Where does opium come from?
- sap derived from the poppy
What is the difference between an analgesic and a narcotic?
- analgesic: pain relieving
- narcotic: opium based analgesic (subcategory)
What are the categories of opioids?
- endogenous (occuring within): endirphin
- alkaloids (directly extracted): morphine and codeine
- semisynthetic (derivative): oxycodone, heroin
- synthetic (structurally different): methadone, fentanyl
What general effects does opium exhibit?
- euphoric (stimulant) and anxiolytic (depressant) effects
- used as a medicine (anti-psychotic)
How is opium (heroin and morphine) administered? What effects are seen?
- oral: mood alleviation, cough suppression
- inhalation: euphoria
- intravenous: euphoria, pain relief
- injection: three stages
What are the three stages of injecting opium?
- stage 1: rush/flash: intense euphoria (sexual orgasm)
- stage 2: on the nod: tranquil drowsiness (lowering testosterone)
- stage 3: withdrawal
What is fentanyl?
- china white, china girl, TNT, apache percopop, duragesic sublimaze
- designed for palliative care (lollipop)
- 100x more potent than morphine
What is the method of intake for fentanyl?
- oral, transdermal, insufflation
- problem: respiratory depression increases with faster absorption
- less nausea and itching
How do the analogues of fentanyl compare?
- 10 000x more potent
- resistant to metabolism
What is desomorphine?
- sedation and analgesia
- 8x more potent than morphine
- increase in respiratory depression, septicemia and cardiac arrest
- synthesized from codeine
How is desomorphine synthesized from codeine?
- paint-thinner, HCL
- reduction by gasoline/kerosine, iodine, phosphorus
- high toxicity
- inflammation liver, kidney, thyroid damage, “phossy jaw”, gangrene
What is the general mechanism of opium?
- agonism
- endogenous neuropeptides
What is the agonist action of opium?
- cleavage: separating molecule into separate chains (internal enzymatic action and active metabolite)
- G-protein metabotropic receptors (allows K influx to return to resting)
What is the action of pure agonist opium?
- pain relief
- fentanyl and morphine
What is the action of partial agonist opium?
- pain relief with no respiratory effect
- buprenorphine
What is the action of mixed agonist-antagonists?
- treating opioid addiction
- naloxone and methadone
What is the agonist mechanism of opium?
- GABA receptor antagonist
- ventral tegmental area: suppression of inhibitory response on dopamine receptors
- nucleus accumbens: activation of mu opioid receptors that inhibit GABA neurons
What is the inhibitory mechanism of opium?
- nociception: sensory pathway related to pain perception
- Adelta and C fibers: sensory pain signal ( inhibited)
- glutamate and substance P: sensory pain signal (activation of medulla inhibits)
Does opium produce tolerance?
- dose dependent
- accrued and relational
- selective to analgesia, euphoria and respiratory depression
Does opium produce withdrawal?
- lasts 5-10 days
- craving
- flu-like symptoms
- pupil dilation, anorexia, piloerection, spastic arm/leg movements
What is evidence for conditioning?
- 90% relapse after withdrawal associated with environment
What assists with long term and short term detoxification?
- methadone and buprenorphine
- agonist or partial agonist
- prevent withdrawal, long-lasting effects, weak/no euphoria
What assists with rapid or ultra rapid detoxification?
- naloxone
- inverse agonist
- binds as an agonist and induces opposite pharmacological response
- increase withdrawal symptoms, decrease duration
- ultra rapid: in conjunction with sedation/anesthetized for first few hours
