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Lecture 5
Downers Part 1
Downers
Opiates/ __________________
Sedative-Hypnotics
Alcohol (covered in the next lecture)
Opiates/Opioids
Based on the __________________poppy
Refined versions and synthetic versions
Opium
Morphine
Codeine
__________________
Hydrocodone
__________________
Heroin
All developed to treat pain, diarrhea, coughs and other illnesses
What’s the difference?
__________________
Opium extracts and semisynthetic opium preparations
Extracts: Morphine, codeine, thebaine
Semisynthetic: heroin, hydrocodone, oxycodone, hydromorphone
Opioids
Synthetic __________________
Methadone, oxymorphone, naloxone
Historical Overview
__________________first
Limited abuse potential
Bad taste- limited strength
__________________
Much stronger euphoria and well-being
“chasing the dragon”
Heat heroin on tin foil and inhale fumes through a straw
Extremely high abuse potential
Morphine etc…
__________________is 10x stronger than opium
__________________is 2x stronger than opium
Heroin: an attempt to find a more effective painkiller without addictive properties
__________________stronger than morphine
Very fat soluble
Morphine is only partly fat soluble (not as strong)
Injecting…
Not only did the __________________and pain relief occur as with inhaling
With injecting, an intense __________________ occurred
Historical note
Opiates were in many __________________and medications
Iatrogenic addiction very common
Physician induced __________________
56-71% of opium addicts were women in the 1880s
Where do we get this stuff?
Golden Crescent
__________________and __________________
Afghanistan grew 92% of the world’s supply in 2006
Golden Triangle
__________________ (Burma), __________________, Laos
5-6% of the world’s supply
US Heroin
Majority has come from Mexico and Columbia
__________________heroin
Most popular on the US west coast
Dissolves easily in water and is smoked easily
Lots of impurities- also, very strong though (40-80% pure)
Biological Effects of Opiates and Opioids
Deals with:
__________________
Pleasure
__________________suppression
Diarrhea control
Substance P
A neurotransmitter that seems to be responsible for the signaling of
__________________
When pain gets intense, body releases __________________and enkephalins
Neurotransmitters that attach to opioid receptors
__________________the release of substance P, thus blocking the pain signal
from beginning
Not a perfect process: some pain signals still get through
Opioids and Opiates
Act like the endorphins and enkephalins __________________ substance P from being
released
Also __________________the receptors of substance P, so that the little that does get
through doesn’t work
Also works on emotional pain
Activates the ____________________________________
Removal of stress can negatively reinforce the user to take more drugs
Mechanisms for pleasure
Works at __________________receptors in the reward centers
Inhibits __________________ (an inhibitory NT)
Leads to increased activity
Activates __________________receptors (increases dopamine neuron activity)
Increases the release of __________________
Here’s the link: Pleasure and Pain
The area of the brain that signals pleasure is the ________________________________
that signals the removal of pain
Further motivates a user to get more drugs into the system
Also leads users to use to relieve withdrawal effects more than to use for the high
or the rush
__________________ is enough of a high for many users
Main receptors for opioids
Naturally occurring opioid __________________
More for the endorphins and enkephalins, than for drugs
Found in the __________________, spinal cord, GI track, autonomic nervous
system, and on various organs
three main types
Mu
__________________
Sigma
Where are they?
Mu and Sigma: trigger __________________pathway, block pain, alter mood, contract
pupils, __________________the autonomic nervous system
Kappa: induces dysphoria (the opposite of euphoria) and mediates pain near the
________________________________________
Opiates/opioids affect the different receptors differently
This is why some are better at blocking pain whereas others are better at inducing
a high
Other activities
Inhibits the __________________center of the brain
Located in the brainstem
Some cough medicines used to have opiates in them
Inhibits the brain areas that controls digestion and intestinal muscles
Also located in the ____________________________________
Many opium addicts have severe constipation
Opioids affect every part of the body
Lowers blood pressure
Messes with the __________________
Lowers breathing rate
Messes with the __________________
Constricted pupils
Messes with the __________________
Slurred speech or raspy voice
Messes with ____________________________________
Coordination is slowed
Messes with __________________
And we’ve already mentioned
__________________centers in the brainstem
__________________centers in the brainstem
Makes users insensitive to pain
Damages the __________________response
Without pain, the body doesn’t respond in a way to fix areas that are damaged
Even __________________desire
Women have delayed periods
Men produce less testosterone
Desire is dulled
Are they addictive?
Of course
Why?
Tolerance develops __________________
__________________ metabolism of the drug
Nerve cells are desensitized to the drug
__________________ the drug faster
Various other methods to compensate for the effects
Your book describes a patient
“After one year of opioid use… using five fentanyl patches, 20 Demerol tablets,
and continuous morphine suppositories.”
