Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Mercury Pharmaceuticals Limited, Capital House, 85 King William Street, London EC4N 7BL, UK
Pharmacotherapeutic group: Analgesics – Phenylpiperidine derivatives
ATC code: NO2AB
Pethidine is a synthetic opioid analgesic similar to morphine although less potent and shorter acting. Its analgesic effect usually lasts for 2 to 4 hours. The analgesic effect occurs after about 10 minutes following parenteral administration. It acts on the CNS system and smooth muscles via the peripheral nervous system. However, it has a weaker action on smooth muscle than morphine and therefore has less effect on cough, bowel motility, biliary tone and secretion of pituitary hormones. Pethidine also causes the release of histamine from mast cells resulting in a number of allergic-type reactions.
Like other opioids, pethidine binds to opioid receptors and exerts its principal pharmacological actions on the central nervous system where its analgesic and sedative effects are of particular therapeutic value. The respiratory depression produced by pethidine can be antagonised by naloxone and nalorphine.
Pethidine has a spasmogenic effect on certain smooth muscles which is qualitatively similar to that of morphine. In equianalgesic doses, pethidine appears to cause less constipation and biliary tract spasm than does morphine.
Pethidine, like other opioids, dilates resistance and capacitance vessels and may thereby decrease the capacity of the cardiovascular system to respond to gravitational shifts. In therapeutic doses, the effects of pethidine on the cardiovascular system are generally not of clinical significance, especially when the patient is recumbent. However, rapid intravenous administration, or administration of pethidine to patients with depleted blood volume or in other situations where ability to maintain blood pressure has been compromised, may result in severe hypotension.
Pethidine is a narcotic analgesic with similar actions to morphine.
Pethidine is rapidly absorbed following intramuscular or subcutaneous injection, however, there are wide interindividual variations. It is widely distributed in the tissues with a volume of distribution of 200-300 litres and is extensively protein bound (60-80%). It is metabolised in the liver by hydrolysis. Following intravenous injection, a rapid decline in plasma concentration occurs due to distribution and this is followed by a slower phase with a half-time of approximately 3 hours. In patients with cirrhosis, the half-life is increased to 6 hours.
Approximately 60% of pethidine in plasma is protein-bound. Older patients have decreased binding to plasma proteins and have higher concentrations in plasma, both of which may account for their increased response to therapeutic doses.
Pethidine is metabolised in the liver by hydrolysis to pethidinic acid or by demethylation to norpethidine and hydrolysis to norpethidinic acid, followed by conjugation with glucoronic acid. About ⅓ of administered pethidine may be accounted for in the urine as N-demethylated derivatives. The accumulation of norpethidine may result in toxicity.
Pethidine is excreted via the urine (70% in 24hrs). Urinary excretion is pH dependent, the lower the pH the greater the clearance. At normal urinary pH only a small amount of pethidine is excreted unchanged. Pethidine has a plasma elimination half-life of about 3 to 6 hours. The metabolite norpethidine is eliminated more slowly with a half-life of up to 20 hours and may accumulate with chronic use, especially in the presence of renal impairment.
Pethidine crosses the placenta and is excreted in breast milk.
Both pethidine and norpethidine cross the blood/brain barrier and are found in the cerebrospinal fluid.
No further relevant information other than that which is included with other sections of the Summary of Product Characteristics.
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