Usage
Pethidine is prescribed for the relief of moderate to severe acute pain. Examples include pain during labor, pre- and post-operative pain, and pain associated with trauma or other acute medical conditions. It’s also occasionally used as an adjunct to anesthesia.
It is pharmacologically classified as an opioid analgesic.
Pethidine’s mechanism of action involves binding to opioid receptors (primarily mu-opioid receptors) in the central nervous system, reducing pain perception and the emotional response to pain.
Alternate Names
- Meperidine (International Nonproprietary Name, INN)
Some popular brand names include Demerol and Dolantal.
How It Works
Pharmacodynamics: Pethidine primarily acts as a mu-opioid receptor agonist. It binds to these receptors in the brain, spinal cord, and other tissues, mimicking the effects of endogenous opioid peptides. This leads to decreased pain perception, altered emotional response to pain, and sedation. It also has some anticholinergic and local anesthetic properties. Unlike other opioids, pethidine does not cause miosis due to its anticholinergic properties.
Pharmacokinetics:
- Absorption: Pethidine is well-absorbed following intramuscular (IM) and subcutaneous (SC) administration, with peak plasma concentrations reached within 30-60 minutes and 60-90 minutes respectively. Oral absorption is less reliable due to significant first-pass metabolism. It can also be administered intravenously (IV) for a rapid onset of action.
- Metabolism: It is primarily metabolized in the liver to norpethidine, an active metabolite with a longer half-life and potential for neurotoxicity (causing tremors, muscle twitching, and seizures). This is particularly relevant in patients with renal impairment as norpethidine accumulates. Pethidine is metabolized mainly by CYP2B6 and to a lesser extent by CYP3A4.
- Elimination: Pethidine and its metabolites are primarily excreted in the urine. Elimination is reduced in neonates and patients with renal impairment.
Mode of Action: Pethidine binds to mu-opioid receptors, inhibiting neuronal activity by reducing neurotransmitter release (such as substance P and glutamate) and hyperpolarizing postsynaptic neurons. It also modulates pain pathways at the spinal cord level.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Primarily a mu-opioid receptor agonist; also inhibits reuptake of serotonin and norepinephrine; moderate anticholinergic activity.
Dosage
Standard Dosage
Adults:
- Moderate to Severe Pain: 25-150 mg IM or SC every 3-4 hours as needed. 25-50 mg IV every 3-4 hours as needed. Oral administration: 50-150 mg every 3-4 hours as needed.
- Obstetric Analgesia: 50-100 mg IM or SC, repeatable every 1-3 hours as needed, up to a maximum of 400 mg in 24 hours.
- Premedication: 50-100 mg IM or SC 30-90 minutes prior to the operation.
- Adjunct to General Anesthesia: 10-25 mg IV as needed.
Children:
- Moderate to Severe Pain: 0.5-2 mg/kg IM or SC every 3-4 hours as needed (maximum single dose of 100 mg).
- Premedication: 1-2 mg/kg IM or SC 30-90 minutes before anesthesia (maximum single dose of 100 mg).
Use a small graduated syringe for accurate administration. Dilute the solution with Water for Injections if graduated syringes are not available.
Special Cases:
- Elderly Patients: Initiate therapy at the lower end of the dosing range due to increased sensitivity. Start with a maximum of 25 mg.
- Patients with Renal Impairment: Dose reduction is necessary due to the risk of norpethidine accumulation. In severe renal impairment, Pethidine is contraindicated.
- Patients with Hepatic Dysfunction: Dose reduction is necessary in moderate to severe hepatic impairment as metabolism is affected. Severe hepatic dysfunction is a relative contraindication to the use of pethidine.
- Patients with Comorbid Conditions: Use caution in patients with respiratory disease, head injury, increased intracranial pressure, seizures, prostatic hypertrophy, biliary tract disorders, hypothyroidism, adrenal insufficiency, and cardiovascular disease.
Clinical Use Cases
- Intubation: Pethidine is not typically used for intubation itself, but may be part of an analgesic regimen for post-intubation pain management.
- Surgical Procedures: Used for pre- and post-operative pain management, and sometimes intraoperatively as an adjunct to general anesthesia.
- Mechanical Ventilation: Pethidine is not typically used for patients solely on mechanical ventilation but may be used as part of a pain management regimen for ventilated patients experiencing moderate to severe pain.
- Intensive Care Unit (ICU) Use: Used cautiously for pain management in critically ill patients, with careful attention to respiratory status and potential drug interactions.
- Emergency Situations: In select emergency situations, it may be used for short-term pain control.
Dosage Adjustments
Dose adjustments are necessary based on patient-specific factors, including age, renal or hepatic function, and presence of comorbid conditions.
Side Effects
Common Side Effects
- Dizziness
- Drowsiness
- Nausea
- Vomiting
- Constipation
- Sweating
- Lightheadedness
- Dry mouth
- Flushing
- Hallucinations
Rare but Serious Side Effects
- Respiratory depression
- Seizures
- Hypotension
- Bradycardia
- Serotonin syndrome
- Allergic reactions (e.g. skin rash, itching, swelling)
Long-Term Effects
- Tolerance
- Physical dependence
- Addiction
Adverse Drug Reactions (ADR)
- Anaphylaxis
- Severe respiratory depression
- Serotonin syndrome
- Seizures
- Norpethidine toxicity
Contraindications
- Hypersensitivity to pethidine
- Significant respiratory depression
- Acute or severe asthma
- Severe obstructive airway disease
- Concurrent or recent use of MAOIs (within 14 days)
- Increased intracranial pressure
- Head injury
- Seizures (e.g., status epilepticus)
- Severe renal or hepatic impairment
- Phaeochromocytoma
- Acute alcoholism
- Delirium tremens
- Diabetic acidosis
- Supraventricular tachycardia
Drug Interactions
- MAOIs: Concomitant use can cause serotonin syndrome, a life-threatening condition.
