Butorphanol

Usage

• Medical Conditions: Butorphanol is prescribed for the relief of moderate to severe pain. The nasal spray formulation is also used for migraine headaches. It’s also used as a component of balanced anesthesia, as a pre-anesthetic/preoperative medication, and for labor pain.
• Pharmacological Classification: Opioid analgesic (agonist-antagonist).
• Mechanism of Action: Butorphanol binds to opioid receptors (primarily kappa, with some mu activity) in the central nervous system, altering the perception of and response to pain. Its agonist-antagonist properties mean it can activate some opioid receptors while blocking others, which offers some benefits in terms of side effects compared to pure agonists.

Alternate Names

• International/Regional Variations: No significant variations.
• Brand Names: Stadol, Torbutrol, Torbugesic, Dolorex.

How It Works

• Pharmacodynamics: Butorphanol exerts its analgesic effects by binding to opioid receptors in the CNS. It has agonist activity at kappa receptors and partial agonist/antagonist activity at mu receptors. This mixed action can provide effective pain relief with potentially fewer side effects compared to pure mu agonists like morphine. It can cause respiratory depression, particularly at high doses or in sensitive individuals.
• Pharmacokinetics:
  • Absorption: Well-absorbed following intramuscular (IM), intravenous (IV), and intranasal administration. Oral absorption is poor due to significant first-pass metabolism.
  • Metabolism: Extensively metabolized in the liver, primarily by glucuronidation.
  • Elimination: Primarily eliminated via the kidneys. Some metabolites are excreted in bile. Elimination half-life is approximately 3 hours.
• Mode of Action: Binds to kappa and mu opioid receptors in the CNS. Agonist action at kappa receptors contributes to analgesia. Partial agonist/antagonist action at mu receptors may limit some side effects (like respiratory depression and euphoria) while still contributing to analgesia.
• Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Binds to kappa and mu opioid receptors. No significant enzyme inhibition or neurotransmitter modulation beyond its opioid receptor effects.
• Elimination Pathways: Primarily renal excretion, with some biliary excretion of metabolites.

Dosage

Standard Dosage

Adults:

• IV: 1 mg every 3-4 hours, as needed. Effective dose range: 0.5-2 mg.
• IM: 2 mg every 3-4 hours, as needed. Effective dose range: 1-4 mg.
• Intranasal: 1 mg (1 spray in one nostril) initially. May repeat with 1 mg after 60-90 minutes if needed. For severe pain, initial dose can be 2 mg (1 spray in each nostril); do not repeat this dose. Maintenance: 1 mg every 3-4 hours.

Children:

• Not recommended for patients under 18 years of age due to lack of established safety and efficacy data.

Special Cases:

• Elderly Patients: Initial dose should be halved (0.5 mg IV, 1 mg IM, or 1 mg intranasal). Increase dosing interval to every 6 hours.
• Patients with Renal Impairment: Same as elderly patients.
• Patients with Hepatic Dysfunction: Same as elderly patients.
• Patients with Comorbid Conditions: Exercise caution in patients with respiratory disease, head injury, increased intracranial pressure, cardiovascular disease, adrenal insufficiency, biliary tract dysfunction, or seizure disorders.

Clinical Use Cases

• Intubation: 2 mg IV shortly before induction.
• Surgical Procedures:
  • Preoperative: 2 mg IM 60-90 minutes before surgery.
  • Intraoperative (balanced anesthesia): 2 mg IV before induction and/or 0.5-1 mg increments during anesthesia (up to 0.06 mg/kg). Total dose typically ranges from 4-12.5 mg.
• Mechanical Ventilation: Dose adjustment may be required based on respiratory status and other medications.
• Intensive Care Unit (ICU) Use: Dose titration based on pain assessment and respiratory status. Continuous monitoring is crucial.
• Emergency Situations: May be used for acute pain management in emergencies, but caution is advised due to the risk of respiratory depression.

Dosage Adjustments:

• Adjust dosage based on patient response, renal/hepatic function, and other medications.

Side Effects

Common Side Effects:

• Drowsiness, dizziness, nausea, vomiting, constipation, dry mouth, sweating, nasal congestion (with intranasal use).

Rare but Serious Side Effects:

• Respiratory depression, apnea, seizures, hallucinations, allergic reactions (e.g., anaphylaxis).

