Opioid Analgesics - Slattery Flashcards
What are the four steps to pain?
- Initiation by local stimulus
- Transmission to brain
- Perception as pain
- Reaction of individual
What types of treatment eliminate the cause of pain?
- Anti-inflammatory (NSAIDs)
- Chemotherapy (including antimicrobials)
- Antiulcer
What types of treatment prevent transmission of pain?
Local anesthetics
What kind of treatments affect the way pain is perceived?
- General anesthetics
- OPIOIDS
What types of treatment affect a patient’s reaction to pain?
- OPIOIDS
- Anxiolytics
In the case of a bear attack, is the descending pain pathway inhibitory/excitatory to the normal ascending pain pathway?
Inhibitory!
(“survival mode” ultimately inhibits transmission of signal between 1° and 2° ascending (afferent) neurons)
What neurotransmitters are released by the descending pathway to inhibit the transmission of signal between 1° and 2° afferent neurons?
- Endogenous opioids
- endorphins
- enkephalins
- 5HT
- NE
What is the difference between “opiate” and “opioid”?
- Opiate = drug derived from opium poppy
- Opium
- Morphine
- Codeine
- Opioid = more generic term, all substances (endogenous and exogenous) that bind opioid receptors
- Endorphins (endogenous)
- Morphine, etc.
The word “narcotic” is now a legal term encompassing what?
Illicit drug use:
-opioids, cannabinoids, stimulants, etc.
What are the four types of opioid receptors?
- Mu
- Kappa
- Delta
- ORL1 - Orphanin opioid receptor-like 1
What opioid receptor is related to analgesia, respiratory depression, decreased gastrointestinal motility, and physical dependence?
Mu receptor
What opioid receptor is related to analgesia, sedation, and decreased gastrointestinal motility?
Kappa
What opioid receptor modulates Mu receptor activity?
Delta
What opioid receptor is structurally similar to Mu, but insensitive to opioid ligands?
ORL1
What kind of receptors are involved in opioid signal transduction?
G-protein coupled receptors (GPCRs)
What action do G-protein coupled receptors have on pre-synaptic and post-synaptic transmission?
- Pre-synaptic:
- inhibit Ca2+ channels
- stop transmission
- Post-synaptic:
- activate K+ channels
- stop transmission
In pre-synaptic inhibition of afferent neurons, opioid receptor activation blocks voltage-gated Ca2+ channels, reducing the release of what?
Glutamate and Substance P
What three potential sites of action could opioid receptors interfere with signal transduction of the afferent (ascending) pathway?
- Peripheral tissues (afferent nociceptor)
- Spinal cord (substantia gelatinosa)
- Thalamus (ventral caudal)
What are the four steps of the descending inhibitory pathway?
- Cortex
- Periaqueductal gray (midbrain)
- Rostral ventral medulla
- Dorsal horn spinal cord
What are four examples of opioid agonists that produce an effect when bound to receptor?
- Morphine (Mu/Kappa agonist)
- Methadone
- Oxycodone
- Heroin
What are two opioid receptor antagonists that produce no effect when bound to the receptor or has a reverse effect of morphine-like opioids?
- Naloxone
- Naltrexone
What opioid is a partial agonist that has less efficacy than full agonists, lower abuse potential, and effects on Mu receptors?
Codeine
What are two examples of opioid mixed agonist-antagonist drugs?
- Pentazocine
- Agonist = Kappa receptors
- Antagonist = Mu receptors
- Buprenorphine
- Agonist (partial) = Mu receptors
- Antagonist = Kappa, Delta, ORL1
What is the clinical relevance of giving opioid mixed agonist-antagonists?
Precipitate withdrawal symptoms if effect shifts at one receptor.
(narcotic abuse tx)
Why does heroin enter the brain more rapidly than morphine?
More lipid soluble
(rapidly crosses BBB)
What route of administration is convenient, but has a high first pass metabolism that can be limiting, slower onset, delayed peak effect, longer duration (relative to parenteral routes), and is better for chronic treatment?
Oral
What route of administration is precise, has accurate dosing, rapid onset, but increased risk of adverse effects, can be bolus or continuous, and can be patient controlled?
Intravenous
What route of administration has rapid onset and a duration in between oral and IV adminstered opioids?
IM/SubQ
What route of administration has longer duration at lower doses than systemic and can avoid some brain-mediated adverse effects such as respiratory depression?
Spinal
(effect opioid receptors in CNS without brain causing respiratory depression)
What route of administration may be easily discontinued?
Rectal suppository
What route of administration has a faster onset than oral, avoids first pass metabolism and is convenient (no injection)?
Buccal/Sublingual
ex. Fentanyl “lollipop”
What route of administration is convenient, avoids first pass metabolism, and is better for chronic treatment?
Transdermal
(e.x. Fentanyl, Buprenorphine)
Why does oral morphine require 3-6x higher dose relative to parenteral administration?
First pass metabolism
(drugs absorbed from GI tract go to liver, then rapidly and efficiently metabolized)
Why does oral methadone only need 1.5-2x higher dose compared to oral morphine?
Less impacted by first pass metabolism
What pharmacologically active opioid metabolite is excreted in the urine, so it can impact morphine’s effect and duration if renal function is compromised?
Morphine-6-glucoronide
(morphine metabolite)
What toxic opioid metabolite can cause excitotoxicity and result in tremor, twitching, and convulsions?
Normeperidine
(a metabolite of meperidine)
Where are opioid metabolites primarily excreted?
Urine
(some glucoronides excreted in feces)
What are five potential therapeutic uses for opioids?
- Analgesia
- Obstetric labor
- Anesthesia
- Cough
- Diarrhea
Why would you use opioids in obstetric labor?
- Crosses placenal barrier
- potential neonatal respiratory depression
- Slows progress of labor
How are opioids used for anesthesia purposes?
- Pre- and post-surgery
- sedative
- anxiolytic
- analgesic
- Cardiovascular surgery
- minimizes cardiovascular depression
What opioid is used for cough suppression?
Codeine
Describe treatment of diarrhea with opioids.
- All opioids effective
- GI effect = constipation
- Loperamide (Imodium)
- opioid that is not able to cross BBB
- Diphenoxylate + Atropine (Lotomil)
- Atropine added to discourage abuse (anticholinergic)
What is Naloxone used for?
- Acute overdose
- short duration of action
- injection to avoid first pass metabolism
- single dose - could relap
