Final Exam Opioids Flashcards
opiates:
drugs derived directly from the opium poppy
How is opium made?
the resin (gum) that seeps from cuts in unripe poppy pods is scraped and dried to make opium
opium poppies have been cultivated for use since at least ___ in ___
3400 BC
Southwest Asia
opium use in the U.S. contributed to the ____, which outlawed the production, use, possession, and distribution of opiate and coca products, except for medical purposes
Harrison Narcotics Tax Act in 1914
Today, about 90% of the world’s supply comes from __
Afghanistan
morphine was first isolated from dried opium poppy resin by Friedrich W. Serturner in the early 1800s–he named it after ___, the Greek god of dreams
Morpheus
Making Herion #1
- opium is boiled in water, producing a clear brown liquid
- impurities are scraped from the top, and lime is added, producing ___
- the solution is filtered to remove impurities
- ___ is added and the solution is reheated
- morphine collects as a solid at the bottom
morphine alkaloid
ammonia
heroin #1, comprises only 10% of ___
raw opium
heroin (diacetylmorphine) is obtained by converting ____ and is sometimes called ___
morphine to heroin base
heroin #2
diacetylmorphine is also known as
heroin
heroin #2 is made by
- morphine base is mixed with ___ and heated to __ degrees Celsius for two hours
- morphine dissolves
- upon cooling, morphine and ___ bond chemically to form heroin
- the heroin is dissolved in water and ___ is added, producing heroin base
acetic acid, 85
acetic acid
sodium bicarbonate
heroin #2 can be snorted but not ___
smoked
heroin base must be purified further to produce ___, which is smokable
heroin #3
Heroin #3 is made by
- heroin #2 is mixed with ___ and stirred until it dries
- the dried past is crushed to form ___
hydrochloric acid
“brown sugar”
heroin #3 is only ___ pure, and is therefore not suitable for injection
20-30%
heroin #4 is ___ pure and injectable
80-90%
Heroin #4 is made by
- hydrochloric acid and __ are added to heroin base (heroin #2)
- the product is filtered and dried to form a white powder
- this powder is compressed into bricks with a heroin press
ether
opioids:
semi- and fully-synthetic opiates that are manufactured chemically
both opiates and opioids are now often referred to as ___
opioids
opiates are very effective pain relievers but their addictive properties led pharmaceutical companies to seek ___ (Koob’s highly charitable interpretation)
synthetic, opioid alternatives
___ (brand name Demerol) and ___ (brand name Dolophine) were developed by German scientists in the 1930s to pursue Hitler’s goal of German independence on foreign markets
pethidine/meperidine
methadone
Many other synthetic opiates (opioids) have been developed and they have similar ___
chemical structures
Name 2 natural and one semisynthetic type of opioids
Natural: morphine (e.g., Dilaudid), codeine (e.g., Vicodin)
Semisynthetic: buprenorphine (e.g., Suboxone, Subutex, etc.)
opioids vary widely in strength, and many are metabolized into ___
other opioids
endogenous opioids:
neuropeptides produced by the body that have “morphine-like” actions
3 endogenous opioids:
enkephalins
dynorphins
endorphins
these endogenous opioids bind to the ___ as opioid drugs of abuse, just not as ___
same receptors
powerfully
What is the Dilemma of Exogenous Opioids?
that nothing relieves pain as well, but nothing is more addictive
The probability of abuse/dependence given ANY use in the past year is highest for __ with about a __% chance
Heroin, close to 70%
The prevalence of prescription opiate addiction is ___
increasing rapidly
use often begins with prescriptions for pain; to which ___ individuals become addicted
genetically vulnerable
drug deaths from prescription opioids increased nearly ___ from 1999-2014, and ___ are increasingly involved
six-fold (six times as great or as numerous) synthetic narcotics (e.g., fentanyl)
many of those who become addicted eventually turn to ___ because it’s cheaper and easier to get
heroin
heroin deaths are up almost ___ since 1999 and ___ are increasingly involved
eight-fold synthetic narcotics (e.g., fentanyl)
True or false? heroin purity is unpredictable, and much stronger opiates (e.g., fentanyl, carfentanil) are sometimes cut in
true
Medical Uses for opioids:
anti-diarrhea properties–used to save lives during dysentery epidemics in the 19th Century
pain relief:
a therapeutic dose of morphine relieves pain for 3-4 hours
much larger effect on dull, aching pain than acute sharp pain (good for survival)
blunted affective reaction to pain
poor at relieving neuropathic pain
analgesia
(pain relief)
What is balanced anesthesia?
