Pethidine (Meperidine); A Therapeutic Friend or Foe????
Pethidine (Meperidine) was synthetically derived in 1938 as an anticholinergic agent (substances which block the action of the neurotransmitter Acetylcholine in the Peripheral and Central nervous system), but was discovered to possess analgesic properties shortly after. Although it’s a weak agonist at the opioid receptor (mu receptor), anecdotal evidence suggests it is a good alternative to Morphine because it circumvents morphine’s most common adverse effects; respiratory depression and chemical dependency. However, clinical experience gives a different dynamic. A quick search of current literature reveals the backed-up benefits of Pethidine, including inducing less spasm on the sphincter of Oddi(smooth muscle that surround the end portion of the common bile duct and pancreatic duct) and the biliary tract, were simply false. Pethidine has not thoroughly been studied in specific populations through randomized controlled trials, so it’s purported benefits over other opioids fall a bit short.
Pethidine brings a set of various disadvantages, including short duration of action (half-life ~2-3 hours) and subpar analgesic effects. At common doses (25-50 mg every 4-6 hours), serum levels were found to be suboptimal, making it a poor choice for acute or chronic pain
.
In acute pain management, Morphine is the gold standard of therapy. Equianalgesic doses of 10 mg of morphine equals 75 mg of Pethidine and 1.5 mg of Hydromorphone. A simple cross-multiply calculation translates 25-50 mg of Pethidine as equal to 3-6 mg of Morphine. Nevertheless, when we take opioid potency and the 24-hour total dose into account to calculate equivalencies, it is clear Pethidine will not be the ideal choice for pain control.
Pethidine’s metabolism brings an additional set of challenges. It is metabolized by 2 distinctive pathways, but the most clinically significant one occurs through the Cytochrome-P450 system that produces the non-opioid active metabolite, Norpethidine. Norpethidine acts as a very weak analgesic and is also a neurotoxin (toxins destructive to nerve tissues) that increases the risk of seizures, delirium, restlessness among other adverse effects. Norpethidine’s main route of elimination is renal, and in normal patients, its half-life is very long (14-21 hours). On the other hand, the half-life of this metabolite can extend up to 35 hours in patients with acute or chronic renal failure, meaning a normal patient will reach significant accumulation of the metabolite way before the parent drug (Pethidine) reaches steady state. Imagine how this can turn out in a chronic kidney disease patient. In addition, the opioid antagonist Naloxone (therapeutic antidote for management of opioid toxicity) has no effect on norpethidine’s actions in the central nervous system. Moreover, Pethidine has serotonergic (serotonin release) and noradrenergic (noradrenaline releasing) properties, so one concern that can’t be dismissed is the potential to induce “Serotonin Syndromme” in patients who take antidepressants like Selective Serotonin
Reuptake Inhibitors,SSRI’s (e.g. Fluoxetine) and Monoamine Oxidase Inhibitors,MAOI’s(e.g.Selegilline,Phenelzine).
According to the Institute of Safe Medication Practices and Joint Commission, Pethidine should be reserved for only brief use (≤48 hours) in moderate to severe pain in patients with normal renal function. Other short-term indications include pre-operative analgesia, post-anaesthesia shivering, and blood product-induced rigors. Appropriate pain management is often overlooked in many healthcare institutions.
Furthermore, the Beers Criteria (which outlines guidelines for appropriate medication use in the elderly) lists Pethidine as an inappropriate medication for individuals older than 65 years. Thus, Pethidine use should be discouraged in this population. One of the cornerstones of pain management is being knowledgeable of dose equivalencies, but Clinicians should also strive to offer the safest alternatives for our aging population. Thorough evaluation of past medical history and current medication therapy is key to assess the risk-benefit ratio for choosing the best opioid. Reducing Pethidine use can be a challenging task, but it must be given the priority it needs. Our most vulnerable patients depend on us to help them avoid this drug’s serious adverse effects.
References:
www.go.drugbank.com/drugs/DB0045
www.reference.medscape.com/drug/demerol-meperidine-
www.pharmacytimes.com/view/meperidine
www.nps.org.au/medicine-finder/pethidine-injection
By: Pharm.Anthony Osei
Drug Information Unit, Pharmacy Department, KBTH