Opioids Flashcards
Opiate
drugs derived from opium. Examples include morphine, thebaine, and codeine
Opium
Substance derived from the seeds of the opium poppy (Papaver somniferum)
Opioid
Term used to describe ALL natural, synthetic, or semi-synthetic compounds that bind to opioid receptors. May be agonists or antagonists. Endogenous peptides may be termed opioids.
Narcotic
Derived from the Greek word for stupor. Narcotic has historically been used to describe opioids. May be used to describe any drug that causes dependence (legal or popular press)
Opioid receptors are G-protein-coupled receptors. True or False.
True
Location of opioid receptors
- Cerebral cortex, thalamus, PAG, spinal cord, dorsal horn
- Peripheral sensory neurons in inflammation
- Non-neurological tissue (immune cells)
Opioid Receptor Effectors
- Receptor dependent potassium channels
- Voltage-gated calcium channels
- Inhibit adenylate cyclase (decrease cAMP)
- Phospholipase C
- MAP kinase
- K+
- Inhibit release of acetylcholine, glutamic acid, dopamine, serotonin, substance P, and norepinephrine
Opioid Receptor Subgroups
µ
- Activated by morphine
- Miosis, analgesia, sedation, bradycardia, hypothermia, respiratory depression, physical dependence
- Endomorphins
- Ednogenous molecules that are produced by the body that react with µ receptors
Opioid Receptor Subgroups:
kappa
- Ketocyclazine
- Miosis, sedation/psychomimmetic effects, anti-ADH, neuroprotective
- Spinal, peripheral distribution
- Dynorphines
- Endogenous molecules that ineract with Kappa receptors
Opioid receptor subgroups:
Delta
- Central (limbic, cerebral, spinal cord)/pierpheral neurons, smooth muscle, lymphocytes
- Emotional behavior, immune function, may MODIFY analgesia, ischemic preconditioning, proconvulsant/antidepressants
- Enkephalins
- Ednogenous molecule that interacts with delta receptors
Nociceptin Receptor (orphanin FQ receptor)
- High structural homology to µ, kappa, and delta recepotrs
- Low affinity for traditional opioid agonists
- Buprenorphine may have some activity
- Nociceptin/orphanin
- Endogenuos opioid
- unique pain modifying and behavioral properties (food intake, memory)
- Antiopioid (pronociceptive) effects
- May affect dopamine/GABA mediated transmission
Sigma receptor
- No structural similarity to opioid recepotrs
- SKF-10,047
- Mydriasis, tachypnea, tachycardia, hallucinations, mania, vasomotor responses
- Activated by drugs unrelated to opioids (phencyclidine, haloperidol)
- Activation not reversed by naloxone or naltrexone
Which drugs reverse opioids?
- Naloxone
- Diprenorphine
- Naltraxone
Epsilon receptor
- Opioid growth factor receptor
- little sequence homology to other opioid receptors
- Regulation of tissue growth
What are the three endogenous opioid peptides and name their receptors
- endorphine - µ receptor
- dynorphin - kappa receptor
- enkephalin - delta receptor
The three endogenous opioid peptides initially identified (endorphines, enkephalines, and dynorphins) are derived from the same precursors. True or False.
FALSE - they are derived from three different precurosrs
three families of endogenous opioid peptides that were initially identified and described extensively (endorphins, enkephalins, and dynorphins) share what in common?
They all share a common amino-terminal sequence: Tyr-Gly-Gly-Phe-(Met or Leu)
Endomorphin
- This is another endogenous opioid that do not contain the characteristic opioid AA core sequence
- High affinity and selectivity for the µ receptor
Endogenous Morphine
- Neuroblastoma cells have the ability to synthesize morphine
- Has been detected in tissues and fluids
CNS effects
- Sedation
- Dysphoria
- Excitment can occur in the horse and cat
- Seizures
- high doses
- Respiratory depression
- Stimulate/inhibit chemoreceptor trigger zone (vomiting/nausea)
- Tolerance/physcial dependence
GI effects
- Vomiting/nausea
- Increased GI tone (nonpropulsive)
- tends to cause constipation
- Decreased small intestinal secretion/increased water absorption
- Loperamide -peripheral agonist
- Decreased pancreatic biliary secretions
- Postoperative ileus
Side effects on body temp
Decreased body temp, except increased in cats
opioids are immunosuppressive. True or False.
True
Opioids increase histamine release/cuase pruritis. True or False.
True
Opioids increase sphincter tone. True or False.
True
Enkephalin Pentapeptides
- Precursor: proenkephalin
- [met]enkephalin
- [leu]enkephalin
- High affinity for the delta receptor
- Low affinity for the kappa receptor
Dynorphins
- Precursor: prodynorphin
- The dynorphins appear to be the endogenous receptor for the kappy recepotr
Edorphins
- Precursor: propriomelanocortin
- Also precuror for adrenocorticotropic hormone, melanocyte-stimulating hormone, and beta-lipotropin
- Derived from the hypothalamus/neurohypophysis
- Beta-endorphin
- Similar affinity for delta and mu receptors and low affinity for kappy receptors
Morphine has a high affinity for which receptor?
MU
Methadone has a high affinity for which receptor?
MU
Etorphine has a high affinity for which receptors?
MU, delta, and kappy
