Exam 3: Opiates Flashcards
dried powdered mixture of 20 alkaloids obtained from unripe seed capsules of the poppy
natural, harvested, contains psychoactive opiates
opium
any agent derived from opium
morphine, heroine
opiate
all substances (exogenous and endogenous) with morphine like properties
opioid
where is opium derived from
opium poppy: Papaver Somniferum
-originated in Asia/Middle east
harvest: only 10 days they produce this opium sac with opiates
sap can be directly or indirectly processed
2 primary psychoactive constituents of opium are
morphine and codeine
what does opium contain
morphine - main ingredient
codeine, thebaine, narcotine and other ingredients
3rd most popular ingredient of opium
thebaine: not used therapetically, causes convulsions
used to make oxycodone
narcotic analgesics
block pain
codeine
cough suppressant, not as much euphoria
heroin
- made by adding 2 acetyl groups to morphine making it more lipid soluble
- 10x more fat soluble - reaches brain faster
- 3x more potent than morphine when injected
- rapid action - dramatic euphoric effects
partial agonists
pentazocine (Talwin), nalbuphine (Nubain), and buprenorphine (Buprenex)
binds receptors with less potency than full agonists (morphine) but fewer side effects and less risk of dependence
-less anti pain and sedation
pure antagonists
naloxone and nalorphine
structurally similar but have no efficacy
- prevent or reverse effects of opioids
naloxone
administered in response to suspected opioid overdose (Narcan)
fully synthetic opioids
not derived from naturally occurring opioids
fentanyl and methadone
fentanyl
50x more potent than heroin
100x more potent than morphine
used for severe pain and cough, detoxification
methadone
long lasting
NMDA antagonist - blocks pain but you do not get a high
- helps opioid addiction - safe since not same abuse liability
5 types of semisynthetic narcotics
krokodil heroin hydromorphone (Dilaudid) oxycodone (percodan) buprenorphine (Buprenex)
6 types of totally synthetic narcotics
Pentazocine (Tawin) Meperidine (Demerol) Fentanyl (sublimaze) methadone (dolophine) LAAM propoxyphene (darvon)
which totally synthetc narcotic has a faster onset and shrter duration than morphine
meperidine (demerol)
schedule II opioids
fentanyl, hydrocodone, morphine, methadone, opium extract, thebaine
schedule I opioids
desomorphine, diacetylmorphine (heroin)
schedule III opioids
buprenorphine
schedule V opioids
codeine
opioids used in surgical intervention
buprenorphine
heroin ROA
nasal, inhalation, injection
“skin-popping”: subcutaneous injection
“mainlining”: IV injection - usually later in addiction
Absorption of heroin
low bioavailability if takn orally - first pass metabolism
rapid when injected/snorted
distribution heroin
heroin 10x more lipid soluble than morphine - faster actions
passes BBB and placental barrier
metabolism and elimination heroin
broken in liver into active metabolites:
morphine and morphine-6-glucuronide
elimination: urine
morphine ROA
intra-muscular injection (hospital setting), oral
absorption and distribution of morphine
absorption: low bioavailability oral (25%)
distribution: crosses brain slower than heroin - less lipid soluble
metabolism and excretion morphine
active metabolite: morphine-6-glucuronide
- gets into brain quicker than morphine
- 10x more potent than morphine
elimination: urine
fentanyl ROA
injection, transdermal patch, oral, intranasal
absorption fentanyl
highest bioavailability is injection intranasal and transdermal patch
lower with oral
distribution fentanyl
100x more potent than morphine - highly lipid soluble - more than heroin and morphine
rapid, widespread distribution to lungs, heart, kidneys, brain, liver, muscles
need less to get strong effects
metabolism and elimination of fentanyl
metabolism: brokwn down in liver into inactive norfentanyl
elimination: urine
synthesized in POMC neurons of the arcuate nucleus and nucleus of solitary tract (NST)
-project to limbic system, brainstem, spinal cord, PAG, mesolimbic DA system
B-endorphins
thalamus, striatum, PAG, spinal cord
enkephalins
striatum, hippocampus, hypothalamus, nucleus accumbens
dynorphins
endogenous opioid peptides
B-endorphin, enkephalins, dynorphins
opioids frequently co-expressed with other neurotransmitters
- GABA in striatum
- GABA and glutamate in spinal cord
effects of opiates mediated by what 3 receptor types
Mu, Delta, Kappa
where are opioid receptors distributed?
