Pethidine (Meperidine): an overview of the opioid analgesic

Pharmacology and mechanism

Pethidine acts mainly at mu-opioid receptors in the central nervous system to produce analgesia, sedation and suppression of respiratory drive. It is available in oral and parenteral forms and is generally less potent than some newer opioids. Because of its distinct chemical structure it has some pharmacological differences from other opioids; for clinical summaries see general opioid information.

Metabolism and specific toxicity

The drug is metabolized in the liver to several products, including the metabolite normeperidine, which is renally excreted and can accumulate with repeated dosing or impaired kidney function. Normeperidine has excitatory central nervous system effects and can increase the risk of tremor, myoclonus and seizures. For this reason pethidine is often avoided for prolonged use or in situations where repeated dosing will be required.

Adverse effects and interactions

Adverse effects are typical of opioids: respiratory depression, sedation, nausea, vomiting, constipation and pupillary constriction. Important drug interactions include potentially dangerous combinations with certain antidepressants — especially monoamine oxidase inhibitors and serotonergic agents (antidepressants) — which can produce serotonin toxicity, and with central nervous system depressants such as benzodiazepines and alcohol, which can deepen sedation and respiratory depression.

• Use with caution in people with liver disease because metabolism may be altered.
• Avoid or adjust dosing in renal impairment due to risk of normeperidine accumulation.
• Caution is warranted in men with enlarged prostate or urinary retention, and in patients with hyperthyroidism.
• Respiratory disease such as asthma increases risk of opioid-related respiratory compromise.
• It may be contraindicated or used cautiously in endocrine disorders such as Addison's disease.
• Patients with a history of epilepsy or other seizure disorders require careful assessment before use.

Clinical use and guidance

Because of the metabolite-related risks and the availability of alternatives, many clinicians prefer agents such as morphine, fentanyl or non-opioid analgesics for extended treatment. When pethidine is selected for short-term use, clinicians limit single doses and frequency, monitor renal and hepatic function, and avoid interacting medicines. Emergency management of overdose follows standard opioid protocols with respiratory support and, when appropriate, opioid antagonists.

History and regulation

Pethidine was widely adopted in the mid-20th century but its use has decreased in many countries. Some formularies restrict its use or recommend alternatives because of safety concerns. Local prescribing guidelines and formularies provide current recommendations; consult authoritative clinical sources for up-to-date, location-specific advice (clinical guidelines).

For further reading and patient information consult reputable drug references and national formularies: basic drug monographs (chemical overview), analgesic comparisons (opioid comparisons), and safety bulletins on interactions and contraindications (antidepressant interactions, benzodiazepine co-use, alcohol cautions, hepatic precautions, prostatic issues, endocrine cautions, respiratory disease, adrenal insufficiency, seizure risk, epilepsy considerations).