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Opioids vs. Opiates vs. Endogenous opioids
- Opioids= all-encompassing term
- Opiates= Alkaloid pharmaceuticals (morphine, codine)
- Endogenous Opioids= Peptides (precursor proteins)
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Origin of opiates
Seed of opium poppies
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Rank in order of strength: Morphine, Codeine, Thebaine
Morphine > Codeine > Thebaine
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Morphine is the parent molecule. When you add a -CH3 you get
Codeine
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Morphine is the parent compound. When you add 2 acetyl (CH3OO)2 what do you get?
Heroin
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4 Therapeutic Categories of Opioids
- Strong Agonists (morphine)
- Mild/Moderate Agonists (codeine)
- Mixed Agonists/Antagonists (Buprenorphine, Butorphanol, Pentazocine)
- Narcotic Antagonists (Naloxone, Alvimopam)
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Receptor that mediates opioid's analgesic and euphoric effects
Mu opioid receptor
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Receptor that mediates opioid's sedation and dysphoric effects
Kappa opioid receptor
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Epsilon receptor is preferentially selective for
B-endorphin
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Opioid receptors= what type of receptor
G-coupled receptor
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5 Clinical Uses of Opioids
- Analgesia
- Acute Pulmonary Edema
- Cough
- Diarrhea
- Adjuncts to anesthesia
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3 Side effects of Opioids
- Miosis
- Constipation
- Increased intracranial pressure
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2 side effects of opioids that are resistant to tolerance
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4 CNS Effects of Opioids
- Truncal rigidity
- Respiratory depression
- Miosis (Edinger-Westphal Nucleus)
- Inhibits sexual drive (w/ repeptitive use)
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Opioids MoA:
Presynaptic Neurons
Kappa, Delta, and Mu receptors present
- Decreases calcium influx
- Decreases transmitter release
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Opioids MoA: Postsynaptic Neurons
Increases K+ conductance -> IPSP
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4 Sites of Opioid Action
- 1)Block Afferent Pain: Substantia gelatinosum @ dorsal horn of spinal cord
- 2)Activate descending inhibitory pain pathway in brain that descends to spinal cord
- 3)Relieve emotional pain by acting on thalamic nuclei
- 4)Mediate pain of inflammation by acting on peripheral receptors
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4 Sites of Opioid Action
- Dorsal horn (spinal cord)
- Midbrain
- Medulla
- Thalamic Nuclei
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3 Strong Agonists
- Morphine
- Methadone
- Meperidine
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Can opioids be administered orally?
Oral route is less effective due to significant hepatic first-pass metabolism
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Opioid Pharmacokinetic Distribution
- Lipid soluble (for CNS penetration); Heroin, codeine, methadone > morphine
- Concentrate in tissue (skeletal muscle primary reservoir)
- Readily crosses placenta
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Major active hepatic metabolite of Morphine
Morphine-6B-glucuronide
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Primary alkaloid in opium
Morphine
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10x more potent than morphine, high abuse liability (no longer used in US)
Hydromorphone
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Another name for heroin
Diacetylmorphine (Schedule I)
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Lollipopo or transdermal patch
Fentanyl
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Tends to dilate pupils
Meperidine
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2 things Meperidine is NOT used for
Cough, diarrhea
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Causes tremors, convulsions w/ large doses
Meperidine
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Meperidine + MAOIs=
Hyperpyrexic coma
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Can cause serotonin syndrome
Meperidine
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Opioid tolerance
Incomplete cross-tolerance (use an opiod rotation)
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Single crushed 80mg tablet is lethal in naive user
Oxycodone
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Antitussive effects
Codeine
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2 Mild Opioid Agonists used to treat diarrhea
- Diphenoxylate
- Loperamide (Imodium)
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Active at more than one opioid receptor, but may block analgesic actions of pure agonists
Mixed Agonists/ Antagonists (Buprenorphine, Butophanol, Pntazocine, Dezocine)
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Weak MOP agonist, blocks NE and 5HT uptake in CNS (Analgesic action not entirely opioid dependent)
Tramadol
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Seizures, suicide risk
Tramadol
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Selective antitussive w/ no analgesia
Dextromethorphan
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Dextromethorphan is an antagonist at what receptor
NMDA glutamate receptors
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Narcotic antagonist that can show acute elevation in BP
Naloxone
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Opioid withdrawal symptoms? Tx?
Nausea, vomiting, rhinorrhea
Naloxone
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Narcotic Antagonists that restore bowel function
- Alvimopan
- Methylnaltexone bromide
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Do NOT use opioids in labor or head trauma!
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Triad of acute opioid intoxication
- Coma
- Pinpoint pupils
- Depressed respiration
Tx: Naloxone
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Most abused opioids are
Prescribed
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Narcotic used for long-term pain that caused seizure
Meperidine
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Dextromethrophan is most likely to have been administered for
coughing relief
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Associated w/ confusion and seizures
Normeperidine
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Recovering from abdominal surgery, presents w/ pinpoint pupils and constipation. Most likely taking
Hydromorphone (dilauded)
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Manage opioid addicts
Methadone
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Exhibits the greates propensity for euprhoria and abuse liability
Hydromorphone (dilauded)
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Exerts its actions solely in the periphery rather than in the CNS
Alvimopan
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Manage long-term opioid withdrawal with
Promethazine (Phenergan) and Clonidine
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