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Lecture Eight


**For the purpose of 476 what is a narcotic? opioid (natural or synthetic) compound that binds to and activates opioid receptors,
**Opioid peptides are a class of neuropeptides highly implicated in ______ modulation and has growing evidence for modulation of _____ and reinforcement behaviours pain, mood
**All opioid peptide receptors are metabotropic or ionotropixc? metabotropic
**All opioid peptide receptors are metabotropic. They are coupled with what protein? Is this protein inhibitory or excitatory? Gi. Its inhibitory
So all opioid peptide receptors are metabotropic ___ _________ coupled receptors Gi protein
**Even though opioid peptide receptors are coupled with Gi proteins which are inhibitory, these peptide receptors can still have positive or negative effects. How? It depends on what system the opioid peptide receptors are acting on for whether it is inhibitory or excitatory
**There are three subtypes of opioid peptide metabotropic receptors. What are they? mu, kappa, delta
**The three subtypes of opioid peptide metabotropic receptors have multi-faceted effects. What are they? Mu is the highest analgesic (pain relief), abuse and respiratory depression potential. Kappa has dysphoric side effects and delta has antidepressant anxiolytic effects.
*Where are opioid receptors in the body? All throughout the CNS but with a high density in the spinal cord* and in the thalamus*, striatum* and brainstem* (where resp depression occurs). Tones are also in the PNS in the small and large intestines
**learn the time line for opium study questions ask for it
**What are the two first primary reasons for narcotic (morphine, codeine, heroin, fentanyl, oxycontin) use? 1) To alleviate pain both physical pain (as an analgesia) and emotional pain (as it creates euphoria so makes you not care about your emotional problems. 2)To induce dif. types of contented euphoria - calm, chilled out, content feeling (dif.to psychostim)
**What is the third primary reasons for narcotic (morphine, codeine, heroin, fentanyl, oxycontin) use? 3) To satiate an addiction
**What are the three mode of actions for Opioids? 1) Analgesia - doesnt nec. eliminate pain but you are no longer bothered by it 2) Euphoria - contented, calm 3) Sedation - because of its anxiolytic, sedative, and hypnosis components.
**What is the MOA for Opioids? Agonist for the opioid receptor (especially Mu).
**What are the possible side effects of opioids? Suppression of cough reflex, respiratory depression, vomiting, pupil constriction, suppression of GI motality.
**You take Narcotics to get a behavioural effect. This can be either therapeutically or recreationally. Describe each one Therapeutically as an analgesia to reduce pain behaviour. Recreationally for contented euphoria
Morphine is a narcotic. **Morphine is more water soluble than lipid soluble. How would this effect pharmacokinetics? Morphine is not going to have good absorption or distribution so it is best administered as IV.
**Describe the Absorption of morphine. oral: ~25% bioavailability. IV 100% bioavailability -so usually given this way
**Describe the Distribution of morphine. ~33% are bound to plasma protein and only ~20% are distributed in to the CNS slowly. Can cross the placental barrier.
**Describe the Metabolism of morphine. There is an active metabolite that acts as potent opioid receptor agonist.
**How is morphine cleared? Renal (kidney)
Codeine is also a narcotic/opioid. What is its ROA? Oral - benefit that morphine doesn't have
**Describe the absorption of codeine. ~ 60% bioavailability so not great but better than morphine orally.
**Describe the distribution of codeine. slow entry into the CNS
**Describe the metabolism of codeine. CYP2D6 metabolism occurs and this is what metabolised codeine into morphine.
** Why is codeine as an analgesic considered a pro-drug? Because it is inactive until it metabolises in the body into morphine.
Oxycodone and Hydrocodone are also narcotics. They have more in common with heroin than codeine so more dangerous. **What is the ROA for these two drugs? Oral
**Describe the Absorption of Oxycodone and Hydrocodone ~70% bioavailability so pretty good oral absorption and better than codeine
**Describe the distribution of Oxycodone and Hydrocodone Higher protein binding occurs so only 30-50% are distributed into the CNS and this is slow entry.
