(10) opioids Flashcards
What opiods are naturally occuring?
- aka Opium
- from opium poppy
- multiple active ingredients: morphine & codeine - strongest effects
- Morphine
- Codeine
- Thebaine
- Narcotine (mainly just unpleasant): causes vomiting
What opiods are semi-synthetic?
- synthesised from naturally occuring:
- Diamorphine/diacetylmorphine (heroin): from morphine
- Desomorphine (krokodil): from codeine
- Buprenorphine
- Hydrocodone
- Oxycodone (aka oxycontin)
What opiods are fully synthetic?
- not derived from naturally occuring:
- Fentanyl: 100x stronger than morphine
- Carfentanil: up to 10,000x stronger than morphine
- Methadone
What basic principle can be determined from these categories?
potency: synthetic > semi-synthetic > naturally occuring
Why is the history of opiods important in understanding where we are today, in terms of opiod addiction?
History repeats itself:
- early-mid 19th c, opiods sold in drug stores: concerns about safety, long-term health issues, dependence
- late 19th c, “problem of morphine has been solved by heroin”: heroin marketed as non-addictive substitute for morphine
- cycle repeated itself w/ buprenorphine & hydromorphone
- cycle repeated itself again w/ Oxycontin & Percocet
- cycle matters: prescription (mis)use predicts subsequent street drug use
What are three routes of opioid administration?
- oral – e.g. methadone substitution
- drug replacement therapy
- inhalation – “chasing the dragon”
- put solution onto foil & heat it up, move solution around in foil while cooking
- use straw to chase smoke
- intravenous injection – “mainlining”
- cooking heroin into solution, put into syringe & inject into vein
What determines potentcy of opioids?
- potency determined by lipid solubility: ability to cross BBB
- e.g. Morphine vs. heroin
- difference: heroin has 2 Acetyl groups, more lipid soluble, higher bioavailability
- Acetyl groups improve BBB permeability
- active metabolites are norm
- related: drug testing for heroin?
- difficult to say if person used it legally/illegally
- look for unique metabolites
- heroin: monacetylmorphine
What is the endogenous opioid system?
- endogenous NTs are large peptides (mini piece of protein)
- peptides cleaved from v. large propeptidespropetides = larger, bigger peptides
- Proopiomelanocortin: produces beta-endorphin
- Proenkephalin: produces met-enkephalin & leu-enkephelin
- Prodynorphin: produces dynorphin A & B, neoendorphins
- Pronociceptin (weird one): produces nociceptin/ orphanin FQ
What are the four types of opioid receptors and differing effects at these receptors?
- beta-endorphin, met- & leu-enkephalin bind to & activate mu & delta receptors
- dynorphin A & B, neoendorphins bind to & activate kappa receptor
- nociceptin binds to & activates ORL-1 receptor
- mu & delta critical for pain relief, euphoria & addiction
- kappa related to occasional hallucinogenic effects of opioids
- e.g. Salvinorin A in Salvia divinorum agonises kappa receptor
- may activate other receptors
- ORL-1: pain-causing
- all endogenous opioid receptors are G-protein coupled receptors (GPCRs)
- activation of receptors reduces neuronal activity
- one effect: activation of receptors open GIRKs
What are GIRKs? Why are they relevant to the effects of opiods?
GIRKs: G-protein-coupled inward rectifying K+ channel
- activate GPCRs, G-proteins bind to & open GIRKs for K+ to flow
- opened GIRKs:
- not much of effect at baseline, as K+ near its equilibrium
- locks membrane into place, more K+ channels open & more K+ flows out to counteract Na+ entering:
- increasing permeability
- block excitation, fix cell around resting membrane potential
- prevent Na+ from depolarising cell
What is euphoria in relation to opioids?
- rush, high, nod (extreme sense of calm & disconnection w/ world), straight (period of normalcy after opioids warn off & before cravings)
- tolerance builds for euphoric effects
- consequence: escalation of intake related to tolerance
What is naloxone? Why is it important? Based on its pharmacodynamics, what effects would you expect if someone were to take naloxone on its own?
- potent opioid receptor antagonist
- for opioid overdose: taken too high of dose, administer naloxone & will block effects
- have opposite effects of opioid agonists
- if taken alone, feels unpleasant & like withdrawal
What are the effects of opiods?
- both CNS & PNS
- explains opioids’ variety of uses thruout history
acute pharmacological effects:
- analgesia
- constipation
- decreased blood pressure
- euphoria
- hypothermia
- relaxation
- respiratory depression
What is the mechanism of analgesia?
- descending pain modulation pathway: pain modulation starts at brain & travels downwards into spinal cord
- brain produces endogenous opioids for pain relief
- endogenous opioids mimic these effects
- opioids block pain signals at multiple sites, including in brain
What is nociception and analgesia?
- nociception: perception of pain
- analgesia: perception of pain relief
