3. What are Opiates?
• Narcotics that
originate from the
poppy plant
• Used to alleviate
pain, suppress
coughing, and
treat diarrhea
http://www.lib.fit.edu/pubs/librarydisplays/arts/poppy.jpg
4. History
• Humans have used poppies for medicinal and
recreational purposes since early civilizations
• Traded throughout western Europe, Mediterranean,
Middle East, and Asia minor
– Used as currency
• “Opium” comes from the Greek opos (juice), and
“morphine” from the Greek god of dreams,
Morpheus
5. Opium Wars
• In the 1800’s, British merchants began trading
contraband opium for more valuable Chinese
products (tea, silk, etc.)
• Commissioner Lin, a Chinese diplomat, sent a letter
to Queen Victoria asking her to stop the trade
• Requests ignored Opium Wars
http://www.emsc.nysed.gov/ciai/socst/ghgonline/turnpoint/images/content/tp45/hong.jpg
6. Where Opiates Come
From
• When the poppy loses its
petals, the bulb is ready to
be cut
• The liquid leaking out of the
bulb is opium gum
• The gum is boiled and
strained, resulting in blocks
of morphine
http://www.rehab-international.org/wp-content/uploads/2008/01/opium.thumbnail.jpg
7. Creation: Heroin
• Made with a variety of
chemicals
– acetic anhydride, sodium
carbonate, activated
charcoal, chloroform, ethyl
alcohol, ether, and acetone
• Original purity of 90%
• Dealers dilute drugs with
caffeine, baking soda, baby
powder, etc.
• Usually <40% pure by the time
it gets to a user
http://www.justthinktwice.com/images/pic_heroine3.jpg
8. How Opiates Feel
• One to two minute rush
– euphoria, relief of tension
• Four to five hour high
– warmth, drowsiness, satisfaction, mild dizziness,
apathy
• First time: causes nausea/vomiting, often
unpleasant
– effects decrease over time
9. Morphine
• Triple carbon ring
• One ring with N-CH3
on it
http://z.about.com/d/chemistry/1/7/f/e/morphine.jpg
http://www.drugs-forum.com/opiate-chemistry.htmlhttp://www.thetoadband.com/Toad/Toad/Images/Morphine_sulfate2.jpg
10. Heroin
• Similar to morphine
(opiate alkaloids)
• Some differences,
highlighted by the
orange boxes
• Carbonyl instead of
hydroxyl groups
http://img.freebase.com/api/trans/image_thumb/wikipedia/images/commons_id/1017373?
maxheight=510&mode=fit&maxwidth=510
http://www.drugs-forum.com/opiate-chemistry.html
11. Codeine
• Difference from
morphine is shown in
the orange box
• Has H3CO instead of
hydroxyl group
http://upload.wikimedia.org/wikipedia/commons/e/ed/Codeine.png
http://www.drugs-forum.com/opiate-chemistry.html
12. Vicodin (Hydrocodone)
• Different conformation
• Methyl instead of OH
• Single bond and C=O
instead of double bond
and OH
http://upload.wikimedia.org/wikipedia/commons/c/cc/Hydrocodone.svg
http://media.canada.com/8975269b-0529-4353-a446-596d133824d2/cnsphoto-strachan-
house.jpg
13. Prescription Opiates
• Prescribed for pain relief
• Generic names: hydrocodone, oxycodone, morphine
sulfate, dihydromorphine
• Brand names: Demerol, Lorcet, Vicodin, Norco,
Lortab, Percocet/Percodan, Oxycontin, RMS/MS
Contin, Dilaudid/Palladone
• Often acetominophen added to decrease addictive
properties, but increases risk of overdose resulting in
liver problems
http://babydollsandbeerbottles.files.wordpress.com/2009/08/pill_bottle_and_pills1.jpg
http://erstories.net/wp-content/uploads/2008/06/pills-red-and-blue.jpg
14. What should the
doctor do?• Read the scenario
• Discuss with your group
• Answer the question: how should the patient
be given morphine?
• Be prepared to justify your answer
• Why do the different methods of drug
administration have different effects?
Source: “Understanding Neurobiology through the study of Addiction.” NIH.
15. What should the
doctor do?• Inhalant or injection
• Goal: quick relief of pain so fracture can set
• Disadvantage of inhalants: amount of drug
that enters blood more variable (some
exhaled)
• With injection, all of the drug enters the
bloodstream
Source: “Understanding Neurobiology through the study of Addiction.” NIH.