**Describe then metabolism of Oxycodone and Hydrocodone CYP2 and CYP3 metabolism occurs.
**Describe the elimination for Oxycodone and Hydrocodone and Codeine? Renal (kidney)
Do Morphine, Codeine and Oxycodone and Hydrocodone and Heroin all have the same form of elimination? Yes, all are renal (kidney)
Heroin is also a narcotic/opioid and is made by making a very small change to morphine. **Why is heroin more dangerous? Because it is lipothilic so gets into the CNS quickly and is 2-3x more potent than morphine! so induces intense high
**What are the three possible ROA of heroin. intranasal (snorting), inhalational and intravenous
**Describe the absorption for heroin Unknown for intranasal and inhalational but 100% for IV.
** Describe the distribution for heroin. Rapid entry into CNS and can cross the placental barrier (just like morphine can cross placental barrier)
**Describe the metabolism of heroin. It is metabolised down to morphine in the body.
**What is the elimination for heroin? Renal (kidney)
**All opioid receptor agonists share the same side effects. What are these again? Suppression of cough reflex, respiratory depression, vomiting, pupil constriction and suppression of GI motility. **However some side effects are exploited as the intended effect.
*Narcotics/opioids can have two THERAPEUTIC EFFECTS/ modes of action e.g. Imodium and Lomoti. What are they? And what are the mechanisms of action behind these? Anti-GI motility:slows down your gut. Anti-tissives:makes you not be able to cough. MOA:activation of opioid receptors in BRAINSTEM->suppression of cough reflex & activation of opioid receptors in INTESTINES:suppression of GI motility (anti diarrhoea)
Why do you not get opiate-like sedation and euphoria with Imodium and Lomoti? Because it doesn't cross the BBB so you don't get behavioural effects.
**What are the three options for overcoming the unpleasant withdrawal symptoms of narcotics? - Cold-turkey (high relapse rate). - Rehab-mediated detoxification. - Or - Hospital assisted detoxification
Hospital assisted detoxification may involved **RAAD (rapid anaesthesia-aided detoxification. Describe this You are put under aneasthesia for around 24 to 48 hours so that you do not feel the negative withdrawal symptoms. Very expensive!
What are the downfalls of RAAD (rapid anaesthesia-aided detoxification) Very expensive! And they do not experience the withdrawal so might be more likely to relapse compared to those who know how bad the withdrawal is and never want to risk that again.
**Many addicts don't make it through the acute withdrawal as they re-use to get rid of the symptoms. For those that do make it through often face what? Protracted Abstinence Syndrome where they experience up to 6 months of depression, anxiety, drug craving. Many re-use to get rid of this dyphoria.
**The main objectives of opioid treatment programs are _____________ of the dependent individual and reduction in __________-associated diseases, _________ drug use and ________ rehabilitation, needle-associated diseases, illicit drug use and crime.
**Compare Methadone and Naltrexone!!!! In test!!! .
**Mechanistically how can opioids be potentially fatal? 1) Significant Respiratory Depression due to high dose,lack of contextual tolerance or synergistic CNS depression.2) Asphyxiation due to cough suppression (SE)-linked to ingestion (eating food and choking), linked with vomiting (SE) (choking on vomit).
**Hmmmm. oral Naxolone use is starting to be promoted...does this make sense? (Why would you put Naxolon which is IV into an oral form? Test question!! Read reading!!!
**Opioid use shows a high degree of co-morbidity with depression and other mood disorders (dual-diagnosis problem). why is this an issue? Because opioid abuse may be a form of self-medication for depression as it makes you feel better/euphoria, yet it may also causes depression in withdrawal symptoms.
**Dependent users of opioids are also often dependent on or abusers of psychostimulants. Why would you see this sort of co-dependence? Because of the CNS effect of opioids. So to get energy back use psychostimulants such as an amphetamine, to get your energy back up.
Created by: alice476