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Pharm1Test2Opioids
Pharm1 Test2 Opioids Barry University
Question | Answer |
---|---|
Where are mu-Receptors located? | Mainly found in the brainstem and medial thalamus. Some located in spinal cord. |
Where are the kappa-Receptors located? | Mainly in the dorsal horn of the spinal cord and some in the brainstem medullary reticular formation. |
Where are the delta-Receptors located? | Mainly in the limbic system. |
Where are the sigma-Receptors located? | Mainly in the hippocampus and amygdala of the limbic system. |
What are the functions of the mu-Receptor? | analgesia, respiratory depression, euphoria, miosis, physical dependence, decreased GI motility. |
What are the functions of the kappa-Receptor? | supraspinal analgesia, sedation, dysphoria (psychoses). |
What are the functions of the delta-Receptor? | analgesia (spinal?). |
What are the functions of the sigma-Receptor? | dysphoria, hallucinations. |
From what substance are endogenous opioids derived? | precursor polypeptides |
What are the three types of endogenous opioids? | endorphins, dynorphins, and enkephalins. |
All endogenous opioids differ in length, but what do they have in common? | The first few (61-65) amino acids. |
What are endomorphines? | newly discovered m-receptor selective tetrapeptides. |
As the body's main painkillers, what are the three modes of action of endogenous opioids? | They act as neurotransmitters, neuromodulators, or neurohormones. |
About how much homology exists among opioid receptors mu, kappa, and delta? | About 65%. |
Where are the receptors that mediate analgesia located? | Dorsal horn of the spinal cord, periaqueductal gray matter, and the thalamus. |
What do opioid receptors in the ventral brainstem do? | Mediate effects on coughing, vomiting, respiration, and pupillary diameter. |
Where are opioid receptors that control neuroendocrine function located? | In the hypothalamus. |
Where are opioid receptors that control mood and behavioral effects located? | Mainly in the limbic system. |
What receptors mainly affect the GI tract and where are they located? | Peripheral mu-Receptors. |
Agonist: | bind to and activate receptor. |
Antagonist: | binds to the receptor, but does not activate it. |
Partial Agonist: | binds to the receptor, but produces less than maximal response. |
Mixed Agonist/Antagonist: | binds to more than one type of opioid receptor, acting as an agonist at one, and an antagonist at others. |
In the CNS, where do opioids primarily act? | brainstem/spinal cord |
In the PNS, where do opioids primarily act? | Peripheral afferent neurons. |
In what form do opioids bind to receptors? | Ionized form |
What is the primary mode of action of opioids? | decreased neurotransmission by presynaptic inhibition of neurotransmitter release (NE, ACh, DA, SubP) |
Opioids act by decreasing neurotransmission by presynaptic inhibition of what neurotransmitters? | NE, Ach, DA, SubP (Norepinephrine, Acetylcholine, Dopamine, and Substance P) |
How do opioids decrease neurotransmission by inhibiting release of neurotransmitters at the presynapse? | Causes increased potassium conductance and/or calcium channel inactivation. |
Other than at the presynapse, where do opioids act to decrease neurotransmission? | At the postsynapse. |
What are the central opioid effects? | Decreased neuronal activity, analgesia, respiratory depression, mood alteration, sedation, miosis, N/V, and endocrine effects. |
How do opioids cause analgesia? | Raises pain perception threshold and increases pain tolerance? |
How do opioids cause respiratory depression? | Decreases respiratory center sensitivity to CO2, and can lead to Cheyne-Stokes resp. |
What effects do opioids have on the endocrine system? | Inhibit LHRH (leutinizing hormone-releasing hormone, aka gonadotropin-releasing hormone) |
What are the peripheral opioid effects? | Histamine release, venous dilatation, smooth muscle contraction, inhibition of ACh release. |
What are the effects of opioid-induced histamine release? | causes peripheral arteriole and venous dilatation, which can decrease blood pressure (sensitive individuals may enter shock following IV dose). |
