Nalbuphine
Author: Dr. Wamiq Ansari
Last Updated:
Classification
1. Class: Opioid Analgesic.
2. Sub-class: Mixed Kappa (κ) agonist and Mu (μ) antagonist.
Mechanism of Action
1. Cellular Mechanism:
a. Binds to G-Protein-coupled Kappa (κ) receptors, in CNS and dosrsal horn of spinal cord, leading to;
- Inhibits Adenylyl cyclase, reducing Cyclic AMP levels.
- Closes Voltage-gated Calcium channels, reducing neurotransmitter release like Substance P, glutamate etc.
- Opens Potassium channels, causing neuronal hyperpolarization and reducing pain signals.
b. Binds to Mu (μ) receptors in CNS.
2. Effects:
a. Kappa Receptors: Inhibits ascending pain pathways producing;
- Analgesia.
- Sedation.
- Dysphoria (distressing, unpleasent emotional state, often described as anxiety).
b. Mu Receptors:
- Blocks Euphoria and addictive effects.
- Reduces repsiratory depression.
Pharmacokinetics
1. Half Life: 5 hours (patients with no renal or hepatic disease).
2. Onset: within 2-3 minutes (IV) and 15 minutes (IM or SC).
3. Peak Effect: 30 minutes.
4. Duration: 3-6 hours.
4. Metabolism: Liver.
5. Excretion: mainly urine.
Indications
1. Moderate to Severe Pain (Post-operative, traumatic, burns).
2. Sedation and Analgesia during mechanical ventilation.
3. Neonates with Opioid withdrawal syndrome.
Contraindications
1. Risk of withdrawal (patient is pure mu-opioid dependent).
2. Severe Respiratory depression or acute asthma.
3. Known Hypersensitivity.
4. Raised Intra-cranial pressure or head trauma (may obscure neurological assessment).
5. Severe hepatic or renal impairement.
Dosage
Parenteral
| Maintenance Dose | 0.1-0.2 mg/kg/dose x every 6 hours. |
| IV Infusion | 1. Loading Dose: 0.1-0.2 mg/kg over 10-15 minutes. |
1. Limited data of use in Neonates and Infants.
2. Use cautiously in minimal dosage.
Maximum Dosage
| Single Dose | 10 mg/dose. |
| Total Daily Dose | 160 mg/day |
Renal Adjustment Dosage
| Mild to Moderate Impairement (CrCl more than 30mL/min) | No adjustment needed. |
| Severe Impairement (CrCl less than 30mL/min) or undergoing dialysis | Use minimum effective dose with caution. |
Hepatic Adjustment Dosage
| Mild to Moderate Hepatic Impairment | Reduce dose by 25-50%. |
| Severe Hepatic Impairment | Avoid use. |
Adverse Effects
1. Gastrintestinal : Nausea, vomiting and constipation.
2. Nervous System: Sedation, dizziness, headache, dysphoria and hallucinations.
3. Respiratory: Mild respiratory depression.
4. Cardiovascular: Hypotension and Bradycardia.
5. Dermatological: Pruritis, sweating and flushing.
6. Misc: Risk of dependence (lower than full m-agonists).
Toxicity
Clinical Findings
1. Respiratory Depression.
2. CNS depression and lethargy.
3. Miosis.
4. Bradycardia and hypotension.
Management
1. Immediate Resuscitation: Maintain Airway, Breathing and Circulation.
2. Antidote Therapy: Nalaxone;
- a. Neonates and Infants: 0.01 mg/kg IV x stat. (may repeat every 2-3 minutes; maximum dose = 0.1mg/kg)
- b. Children: 0.1 mg/kg IV x stat. (maximum dose = 2 mg).
- c. Continuous Infusion: Two-third of the initial effective bolus dose per hour as 24 hour infusion.
References
1. Vanderah, Todd W. Basic and Clinical Pharmacology 16th Edition. McGraw Hill Professional, 3 Nov. 2023.
2. Tripathi, K D. Essentials of Medical Pharmacology. New Delhi, Jaypee Brothers Medical Publishers (P) Ltd, 2015
3. The, et al. The Harriet Lane Handbook, 23 Edition: South Asia Edition - E-Book. Elsevier Health Sciences, 20 June 2023.
4. Hongmin Cao, Chunying Bao, Haiya Tu, Jing Gao, Jinjin Huang, Qixing Chen - Impact of intravenous administration of nalbuphine at different time points for postoperative analgesia and sedation in adenotonsillectomized children: a prospective, randomized controlled trial: World Journal of Pediatric Surgery 2023;6:e000662.
5. Kubica-Cielińska A, Zielińska M. The use of nalbuphine in paediatric anaesthesia. Anaesthesiol Intensive Ther. 2015;47(3):252-6. doi: 10.5603/AIT.2015.0036. PMID: 26165241.