Opioids: Nov 26th Flashcards
where is opium derived from
Sap derived from the poppy (Papaver somniferum)
how long have the properties of opium been known for
1000s of years over the contents (hot climate where you can grow it
what is the difference between an analgesic and a narcotic
analegisic= pain relief narcotic= opium based pain killers
anesthetics vs analgesics ?
anes= knock out analgesic= alieviate pain
which is mj
analgesic
narcotic is a subcategory od opium
t
4 categories of opium
endogenous
alkaloids
semisynthetic
synthetic
example of a endogenous opium
endorphin (release to alleviate pain during physical endurance)
T: directly derived from sap
alkaloids
example of alkaloids 2
morphine and codeine (potency difference)
T: derivatives of directly extracted substance
semisyn
2 examples of semi
heroine (from codeine)
oxycodone (from morphine)
T: structurally different opiates (perfect molecule influence receptor)
synthetic
2 examples of synthetics
methadone and fentanyl
which class of drugs are opium
Exhibit euphoric (stimulant) and anxiolytic (depressant) effects, used as a medicine (anti-psychotic) NOT A HAL
which category of opiate has different subjective effects
derived= semisyn
since opium has no hallucinogenic properties we can rule what out
seretonin influence
different intake methods depend on what property of the drug
potency and resistance to metabolism
what effects do you have from oral opiod ingestion
mood alleviation (happy and relaxed), cough suppression (not coating throat)
what form of intake causes euphoria
inhalation
what are the 2 effects of intravenous
euphoria, pain relief
what happens to body temp and pupils
Decreased body temp (risk of hypothermia), pupil constriction (hal=widen opioids close to prep you for sleep)
how long does it take opioids to kick in when injected
2 min
why would anyone put themselves through injection
“rush” “flash”: intense euphoria = emotion within 2 min
other than euphoria what happens in stage 1 injection
Tingling/warmth in “lower abdomen” resembling sexual
orgasm = v reinforcing !!!
what is stage 2 after injection (2-3 hours after)
“on the nod”: tranquil drowsiness = soothed
what happens to sexual interest in stage 2
Reduction of sexual interest as a result of lowering testosterone levels
what is stage 3 after injection
withdrawal = SO RAPID
how does the injection cycle relate to poor outcomes for users
lower testosterone= low social dom and lack of interest in partner = isolation
T: street name China white, China girl, TNT, Apache, percopop
fentanyl (hit us before rest of world first)
trade name for fentanyl
Duragesic, Sublimaze around since the 70s
which opioids are which schedule
Schedule I = Heroin
Schedule II = Morphine, Methadone, Fentanyl Schedule V = Codeine, Oxycodone
3 ways fentynol is given
Demerol – anaesthetic, “lollipop” – palliative care, Duragesic – chronic pain (analgesia)
how does it compare to morphine in potency
100x (carfenanyl 1000x)
what is the fentaynol crisis
crisis of contamination
3 ways to intake fentanyl
oral, transdermal, insufflation
what is the problem and gain with fast fentanyl absorption
respiratory depression increases with faster
absorption but less nausea and itching
what makes fentanyl so effective
potent and resistant to metabolism
what is the synthetic opid used for sedation and analgesia
Desomorphine
why was desomo created
powerful surgical anesthetic back in 1930s (8x more potent than morhpine
what were the downside of desomorphines potency
Increase in respiratory depression, septicemia, and
cardiac arrest
what is septicaemia
arge amounts of bacteria are present in the blood from toxins in poop not going anywhere
how is crocodile related to desomorphine
synthesized version of desomorphine from codeine
3 street names for desomorphine synthesized from codeine
Krokodil, zombie, flesh-eating
krokodile has high toxicity from impure.. 2
preparation or reduction methods
2 things that are added to Kroc during preparation
paint thinner, HCL
what does the impure preparation cause 2
Inflammation liver, kidney
3 this created during impure reduction method
gasoline/ kerosine, iodine. phosphorus
3 things impure reduction methods cause
Thyroid damage, “Phossy Jaw”, gangrene
T: a condition that occurs when body tissue dies
gangrene
you can’t get addicted to Kroc due to terrible adverse effects
f such a powerful painkiller you don’t feel it until it wears off
how is Kroc related to desomorphine
when someone tries to create desomorphine
what is opium doing inside the body
agonizing the endogenous opiod system
Proopiummelancortin, proenkephalin, prodynorphin what are these
endogenous opiod chemicals= free floating in bodies but bound to other things= under high duress enzyme cuts active portion out from rest of molecule
T: separating the molecule into separate chains
cleavage
what are the 2 steps to cleavage
- internal enzymatic action
2. active metabolite= morphine (cut morphine from molecule)
Enzyme … converts codeine to morphine
CYP2D6 (responsible for endogenous functions as well)
2 ways opium macts as a agoist
- cleavage
2. g protein metabotropic receptors
what enzyme is responsible for cleavage
CYP2D6
is the molecule after cleavage active
yes= double whammy!
