Opioids Flashcards
Father of Modern Medicine
- Canadian physician Sir William Osler
- co-founder of the Johns Hopkins Hospital
- instituted the residence program for the training of physician
Medicinal History of Opium Poppy
- poppy pots (Spain 4200 BC)
- Ebers Papyrus (Egypt 1500 BC)
- Poppy goddess Crete 1300 BC
- Canon of Medicine Europe 1483
- Opium medicine late -1800s
- heroin cough syrup 1898- 1910
Papaver somniferum (Opium Poppy
- annual, long-day plant
- growth cycle ~ 120 days
- germination after 7-14 days
- stems terminate in flower buds
- upper part of each stem elongates and forms a distinctive hook
- upper stem straightens and the flower open after ~90 days
- mature plant up to 5 feet in height
What environment does the Papaver Somniferum grow best in?
grows best in temperate, warm climates with low humidity
What type of soil does the Papaver somniferum grow in
grows in variety of soils - clay, sandy loam (good moisture/nutrient-retention), sandy
Why is there a global opiate shortage?
most developing countries are underestimating their requirement for opiate analgesics or not putting forth any useful estimates
Tasmanian Poppy Industry
- largest ilicit producer of opium alkaloids
- over 20 000 hectares in production
- paid on the basis of alkaloid content
- average payment to farmers $3000 per hectare
- licenses issued by the Poppy Advisory control board after farmers have been contracted by a licensed manufacturer
- warning notices on all roadside fences
What are the three opioid receptors?
mu, kappa, delta
Location, function, endogenous peptide and synthetic opioid of the Mu Receptor
- brain, cortex
- fx: respiratory depression, euphoria, sedation, physical dependence
- endogenous peptide: B-endorphin, enkephalin
- synthetic opioid: morphine, fentanyl, sufentanil
Location, function, endogenous peptide and synthetic opioid of the Kappa Receptor
- brain
- fx: analgesia, dysphoria
- endogenous peptide: met-enkephalin, Leu-enkephalin
- synthetic opioid: deltorphin
Location, function, endogenous peptide and synthetic opioid of the Delta Receptor
- brain
- fx: analgesia, anti-depression
- endogenous peptide: dynophrin A, dynorphin B
- synthetic opioid: buprenorphine
Opioid Receptor Agonists
morphine, heroin
Opioid Receptor Antagonists
- naloxone, naltrexone, beta-funaltrexamine
What physiological effects does the endogenous opioid system mediate?
pain, respiratory control, appetite, and thermoregulation
Opioid receptors in the respiratory control centres
- very abundant in the respiratory centres that include the brainstem, but also in mechanosensory receptors located in the epithelial, submucosal and muscular layers of the airways which relay mechanical and sensory information from the lungs
Opium Chemistry
- heroin (diacetylmorphine) is the opioid synthesized by adding two acetyl groups to a molecule of morphine
- is the 3,6-diacetyl ester of morphine and functions as a morphine prodrug (is metabolically converted to morphine inside the body to work)
how much more potent is heroin in comparison to morphine
- three times as potent
Opium Harvesting
- occurs in late afternoon
- incision is made in the capsule by a sharp knife (latex oozes out from the cut)
- fresh latex is milky white
- turns brown when exposed to the air
- latex flows out overnight
- by morning latex has coagulated
- brown mass is scraped off and placed in clay pots
- same capsule can be re-bled 3-10 times
Norman poppy
- thebaine and oripavine only
- EMS mutation of commercial morphine seed
developed in 1994-1996 - first sales in 1998
- IP protection: patent
Commercial Relevance of Norman Poppy
- reduced the reliance on opium to extract thebaine and oripavine
O-Demethylation in humans
CYP2D6
- liver cytochrome P450
- detoxifies ~25% of all pharmaceuticals
- catalyzes the 3-O-demethylation of codeine to morphine
