Opioids Flashcards
Where do opioids come from
Poppies - papavar somniferum. After it dies the middle swells where opium is extracted
What drugs to opium turn into
Morphine, codeine, Thebaine,
Morphine - heroin or hydro morphine
thebaine - oxycodone, etorphine
They all belong to narcotic analgesics
Pharmacokinetics of opioids
Administered in all possible routes, absorption distribution depends on compound. Mainly metabolized in the liver
Half life of certain drugs (heroin, morphine, fentanyl, oxycodone, hydro morphine)
Heroin - 15-30 min
morphine - 2 hrs
Hydro morphine - 2.5hrs
Oxycodone - 3-5 hrs
Fentanyl - 3-7hrs
What are the 3 opioid receptors
Mu (u) - most important- high affinity for morphine, located in brain and spinal cord
Delta (S) - forebrain, regulate motor, cognitive, and olfaction
Kappa (K) - regulate pain, hunger, temp. Located in hypothalamus, amygdala, etc.
All are G proteins metabotropic receptors with several actions
Postynaptic inhibition of opioids
Open k+ channels, so they leave the cell (inhibitory) causes a change within the neuron
Axoaxonix inhibition
Closes Ca2+ channels, opioid neurons cause transmitters of calcium to close and block calcium receptors
Endorphins
Made in the pituitary, target mainly forebrain and spinal cord.
Functions: analgesia (#1), cardio and resp. Depression, vomiting, atitussive, etc.
Analgesia and opioids
Inhibits pain, both endocrine and neural responses are modulated on multiple levels
How do opioids reduce pain
Cause release of interneruons that inhibit activation of spinal cord neurons
Descending modulatory pathways - inhibit excitatory neurons, and block downstream signals resulting in no transmission (mainly PAG pathway)
What forms of pain control depend on opioids
Accupuncture, releases endogenous opioids
Gene therapy, gene for proenkephalin through a modified virus
Dual inhibition of peptidases, inhibits two enzymes that degrade enkephalin
Partial agonists
Produce weaker biological effects. Act as agonists for some receptors and antagonists for others - morphine
Neutral antagonists
Drugs that produce no pharmacological activity - from morphine such as nalaxone and nalorphine
What areas do opioids produce the most important effects
The CNS and gastrointestinal tract, can relief diarrhea and coughing
NOP-R
One of 4 opioid receptors, in the CNS and peripheral nervous system
With u-receptor is effective in reducing pain without narcotic side effects
Endorphins
Group of endogenous peptides that stimulate mu and delta receptors, reducing pain and enhancing general mood
Proenkephalin
A large opioid pro peptide precursor. Broken down to form smaller active opioids called enkephalins in the brain
Are opioid receptor mediated cellular changes inhibitory to excitatory
Inhibitory
Early pain vs. Second pain
First is immediate
Second is after - more emotional, opioids as analgesics mainly reduce secondary pain
Where do opioids mainly inhibit pain
Spinal cord
Cross - dependence
Withdrawal sings occurring in a dependent individual can be terminated by administering drugs in the same class
Brain areas in opioid abstinence syndrome
Several areas do, no particular one. Gastrointestinal tract and autonomic nervous system involved
Structure involved in reinforcement of drugs
NAcc - a limbic structure, important for reinforcement value of many abused substances
how is withdrawal in opioids explained
Himmelsbach hypothesized that the nervous system adapts to presence of a drug (tolerance) when the drug is taken away, the adapted function continues (withdrawal) -
Morphine inhibits cAMP, so when taken away larger amount of it are produced
Electroacupuncture
30 minutes of EA 12 hours after drug administration reduced signs of withdrawal, gets better the more you do it
Treatment for opioid use disorder
1st - detoxification
2nd - support and counseling (methadone maintenance program)
3rd. Buprenorphine maintenance
4. Narcotic antagonists - blocks effects of self administered opioids
5. Vaccines for addiction treatment
Neural adaptation observed following chronic opioid use
Increased firing rate of neurons in the locus coeruleus
Suboxone (burprenorphine and naloxone) and naloxones purpose in it
A combination of the two drugs. Naloxone within it is intended to interfere with attempts to abuse suboxone when take intravenously
Symptoms of opioid withdrawal include
Hyperalgesia, diarrhea, and flu-like symptoms
Cross-tolerance
When tolerance for one opioid drug, effectiveness for others also declines
