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Snapshot
  • A 22-year-old male is brought into the emergency department by the police due to depressed mental status. He was found in the park with an empty syringe by his side. Vital signs are notable for a respiratory rate of 7 breaths/min. Physical exam is significant for bilateral track marks, and miotic pupils.
Introduction
  • Opioids act on mu (most important), kappa, and delta transmembrane receptors in the central and peripheral nervous system
    • mu, kappa, and delta receptors are Gi protein coupled
      • inhibition of adenylyl cyclase → decrease cAMP concentration → increased K+ conductance + decreased Ca2+ conductance
        • inhibits presynaptic neurotransmitter release
          • prevents release of acetylcholine, norepinephrine, serotonin, glutamate, substance P
        • inhibits postsynaptic depolarization
  • Endorphines, enkephalins, dynorphins are examples of endogenous opioid peptides
  • Pharmacokinetics
    • morphine, hydromorphone, oxymorphone undergo first pass metabolism
      • morphine gets metabolized to morphine-6-glucoronide, which is highly active (the active analgesic)
    • opioids are generally metabolized by liver into inactive glucuronide conjugates
      • after metabolism they get excreted by the kidneys
    • codeine, oxycodone, hydrocodone are metabolized by hepatic cytochrome enzymes
      • cytochrome has genetic variability → variable analgesic response
    • meperidine can get metabolized to normeperidine N-demethylation
      • normeperidine can lead to anxiety, tremors, seizures
    • heroin gets metabolized into 6-monoacetylmorphine, which can be detected on urine screening
Clinical Uses
 
Drug Classification
Subclass Medication

Agonists

  • Morphine
    • pain management
  • Methadone
    • detoxification and maintenance (agonist) treatment of opioid addiction 
    • pain management
  • Codeine
    • pain management

Mixed agonist-antagonist

  • Buprenorphine
    • maintenance treatment of opioid addiction
    • pain management
    • withdrawal symptoms 
Antagonists
  • Naltrexone
    • treatment of alcohol dependence
    • opioid overdose
  • Methylnaltrexone
    • opioid-induced constipation
  • Naloxone
    • opioid overdose
      • for reversal of opioid depression
Antitussives
  • Dextromethorphan
  • Codeine
Others
  • Tramadol
    • pain management
  • Butorphanol
    • pain management
  • Loperamide/dyphenoxylate
    • manages diarrhea
 
Side Effects by System
 
Opiate Pharmacologic Effects by System
System Side Effect

Central nervous

  • Analgesia
  • Euphoria/dysphoria
  • Miosis
    • tolerance does not develop in miosis
  • Sedation
  • Cough reflex inhibition

Cardiovascular

  • Vasodilation
  • Hypotension
Pulmonary
  • Respiratory depression
Gastrointestinal
  • Constipation
    • tolerance does not develop to constipation
  • Increased tone/pressure in the biliary sphincter
  • Nausea and vomiting
Genitourinary
  • Urinary retention
  • May prolong labor
Endocrine
  • Increases antidiuretic hormone (ADH) and prolactin secretion
  • Decrease luteinizing hormone (LH) secretion
Dermatological
  • Pruritus
  • Flushing
 
Toxicity
  • Acute overdose triad
    • miosis, respiratory depression, coma
      • respiratory depression due to ↓ response to ↑ pCO2
  • Tolerance
    • a decrease in pharmacologic effect after prolonged drug usage
      • secondary to down-regulation of opioid receptors
    • miosis and constipation are not affected by tolerance
    • NMDA receptor antagonists (eg, ketamine) and delta-receptor antagonists have been reported to prevent opioid tolerance
  • Withdrawal side effects
    • pain originating from the CNS
    • flu-like symptoms
      • lacrimation, sweating, rhinorrhea, salivation
      • muscle cramps and spasms
  • Drug specific side-effects
    • meperidine (seizures and serotonin syndrome with MAOIs/SSRIs)
    • nalbuphine (hallucinations)
Contraindications
  • Head trauma
    • ↑ pCO2 can cause vasodilation and ↑ intracranial pressure
  • Pulmonary dysfunction
    • patient may not be able to compensate for respiratory depression
  • Liver/kidney dysfunction
    • poor excretion mechanisms may result in accumulation
  • Adrenal/thyroid deficiencies
    • opiates may show greater effects
  • Pregnancy
    • fetus may show dependency
    • exception is meperidine
 

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