16. How Opiates Work
• Attach to endorphin (a.k.a. opiate) receptors
• Two kinds of opiates
– Agonists: activate receptors
– Antagonists: block receptors, prevent action of
agonists
• Concentrated in reward pathway and pain
pathway
17. Opiates And
Endorphins
• Opiates have similar
structures to
endorphins,
enkephalins, and
dynorphins
• All are peptides
http://theoncologist.alphamedpress.org/cgi/content/full/9/6/717/F1
18. Opiate Receptors
• Three kinds: mu,
delta, and kappa
receptors
• Morphine acts as a
strong agonist at the
mu subtype and as a
weak agonist at the
delta and kappa
subtypes
• All G-protein coupled
receptors
http://www.nida.nih.gov/pubs/teaching/largegifs/slide-5.gif
20. Mu Opiate Receptors
• Primary target for opiates
• Highly concentrated in the thalamus,
cerebral cortex, visual cortex, and
basal ganglia
– Number of receptors varies
between individuals (genetic)
– More receptors more pain
tolerance
• Also, highly concentrated in nucleus
accumbens (in reward pathway)
• Mice lacking mu receptors are more
sensitive to pain and do not become
morphine dependent https://www.scientificamerican.com/article.cfm?id=personal-pain
21. Pain Pathway
• Nociceptors (pain-sensing
neurons) perceive pain reflex
and message sent to brain
• Neurons in pain pathway
synthesize endorphins
• Endorphins suppress glutamate
release in pre-synaptic neurons
and hyperpolarize post-synaptic
neurons
– Prevent the passage of
nociceptive signals
• Opiates work like endorphins
– Only stronger because self-
administered and we can
control how much we receive
http://www.dana.org/uploadedImages/Images/Spotlight_Images/DanaGuide_CH09B05_P167a_spot.jpg
22. Reward Pathway
• Stimulated normally by
food, sex, water, etc.
• VTA (ventral tegmental
area) connects to the
nucleus accumbens and
prefrontal cortex
• Neurons in VTA contain
dopamine, which is
released in the nucleus
accumbens and prefrontal
cortex in response to the
rewarding stimulus
http://www.drugabuse.gov/pubs/teaching/Teaching2/largegifs/slide11.gif
23. Dopamine Release
• Gluatamte (excitatory) usually
causes neighboring neurons to
release GABA (inhibitory)
dopamine neuron blocked
– Prevents over-excitation
• Endorphins and opiate agonists
disrupt these inhibitory
mechanisms
– Block GABA response
– Dopamine release
sensation of pleasure
http://www.drugabuse.gov/pubs/teaching/Teaching2/Teaching4.html
25. Action of Opiate
Agonists• Binding to endorphin
receptors in pain
pathway (thalamus,
brain stem, spinal cord)
analgesia
• Binding to receptors in
reward pathway
dopamine released
person feels good
http://www.drugabuse.gov/pubs/teaching/Teaching2/Teaching4.html
26. Effect on the Rest of
the Body• Vomiting center in brain (causes stomach muscles to
contract)
– First uses vomiting/nausea
– Effect dulls over time
• Respiratory center in brain (regulates breathing)
– Inhibits decreased frequency and depth of
breathing
– Overdose stop breathing
http://mayoclinic.com/images/image_popup/r7_respiratory.jpg
27. Effect on the Rest of
the Body• Endocrine System
– Slightly lowers body temperature, cortisol, and
testosterone production
– With tolerance, effect dulls
• Pupils contract (miosis)
• Histamine released widened veins, flushed
appearance, itching, sweating
• Intestines (also have opiate receptors)
– Inhibit intestinal peristalsis constipation
28. Negative Effects
• Can cause circulatory collapse, coma, cardiac
arrest, depressed appetite and sex drive
• Related dangers (injection): HIV, Hepatitis B
and Hepatitis C
• Relatively few long-term health effects (not
like alcohol/smoking)
• Very easy to overdose
• Worst “side” effect: addiction
http://www.waukeshafp.org/images/residents_faculty/injection.jpg
29. Who is the Addict?
• Read about Pat and Chris
• Discuss with your group: who is the addict?
• Be prepared to justify your answer
Source: “Understanding Neurobiology through the study of Addiction.” NIH.
30. Who is the Addict?
• What did your group decide: who is the
addict? Why?
• What are the differences in why and how
Chris and Pat take morphine?
• How does this affect whether or not they are
are addicted?
Source: “Understanding Neurobiology through the study of Addiction.” NIH.
31. Who is the Addict?
• Difference in reason for taking drugs
– Pat took to escape problems, also expected high
– Chris took to reduce pain, without motivation for
getting high
• Pain patients are actually at a low risk for
becoming addicted
Source: “Understanding Neurobiology through the study of Addiction.” NIH.
