NEUR 3204 Lecture Notes - Lecture 9: Buprenorphine, Autonomic Nervous System, War On Drugs
16 Jul 2020
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Lecture 9: Opiates and Opioids
• The opioid epidemic
o How did we get here?
▪ Oxycodone is a semisynthetic opioid that was used as the primary ingredient in
OxyContin;
▪ OxyContin was marketed and sold throughout North America as a non-addictive
pain killer (Purdue Pharma);
▪ OxyContin became a very popular street drug because it produced heroin like
effects. It was cheap. Doctors prescribed it for money (i.e. pill mill’s) and
patients took advantage (i.e. doctor shopping);
▪ Eventually, FDA/DEA forced regulations on oxycodone, and therefore
OxyContin;
▪ Pharmaceutical industry pulled the drug completely and replaced it with a
tamper resistant formulation, OxyNeo.
• ○ If try to crush it, it turns into sharp crystals
• ○ Cannot be dissolved to be injected
▪ This created a vacuum for millions of Canadians and Americans dependent on
oxycodone;
▪ Created fertile ground for the illicit drug market place;
▪ Heroin became mainstream in major US cities;
▪ More and more powerful drugs were synthesized and sold in the illicit drug
market place to fill this need (e.g. fentanyl, carfentanil, isofurylfentanyl W-18, U-
47700, kratom, etc.).
• Saving lives with naloxone
o Naloxone is a powerful opioid receptor antagonist.
▪ Blocks the effects of an opioid overdose;
▪ Outcompetes powerful opioids for receptor binding sites.
• Opioids overdose is reversed almost immediately
o It comes in injectable formulation, as well as a Nasal spray (Narcan©).
o Available at “any” community pharmacy for free.
o Go get one. Why not?
• The opium poppy
o Opium is an extract of the poppy plant Papaver somniferum (L. the poppy that causes
sleep).
o Pre-ripe poppy plants yield a thick white substance (latex), that dries and thickens into a
dark syrupy material: black tar.
▪ ○ Black tar heroin = not very processed, very raw
▪ ○ White china heroin = very fine, not sticky
o Cultivation typically occurs in Southeast Asia, India, China, Iran, Turkey, Southeastern
Europe, etc.
o Until the Harrison Narcotic Tax Act was passed in 1914, opium was bought and sold
regularly for both medicinal and recreational purposes.
o In the 1920’s, the Supreme Court ordered the prescription of opium strictly for medical
purposes, leaving many dependent individuals without their drug.
o
o Raw opium contains over 20 alkaloid substances.
o Morphine is one that acts as an anesthetic without decreasing consciousness.
o One of the most powerful analgesics we know.
o However, it also depresses the respiratory system.
▪ The higher concentration of drug = slower breathing that could become fatal
▪
o Morphine was used extensively as a painkiller for soldiers in the Civil War.
o As a result, many soldiers returned home with an opioid dependency, and was termed
“soldier’s disease”.
o This lead researchers to search for a potent painkiller that was not addictive.
o The result of this research led to the synthesis of Heroin by The Bayer Pharmaceutical
Company in Germany.
▪ Synthetic -not natural
▪ Much more addictive
• Opiates vs. opioids
o Opiate = specifically substances derived directly from the opium poppy;
▪ Morphine, codeine, and thebaine
• All derived from the opium
o Opioid = broader term that includes opiates, synthetic substances, and endogenous
peptides that bind to opioid receptors.
▪ Not all opioids are opiates, but all opiates are opioids
o Endogenous opioids are naturally produced by our bodies. They act as
neurotransmitters
• Routes of administration
o Morphine, and most other opioids, can be given orally, rectally, IM, IV, SQ, or injected
into the epidural or subarachnoid space.
▪ Thus, very good at crossing membranes and getting into the body
o Morphine’s analgesic effects occur at the level of the spinal cord.
▪ Epidural injections (3-7mg) can provide pain relief for 12-24 hours.
o Route of administration (fast vs. slow) will dictate the physiological and subjective
effects of the drug.
o The faster the onset of actions, the stronger the physiological effects
▪ If you inject or snort the drug you have a much stronger euphoric effect and
therefore more addictive properties
▪ This is why you are less likely to become dependent on oxycontin from the
dentist because it is given orally
• Molecular structure and behavioural effects
o The physiological and behavioral effects of opioids are dependent on the (tiny)
differences in molecular structures;
▪ Early on, pharmacologists learnt that they could tinker with the morphine
molecule with varying effects;
▪ Each modification changes the behavioral effects, as well as the potency, of the
drug.
• Potency refers to affinity
▪ Molecular structure will dictate not only affinity to opioid receptors, but also
lipid solubility (and therefore accessibility).
• Big difference between heroin and morphine – heroin gets into system a
lot faster because it is more lipophilic thus more accessibility and
potency
o Partial agonists: high affinity for opioid receptors, but produce less physiological activity
(e.g. Buprenorphine)
▪ Why we treat buprenorphine to treat opioid dependence
▪ Buprenorphine has a lower affinity to opioid receptor but naloxone has a higher
affinity
o Full antagonist: high affinity for opioid receptors, and prevent any physiological activity
(e.g. Naloxone)
▪ No efficacy! Cannot turn it on
▪ Just sits of receptor and does not let them be activated
o
o We use buprenorphine (partial agonist) fir the treatment of addiction (its safe)
o However, you have to get the drug every morning from the pharmacy (walk of shame).
o
• Bioavailability of opioids