Long-Term Effects:

• Potential for physical dependence and withdrawal symptoms with prolonged use. Adrenal insufficiency and hypogonadism have been reported with chronic opioid use.

Adverse Drug Reactions (ADR):

• Severe respiratory depression, anaphylaxis, seizures.

Contraindications

• Significant respiratory depression, acute or severe bronchial asthma (in unmonitored settings), known or suspected gastrointestinal obstruction, hypersensitivity to butorphanol.

Drug Interactions

• CNS Depressants: Increased risk of respiratory depression and sedation (e.g., alcohol, benzodiazepines, barbiturates, other opioids).
• CYP450 3A4 Inhibitors/Inducers: May affect butorphanol metabolism.
• Other: Anticholinergics, antihypertensives, certain antidepressants (SSRIs, tricyclics), MAOIs.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: Category C (for pregnancy before 37 weeks gestation); Category D (during labor and delivery). Butorphanol can cause fetal harm and neonatal opioid withdrawal syndrome with prolonged use during pregnancy. Use during labor can cause respiratory depression in the neonate.
• Breastfeeding: Butorphanol is excreted in breast milk. Monitor infants for excessive sedation and respiratory depression.

Drug Profile Summary

• Mechanism of Action: Opioid agonist-antagonist, primarily kappa receptor agonist, with some mu activity.
• Side Effects: Drowsiness, dizziness, nausea, vomiting, constipation, respiratory depression.
• Contraindications: Respiratory depression, asthma (acute/severe), GI obstruction, hypersensitivity.
• Drug Interactions: CNS depressants, CYP3A4 inhibitors/inducers, other opioids.
• Pregnancy & Breastfeeding: Use with caution; risk of fetal harm and neonatal withdrawal syndrome. Excreted in breast milk.
• Dosage: See detailed section above.
• Monitoring Parameters: Respiratory rate, oxygen saturation, blood pressure, heart rate, level of consciousness, pain assessment.

Popular Combinations

• Often used alone. May be combined with non-opioid analgesics for enhanced pain relief.

Precautions

• Pre-screening for allergies, respiratory conditions, and GI function.
• Monitor patients with renal or hepatic impairment, the elderly, and those with comorbid conditions closely.
• Caution against driving or operating machinery due to potential sedation.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Butorphanol?

A: See detailed dosage section above. It varies depending on the route of administration, patient age, and health status.

Q2: How does Butorphanol differ from other opioids like morphine?

A: Butorphanol is an agonist-antagonist, binding primarily to kappa receptors and having mixed activity at mu receptors, unlike morphine, which is a pure mu agonist. This may result in a lower risk of some side effects, such as respiratory depression and euphoria, but a ceiling effect on analgesia is also possible.

Q3: Can Butorphanol be used in patients with asthma?

A: It is contraindicated in patients with acute or severe asthma in unmonitored settings. Caution is advised in patients with any respiratory disease. Careful monitoring is necessary.

Q4: Is Butorphanol safe during pregnancy?

A: Butorphanol is a Pregnancy Category C (before 37 weeks gestation) and D (during labor and delivery) drug. It carries a risk of fetal harm and neonatal opioid withdrawal syndrome. It should be used with extreme caution and only if the potential benefits outweigh the risks.

Q5: What are the signs of a Butorphanol overdose?

A: Respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils. Pulmonary edema, bradycardia, and hypotension can also occur.

Q6: Can Butorphanol be used for chronic pain?

A: While it can be used for extended periods for severe pain when other treatment options are inadequate, long-term use carries the risk of dependence and withdrawal symptoms. Regular reassessment of pain and consideration of alternative therapies are crucial.

Q7: What are the most important drug interactions to be aware of with Butorphanol?

A: Interactions with other CNS depressants (alcohol, benzodiazepines, other opioids), CYP3A4 inhibitors/inducers, and some antidepressants and antihypertensives can be significant.

Q8: Can Butorphanol be administered intranasally and parenterally to the same patient?

A: Yes, but careful dosage adjustments are necessary. Closely monitor patients for cumulative effects and potential side effects, particularly respiratory depression.

Q9: What are some withdrawal symptoms associated with Butorphanol cessation?

A: Anxiety, agitation, insomnia, sweating, abdominal cramps, diarrhea.

Q10: Can Butorphanol trigger seizures?

A: Yes, particularly in individuals with a history of seizure disorders. It can lower the seizure threshold.