CNS: cortex, limbic system, basal ganglia, spinal cord, enteric nervous system
endogenous peptide of mu receptors
endorphin
where are mu receptors for analgesia
medial thalamus, PAG, median raphe, spinal cord
where are mu receptors for feeding and positive reinforcement
nucleus accumbens and hypothalamus
where are mu receptors for mood
amygdala
where are mu receptors for cardiovascular and respiratory depression, cough control, nausea
brainstem - medulla
where are mu receptors for sensory integration
thalamus, striatum
where are delta receptors most commonly found and then other location
forebrain
cerebral cortex, thalamus, striatum, spinal cord
endogenous peptides of delta receptors
endorphin and enkephalin
role of delta receptors
modulate olfaction, motor integration, reinforcement, cognitive function
learning, memory, attention
overlap of mu and delta receptors suggest
modulation of both spinal and supraspinal analgesia
major peptide of kappa receptors
dynorphin
where are kappa receptors found
striatum, hippocampus, amygdala, hypothalamus, and pituitary
what do kappa receptors have a role in
regulation of pain perception, gut motility, dysphoria
make you feel bad when they are activated
effects of heroin, morphine, methadone at mu receptor
agonists
effects of buprenorphine at mu receptor
partial agonist
effects of naltrexone and narcan at mu receptors
antagonists
3 ways opioids inhibits nerve activity
postsynaptic inhibition
axoaxonic inhibition
presynaptic autoreceptors
all opioid receptors are
inhibitory and metabotropic
postsynaptic inhibition
receptors activate a G protein that opens K+ channels so K+ leaves cell, hyperpolarizing postsynaptic cells reducing the firing rate
axoaxonic inhibition
receptors activate G protein that close Ca channels, reducing release of neurotransmitter
in this case an opioid is inhibiting a different presynaptic neuron
presynaptic autoreceptors
activate G proteins and reduce release of co-localized neurotransmitter
limiting the same presynaptic neuron
how to get reinforcing aspects of opioids
B-endorphin and opioid drugs inc VTA cell firing by inhibiting the inhibitory GABA cells which disinhibits and turns on DA
effects of dynorphin on mesolimbic dopamine
it acts on kappa receptors on DA terminals and reduces release of DA causing dysphoria
it does this through axoaxonic synapses
when it binds it prevents VTA from releasing DA, get dysphoria associated with withdrawal symptoms
chronic use of opiates leads to
neuroadaptive changes, responsible for tolerance, sensitization, and dependence
tolerance and opioids
- opioid receptor desensitization and internalization with chronic use
- internalized so less receptor available
- does not respond to natural levels of opioids, need more drug to get effects
- compensation: upregulation of opioid receptors - body thinks receptor is broken so it makes more - this is problem when stop using opioids bc you have lots of receptors to bind transmitter and get huge sensitization
- cross tolerance
opioid overdose
-respiratory failure
-not all symptoms undergo tolerance at the same time (first euphoria goes away)
so people say lets take higher doses to get euphoria but you do not have tolerance to respiration yet, so when people take high doses it shuts down the ability to breathe - die
what are the opiate user’s desired effects?
analgesia
cough suppression
sedation - to help sleep
euphoria
Mu1
analgesia and euphoria
Mu2
constipation, respiratory depression
Kappa
spinal analgesia, dysphoria
delta
analgesia through endorphin, enkephalin, dynorphin system
also dysphoria
2 pain pathways mediated by mu
ascending pathway: from periphery to brain - tells us we are hurt
descending pathway: PAG
- shuts down the ascending pathway to stop pain
how do opioids effect pain pathway
they inhibit the ascending pathway so brain does not get signal there is pain this is bc opioid receptors are in spinal cord
disinhibit (activate) descending pathway to stop pain
affective component of pain - emotional pain is regulated by what
anterior cingulate cortex
common symptoms of opiate intoxication
- miosis: pin point pupils
- nodding
- hypotension
- depressed respiration
- bradycardia
- euphoria
- floating feeling
acute effects of opiates
euphoria, drowsiness, body warmth, heavy feeling in limbs, dec sex drive, impaired social interactions
physiological effects of opioid use
respiratory depression
lowered core body T, flushed skin
itching - release of histamine
pupillary constriction - pin point
long term effects of opioid use
impotence - sexual dysfunction constipation-people take imodium when do not have access to opiates -hypoxia -collapsed veins -dec immune function
what do people tale when do not have access to opiates, it is for constipation
imodium
opioid withdrawal results in
rebound hyperactivity - opposite symptoms of opioid use
fentanyl and withdrawal
symptoms 4-6hrs after last use
peak 12 hrs post use
last 5 days
morphine/heroin and withdrawal
symptoms 6-18 hours after last use
peak 36-72 hrs post use
last 7-10 days
methadone and withdrawal
symptoms 24-48 hrs after last use
peak 3-21 days post use
last 6-7 WEEKS
