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70 Cards in this Set
- Front
- Back
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Morphine MOA
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Agonist at Mu opioid receptor, inhibits cAMP
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How is morphine metabolized and excreted?
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Metabolized in liver
metabolites are excreted by kidneys |
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Morphine's therapeutic uses?
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1) analgesic
2) antidyspneic (often used for newborns w/ dyspnea or tachynyptic) |
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Morphine CNS side effects
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a. analgesia
b. drowsiness c. calming d. euphoria/ reinforcing effects/dysphoria e. substance dependence f. nausea and vomiting g. muscular rigidity h. respiratory depression i. neuroendocrine effects |
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Morphine effects on neuroendocrines?
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i. decreased GnRH, CRF, LH, FSH, ACTH, testosterone, cortisol
ii. increased prolactin |
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Morphine cardiovascular effects
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Decreased total peripheral resistance by:
1) histamine release (vasodilator) 2) blocking baro & chemo receptor reflexes Decrease myocardial work |
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Morphine effects on uterus
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Prolongs labor
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Morphine effects on skin
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itching
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Morphine effects on urine & GI
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Decreases GI motility & secretions (constipation)
Decreases urination |
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Morphine and seizures?
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lowers seizure threshold!!!
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Codeine MOA
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Its metabolized to morphine so it becomes an opioid analgesic
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Therapeutic uses for Codeine?
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Antitussive (used in cough syrups)
Diarrhea Analgesic |
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Oxycodeine MOA & thereapeutic use
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Metabolized to oxymorphine
Analagesic |
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Heroin MOA?
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Enters the CNS more rapidly than morphine
Morphine is one of its metabolites |
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Heroin metabolism
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B/c it breaks down to morphine, its very dangerous to those w/ kidney dysfunction
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meperidine MOA?
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Mu opioid receptor agonist
Better oral bioavailability than morphine |
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Meperidine uses?
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Analgesia (only used short-term due to metabolite toxicity)
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Differences btw Meperidine and Morphine?
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a. possibly less increase in biliary pressure
b. no depression of uterine contractions c. a metabolite (nor-meperidine) may induce tremors, muscle twitch, seizures (may not reverse with opioid antagonist) |
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Meperidine side effects?
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SEROTONIN SYNDROME!!!
Potentially fatal interaction with MAO inhibitors -severe respiratory depression, high fever, delirium, convulsions - “serotonin syndrome” |
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Which has better oral availability? Morphine or meperidine?
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Meperidine!
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Codeine MOA
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Its metabolized to morphine so it becomes an opioid analgesic
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Therapeutic uses for Codeine?
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Antitussive (used in cough syrups)
Diarrhea Analgesic |
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Oxycodeine MOA & thereapeutic use
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Metabolized to oxymorphine
Analagesic |
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Heroin MOA?
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Enters the CNS more rapidly than morphine
Morphine is one of its metabolites |
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Heroin metabolism
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B/c it breaks down to morphine, its very dangerous to those w/ kidney dysfunction
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meperidine MOA?
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Mu opioid receptor agonist
Better oral bioavailability than morphine |
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Meperidine uses?
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Analgesia (only used short-term due to metabolite toxicity)
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Differences btw Meperidine and Morphine?
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a. possibly less increase in biliary pressure
b. no depression of uterine contractions c. a metabolite (nor-meperidine) may induce tremors, muscle twitch, seizures (may not reverse with opioid antagonist) |
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Meperidine side effects?
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SEROTONIN SYNDROME!!!
Potentially fatal interaction with MAO inhibitors -severe respiratory depression, high fever, delirium, convulsions - “serotonin syndrome” Also causes tremors that CANNOT BE REVERSED by opioid antagonists! |
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Which has better oral availability? Morphine or meperidine?
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Meperidine!
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diphenyloxylate MOA & therapeutic use?
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Mu agonist & strong constipating effect!!!
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Diphenyloxylate abuse potential?
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able to cross BBB so must be cautious to avoid abuse potential
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Fentanyl MOA
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VERY potent Mu agonist;
Highly lipid soluble so quickly crosses BBB |
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Fentanyl therapeutic uses and benefits?
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Profound analgesia (given IV)
Anesthetic adjunct (post surgery) Fewere cardiac events (also available transdermal patch and transmucosal lozenger) |
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remifentanyl compared to fentanyl?
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Both are Mu agonists, but remifentanyl is even MORE RAPID
CLEARED BY ESTERASES!!! --> THIS IS SOMETHING THAT CAN BE GIVEN TO THOSE W/ KIDNEY OR LIVER PROBLEMS! Recovery time is relatively independent of duration of infusion. |
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Methadone MOA?
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Mu OR agonist with actions similar to morphine - excellent clinical analgesia
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Methadone therapeutic use?
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Good oral bioavailability coupled with long half-life and slowly releasable tissue store make it favorable for use as replacement therapy in heroin abusers
Analgesic |
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How is methadone metabolized?
