1. Opiates
Presented By:
Devin Daniel, Ally Ferring, Lily Hurt, Kaitlin Robertson, and Delia Smith

2. History and Evolution
-Opiates are natural analgesics that are from opium, which is found inside the poppy plant, also known as Papaver setigerum, which is a Mediterranean-growing wild strain.
-The cultivation of opium goes back 5,000 years to Mesopotamia, and can also be linked to Persia and Egypt.
-Evidence of fossilized poppy seeds shows that Neanderthals may have used opium from poppies over thirty thousand years ago.

3. Opiates
An opiate (or also known as an opioid) is a strong analgesic which means that the drugs kill pain by preventing the transmission of pain impulses in the brain, rather than the source of pain.
Opioid receptors are are a group of inhibitory G protein-coupled receptors inside the brain that the analgesics bond to temporarily. The binding blocks the transmission of impulses between brain cells that would signal pain.
Analgesics interfere with the perception of pain without depressing the central nervous system.

4. Types of Opiates -Codeine -Morphine -Diamorphine (Heroin)
*These are the three that IB focuses on but there are many more!

5. Effect on the brain
Having the analgesics act on the brain, it can cause changes in mood and behavior, known as narcotics.
For the drugs to enter the brain, it must go through the blood-brain barrier. The BBB protects the brain by restricting the chemicals that can enter from the blood.
Blood Brain Barrier: a non-polar environment that isn’t easily crossed by polar molecules
Drugs that are more non-polar and lipid-soluble are more likely to enter the brain.

6. Structures - Morphine Arene Ether Alkenyl Hydroxyl (2) Tertiary amino
Obtained from raw opium (10%)

7. Morphine Morphine is the principal drug derived from Opium
The 2 -OH groups gives morphine some polarity which limits its ability to cross the blood-brain barrier
Blood-brain barrier: a hydrophobic, non-polar environment, not easily crossed by polar molecules
Because of this, the effects are not as strong
Morphine is a chiral molecule
The other isomer, which does not occur in nature, has no analgesic activity

8. Structures - Codeine Arene Ether (2) Alkenyl Hydroxyl (1)
Tertiary amino
Raw opium (5%)
Usually prepared from morphine

9. Codeine AKA Semi-Synthetic Drug
Commonly prepared from methylation of morphine
The reaction converts one of the hydroxyl groups of morphine into the methyl ether
Because of the reaction, codeine is a less polar molecule and so can cross the blood-brain barrier more easily
Also causes a significant drop in the binding at opioid receptors, which makes codeine a weaker analgesic than morphine

10. Structures - Diamorphine
Arene
Ether (2)
Alkenyl
Ester (ethanoate) (2)
Tertiary amino
Obtained by reaction from of morphine

11. Diamorphine AKA Heroin
Prepared from an esterification reaction from morphine
Both Hydroxyl groups in morphine are converted into ester groups by a reaction with ethanoic acid or ethanoic anhydride
Esterification significantly reduces polarity, making diamorphine much more lipid soluble than morphine
More able to cross blood-brain barrier
Faster acting than other opioids

12. Diamorphine inside the brain
Must undergo metabolic change first
Ester links are broken by enzymes called esterases
Diamorphine = pro-drug
Pro-drug: its metabolic products, mostly morphine, actually bring about its effects

13. Difference in Effectiveness
Codeine: increasing strength as analgesic
Morphine: increasing narcotic effects
Diamorphine: increasing side effects

14. Relationships between Opiates
All opiate affect the opioid receptors in the brain which give these analgesics the properties
Primarily morphine and its derivatives are used from opium
They all (codeine, morphine, and diamorphine) have a CH3CH2 group from the tertiary amino
All opioids target brain cells that transmit pain signals; opioids block the receptors from transmitting the pain signals
Since the 3 have only a common basic structure, they have similar properties but some different functional groups
Codeine - crosses the blood brain barrier (-OH group from methylation) because it’s less polar than it’s original morphine
Diamorphine - It’s ester groups, making it one of the faster opioids to cross the blood brain barrier.