In what way do opioids affect the venous system? | besides histaminic component, there is a direct opioid receptor action to cause venous dilatation. |
Where do opioids mainly affect smooth muscle contraction? | cause contraction in biliary and bladder sphincter muscles. |
Where do opioids inhibit ACh release? | in mesentery, this decreases peristalsis, and causes constipation. |
What are the most common therapeutic opioid uses? | 1. Analgesia – both acute and chronic. 2. Pre-op sedation, anesthesia, epidural analgesia. 3. Diarrhea. 4. Cough suppression. 5. Opioid addiction withdrawal. 6. Opioid overdose (antagonist). |
What are the major opioid side effects? | 1. Respiratory depression. 2. Nausea and vomiting. 3. Hypothermia. 4. Constipation. 5. Histamine release and its effects. 6. Muscular rigidity due to inhibition of dopamine release in the striatum (Parkinson-like). |
True or False: While opioids are well absorbed from the GI system, they do not have much first-pass effect. | False. Because they are well absorbed from the GI, most undergo large first-pass metabolism following oral dosing. |
Opioids distribute well. Which types reach higher CNS concentrations faster? | More lipid-soluble opioids reach higher CNS concentrations faster. |
What are the implications of opioids on a fetus? | Most cross placenta well, but fetus can not metabolize much, so conc. is high. |
Metabolism varies among each compound, however all are metabolized to some extent. Where are most metabolites excreted? | Excretion mainly via renal and biliary mechanisms of metabolized forms. |
What are the two chemical classes of opium alkaloids? | Phenanthrenes and benzolisoquinolines. |
What is the structure of phenanthrenes? | 4 ring-system with a tertiary amine with pKa of >8.0, so mostly ionized at physiologic pH |
Levo isomers of phenanthrenes are more active. What are the three levo isomers of phenanthrenes? | Morphine, codeine, and thebain. |
The benzolisoquinolines lack standard opioid activity. What are the two benzolisoquinolines? | Papavarine and noscapine. |
Papavarine is a benzolisoquinoline. What does it do? | a smooth muscle relaxant – phosphodiesterase inhibitor, increases cAMP. |
Noscapine is a benzolisoquinoline. What does it do? | antitussive and anticancer(?) – sigma-activity? |
What are the three opioid agonists that begin with the letter "M?" | Morphine(MS Contin), Meperidine(Demerol), Methadone(Dolophine). |
What are the three opioid agonists that begin with the letter "H?" | Hydromorphone(Dilaudid), Hydrocodone (Vicoden), and Heroin. |
What are the three opioid agonists with "fent" in their names? | Fentanyl (Sublimaze), Sufentanil(Sufenta), and Alfentanil(Alfenta). |
List all opioid agonists: | Morphine(MS Contin), Hydromorphone(Dilaudid), Oxymorphone, Codeine, Hydrocodone(Vicodin), Oxycodone (Oxycontin), Heroin, Levorphanol(Levo-Dromoran), Dextromethorphan, Meperidine(Demerol), Methadone, Propoxyphene(Darvon), Fentanyl, Sufentanil, Alfentan |
A natural alkaloid, Morphine is derived from what plant? | Papaver somniferum. |
At what receptors does Morphine act? | Primarily mu (some kappa). |
True or false: It takes a long time to develop tolerance to Morphine. | False. Morphine users quickly develop tolerance. |
There has been a recent resurgence in the use of Morphine. What is it most commonly used for? | Analgesia. |
What is the chemical name of Heroin? | Diacetylmorphine |
Heroin is a synthetic compound. How is it prepared. | Easily prepared from Morphine. |
How does Heroin compare to Morphine? | Approximately twice as potent as morphine, but much more lipid-soluble. |
Heroin is not approved for clinical use due to high addiction probability. It enters the CNS quickly to cause euphoria due to what property? | High lipid-solubility. |
How does Codeine compare to Morphine? | For analgesia, about 1/10th the potency. |
Codeine is a potent antitussive and has little risk for addiction or respiratory depression. What accounts for its analgesic qualities? | It is partially converted to Morphine in the body. |
How does Oxycodone(Oxycontin) compare to Morphine? | It is about twice as potent as an analgesic. |