ipiods become G-protein bound to Metabotropic receptors- what does this mean
it changes the system- makes neurons return to resting potential sooner- they don’t fire
how does opium return neurons to resting potential sooner
allowing k to influx inwards
what is sensation vs perception
p: subjective interpretation of sensory signals
sensation: sensory experience
how fast do neurons fire when you feel pain
fast
how do opioids influence the system long term
makes neurons less likely to fire (depressant aspects)
how can this explain runners high
produce endogenous endorphins so you can endure physical pain
function of a pure agonist
pain relief
2 pure agonists of the endoginist system
fentanyl and morphine (medical)
function of partial agonism of endogenous system
Pain relief with no respiratory effect
example of partial agonist
Buprenorphine (less potent)
function of a mixed or agonist antagonist on endog system
Treating opioid addiction (occupy receptor s.o.a., block drug/other receptor)
2 examples of mixed agonist antagonists
Naloxone, methadone (no high but dependance)
why are they called mixed
they are agonizing receptors but they do nothing subjectively= antagonizing other chemicals e.g. the drug (implies how we use)
the mixed antag/ agnostics are used as … in some countries
anxiolytic
what are the 3 areas of pain perception you can target
periphery, CNS, protections from brain (proximal= brain/ distal= body)
opioids agonism what?
endogenous opiod system
how do opioids agonise the endo opiod system
by antagonizing the gABA (antagonist) system which stops endo opioids pain relief
gaba supresses the inhibitory response of … receptors
dopamine = influx= reinforcing
Suppression of the inhibitory response on dopamine receptors: where in brain does this happen
VTA
what does opioids do in the Nucleus accumbans
Activation of u opioid receptors that inhibit the GABA neurons (inhibit GABA all over)
as opium antagonists GABA what happens to dopamine
Allows dopamine to be released in VTA, and “enhancement” of the dopaminergic response
what does the enhacement of the dopamine system do
motor and reward control
ONE study in 1999 found relationship between opioids and reduce … receptor as a secondary function
glutamate = reason they don’t show excitement in response to down regulation of system 41:40
what mechanism is acting in the body
inhibitory
T: sensory pathways related to pain
perception
nociception
T: in charge of sensory pain signal from receptor to spinal chord
Ad & C fibers
what do opioids do at ad and c fibers
Inhibition of neurotransmission
sensory pain signal
from spinal chord to Thalamus what NT involved 2
Glutamate & substance P
what do opiods do to stop glutamate and substance p from sending pain signal to thalamus
Activation of medulla inhibits neurotransmission to thalamus
2 ways to stop pain from getting to the brain?
2 ways to stop pain once in the brain?
slides 7-8=. 4 ways to stop pain in the body
when pain meds targeting the PNS how is its effect on pain described
“dulling”/”blunting” of pain= take edge off
how long until you see withdrawl with opioids
3-4 hours
is there tolerance with opium
oh yes withdrawl tells you that
is the tolerance rapid? dose dependant?
not rapid but dose dep
what does it mean to say opiod tolerance is Accrued
the more you take the more tolerance
what does it mean to say tolerance is relational
proportional to the amount you take
opiod tolerance abides by allostatic principles what does this mean
system changes more permanently to adapt to enviro demands to try and achieve homeostasis
opiod tolerance is selective to which properties 3
analgesia, euphoria, and respiratory depression
how sensitive is opiod tolerance to conditioning effects
extremely= less of a dose in unfamiliar place= OD
how long does withdrawl last
5-10 days ( can stretch out or take full hit now)
what do you see in first 4-6 hours of withdrawl that intensifies at 3-4 day mark
craving = psycholigal
when does the physioligcal aspect kick in and what is it
8-12 hours with flu symptoms =respritory and hyperthermia
what is the third stage of withdrawl that kicks in at 48- 72 hours
secondary effects: pupil dilation (opposite of when on the drug), anorexia, piloerection (goosebumbs= cold turkey), spastic arm/leg movements (“kicking the habit”)
does pupil dilation happen similarly in hallucinogens and opioids
f when on Hal when coming off opioids
…% relapse after withdrawal associated with environment
90= evidence for conditioning
why 90% relapse if not as dangerous as alc and barbiturates withdrawl
not dealing with psychological component causing relapse
how long does LT vs short term detox last
LT 180 days
ST 30 days
3 benefits to methadone and buprenorphine as detox
Prevent withdrawal, long-lasting effects, weak/no euphoria
how well does methadone and bupren work for ST detox
moderate withdrawal for short-term
what is the debate with using methadone clinics
Institutional control of addicts (i.e. not real treatment)
how long is rapid vs ultra rapid detox
rapid= 10 days ultra= 2 days
can you go through rapid and ultra rapid awake
no induce coma
T: binds as an agonist and induces opposite pharmacological response
inverse agonist (mixed agonist antag)= lowers response
what inverse agonist is used in detox
naloxone
how is buprenorphine different from methadone
does have analgesic properties= better for those who have been using for long time
naloxone dereases withdrawal symptoms, decrease duration
f increases withdrawl
Ultra-rapid in conjunction with …. for first few hours
sedation/anesthetized
