Pethidine Other names: Pethidine Pethidine Hydrochloride

Pethidine is a narcotic analgesic with similar actions to morphine. 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.

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. The analgesic effects of pethidine are detectable about 15 minutes after oral administration, reaching a peak in about 2 hours and subsiding gradually over several hours.

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.

Ambulatory patients given pethidine may experience syncope associated with hypotension but symptoms rapidly clear on lying down. Otherwise in therapeutic doses pethidine has no significant untoward effects on the cardiovascular systems, especially if patients are lying down. Pethidine combines analgesic and antispasmodic properties; it is relatively short acting and has little soporific effect. These properties make pethidine particularly useful for pain relief in labour and as an adjunct to nitrous oxide-oxygen anaesthesia.

Peak plasma concentrations are normally observed between 1 and 2 hours after oral administration. However, only about 50% of the drug escapes first pass metabolism to enter the circulation. About 60% is protein bound in plasma.

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%).

Pethidine is mainly metabolised in the liver by hydrolysis to pethidinic acid, or by N-demethylation to norpethidine, followed by hydrolysis to norpethidinic acid. Subsequent, partial conjugation with glucuronic acid may also occur. About ⅓ of administered pethidine may be accounted for in the urine as N-demethylated derivatives. The accumulation of norpethidine may result in toxicity.

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. Heavy alcohol drinkers have an increased apparent volume of distribution with consequent initially lower pethidine plasma concentrations. In patients with cirrhosis, the half-life is increased to 6 hours. 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 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.

None stated.