What drug comes in a 160mg extended release tablet form and is widely abused as "Hillbilly Heroin?" | Oxycodone(Oxycontin). |
What do idiots do to Oxycodone(Oxycontin) to make it more lethal? | Chewing up the extended release form. |
Levorphanol(Levo-Dromoran) is a congener of Morphine, which means it is in the same chemical class. How do they compare? | Very potent synthetic morphine analgesic congener (5X). Less constipating and longer lasting. |
What is Dextromethorphan(Dimetane)? | A dextro-rotary isomer, which means it has no analgesic activity, but is an effective antitussive. |
What is the most widely used synthetic congener? | Meperidine(Demerol). |
Compare Meperidine(Demerol) to Morphine. | Only one-tenth the mg. potency of morphine as an analgesic, and has a shorter duration of action. |
Why is Meperidine(Demerol) abuse more difficult to detect? | It does not cause miosis. |
How can Meperidine(Demerol) cause seizures? | Metabolized to Normeperidine, a CNS stimulant. Decreased renal function can allow metabolite build-up, and potential seizures. |
What is a contraindication of Meperidine(Demerol)? | MAOI therapy. |
Compare Methadone(Dolophine) with Morphine. | About the same analgesic potency, but Methadone(Dolophine) causes much less sedation. |
Why is Methadone used to counter withdrawal symptoms? | Longer duration of action, due to slower elimination. |
Compare Propoxyphene(Darvon) to Methadone. | Structurally related to Methadone, but less than one-tenth as potent per mg. |
Propoxyphene(Darvon) has properties similar to other Opioid analgesics. Why has its benefit been questioned? | Questions have been raised concerning its benefit in dose strengths found in most products. |
Fentanyl(Sublimaze) is chemically related to Meperidine. Compare Fentanyl(Sublimaze) to Morphine. | Approximately 80X as potent an analgesic as Morphine (similar potency among its other effects also). |
What is the main advantage of Fentanyl(Sublimaze)? | Main advantage is its short half-life of redistribution (12.5 min.). |
What common opioid is also used for continuous epidural and transdermal analgesia? | Fentanyl(Sublimaze). |
What drugs are used similarly to Fentanyl(Sublimaze)? | Sufentanil (Sufenta) (800X), Remifentanil (Ultiva) (80X), and Alfentanil (Alfenta) (20X) have similar uses. |
Fentanyl(Sublimaze) is often used in conjunction with what? | Often combined with other agents for anesthesia such as neuroleptics. |
Remifentanyl(Ultiva) is selective to what? | Selective mu-Receptor agonist. |
How does Remifentanyl(Ultiva) differ from other Fentanyl(Sublimaze) derivatives? | Differs from other Fentanyl derivatives by having an ester-linkage. |
How does Remifentanyl(Ultiva)'s ester-linkage cause its short duration of action? | Causes short duration of action due to hydrolysis by non-specific esterases. |
What are the benefits of Remifentanyl(Ultiva)? | This allows an agent of short duration that can be more carefully titrated to needs and allows rapid recovery. |
Compare Etorphine(Immobilion, M99) to Morphine. | 1000X Morphine potency. |
Why is Etorphine(Immobilion, M99) is a large animal immobilizer. Why is it veterinary use only? | Toxic to humans, one drop on skin can be fatal. |
What relative of Etorphine(Immobilon, M99) is used on humans in China? | Dihydroetorphine used in China as a painkiller, it appears to be less addictive(??) |
Define Opioid Antagonists: | Have receptor affinity but no intrinsic activity. |
What receptors do Opioid Antagonists mainly block? | Act by blocking mu-Receptors mainly (some kappa blockade also). |
What actions do Opioid Antagonists usually block? | Blocks analgesic, respiratory, euphoric, miosis, hypotension, and smooth muscle actions of the Opioids and endogenous b-endorphin and enkephalins. |
What is the clinical use of Opioid Antagonists? | Used clinically to reverse opioid-induced respiratory depression and in the treatment of “addicts”. |
What is a pure opioid antagonist given IV? | Naloxone (Narcan) is a pure antagonist normally given IV. |
Compare the opioid antagonist Naltrexone(Trexan) to Naloxone(Narcan). | Naltrexone (Trexan) is similar, but has a longer half-life, and can be given orally (Nalmefene (Revex) too). |
