pethidine
opioid analgesic· Brands: Demerol, DolantinIMIVPOSC
Mechanism of action
Pethidine is a synthetic opioid agonist that acts primarily at mu-opioid receptors within the central and peripheral nervous systems, producing analgesia, sedation and euphoria. It also has weak local anaesthetic activity and may cause less smooth muscle spasm than morphine. Its active metabolite, norpethidine, has convulsant properties and can lead to neurotoxicity and seizures with repeated or high-dose use.
Pharmacokinetics
Pethidine is well absorbed following oral and parenteral administration. It undergoes extensive first-pass hepatic metabolism, with oral bioavailability around 50%. It is metabolised to norpethidine, which accumulates with repeated dosing and has a longer elimination half-life than the parent drug. Excretion is predominantly renal, and norpethidine clearance is prolonged in renal impairment, increasing the risk of toxicity. The elimination half-life of pethidine itself is approximately 3 to 4 hours.
Indications & dosing
Acute moderate to severe pain
Pethidine has a shorter duration of action than morphine; use with caution in renal impairment.
- adult · IM: 25–100 mg every 4 hours · Pethidine has a shorter duration of action than morphine; use with caution in renal impairment.
Obstetric analgesia (labor pain)
May be given IV in some settings; ensure fetal monitoring.
- adult · IM: 50–100 mg every 4 hours · May be given IV in some settings; ensure fetal monitoring.
Biliary or renal colic
Some prefer pethidine over morphine for biliary colic due to less sphincter of Oddi spasm; practice varies.
- adult · IM: 25–100 mg every 4 hours · Some prefer pethidine over morphine for biliary colic due to less sphincter of Oddi spasm; practice varies.
Contraindications & precautions
- Severe renal impairment · Risk of norpethidine accumulation leading to CNS excitation and seizures.
- Concomitant use of monoamine oxidase inhibitors (MAOIs) · Risk of serotonin syndrome and severe interactions.
- Severe respiratory depression · Opioids exacerbate respiratory depression.
- Severe hepatic impairment · Reduced metabolism may lead to accumulation and increased toxicity.
- Seizure disorder · Pethidine and its metabolite norpethidine lower the seizure threshold.
- Head injury or raised intracranial pressure · Opioids may obscure neurological assessment and increase ICP.
- Reduce dose in elderly or debilitated patients.
- Avoid or use with caution in renal impairment; consider alternative opioid.
- Use with caution in raised intracranial pressure or head injury; monitor neurological status.
- Monitor respiratory rate, especially in patients with compromised respiratory function.
- Do not use concurrently with MAOIs or within 14 days of stopping MAOIs.
- Caution in patients with a history of seizures; norpethidine is proconvulsant.
Adverse effects
- Constipation
- Nausea and vomiting
- Dizziness and lightheadedness
- Sedation and somnolence
- Respiratory depressionserious
- Hypotensionserious
- Seizures (due to norpethidine accumulation)serious
- Serotonin syndromeserious
Renal & hepatic adjustment
- eGFR 30–60: Consider reducing the dose or extending the dosing interval. Monitor closely for signs of opioid toxicity and normeperidine accumulation.
- eGFR 0–30: Avoid use due to the risk of normeperidine accumulation, which may cause CNS excitation and seizures. (avoid)
- Hepatic impairment (mild): No specific dose adjustment usually required, but monitor response and side effects.
- Hepatic impairment (moderate): Consider reducing the dose and extending the dosing interval. Monitor closely for signs of opioid toxicity.
- Hepatic impairment (severe): Avoid use. Consider an alternative opioid with a better safety profile in hepatic impairment. (avoid)
Monitoring, pregnancy & toxicity
- Respiratory rate · Before each dose
- Sedation level · Before each dose
- Pain score · Regularly
- Blood pressure and heart rate · Regularly
- Renal function (eGFR) · Before initiating and periodically
- Signs of normeperidine toxicity (tremors, myoclonus, seizures) · Especially in renal impairment or prolonged use
- Pregnancy: Use only if the potential benefit justifies the potential risk to the fetus. Consider alternative opioids when appropriate. Prolonged use during pregnancy may lead to neonatal opioid withdrawal syndrome. Use in labour may cause respiratory depression in the neonate.
- Toxicity: Respiratory depression, bradypnoea, hypoxia · Provide supportive care, administer naloxone as required, and monitor respiratory function closely.
- Toxicity: CNS depression, sedation, confusion · Provide supportive measures, avoid concurrent CNS depressants, and consider naloxone if respiratory depression is present.
- Toxicity: Seizures due to normeperidine accumulation, especially in renal impairment · Administer benzodiazepines, correct any electrolyte imbalances, and consider switching to an alternative opioid.
- Toxicity: Cardiovascular effects: hypotension, bradycardia · Monitor vital signs, administer IV fluids, and use atropine for severe bradycardia if indicated.
Clinical notes
Pethidine is reserved for short-term management of moderate to severe pain, such as in obstetrics or procedural pain. It is not recommended for chronic pain because norpethidine accumulation may precipitate seizures, particularly in patients with renal impairment or those receiving high doses. It is contraindicated in patients taking monoamine oxidase inhibitors due to the risk of serotonin syndrome. Use with caution in the elderly and in those with hepatic or cardiac disease. Dose reduction is required in renal impairment.
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BNF; local formulary