Opioids Flashcards
What are the naturally occurring opioids?
Morphine
Codiene
What are the opioid receptors?
Mu
Kappa
Delta
What are the endogenous opioids?
encephalin
endorphin - mu
dynorphin - Kappa
Mu-1 receptor responsible for what effects?
Analgesia
Mu-2 receptor is responsible for what effects?
hypoventilation
bradycardia
physical dependence
Kappa receptor is responsible for what effects?
dysphoria
diuresis (- reg of ADH)
may antagonize some of the effects at the Mu receptor
Natural ligand is dynorphin
What function does delta receptors have?
modulate mu receptor activity
Describe the intracellular action of opioid receptor activation
coupled to G proteins
- reduction of intracellular cAMP and inhibition of voltage-gated calcium channels = decreases intracellular calcium
- activates K+ (inward rectifier)
- Activates MAPK
net result is decreased neuronal transmission
How does lipid solubility affect onset of opioids?
Higher lipid solubility = faster onset (fentanyl)
Which two opioids may require decreased dosing in renal failure due to active metabolites?
Meperidine –> normeperidine –> SEIZURES in patients with renal failure
Morphine –> morphine-6-glucuronide, which may accumulate in neonates and those with renal failure –> Resp depression
What aspect of the molecular structure of remifentanil influences its primary mode of metabolism?
Ester linkage –> rapidly metabolized by plasma and red blood cell esterases (NOT affected by atypical or pseudocholinesterase deficiency)
= shortest acting of all opioids
How does the lipid solubility of an opioid effect is time to onset and duration when administered in the epidural space?
Epidural - requires diffusion across dura, requires 5-10x dose vs. intrathecal
Lipid soluble drugs like fentanyl - more rapid absorption and shorter duration of action
More water-soluble drugs like morphine = longer onset and duration of action
What are the effects of opioids on circulation and how does meperidine differ from most opioids?
bradycardia from stimulation of the central vagal nucleus
morphine–> histamine from mast cells –> peripheral vasodilation and hypotension
hypovolemic patients - orthostatic hypotension d/t impairment of the compensatory sympathetic nervous system
Meperidine, in contrast to other opioids –> tachycardia, may be related to its structural similarity to atropine and mydriasis
What are the effects of opioids on the GI tract?
reduce biliary, pancreatic, and intestinal secretions
increase resting tone in intestines –> increase in nonpropulsive contractions (bowel spasm)
net effect = slow passage of intestinal contents, increase their viscosity, and induce constipation
What are the effects of opioids on the eyes?
pupillary constriction (miosis)
What are the effects of opioids on the MSK system?
Skeletal muscle rigidity can occur after a rapid intravenous bolus - usually fentanyl
Vocal cord closure
What is opioid tolerance?
a reduction in opioid effect over time (2-3weeks)
or an increase in dose over time for the same desired effect
Define opioid dependence
development of a withdrawal syndrome (agitation, diarrhea, and hyperalgesia) with abrupt cessation and/or administration of an antagonist (e.g. naloxone).
Ave. 25 days
Define opioid addiction
drug-seeking behavior motivated by strong efforts to acquire the drug for non-therapeutic self-administration
Behaviors:
- continued use despite harm
- compulsive use
- craving
- selling, forgery, stealing
What is hyperalgesia and how does it relate to tolerance?
an increase in the magnitude of pain experienced from any given painful stimulus - can occur after stopping an opioid (REMI)
This is a variant of tolerance
How can one reduce the incidence of hyperalgesia?
use NMDA-agonists such as ketamine
methadone (also a u-opioid agonist)
COX-2 inhibitors.
How is Naloxone administered for opioid overdose?
0.4-2mg every 2-3 minutes as needed
What is unique about methylnaltrexone?
opioid agonist-antagonist that does not cross the BBB
used to tx constipation for those on chronic narcotics
What are the effects of opioids on respiration?
Depression
- alter vent response to CO2 in medulla
- Low threshold where patient becomes apneic (40mmHg)
What are the effects of opioids on urinary system?
Urinary retention
- > males
- > intrathecal or epidural
- inc sphincter tone, dec bladder tone
What are the effects of opioids on testosterone and cortisol?
Decreases
What drug is a pro-drug metabolized to morphine?
Codeine
10% of population has low CYP2D6 = not metabolized = no effect
What receptors does Meperidine act and its main use?
Post-op shivering (a-2 agonist)
Serotonin re-uptake inhibitor
Where is can large stores of inactive fentanyl develop?
Lungs
What form of fentanyl has no 1st pass effect and higher [peak]?
Oral transmucosal fentanyl citrate
How is alfentanil metabolized?
CYP3A4 - significant variability b/w people
What is the most potent opioid?
Sufentanil = 1000x stronger than morphine
Some post-op analgesia (longer context sensitive half-time vs. Remi)
At what receptors does methadone act?
- L-isomer = opioid agonist
- D-isomer = NMDA antagonist
- Serotonin & NE reuptake inhibitor
What is the half-life of methadone?
About 35 hours!
How does alfentanil compare to fentanyl in terms of potency, onset and duration?
1/5-1/10 as potent
More rapid onset (1.5min)
Shorter duration
Which opioid has anticholinergic properties?
Meperidine - atropine-like structure
What opioids are contraindicated with MAOIs (selegiline)?
Meperidine, methadone and tramadol —> serotonin syndrome
Best method for post-op pain control in patient on Naltrexone?
Stop 24 hours b4 surgery (its duration of action)
What signs and symptoms do NOT develop tolerance with opioid use?
Miosis and constipation always will occur
What is the mechanism of action of Tapentadol (Nucynta)
NE-reuptake inhibitor
Mu agonist
Do not use w/ MAOIs, SSRIs
