Pethidine

Products

Pethidine is commercially available as a solution for injection. It has been approved in many countries since 1947. The drug is subject to strict control as a narcotic and is available only by prescription.

Structure and properties

Pethidine (C15H21NO2, Mr = 247.3 g/mol) is a phenylpiperidine derivative. In pharmaceuticals, it is present as pethidine hydrochloride, a white crystalline powder that is very soluble in water. It was originally synthesized as an anticholinergic derivative of atropine, but it was soon found to be analgesic.

Effects

Pethidine (ATC N02AB02) has analgesic properties. Whether it has a spasmolytic component of action is uncertain. Its effects are due to binding to µ-opioid receptors. Its use is not uncontroversial among experts because Pethdin is short-acting, has no advantages over other opioids, and has certain compound-specific side effects. Modern registration studies are lacking. For a detailed critique, see, for example, Latta et al (2002).

Indications

Pethidine is approved for the treatment of moderate-to-severe acute and persistent pain when nonopioid analgesics or weak opioids fail.

Dosage

According to the drug label. For the tablets, it is recommended to take after meals.

Contraindications

  • Hypersensitivity
  • Respiratory insufficiency, respiratory depression, acute bronchial asthma.
  • Increased intracranial pressure
  • Certain cardiac arrhythmias
  • Pheochromocytoma
  • Seizure states
  • Concurrent treatment with MAO inhibitors.
  • Alcoholism, delirium tremens
  • Diabetic acidosis
  • Severe liver disease
  • Hypothyroidism
  • Addison’s disease

Full details of precautions and interactions can be found in the drug label.

Interactions

Pethidine is biotransformed in the liver by cytochromes, has high first-pass metabolism, and interindividually variable pharmacokinetics. Pethidine must not be combined with MAO inhibitors because life-threatening side effects are possible with this combination ( serotonin syndrome). Centrally depressant drugs such as sedatives, sleeping pills, antidepressants, neuroleptics, or alcohol may increase adverse effects. Other interactions are possible.

Adverse effects

Possible adverse effects include hypersensitivity reactions, hyperglycemia, psychiatric disturbances, dullness, dizziness, confusion, headache, dose-related respiratory depression, nausea, vomiting, constipation, hypothermia, visual disturbances, dizziness, deep pulse, deep blood pressure, histamine release, skin reactions, dependence, anticholinergic side effects, muscle discomfort, and seizures.