Flashcards in Opioids and Drug Addiction Deck (80)
How is pain transmitted?
-Stimulation of pain receptors (nociceptors)
-Sub P released and activates ascending pathways
-Glutamate activates AMPA and NMDA receptors
-Pain sense is projected to brain
Where is the perception of pain occurring?
Where is the localization of pain occurring?
Where are the behavioral and emotional responses to pain occurring?
Hypothalamus and limbic system
How do endogenous opioids and opioid meds treat pain?
-Inhibit ascending pain transmission from spinal cord (mu, delta, kappa receptors)
-Activates descending inhibitory pathways
-Agonism at mu and delta receptors stimulates release of dopamine (leads to euphoria, activation of "reward center")
What receptors increase the pain threshold resulting in dulling of the pain sensation?
Mu, delta, kappa
What do mu, delta, and kappa receptors do?
-Part of inhibiting ascending pain transmission from spinal cord
-Increase pain threshold
-Dulls pain sensation
What are the types of mu receptors and what do they do?
Mu 1: analgesia
Mu 2: sedation, vomiting, respiratory depression, pruritus, euphoria, anorexia, urinary retention, physical dependence
*None of our opioid meds are mu-1 selective unfortunately!*
What are the naturally occurring opiates?
Morphine and codeine
What do opioid meds bind to?
G-coupled opiate receptors in brain, spinal cord, periphery (GI)
What are the primary actions of opioid meds?
1. Close presynaptic Ca channels (results in decreased NT release including Sub P)
2. Open K channels (hyperpolarize and inhibit postsynaptic neurons)
Which neurotransmitters are inhibited when opioid meds close Ca channels?
Opioid meds pharmacokinetics (generally)
-Extensive 1st pass with oral formulations
-Distributes well into highly perfused areas (brain, kidney, liver, lungs, spleen)
-Highly lipophilic (accumulate in adipose tissue)
-CYP2D6 (MC esp codeine, hydrocodone)
-CYP3A4 (mainly fentanyl, methadone)
What is important to remember regarding CYP2D6 metabolism of opioids?
-Some individuals have NO CYP2D6 activity leading to NO metabolism
-Some have high levels leading to rapid metabolism
*Codeine has to be converted to morphine
Which opioids should be used in patients with renal dysfunction?
Methadone and fentanyl
Which opioids do not go through phase 1 CYP metabolism?
Morphine, hydromorphone, oxymorphone
Describe opioids analgesia effect
Decreases both sense and affect of pain
CNS effects of opioids
CV effects of opioids
-Hypotension (likely from histamine release)
GI effects of opioids
-Decreased motility, HCl secretion
-Increased tone and H2O reabsorption
Biliary tract effects of opioids
-Contracts smooth muscle (colic)
-Increases pancreatic enzymes
Renal effects of opioids
-Decreased plasma flow
-Antidiuretic effect (increased reabsorption of Na)
Uterine effects of opioids
May prolong labor (unknown mechanism)
Skin effects of opioids
Pruritus (due to histamine release)
-Pro drug, weak opioid agonist
-Requires conversion to morphine via CYP2D6
-Antitussive, not a great pain reliever
-ADEs limit use
Metabolism of hydrocodone
-Weak opioid agonist
-Metabolized to hydromorphone via CYP2D6
Describe oxycodone (formulation, metabolism, etc.)
-Weak opioid agonist
-PO formulation only
-CYP2D6 to oxymorphone
-Addiction potential higher than morphine
-Commonly sold on street (hillbilly heroin)
-Often paired with acetaminophen (Percocet)
-Strong opioid agonist
-Metabolized by glucoronidation to M3G (side effects) and M6G (analgesia)