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In the liver; ergo drugs that induce CYP metabolism can remove methadone from system rapidly
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Methadone side effects?
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QT prolongation possible at high or rapidly escalated doses
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Problems with methadone?
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Need to go to the clinic daily to receive dose
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How is methadone tolerance produced?
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By causing μ receptor internalization
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Does methadone have a slower or faster withdrawal onset and length than morphine/heroine??
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Slower, the onset takes days and the withdrawl can last 2-3 weeks
Heroine has an onset of 6-10 hours peaking around day 2 but done within 1 week |
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Is methadone maintenance therapy better at higher or lower doses?
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Higher doses!
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What is Pentazocine's moa?
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weak partial agonist at mu (so can act as antagonist); kappa agonist
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Pentazocine's therapeutic uses?
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Analgesia, sedation, respiratory depression, dysphoria
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Pentazocine's side effects?
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Resp depression
dysphoria High doses cause increased blood pressure, increased heart rate, can increase Left Ventricular End-Diastolic Pressure (LVEDP), pulmonary artery pressure, cardiac work Can precipitate withdrawal |
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What will patient's claim to be "allergic" to if they are heroine addicts?
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Pentazocine !!!!
Because its a partial agonist it can preciptate withdrawal in opioid dependent person!!! |
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Naloxone MOA
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Antagonist at mu, kappa, and delta opioid receptors
10x more selective for Mu receptor than kapa!!!! |
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Naloxone's therapeutic uses?
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Tx opioid overdose
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Naloxone's pharmaokinetic properties
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Extensive 1st pass (cannot give oral)
Short half-life relative to most opioid analgesics --> DANGER!!! of return of respiratory depression |
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Naltrexone differences from naloxone?
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Longer half life, effective orally
Reduces craving |
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NALTREXONE uses?
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Approved for treatment of opioid abuse (effectiveness limited), and for reducing craving in alcoholism
Does not work in conjunction with abstinence Puportedly blocks rewarding effects of endorphins released by alcohol administration |
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Who is naltrexone best for?
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People who "have their lives together"
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Explain the sinclaire method and what drugs it applies to?
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Naltrexone is taken in conjunction with normal drinking, and this reduces craving over time; persists as long as the alcoholic does not drink without first taking naltrexone.
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methylnaltrexone therapeutic use?
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administered subcutaneously--approved for counteracting opioid-induced constipation in patients using chronic opioids who have failed laxative therapy
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What is different about methylnaltrexone?
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It doesn't cross the BBB so only active peripherally
Ergo you can give it to relieve constipation but not loose analgesic effects |
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What are different mechanisms of tolerance development?
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1) Receptor selective-may involve receptor uncoupling, and internalization
2) Downstream effects a) upregulation of cAMP b) release of excitatory transmitters(which are downregulated by opioids) |
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What specific symptoms are unique to withdrawal from Opiates as opposed to barbituates?
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YAWNING, RUNNY NOSE, PUPILLARY OPENING (MYDRIASIS), watery eyes
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What is more sensitive to tolerance:
Respiratory depression & nausea vs Constipation and miosis |
Respiratory depression and nausea have higher levels of tolerance
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What is Conditioned withdrawal?
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stimuli associated with drug use or with previous withdrawal can trigger craving and withdrawal signs
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If withdrawl is more pharmacologic effects, what defines abuse?
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Key quality for abuse liability is positive reinforcement and subsequent craving
Desire to reduce the unpleasant withdrawal effects can contribute to continued abuse |
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What parts of the brain are implicated in "reward pathway"
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Ventral Tegmental area
Nucleus Accumbens Frontal cortex |
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What are the goals of "maintenance therapy"
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Prevent withdrawal
Prevent craving Prevent illicit opioid use Permit patients to function normally in both job-related and social environments. |
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What is bupenorphine MOA?
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partial Mu agonist & possible Kapa antagonist??
High 1st pass metabolism; give sublingual |
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Bupenorphine thereapeutic use?
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approved for treatment of opioid dependence but can precipitate withdrawal in opioid dependent person (not as effective as methadone)
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What is unique about Bupenorphine
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It has a long receptor dissociation time, so its duration is longer than half life
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dextromethorphan MOA?
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antagonist at NMDA receptor --> causes hallucinations!!!
(used for cough) |
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Does Bupenorphine work if patients are not yet in withdrawal?
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No! B/c it is a partial agonist, it can INDUCE withdrawal in patients, ergo patients must be in mild withdrawal already (running nose, etc)
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What is a unique property conveyed by heterodimers btw opioid receptros?
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These heterodimers appear to be important for regulating tolerance but not necessary for acute analgesic effects of opioids
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Path of nociception afferents?
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Nociceptor afferents (A) synapse onto spinal cord dorsal horn (B).
Projection neurons ascend contralaterally in anterolateral cord Major tract is through thalamus (C) and projects to cortex, where nociception is processed as pain |
