Opiates 091111082757-phpapp01

opiates

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

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

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

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

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

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

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

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

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

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

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

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.

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


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

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

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

G protein Cascade

http://theoncologist.alphamedpress.org/content/vol9/issue6/images/large/717_fig2.jpeg

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

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

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

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

Dopamine Release

http://www.cnsforum.com/content/pictures/imagebank/hirespng/moa_heroin_delta_kappa.png

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


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

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

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

Who is the Addict?• Read about Pat and Chris

• Discuss with your group: who is the addict?• Be prepared to justify your answer


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?


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


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)

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


House

http://www.youtube.com/watch?v=gQmlsmOZl6c

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

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 ?

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%


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

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


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

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

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

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

How Buprenorphine

Works

http://www.naabt.org/education/images/Receptors_HiRes.jpg

How Buprenorphine

Works


How Buprenorphine

Works


How Buprenorphine

Works


Education

Opiates 091111082757-phpapp01