Opioids Flashcards

1
Q

What are the naturally occurring opioids?

A

Morphine

Codiene

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2
Q

What are the opioid receptors?

A

Mu
Kappa
Delta

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3
Q

What are the endogenous opioids?

A

encephalin
endorphin - mu
dynorphin - Kappa

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4
Q

Mu-1 receptor responsible for what effects?

A

Analgesia

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5
Q

Mu-2 receptor is responsible for what effects?

A

hypoventilation
bradycardia
physical dependence

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6
Q

Kappa receptor is responsible for what effects?

A

dysphoria
diuresis (- reg of ADH)
may antagonize some of the effects at the Mu receptor
Natural ligand is dynorphin

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7
Q

What function does delta receptors have?

A

modulate mu receptor activity

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8
Q

Describe the intracellular action of opioid receptor activation

A

coupled to G proteins

  1. reduction of intracellular cAMP and inhibition of voltage-gated calcium channels = decreases intracellular calcium
  2. activates K+ (inward rectifier)
  3. Activates MAPK

net result is decreased neuronal transmission

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9
Q

How does lipid solubility affect onset of opioids?

A

Higher lipid solubility = faster onset (fentanyl)

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10
Q

Which two opioids may require decreased dosing in renal failure due to active metabolites?

A

Meperidine –> normeperidine –> SEIZURES in patients with renal failure

Morphine –> morphine-6-glucuronide, which may accumulate in neonates and those with renal failure –> Resp depression

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11
Q

What aspect of the molecular structure of remifentanil influences its primary mode of metabolism?

A

Ester linkage –> rapidly metabolized by plasma and red blood cell esterases (NOT affected by atypical or pseudocholinesterase deficiency)

= shortest acting of all opioids

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12
Q

How does the lipid solubility of an opioid effect is time to onset and duration when administered in the epidural space?

A

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

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13
Q

What are the effects of opioids on circulation and how does meperidine differ from most opioids?

A

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

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14
Q

What are the effects of opioids on the GI tract?

A

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

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15
Q

What are the effects of opioids on the eyes?

A

pupillary constriction (miosis)

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16
Q

What are the effects of opioids on the MSK system?

A

Skeletal muscle rigidity can occur after a rapid intravenous bolus - usually fentanyl

Vocal cord closure

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17
Q

What is opioid tolerance?

A

a reduction in opioid effect over time (2-3weeks)

or an increase in dose over time for the same desired effect

18
Q

Define opioid dependence

A

development of a withdrawal syndrome (agitation, diarrhea, and hyperalgesia) with abrupt cessation and/or administration of an antagonist (e.g. naloxone).

Ave. 25 days

19
Q

Define opioid addiction

A

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
20
Q

What is hyperalgesia and how does it relate to tolerance?

A

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

21
Q

How can one reduce the incidence of hyperalgesia?

A

use NMDA-agonists such as ketamine
methadone (also a u-opioid agonist)
COX-2 inhibitors.

22
Q

How is Naloxone administered for opioid overdose?

A

0.4-2mg every 2-3 minutes as needed

23
Q

What is unique about methylnaltrexone?

A

opioid agonist-antagonist that does not cross the BBB

used to tx constipation for those on chronic narcotics

24
Q

What are the effects of opioids on respiration?

A

Depression

  • alter vent response to CO2 in medulla
  • Low threshold where patient becomes apneic (40mmHg)
25
What are the effects of opioids on urinary system?
Urinary retention - >males - >intrathecal or epidural - inc sphincter tone, dec bladder tone
26
What are the effects of opioids on testosterone and cortisol?
Decreases
27
What drug is a pro-drug metabolized to morphine?
Codeine 10% of population has low CYP2D6 = not metabolized = no effect
28
What receptors does Meperidine act and its main use?
Post-op shivering (a-2 agonist) Serotonin re-uptake inhibitor
29
Where is can large stores of inactive fentanyl develop?
Lungs
30
What form of fentanyl has no 1st pass effect and higher [peak]?
Oral transmucosal fentanyl citrate
31
How is alfentanil metabolized?
CYP3A4 - significant variability b/w people
32
What is the most potent opioid?
Sufentanil = 1000x stronger than morphine Some post-op analgesia (longer context sensitive half-time vs. Remi)
33
At what receptors does methadone act?
* L-isomer = opioid agonist * D-isomer = NMDA antagonist * Serotonin & NE reuptake inhibitor
34
What is the half-life of methadone?
About 35 hours!
35
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
36
Which opioid has anticholinergic properties?
Meperidine - atropine-like structure
37
What opioids are contraindicated with MAOIs (selegiline)?
Meperidine, methadone and tramadol ---> serotonin syndrome
38
Best method for post-op pain control in patient on Naltrexone?
Stop 24 hours b4 surgery (its duration of action)
39
What signs and symptoms do NOT develop tolerance with opioid use?
Miosis and constipation always will occur
40
What is the mechanism of action of Tapentadol (Nucynta)
NE-reuptake inhibitor Mu agonist Do not use w/ MAOIs, SSRIs