Drugs and Behavior Week 8

Opioid Side Effects

Behavioral: drowsiness, inability to concentrate. Dysphoria, restlessness and anxiety. At high doses, it may lead to unconsciousness. Physiological: Constricted eye pupils. Nausea and vomiting. Affect area postrema in brainstem that elicits vomiting. Constipation. (have been used to treat diarrhea)

Opioid

Act on opioid receptors to produce morphine-like effects. Include opiates, referring to drugs derived from opium, including morphine.

Excretion

After metabolized in the liver, most excreted in the urine within 24 hours. Morphine can be detected for 1-2 days. Chronic use? 4-5 days.

Opioid Receptors

Drugs exert their effects via endogenous opioid receptors in the CNS. THE μ-receptor has a high affinity for morphine. Locations of the μ-receptors reflect the effects of morphine. Analgesia--> medial thalamus, periaqueductal gray, median raphe, spinal cord. Positive Reinforcement--> nucleus accumbens, VTA Cardiovascular and respiratory depression, cough control, nausea and vomiting--> brainstem

Opioid Effects: Pharmacodynamics

Effects of opioids on CNS related to dose and rate of absorption. Low to moderate results in pain relief, relaxation, dreamy relief. Some researchers think it relieves anxiety, aggressiveness, and feelings of inadequacy. At higher doses, there is an abnormal state of elation or euphoria, the kick, bang, or rush. Rush acts as powerful reinforcer.

Morphine

Extracted from the poppy plant. First time an active ingredient of any medicinal plant was isolated. Allowed doctors to prescribe it in known dosages. Very powerful analgesic and euphoric drug.

Opium

Has been used recreationally and in medicine for thousands of years (5000 BC in China). Extract of a poppy plant. Is prepared by drying and powdering the milky juice taken from the seed capsules of the opium poppy just before ripening. Opium contains morphine, codeine, thebaine, narcotize and other ingredients.

Codeine

Has less analgesic effect and fewer side effects than morphine. Potent cough suppressant.

Opioids--Metabolism

Most opioids undergo extensive first-pass metabolism in the liver before entering systemic circulation. First-pass metabolism reduces the bioavailability. Metabolized vida CYP mediated oxidation (codeine, methadone) and have substantial drug interaction potential (exception--morphine). Morphine starts to take effect quickly. It reaches peak levels within 1 hour when taken orally, 30 min when injected. Has a half-life of about 1.5-3 hours.

Naloxone/Naltrexone

Naloxone is more commonly used because it has a longer duration than that of naloxone, is effective when taken orally, and has few side effects. Method is effective for highly motivated individuals. Craving for drug is not eliminated.

Physical Dependence

Neuroadaptive state in response to long-term occupation of opioid receptors. Does NOT necessarily lead to abuse or addiction. When it is no longer present, cell function returns to normal and overshoots basal levels (levels necessary to maintain health/life). Effects are seen in withdrawal symptoms.

Opioids--Routes of Administration

Often smoke opium fro rapid absorption from the lungs Morphine, hospitals provide IV, IM, SC injection or given orally Oxycodone, Vicodine-pills "Snorting" heroin leads to rapid absorption through nasal thing. SC may precede more dangerous IV

Opioids--Distribution

Only a small fraction of morphine crosses BBB. Heroin is more fat soluble and reaches brain faster, so it is much more potent than morphine when injected. Opioids easily cross placenta. Newborns can suffer withdrawal symptoms but can be stabilized with low doses of opioids.

opiates, natural opioids, semisynthetic opioids, synthetic opioids, endogenous opioids.

Opiates--> derived from opioid, including morphine Semisynthetic opioids--> oxycodone. heroin. Dilaudid. Etrophine. Controlled release of formula/modified Synthetic Opioids--> Totally made by humans/not naturally occurring. Talwin, Demerol, Subilmaze, Dolphin, LAAM, Darvon Endogeneous--> Having internal cause. Produced in the body. Endorphins, enkephalin, dynorphin. The weird u

Methadone/Burprenorphine

Opioid receptor agonist. Treatment for Opioid addiction. Substitution for heroin, reduce symptoms to a more comfortable level. Detoxification. Methadone is most common! Relieves craving, long-acting, cross dependence with heroin, prevents severe withdrawal symptoms.

Narcotic Analgesics

The opioid drugs. Sleep inducing (narcotic) and pain relieving (analgesic). Best painkillers known + produce sense of euphoria. Create a sense of relaxation + sleep and at a high dose, coma + death

Opioid Overdose

Unconsciousness. Body temp and blood pressure fall. Pupils become constricted. Opioids act on brainstem's respiratory center, failure is ultimate cause of death. Naloxone is antidote

Heroin

Was developed by Bayer company to be more effective in relieving pain without danger of addiction. Added to acetyl groups to Morphine, MORE LIPID SOLUBLE. Responsible for DRAMATIC euphoric effects. Phamacological effects of morphine and heroin are essentially identical bc heroin is converted to morphine in the brain.

Agonists + Antagonists, Burprenophine + Naloxone (Suboxone)

uh. yay together.

Chronic Use of Opioids

Leads to neuro-adaptive changes, responsible for tolerance, sensitization and dependence. Opioids have significant reinforcing properties.

Mechanism of Action

Metatophic! Can act at two sites Presynaptic inhibition--Receptors activate G proteins that close Ca+ channels, reducing release of NT Postsynaptic inhibition--receptors activate a G protein that opens K+ channels to hyper polarize the postsynaptic cells, reducing firing rate.

Tolerance

Milder than normal response. Cross tolerance.

Mechanism of Action (pain + reward)

PAIN PATHWAY--In spinal cord and brain. 1) suppress ascending pain signals to brain through reduction of glutamate from axon terminals and hyper polarization of neurons in spinal cord. 2) facilitate descending inhibition from the brain (from PAG) REWARD PATHWAY--(mesolimbic: VTA --> Nacc) Opiods supress GABA synapses on dopaminergic neurons. Opioids microinjected into the VTA increase dopaminergic cell firing, which subsequently increases release of dopamine within the NAcc. Continued activation of the dopaminergic reward pathway leads to the feelings of euphoria and the 'high' associated with opiate use

Oxycodone

Semi-synthetic derived from thebaine. Popular street drug, when crushed produces heroin like euphoria. Readily dissolves in water, encourages IV injection. Deaths