Week 11: Opioids and Cannabinoids Flashcards
Naturally occurring opioids
- Morphine (Extract from opium resin)
- Codeine
Semisynthetic opioids
- Semisynthetic: Synthesized w/ naturally occurring opioid as base
- Bureprenorphine Diacetlymorphine (Heroin)
- Hydrocodone (Vicodin)
- Oxycodone (Oxycontin)
Fully synthetic
- Fully synthetic: Fully synthesized in lab (no structural similarity w/ naturally occurring/completely independent from morphine/codeine)
- Significant contribution to opioid epidemic
- Fentanyl
- Levacetylmethadyl (LAAM)
- Methadone (Dolophine)
Opioids and the BBB
- Morphine and heroin easily cross the BBB
- Heroin > morphine
Opioid absorption
- Differ in lipid solubility
- Primarily metabolized in liver, often producing metabolites that have bio effects
- Active metabolites depend on parent compound
Main metabolites
- Morphine –> Morphine-6-glucuronide
- Codeine –> Morphine –> Morphine 6 glucuronide
- Heroin –> Monoacetylmorphine –> Morphine –> Morphine-6-glucoronide
- Acetylcodeine –> Codeine –> Morphine –> Morphine-6-glucoronide
Opioid elimination
- Elimination rate of opioids varies from drug to drug
- Methadone takes up receptor heroin uses, weakening heroine effects
Endogenous opioid system
- Neuropeptide NTS: System includes opioid NTs and receptors
- Propeptide: Large chain of amino acids; propeptides for eventual neuropeptide
Common effect in opioid receptors
Analgesia (help respond to pain & inflammation)
Opioid receptors
- G-protein-coupled metabotropic receptors
- Reduce metabollic activity within neurons
- Inhibitory mechanism = activation of inwardly rectifying K+ channels (support maintenance of cell at baseline)
Where are opioid-synthesizing neurons located in the CNS?
- Cerebral cortex
- Stratum
- Arcuate nucleus
- Nucleus of solitary tract
- Rosffal ventromedial medulla
- Dorsal hor
Where are opioid receptors located in the CNS?
- Thalamus
- Nucleus accumbens
- Amygdala
- Hippocampa formation
- Hypothalamus
- Periaqueductal gray
- VTA
- Locus ceruleus
- Nucleus ambiguus
Opioid effects in reward circuitry
- Decreases/inhibits GABA release in VTA
- Increases Dopamine neuroactivity along dopamine neuron to NA
- Increased dopamine lvls = increased reinforcement effects
- Less GABA activity = more reinforcing effects
Pain system
Nociceptors —> dorsal horn –> spinothalamic tract –> thalamus –> somatosensory cortex/limbic system
Where do input and output pain signals meet?
Dorsal horn (come into brain and come out of spinal cord into PNS)
Most of the opioid drugs used act on ____ opioid receptors
- mu (symbol)
- Psychoactive effects depend on this
Pure opioid receptor agonists
- Produce full agonist actions at mu receptor
- Enhances mu activation
- Ex. Fentanyl and morphone
Partial opioid recept agonists
- Produce partial agonist actions at mu opioid receptors
- Enhances mu activation
- Ex. Buprenorphine
Pure opioid receptor antagonists
- Act as full-receptor antagonists at mu receptor
- Fails to activate mu
- Ex. Naloxone and naltrexone
Mixed opioid receptor agonist-antagonists
Exhibit agonist actions at some receptors and antagonist actions at others (ex. Pentazocine)
Subjective effects of opioid agonists
- Rush: Initial & rapid onset of euphoria
- High: Feelings of joy & ease
- Nod: Calm, disinterest, unaware
- Straight: Normalcy b/w craving opioid and feeling euphoric/other positive effecfts
Conditioned place preference
- Demonstrate a preference for the compartment they previously received an injection of heroin, demonstrating its reinforcing and associative properties
- Strongly prefer place they experienced morphine
____ ____ receptors prevented morphine-induced CPP
- Blocking NMDA
- Also exhibit w/ NMDA inhibition
Opioid overdose
- Sever respiratory depression, weakness, weak pulse, bluish colour to lips and skin, inability to talk, and potentially, unconsciousness
- Respiratory depression from inhibitory effects in the medulla
- More severe than w/ ethanol b/c of dosage/concentration required