use of different opioids before and during surgery to induce analgesia (pain relief), amnesia, muscle relaxation, and abolition of reflexes (e.g., fentanyl, alfentanil, remifentanil)
Pharmacokinetics: blood levels of smoked heroin peak in ___ and decline rapidly to minimum limits of detection within __
1-5 min
30 min
What does it mean that heroin is a prodrug?
it has no pharmacological activity, but it’s active metabolites do
Koob et al. (2014) describe opioids as ___ drugs of addiction
“classic”
a few people ___are able to maintain quasi-controlled use patterns–>this is playing with fire because __
“chippers”
it often precedes (come before something in time) compulsive use
early outcome data suggested that heroin addiction is a ___, and that __ of addicts die
lifelong condition
half
In the 1960s compulsory drug treatment centers predominantly use ___ for treatment
methadone maintenance
Methadone maintenance was replaced with ___ because ___
suboxone
methadone itself is an addictive opioid (marketed originally as a pain killer by Eli Lilly)
True or False? Although data are hard to collect, opioid addicts do recover in self-help groups such as Narcotics Anonymous without maintenance therapy
True
Treu or False? there may be a need for maintenance therapy for some, but abstinence is possible and should not be ruled out
true
opioid intoxication following injection or smoking of 1-3mg heroin or 3-15mg morphine is described in four stages by Koob et al. (2014):
- Rush (45s) intense pleasure/euphoria
- Nod (15-20min) escape from reality detached
- High (several hours) state follows rush general feeling of wellbeing
- Being straight (up to 8h) is not experiencing the 3 states but also not experiencing the withdrawl
In the opioid intoxication stages, the ___ is resistant to tolerance but the __ and __ are not
rush
nod, high
opioid tolerance: tolerance to the sedative, euphoric, and analgesic properties of opioids builds ___
rapidly
opioid tolerance: those who are addicted can inject doses up to __ times the lethal dose for a drug-naive individual
70
opioid tolerance: tolerance also shortens the duration of ___
drug action
True or false? opioid tolerance: cross-tolerance also develops (e.g., switching from codeine to morphine)
True
tolerance occurs for two reasons:
- neuro-adaptive down-regulation of the opioid system
2. conditioning to place of use and associated compensatory body reactions in the opposite direction of opioid effects
opioid withdrawal: like other drugs of abuse, early use is driven by ___ and after tolerance develops, ___ drives use
positive reinforcement (feeling of elation and euphoria) negative reinforcement (avoiding withdrawal)
opioid withdrawal symptoms peak at
48-72 hours
many of those who are addicted will go to great lengths to avoid __
acute withdrawal
True or false? Many treatment providers believe acute withdrawal should be prevented, hence maintenance therapy with methadone, suboxone, etc.
True
notably, methadone and suboxone withdrawal are more ___ than heroin withdrawal
protracted (lasting for a long time or longer than expected or usual.)
why the different approach with opioids vs. other drugs?
notably, in contrast to some drugs of abuse (alcohol, benzodiazepines), opioid withdrawal is not life-threatening
some withdrawal symptoms, including increased pain and stress sensitivity, dysphoria, and certain metabolic changes can persist for about 5 months, a phenomenon known as ___
post-acute withdrawal
since opioids cross the ___, infants born to opioid-addicted mothers suffer withdrawal
placental barrier
endogenous opioids were not discovered until the __
1970s
it was quickly discovered that opioids have ___, and that animals will self-administer when delivered directly into the brain
analgesic properties (they relieve pain. Unlike medications used for anesthesia during surgery, analgesics don’t turn off nerves, change the ability to sense your surroundings, or alter consciousness. They are sometimes called painkillers or pain relievers)
analgesia occurs through direct injection into various sites (4):
rahpe nuclei
periaqueductal gray
certain medullary nuclei
spinal cord
animals will also self-inject into the ventral tegmental area and the nucleus accumbens (the mesolimbic reward system). Given that opioids are not ___, this was (and is) perplexing
dopamine agonists
one possibility as to why animals will also self-inject into the ventral tegmental area and the nucleus accumbens (the mesolimbic reward system) even tho opioids are not dopamine agonists is that ___
μ opioid agonists disinhibit inhibitory GABA interneurons, raising midbrain DA levels indirectly
the μ opioid receptor is most important for the ___
δ and κ receptors are implicated in ___
addictive properties of opioids
tolerance and dysphoria
analgesic properties are caused by ____ in both the brain and spinal cord
direct inhibition of nociceptive activity
nociception:
sensory nervous system response to harmful or potentially harmful stimuli
True or false: intoxication results from blocking the affective component of pain (brain only)
True