What is the partial opioid agonist? | Buprenorphine (Buprenex) shares structural components of Codeine and Naltrexone. |
How does Buprenorphine(Buprenex) work? | Binds to mu-Receptors, and elicits a weaker maximal response than other agonists. |
Buprenorphine(Buprenex) binds to mu-Receptors and elicits a weaker maximal response than other agonists. How is it used? | It has less abuse potential, and has been used to counteract Heroin and Morphine addiction without causing full-blown withdrawal symptoms. |
What are the mixed opioid agonist/antagonists? | Nallorphine(Nalline), Pentazocine(Talwin), and Nalbuphine(Nubain). |
What are Nallorphine(Nalline)'s agonist/antagonist properties? | Is a mu-Receptor antagonist and a weak agonist at kappa-Receptors. |
What is the outcome of Nallorphine(Nalline)'s antagonism at mu-Receptors and agonism at kappa-Receptors? | While it blocks mu-Receptor-mediated analgesia and euphoria, it also stimulates kappa-Receptor induced analgesia and sedation. |
What are some side effects of large doses of the mixed opioid agonist/antagonist Nallorphine(Nalline)? | Large doses may cause dysphoria and hallucinations. |
How do Pentazocine(Talwin) and Nalbuphine(Nubain) compare to Nallorphine(Nalline)? | Pentazocine (Talwin) and Nalbuphine (Nubain) have similar actions, but are stronger kappa mediated analgesics. |
Tramadol(Ultram) is a newer analgesic with similarities to what two drugs? | Opioids and NSAIDs. |
True or False: Both the parent compound and an active metabolite have weak affinity for mu-Receptors, however, their analgesic effect is not entirely reversed by Naloxone. | True. |
In addition to Tramadol(Ultram)'s affinity for mu-Receptors, how else does it cause analgesia? | Also acts to block re-uptake of serotonin and norepinephrine in central synapses, which then decreases pain information transmission in the brain. |
True or False: Tramadol(Ultram) is similar in strength to Fentanyl? | False. Its analgesic strength is similar to Codeine-Acetaminophen agents. |
What are some SE of Tramadol(Ultram)? | Can cause dizziness, sedation, seizures and hallucinations. |
What opioid effects cause its high abuse potential? | Euphoria and sedation. |
Opioids are physically and (blank) addictive. | Psychologically. |
What does rapid tolerance mean? | Rapid tolerance development means higher and higher doses requires to achieve same euphoria. |
Because rapid tolerance causes opioids to become less pleasurable, why do addicts continue to use them? | Many “addicts” only continue to take the opioids to avoid the uncomfortable withdrawal symptoms. |
In addition to pharmacologic therapy (Methadone), what do many addicts require? | Proper addiction therapy often requires years of psychological therapy as well as pharmacologic therapy (ex.- Methadone). |
What are the three main ways opioids are used in anesthesia? | 1. Spinal analgesia/anesthesia 2. Pre-op 3. Surgical adjuvant(assistant). |
Why are opioids used in pre-op? | To decrease pre-surgical pain, surgical pain, and to provide mild sedative effects. Use allows the amount of general anesthetic required to be decreased. |
Why are opioids used as surgical adjuvant? | Can be used alone in some cases, or provided with lower doses of other agents such as anesthetics, muscle relaxants, neuroleptics. |
What is a neuroleptic? | A tranquilizer used to treat psychotic conditions when a calming effect is desired. |
What is neuroleptic anesthesia? | butyrophenone i.e. droperidol – a D2 blocker with antiemetic properties + opioid i.e. fentanyl + nitrous oxide), etc. |
What are some future opioid therapeutic possibilities? | Use of peptide-type opioid receptor agonists for pain relief, and transplantation of adrenal medullary chromaffin cells (which secrete opioid peptides) into the spinal subarachnoid space. |
Why are peptide-type opioid receptor agonists for pain relief being developed? | These are being designed to target specific receptor sub-types. |
Why would you transplant adrenal medullary chromaffin cells into the spinal subarachnoid space? | Because they secrete opioid peptides and could theoretically provide long-term pain relief to chronic pain sufferers without exogenous opioid SE’s. |