However
__________________ develops at different rates for the different body systems
May develop a tolerance to the pain relieving effects, but develop no tolerance to
the __________________ __________________
Do opioids change the brain?
Some evidence says there may be __________________effects from taking strong
opioids
Nestler (1997) gave rats lots of __________________
Found that their dopamine producing cells shrunk by about ¼
Body produces less dopamine naturally
Less ability to feel pleasure after drug use stops
Leads to a desire to use yet again
Cross dependence very strong
Basis of __________________as a treatment for heroin users
Users build up a physical dependence on __________________
Can relieve the withdrawal symptoms with a less damaging drug: methadone
Not all opioids work on the same receptors though (remember mu, sigma, and
kappa), so some may create tolerances more than others (at at different receptors)
Three stages of Opium withdrawal
__________________withdrawal
Body tries to go back to normal a bit too fast
Cramps
Uncontrollable jerking and kicking
Vomiting
Insomnia
“Creepy crawlies”
Delirium
____________________________________withdrawal
Emotional disturbances still there, but physical symptoms of withdrawal are
mainly gone
Sleep problems and mood swings still
Protracted withdrawal
____________________________________cued withdrawal
Can last for years, even decades after the user has stopped using
Norepinephrine plays a large role
Opioids stop the release of ____________________________________
Body stores more and more
When the user stops using, tons of norepinephrine is released in the brainstem
Probably why withdrawal includes __________________- insomnia
The main sleep area (locus coeruleus) is largely affected here
More on withdrawal
Opium withdrawal is almost never ____________________________________
Although it may feel that way
Other issues
Flesh eating bacteria
Sedatives and Hypnotics
Need to be careful of iatrogenic addiction
__________________induced addiction
Sedatives: calming drugs
Valium, Xanax etc…
__________________: sleep inducers
Short-acting barbiturates and benzodiazapines
How do they work?
Typically will work on
__________________
Serotonin
__________________
Controls anxiety and restlessness
More specifics please
Not completely sure of the link, but here’s my take
Book describes __________________ as causing:
Muscle relaxation
Heat loss
Lowered __________________
Reduced coordination
Sounds similar to alcohol to me
Probably due to the affects on __________________
The main inhibitory NT in the brain
What about serotonin and dopamine?
__________________
Linked to mood and sleep changes
__________________
Reinforces the desire to take the drug
Hypnotics
Work on the brainstem primarily
__________________
Muscle coordination
Quick History of Sedatives/hypnotics
__________________
First used in the 1850s
Metabolized slowly so… it could lead to toxic levels in the body
____________________________________
Used to treat DT’s and pregnancy symptoms
The original “mickey” slipped into drinks
Started in 1869
The famous ones
__________________
Very popular in the 1930s and 40s
Phenobarbital, secobarbital
Low margin of safety, high addiction potential
__________________
Popular in the 50s
“mother’s little helper”
Replaced barbiturates as the preferred sedative drug
Benzodiazapines
Librium, __________________, Xanax
Work like barbiturates
Less __________________though
Other sedatives
What about __________________, Ambien and Lyrica?
Marketed as ____________________________________
Has NOT been proven experimentally
Biological Effects
Benzodiazapines
Agonist to GABA, __________________, and serotonin
Inhibits anxiety and stimulation; thus it calms
Some of the ____________________________________ (the parts that they
break down into) are active substances that can cause more effects
Tolerance
Typically develops as the liver becomes better at processing the drug
____________________________________reverse tolerance
Older people need less of the drug than younger people
__________________dependence
Only happens quickly when patients take 10-20x the prescribed dosage
With normal doses, it takes over a year
Withdrawal
Much of the dependence may be psychological- not physical
If physically addicted, withdrawals can be __________________
If use isn’t tapered off slowly, __________________or death may occur
Due to low GABA, and excess levels of norepinephrine and epinephrine
If addiction was caused by long term normal dosages, withdrawal symptoms are
__________________
Memory problems?
May disrupt __________________systems in the brain
Used as “date rape” drugs
Barbiturates
Act like benzodiazapines, although the symptoms/effects are more like
__________________
A user’s current mood will typically be amplified with barbiturates (and alcohol)
More likely to ____________________________________with barbiturates than
with benzodiazapines
Does tolerance develop?
Two main types
____________________________________ tolerance
Metabolism of the drug increases
____________________________________ tolerance
Nerve cells are less sensitive to the drug
Withdrawal and Dependence
Tissue dependence happens after long periods of high use
__________________can be very dangerous
Very similar to the properties of benzodiazapines
Ambien, Lunesta and others
Most non-barbiturate, non-benzodiazapine sedatives work as an agonist to GABA
Basically work very similarly to ____________________________________
Can become habit forming long term, but typically are safer than benzodiazapines