breathing)
Change in respiratory patterns with opioids:
Low dose: ↓ RR, ↑ TV
High dose: ↓ RR and TV… then apnea
Ventilatory response curve after opioid administration:
Reduced and shifted to right
Unique characteristic of fentanyl’s peak effect:
Sequestration in lungs leads to two peaks
Respiratory depression in fentanyl vs. morphine:
Respiratory depression from morphine is slower to peak but lasts longer
Factors that increase opioid respiratory depression:
↑ dose Intermittent bolusing (allows for stacking/tissue sequestration) Faster injection Synergy with other drugs ↓ clearance Age Alkalosis
Skeletal muscle rigidity results from:
GABA inhibition
↑ dopamine
Renal/GI/liver effects of opioids:
↑ peristalsis, tone of ureters (urgency) Blockade of catecholamine/cortisol release Sphincter of Oddi spasm Constipation Delayed gastric emptying
Treatment for opioid-induced sphincter of Oddi spasm:
Glugacon 3mg
Penetration into CSF with epidural administration depends on:
Lipid solubility (Very lipid soluble opioids will reach peak plasma as fast IV as intrathecal)
Side effects of neuroaxial opioid administration:
Pruritis (most common)
N/V
Urinary retention
Ventilatory depression