32. Tolerance and
Dependence• Tolerance
– Develops quickly to pain-relieving effects of opiates
– Morphine binds to receptors enzyme that causes cell to
continue impulse firing inhibited
– Frequent use adaptation no longer causes enzyme
change
– Need increasing amounts to relieve pain
• Dependence
– Drug needed to function normally
– Very uncomfortable withdrawal (nausea, muscle spasms,
cramps, anxiety, fever, diarrhea)
33. Addiction
• Can be dependent but not
addicted
– Reward pathway underlies
addiction, pain pathway
underlies dependence
• Myth: therapeutic
painkillers produce high
rate of addiction
– Patients managing pain can
experience withdrawal
– Not addicted because do not
want it after taken off
• Addiction to one opiate is
often treated by another
http://www.drugabuse.gov/pubs/teaching/Teaching2/Teaching4.html
35. Drug Addiction
Treatment• Addiction is a chronic disease
• Often thought of as self-inflicted
• Initial choice to use, but afterwards compulsive
• Similar to other chronic diseases (ex. hypertension,
diabetes)
• Voluntary choices also contribute to severity of other
chronic diseases
• Treatment requires medical compliance
• Adherence to a doctor’s treatment plan
36. Treatment
• Which disease has the highest rate of medical
compliance?
• Medical compliance is following a physician’s
treatment orders
Disease Medical Compliance
Heroin Addiction ?
Hypertension ?
Diabetes ?
37. Treatment
• Heroin treatment has a higher rate of medical
compliance than other chronic diseases
• As a result, treatment is often more successful than
treatment for other chronic diseases
• Successful treatment usually uses a combination of
behavioral and pharmacological treatments
Disease Medical Compliance
Heroin Addiction 60%
Hypertension <30%
Diabetes <50%
Source: “Understanding Neurobiology through the study of Addiction.” NIH.
38. Behavioral
Treatment• In conjunction with pharmacological
treatments
• Addicts learn to deal with the environmental
factors that could trigger drug use
• Counseling individually or as a group
• Relapse
– Does occur
– Is considered a part of treatment process
39. Pharmacological
Treatments• Opiate receptor agonist
– Binds to opiate receptor
– Therefore prevents other agonists from binding
(competes with them)
– Example: Methadone
• Opiate receptor antagonist
– Entirely blocks other agonists from binding to
receptor
– Example: Naxolone
Source: “Understanding Neurobiology through the study of Addiction.” NIH.
40. Treatment:
Methadone• Opiate receptor agonist
• Treats heroin addicts
– Because heroin causes release of extra dopamine,
addicts need an opiate to occupy the receptor
• Methadone is used to occupy the receptor
– Can be taken orally in liquid or pill form
– Withdrawal suppressed for 24-36 hrs
– Does not produce a euphoric high
• Methadone withdrawal is slower
http://www.drugscope-dworld.org.uk/wip/24/images/methadone.JPG
41. Methadone
problems• Highly addictive
• Sold in large quantities on
the black market
• High risk of overdose
• Use needs to be
supervised by drug
counselors or medical
personnel
http://content.answers.com/main/content/img/oxford/Oxford_Chemistry/0192801015.methadone.1.jpg
42. Treatment:
Naxolone• Opiate receptor
antagonist
• Used in cases of
overdose
• Causes effect only
after opiate use
• No narcotic effect
cravings still persist
http://opioids.com/naloxone/naloxone.jpg
43. Treatment:
Buprenorphine• Partial agonist
• Agonist properties: can’t get
high because activation does
not occur fully
• Not nearly as addictive as
methadone so is better for
treatment
– No withdrawal symptoms or high
http://www.drugs.com/pro/images/23aa1bb3-cecf-4e62-29bb-48488bb66fc3/xen-0327-1.jpg
Diamond yellow = dopamine, Blue = dopamine receptor, red uptake pump removes, Endorphin = works as neuromodulator, efftects signal within postsynaptic cell
Morphine binds to G prot receptor shape change interacts w/ G protein expels its GDP molecule and picks up GTP G protein breaks in two pieces here ½ binds to adenylyl cyclase and inhibits formation of
Other times activated G prot change activity of ion channel/enzyme
GTP breaks down GDP returns to resting conformation
Dopamine = BLUE, dopamine receptors = purple
Binding of opiates inhibits GABA release decreased inhibition of dopaminergic neurons more dopamine HIGH
At mu receptor, acts as stronger agonist
Red = reward pathway, green = areas where opiates bind
