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Bind to opioid receptors; specifically, analgesia takes place at the mu receptor.

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Indications: moderate to severe pain.

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Opioid receptor–specific agonists (see below for meperidine, methadone, and tramadol):

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SystemEffects
Cardiovascular
  • HR and BP decrease usually due to decreased sympathetic tone with pain relief
  • Dose-dependent increase in vagal tone may cause bradycardia
  • Histamine release from morphine may cause hypotension and resultant tachycardia
  • Minimal effect on contractility
  • May enhance myocardial depressant effects of other medications
Respiratory
  • Decrease in RR due to decreased response to CO2
  • Increased tidal volume
  • Decreased minute ventilation
  • Suppression of cough reflex
  • Muscle rigidity with large IV boluses that can make ventilation difficult without paralysis (may be prevented with benzodiazepine premedication)
Ophthamological
  • Miosis via stimulation of the Edinger–Westphal nucleus
Gastrointestinal
  • Nausea/vomiting from direct stimulation of chemoreceptor trigger zone (usually happens at initiation of therapy or with dose changes)
  • Gastric stasis (may also be cause of nausea/vomiting)
  • Constipation; most patients never become tolerant to constipation (thus requiring laxatives and stool softeners)
  • Spasm of sphincter of Oddi
Endocrine
  • May block stress response at high doses
  • Decrease testosterone levels with long-term use at high doses (to the point that supplementation is needed to treat sexual dysfunction)
Obstetrical/neonatal
  • Neonatal CNS and respiratory depression (cross placenta)
Genitourinary
  • Urinary retention due to increased ureter tone (can be reversed with atropine)
Central nervous system
  • Analgesia
  • Sedation
  • Euphoria, dysphoria, or agitation
  • Unreliable amnesia (at high doses)
  • Decreased CBF and metabolic rate
  • Increased ICP (if opioid-induced hypoventilation is uncontrolled)
  • Withdrawal symptoms may occur with abrupt discontinuation
  • Addiction
Skin
  • Histamine release (from morphine and meperidine)
  • May cause pruritus, redness, and hives at injection site
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Meperidine (in addition to those listed above for opioid receptor–specific agonists):

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SystemEffects
Cardiovascular
  • Myocardial depressant
  • May cause increased HR and contractility due to anticholinergic effect
  • Histamine release may cause hypotension and resultant tachycardia
Gastrointestinal
  • Sphincter of Oddi spasm may be decreased compared with other opioids
Central nervous system
  • Seizures may result from accumulation of the metabolite normeperidine
Skin
  • Histamine release
  • May cause pruritus, redness, and hives at injection site
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Methadone (in addition to those listed above for opioid receptor–specific agonists):

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SystemEffects
Cardiovascular
  • QT prolongation usually above 100 mg daily dose
  • Review EKG if increasing dose over 100 mg per day
Respiratory
  • Unexpected and delayed respiratory depression due to prolonged biphasic elimination
  • Especially with rapid dose increases causing accumulation
Central nervous system
  • Unexpected and delayed sedation due to prolonged biphasic elimination (especially with rapid dose increases causing accumulation)
  • May have a role in the treatment of neuropathic pain due to NMDA receptor antagonist activity
  • Thought to cause less tolerance than other opioids
  • Useful in opioid maintenance therapy and detoxification due to long duration of action
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Tramadol...

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