Morphine

Drug Name

Generic Name: Morphine Sulfate
Pronunciation: mor-feen
Common Brand Names (US): Duramorph® (preservative-free for neuraxial use), Infumorph® (epidural infusion), Astramorph®

Drug Class

Pharmacologic Class: Opioid Agonist (Phenanthrene derivative)
Therapeutic Class: Opioid Analgesic
Schedule: Schedule II Controlled Substance

Mechanism of Action (MOA)

Morphine is the prototypical µ-opioid receptor agonist. It binds to µ-opioid receptors primarily in the CNS and gastrointestinal (GI) tract. This binding:

Inhibits the presynaptic release of excitatory neurotransmitters.
Hyperpolarizes postsynaptic neurons.
Ultimately blocks pain signal transmission, resulting in profound analgesia, sedation, and other characteristic opioid effects.

Pharmacokinetics

Onset: Slower than fentanyl (5-10 minutes IV) due to lower lipophilicity, resulting in slower crossing of the blood-brain barrier.
Distribution: Distributes widely, but less rapidly than fentanyl.
Metabolism: Undergoes extensive hepatic metabolism via glucuronidation to two primary metabolites: Morphine-6-Glucuronide (M6G), which is a potent µ-agonist and contributes significantly to analgesia and prolonged respiratory depression, and Morphine-3-Glucuronide (M3G), which is largely inactive or may have neuroexcitatory properties.
Excretion: Both morphine and its metabolites are excreted by the kidneys. The half-life is 2-3 hours, but the clinical effect is prolonged by the active metabolites.

Pharmacodynamics

Pharmacodynamics describes the drug's effects on the body. The effects of morphine are characteristic of potent µ-opioid agonism but have distinct features compared to more synthetic opioids:

Analgesia: Provides effective analgesia for moderate to severe pain.
Sedation & Euphoria: Produces significant sedation and a sense of well-being (euphoria).
Respiratory Depression: A significant adverse effect. The onset is slower than with fentanyl, but the duration is prolonged, especially with repeat dosing, due to active metabolites.
Cardiovascular Effects: Can cause histamine release, leading to peripheral vasodilation, hypotension, flushing, and pruritus. Bradycardia is less common than with fentanyl.
Gastrointestinal Effects: Strongly increases smooth muscle tone in the GI tract, leading to constipation and a high risk of biliary colic by causing spasm of the sphincter of Oddi.
Miosis: Causes pinpoint pupils via µ-receptor action.

Dosing & Administration

Route: Intravenous (IV), Intramuscular (IM), Oral (PO), Epidural, Intrathecal.
IV Dosing (for moderate-severe pain):
- Bolus: 0.05-0.1 mg/kg (typically 2-4 mg), titrated to effect every 5-10 minutes.
- Infusion: Less common intraoperatively, but can be used for postoperative analgesia (e.g., 1-5 mg/hr).
Administration Note: IV bolus should be administered slowly over 2-3 minutes to minimize the risk of histamine-induced hypotension.

Clinical Uses / Indications

Post-Operative Analgesia: The classic and most common use in the perioperative period.
Neuraxial Analgesia/Anesthesia: Excellent choice for epidural or intrathecal administration due to its hydrophilic nature, which provides a long duration of action and limited rostral spread.
Acute Myocardial Infarction: Historically a cornerstone of "MONA" (Morphine, Oxygen, Nitroglycerin, Aspirin) for pain relief and anxiolysis, though its use is now more cautious due to hemodynamic effects.
Moderate to Severe Cancer Pain.

Contraindications

Absolute:
- Known hypersensitivity to morphine.
- Acute or severe bronchial asthma (in an unmonitored setting).
Relative:
- Severe Renal Impairment/Failure: Due to the accumulation of the active metabolite M6G, leading to profound and prolonged respiratory depression.
- Increased Intracranial Pressure (ICP): Respiratory depression can lead to CO2 retention, further increasing ICP.
- Head Injury.
- Paralytic ileus or suspected GI obstruction.

Adverse Effects / Side Effects

Respiratory: Apnea, respiratory depression (prolonged).
Cardiovascular: Hypotension (due to histamine release), flushing, pruritus.
Gastrointestinal: Nausea, vomiting, severe constipation, biliary colic.
CNS: Sedation, dizziness, headache.
Other: Urinary retention, miosis.

Drug Interactions

CNS Depressants: (e.g., benzodiazepines, propofol, alcohol, other opioids) have additive sedative and respiratory depressant effects.
Anticholinergics: Can increase the risk of severe constipation and urinary retention.
Note: Unlike fentanyl, morphine is not primarily metabolized by the CYP450 system, so it has fewer interactions with inhibitors/inducers of that system.

Monitoring Parameters

Standard Anesthesia Monitoring: ECG, NIBP, SpO2, EtCO2, Temperature.
Respiratory Status: Continuous monitoring of end-tidal CO2 and respiratory rate. The effect is prolonged, so post-operative monitoring is essential.
Blood Pressure: Monitor closely after IV administration for hypotension secondary to histamine release.
Renal Function: Assess baseline renal function and monitor with repeated dosing.

Key Considerations for the Anesthesia Provider

Histamine Release is Key: Always be prepared to treat hypotension and pruritus. Administer IV pushes slowly.
Renal Function is a Deal-Breaker: Morphine is generally contraindicated in patients with significant renal failure. Choose an alternative like fentanyl or hydromorphone.
Not for Rapid Titration: Its slow onset makes it a poor choice for treating acute intraoperative hemodynamic lability. Fentanyl or remifentanil are superior for this purpose.
Ideal for Neuraxial Use: Its hydrophilicity makes it a superb choice for long-lasting spinal or epidural analgesia with a low risk of rostral spread and delayed respiratory depression compared to lipophilic opioids.

Summary / "Bottom Line"

Morphine is the prototypical opioid, effective for post-operative and neuraxial analgesia. Its clinical use is defined by two key characteristics: histamine release, which can cause hypotension, and the formation of active metabolites cleared by the kidneys, making it unsuitable for patients with renal impairment and for rapid intraoperative titration.