15. Physiological Benefits
Pain relief caused by the blocking of opiate receptors which prevent pain
Drowsiness
Euphoria

16. Side Effects Drowsiness Euphoria Nausea Constipation Bloating
Suppression of cough reflex
Constriction of pupil in eye
Dependence and withdrawal

17. Pain Management
The World Health Organization has developed a 3 step “analgesic ladder” to be a guideline for a global standard of pain management.
Step 1: use a mild analgesic (mild pain)
Step 2: use a weak opioid like codeine (moderate pain)
Step 3: use a strong opioid like morphine (severe pain)

18. Impact on Society
With the exposure of opioids, there were more doctors prescribing the drugs without knowing how addictive they are
Lead to drug trafficking through Latin America
The response to the drug epidemic was Congress passing the Comprehensive Addiction and Recovery Act
The bill is to continue care from primary prevention to recovery support, including significant changes to expand access to addiction treatment services and overdose reversal medications
Stop “doctor hoping”
Tighter border control regulations to reduce the influx of drugs into the country

19. Article Research: OxyContin
-There have been many different reformulations of OxyContin to prevent its ability to be abused
-ERO abuse after reformulation was tested in 189 subjects
-Results concluded that ERO was not as abused as it was previously when compared to reformulation but IRO was wildly abused among prior drug addicts illustrating some of the harmful side effects of opiates.

20. Article Research: Morphine
Article Topic: comparing the rates of efficacy in morphine and methadone (in oral form) for opioid dependent patients that have been treated with methadone
The purpose of the study is to find if slow release oral morphine can be as effective as methadone when you treat patients with an opioid use disorder.
having medication treatment and psychosocial support, it can help stabilize dependent patients.
For the treatment, Methadone has had successful outcomes but it has side effects that mess with treatment retention.

21. Understanding Heroin Overdose:
A study of the Acute Respiratory Depressant Effects of Injected Pharmaceutical Heroin
Respiratory depression caused by intravenous heroin is poorly understood
10 patients undergoing supervised injectable opioid treatment for heroin addiction
Received usual IOT and oral opioid
Measures: Pulse oximetry (SpO2), end-tidal (CO2), and neural respiratory drive
Significant respiratory depression was defined as absence of inspiratory airflow >10s, SpO2% < 90% for >10s and ETCO2% per breath >6.5%
Conclusion: significant acute respiratory depression is commonly induced by opioid drugs prescribed to treat opioid addiction
8/10: increases in CO2, 4/10:SpO2% indicated respiratory depression

22. Article Research: Methadone
Discuss the effectiveness of Methadone Maintenance Treatment (MMT) on opiate addiction in China.
Drug abuse in China is big, so the Chinese government launched MMT clinics.
These clinics participated in a study in which subjects were surveyed for five years with one of three types of MMT treatments: MMT only, MMT with counseling psychology (CP), and MMT with contingency management (CM).
Overall, these treatments helped decrease the retention rates of opiate usage.

23. Article Research: Vicodin
Vicodin was first introduced to the US market in 1978.
Vicodin is a highly addictive analgesic, and because oral surgeons feel most comfortable prescribing this strong opioid in unnecessary cases it can lead to drug seekers coming into offices.
Oral surgeons prescribe Vicodin more than any other pain reliever because they don’t want to under prescribe patients, so they feel that it is better to “over-prescribe”.
In clinical trials to test for pain relief, oral surgeons found that 10-20% of the placebo group experienced complete pain relief if it was a minor episode of pain.

24. Works Cited
Brown, Catrin and Mike Ford. Pearson Baccalaureate Standard Level Chemistry. 2nd ed. Pearson Education, Print.
Osler, Sir William. “The Plant Of Joy.” A Brief History of Opium. N.p., n.d. Web. 20 Mar
Waismann, Claire. "The Devastating Effect Of Opioids On Our Society". TheHill. N.p., Web. 21 Mar
“The Effects of Opiate Use.”Drug Abuse.com. N.p.,29 Jan Web. 20 Mar
Wang, Lirong, Xiaoli Wei, Xueliang Wang, Jinsong Li, Hengxin Li, and Wei Jia. "Long-Term Effects of Methadone Maintenance Treatment with Different Psychosocial Intervention Models." PLOS ONE. Public Library of Science, 3 Feb Web. 13 Mar
Jennifer R. HavensCarl G. LeukefeldAngela M. DeVeaughGeissPaul CoplanHoward D. Chilcoat The impact of a reformulation of extendedrelease oxycodone designed to deter abuse in a sample of prescription opioid abusers (2014),