- CNS depressants: (e.g. alcohol, benzodiazepines, other opioids): Additive CNS depression, increasing the risk of respiratory depression and coma.
- CYP3A4 inhibitors or inducers: May affect pethidine metabolism and clearance, requiring dose adjustments.
- Ritonavir: Contraindicated as it leads to elevated levels of norpethidine.
- Anticholinergic drugs: Additive anticholinergic effects.
- Serotonergic drugs: (e.g. SSRIs): Increased risk of serotonin syndrome.
Pregnancy and Breastfeeding
Pethidine crosses the placenta and is excreted in breast milk.
- Pregnancy: While generally considered safe for short-term use during pregnancy, especially in the first and second trimesters, prolonged use or high doses close to delivery can cause neonatal respiratory depression and withdrawal symptoms in the newborn.
- Breastfeeding: Pethidine is excreted in breast milk and can affect the infant. Use with caution and monitor the infant for drowsiness and feeding difficulties.
Drug Profile Summary
- Mechanism of Action: Mu-opioid receptor agonist, inhibits reuptake of serotonin and norepinephrine, moderate anticholinergic activity.
- Side Effects: Dizziness, drowsiness, nausea, vomiting, constipation, respiratory depression, seizures, hypotension, serotonin syndrome.
- Contraindications: Hypersensitivity, significant respiratory depression, acute/severe asthma, severe obstructive airway disease, MAOI use, increased intracranial pressure, seizures, severe hepatic/renal impairment.
- Drug Interactions: MAOIs, CNS depressants, CYP3A4 inhibitors/inducers, ritonavir, anticholinergics, serotonergic drugs.
- Pregnancy & Breastfeeding: Crosses placenta, excreted in breast milk; use with caution; risk of neonatal respiratory depression and withdrawal.
- Dosage: Adults: 25-150 mg IM/SC/PO q3-4h; IV 25-50mg q3-4h PRN. Children: 0.5-2 mg/kg IM/SC q3-4h. Elderly: Initiate at lower doses.
- Monitoring Parameters: Respiratory rate, heart rate, blood pressure, oxygen saturation, level of consciousness, pain scores.
Popular Combinations
Pethidine is sometimes used in combination with an antiemetic (such as promethazine) to reduce nausea and vomiting, which are common side effects of pethidine.
Precautions
- Assess respiratory and cardiovascular status before and during administration.
- Use with caution in elderly patients, patients with renal or hepatic impairment, and those with comorbid conditions.
- Monitor for respiratory depression and other side effects.
- Avoid abrupt discontinuation after prolonged use due to risk of withdrawal syndrome.
- Counsel patients about the risks of dependence and addiction.
- Advise against driving or operating machinery while taking pethidine.
- Avoid alcohol consumption during treatment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Pethidine?
A: Adults: 25-150 mg IM or SC every 3-4 hours as needed; 25-50 mg IV every 3-4 hours as needed; 50-150 mg PO every 3-4 hours as needed. Children: 0.5-2 mg/kg IM or SC every 3-4 hours as needed (maximum 100mg single dose). Elderly patients should start at lower doses.
A: Pethidine is primarily metabolized in the liver to norpethidine, an active metabolite with a longer half-life and potential neurotoxicity, by CYP2B6, and to a lesser extent CYP3A4.
Q3: What are the major contraindications to Pethidine use?
A: Hypersensitivity to pethidine, severe respiratory depression, acute or severe asthma, concurrent use of MAOIs, increased intracranial pressure, seizures, severe renal/hepatic impairment.
Q4: What are the common side effects of Pethidine?
A: Dizziness, drowsiness, nausea, vomiting, constipation, sweating, lightheadedness, dry mouth.
Q5: What are the serious side effects of Pethidine?
A: Respiratory depression, seizures, serotonin syndrome, hypotension, bradycardia, allergic reactions.
Q6: Can Pethidine be used during pregnancy and breastfeeding?
A: Pethidine crosses the placenta and enters breast milk. Use with caution and monitor for neonatal respiratory depression and withdrawal symptoms, as well as infant drowsiness and feeding difficulties.
Q7: How should Pethidine be administered?
A: It can be administered intravenously (slowly), intramuscularly, or subcutaneously. An oral formulation is also available but is less reliable due to first-pass metabolism.
Q8: What is the duration of action of Pethidine?
A: Pethidine provides analgesia for approximately 2-4 hours.
Q9: Does Pethidine have any drug interactions?
A: Yes. Significant drug interactions exist with MAOIs, other CNS depressants (alcohol, benzodiazepines), CYP3A4 inhibitors/inducers, and serotonergic drugs (SSRIs). Co-administration with Ritonavir is contraindicated.
Q10: What monitoring parameters are important when administering Pethidine?
A: Respiratory rate, oxygen saturation, blood pressure, heart rate, and level of consciousness are crucial to monitor. Pain scores should also be assessed regularly.
