G-Pethidine

• Management of moderate to severe acute pain, including postoperative pain.
• Analgesia during labor.
• Pain relief during diagnostic or surgical procedures.
• Adjunct to anesthesia for perioperative pain control.
• Off-label: Treatment of severe chronic pain when other opioids are unsuitable.
• Control of postoperative shivering.

• Route: Intramuscular (IM), intravenous (IV), subcutaneous (SC), or oral administration.
• Adults:
• IM/SC: 25–100 mg every 3 to 4 hours as needed.
• IV: 12.5–50 mg every 3 to 4 hours, titrated to effect.
• Oral: 50–150 mg every 3 to 4 hours; less bioavailable than parenteral routes.
• Maximum daily dose generally should not exceed 600 mg.
• Pediatrics:
• 1–1.5 mg/kg every 3 to 4 hours via IM or SC route; individualized per clinical condition.
• Elderly:
• Initiate at lower doses with cautious titration due to increased sensitivity and reduced clearance.
• Special Populations:
• Renal impairment: Use with caution; reduce dose to prevent accumulation of neurotoxic metabolite norpethidine.
• Hepatic impairment: Use cautiously; metabolism may be impaired.
• Duration: Use the lowest effective dose for the shortest duration necessary.

Pethidine hydrochloride is a synthetic opioid analgesic that acts primarily as an agonist at central mu-opioid receptors. Activation of these G-protein-coupled receptors inhibits transmission of nociceptive signals by reducing neurotransmitter release and neuronal excitability, leading to analgesia and altered pain perception. Pethidine also exhibits weak anticholinergic effects and mild local anesthetic properties, contributing to its pain-relieving actions.

• Absorption: Rapid absorption after IM or SC injection; oral absorption is variable and reduced due to first-pass metabolism.
• Distribution: Widely distributed with volume of distribution approximately 3–5 L/kg; crosses blood-brain barrier and placenta.
• Metabolism: Hepatic demethylation to active metabolite norpethidine, which has neurotoxic potential.
• Half-life: Approximately 3 to 5 hours; norpethidine half-life is prolonged (~15–20 hours).
• Elimination: Primarily renal excretion of metabolites; small amounts of unchanged drug in urine.

• Pregnancy: FDA Category C. Use only if clearly needed; crosses placenta and may cause neonatal respiratory depression.
• Lactation: Excreted in breast milk in small amounts; caution advised due to possible opioid effects in nursing infants.

• Class: Opioid analgesic
• Subclass: Synthetic phenylpiperidine opioid

• Known hypersensitivity to pethidine or excipients.
• Severe respiratory depression.
• Acute or severe bronchial asthma.
• Paralytic ileus.
• Concurrent or recent (within 14 days) use of monoamine oxidase inhibitors (MAOIs).
• Severe hepatic impairment.
• History of seizure disorders (due to risk of lowering seizure threshold).

• Risk of dependence, tolerance, and addiction; use as prescribed.
• Monitor for respiratory depression, especially in opioid-naïve patients or those on CNS depressants.
• Norpethidine accumulation can cause seizures, especially in renal impairment or high doses.
• CNS effects include sedation, dizziness, confusion; caution when performing activities requiring alertness.
• Potential for serotonin syndrome when combined with serotonergic drugs.
• Avoid abrupt discontinuation to prevent withdrawal symptoms.

• Common:
• CNS: Drowsiness, dizziness, sedation, headache.
• GI: Nausea, vomiting, constipation, dry mouth.
• Cardiovascular: Hypotension, flushing.
• Other: Sweating, itching.
• Serious/Rare:
• Respiratory depression.
• Seizures (related to norpethidine).
• Allergic reactions, including anaphylaxis.
• Serotonin syndrome with serotonergic co-medications.

• CNS depressants (e.g., benzodiazepines, alcohol): Enhanced sedation and respiratory depression.
• MAO inhibitors: Contraindicated due to risk of severe toxicity.
• Serotonergic drugs (SSRIs, SNRIs, triptans): Risk of serotonin syndrome.
• Enzyme inducers/inhibitors may alter metabolism.
• Other opioids: Additive effects; caution advised.

• Increased caution recommended due to risks of neurotoxicity from norpethidine metabolite.
• Guidelines advise limiting duration and dosage, and monitoring renal function.
• Awareness of serotonin syndrome risk has been emphasized.
• Prefer alternative opioids when possible to minimize toxicity.

• Store at controlled room temperature 20°C to 25°C (68°F to 77°F).
• Protect from light and moisture.
• Keep container tightly closed.
• Do not freeze.
• Use diluted solutions promptly as per product instructions.