Opiates Flashcards
General info about opiates?
POTENT analgesics (primary medicinal use)
Very reinforcing
When did opiates start getting used?
May predate history of man
7000 years +
What are the main effects of opiates?
Analgesic
Antitussive (cough-supressant)
Sedative
Gastro-intestinal muscle relaxant (you poop)
Where were opiates derived from historically?
Poppy plant
What (ecologically) is opium?
The resin that oozes out of poppy plants
Where do you get morphine / codeine from?
Extracted from opium
What are the endogenous opioids?
Enkephalins
Endorphins
Dynorphins
What are synthetic opiates like compared to naturally-occuring?
e.g. fentanyl
100x as powerful as morphine
What pharmacological factor varies administration of opiates?
Fat solubility
How is morphine generally administered?
Orally, by inhalation, or by injection (injection fastest, it’s slow-absorbing)
How is heroin generally administered?
What is its fat solubility compared to morphine?
Smoked or injected.
Increased lipid solubility
What happens to heroin once it’s in the CNS?
Converted to morphine
What do naloxone/naltrexone do?
Direct opiate antagonists
Synthetically developed
Used in EMT cocktail
What happens to codeine in the CNS?
Where are its effects?
Converted to morphine (like heroin)
Little effect on its own, only cough centers in brainstem
Where are all the opiates metabolized?
Liver; excreted by kidney in urine
What do the half-lives of morphine / heroin look like?
~4 hr
What do the half lives of opiates in general look like?
Widely variable
What is the basic pharmacodynamic effect of opiates?
Direct agonists
Which receptors do opiates work on?
Opiate receptors (three main kinds)
Are opiate receptors metabotropic or ionitropic?
Metabotropic
What happens to changes in ion conductances with opiates?
Inhibition
Decrease excitability (K+)
Synaptic transmission (Ca2+)
How do opiates affect K+ channels?
Increase opening for leak channels
As an EPSP comes along, driving force for K+ gets changed
What happens with opiates and postsynaptic inhibition?
Open K+ channels
What happens with opiates and axoaxonic inhibition?
Close Ca2+ channels
What happens with opiates and presynaptic autoreceptors?
Reduce neutrotransmitter release
Colocalization with neurotransmitter / opioid
Who first discovered opiate receptors?
Snyder and Pert, 1972
What is the Mu receptor?
Opiate receptor
Most sensitive to morphine / heroin / codeine. It’s the one that binds these.
How / where do opiates alter pain sensitivity? What is the first place possible?
Dorsal horns are the first place, chock full of opiate receptors
(And where is the first place touch can get modulated?)
Medulla, somatosensory axons just project directly there (pain axons stop at dorsal horns)
Why does rubbing help with pain?
Somatosensory neurons have inputs to pain-modulating inhibitory interneurons
These interneurons get excited by the somatosensory neurons
Interneurons project to pain neurons, inhibiting them
What physiological responses to Mu receptors modulate?
Euphoric, brain and spinal analgesic, sedative, GI motility effects
What do opiates do to peristaltic contraction in the GI tract?
Inhibit it (lots of opiate receptors in GI tract!)
What are Delta opiate receptors? What is the difference between them and Mu?
More sensitive to endogenous opiates (e..g enkephalins)
Involved in spinal mechanisms of analgesia
What are Kappa opiate receptors?
Most sensitive to dynorphin
Not involved in rewarding properties of opiates
Mostly in spinal cord, brainstem
What is nociceptin/orphanin (NOP-R)?
No clue, but it’s new
learning, motor function, neuroendocrine? regulates hormonal pathways / stress response…
Who discovered the endogenous opiates?
Both Kosterlitz and Hughes, 1975. Discovered them independently
What did both kosterlitz and Hughes isolate?
Enkephalins - changes to endorphins (‘naturally occurring substance that acts like DA’)
How do the endogenous opiates begin prior to synthesis?
Begin as large molecules made by neurons
proopiomelanocortin, etc
How are the endogenous opiates synthesized?
Large molecules cleaved into different types of chemical messengers
What is the potency of large molecule opiate precursors?
Much more potent than most endogenous opiates
When are endogenous opiates released?
Stress response, times of pain, strenuous exercise (childbirth, fight, long-distance running)
What (generally) are the behavioral effects of the opiates?
Sedative-hypnotic like
But not considered sedative hypnotics b/c they have other effects
What opiate receptor subtype is most involved in analgesic effects?
Mu
What opiate receptor subtype is most involved in euphoric effects?
Mu
Which opiate receptor subtype is most involved generally?
‘Mu leads the way’
What brain areas are involved in pain sensation?
NAcc
Amygdala
Thalamus
What brain areas are affective during pain?
NAcc
ACC
Thal
What is the first place pain is modulated at?
Dorsal horn, right when it enters spinal cord
Where does pain sensation go after?
Medulla > through pons > reticular formation/periaquaductal grey in midbrain > up to somatosensory cortex
Where does supraspinal control of pain begin?
Frontal lobes / hypothalamus
Where is the periaquaductal grey?
Encircles cerebral aquaduct
FULL of receptors involved in control of pain
Activates during anxiety / stress, mutes perception of pain
What is the locus coereleus and when does it activate?
It’s the brain’s equivalent of adrenal gland - release EP, NE (adrenaline) when you’re stressed
Where is the LC?
Junction of mesencephalon and pons
How do opiates reduce pain in the spinal cord?
A) Inhibit projection neurons
B) Inhibit interneurons that activate projection neurons
C) Exciting interneurons that inhibit projection neurons
How quickly does opiate tolerance develop?
Incredibly fast, and LOTS of tolerance - way more than anything else
What protein kinase do opiate second messengers modulate?
Why is this important?
PKC
Modulates NMDA receptors; opiate tolerance can be reduced by concurrent administration of NDMA antagonists
What is the difference between conditioned and contingent tolerance?
Conditioned = pavlovian - environmental. Environment becomes stimulus for the response. “Where am I taking drug”
Contingent = tolerance dependent on the activity of a specific neural circuit when an analgesic is present. “What am I doing while taking drug”
How do you reduce opiate tolerance with a drug?
Apply an NMDA antagonist
Because opiate receptors activate PKC, which agonizes NMDA receptors
How bad is opiate withdrawal?
Real bad, but not as bad as the press makes out
Bad case of the flu in worst case scenario
What are the physical effects of opiate withdrawal?
Anxiety, runny nose, nausea, fever, etc
What are the psychological effects of opiate withdrawal?
Fueled by negative reinforcement (avoidance of withdrawal) and positive (seeking rewarding effects)
