MeperidineEdit
Meperidine, also known as pethidine in some markets, is a synthetic opioid analgesic belonging to the phenylpiperidine class. It was introduced in the mid-20th century under brand names such as Demerol and became a widely used option for acute pain management in both surgical and non-surgical settings. Compared with morphine, meperidine has a distinct pharmacological profile, including a relatively rapid onset and shorter duration of action, as well as anticholinergic properties that have led clinicians to select it in particular clinical contexts. However, its use is tempered by concerns about a toxic metabolite, normeperidine, which can accumulate with repeated dosing or impaired kidney function and provoke central nervous system excitation and seizures. These safety considerations have contributed to a shift away from meperidine in favor of other opioids for most routine indications.
The medical community today generally reserves meperidine for specific, short-term applications or when other analgesics are contraindicated. It is typically administered by intramuscular or intravenous routes, and less commonly by mouth. In obstetric and biliary pain scenarios, meperidine has historically been used for reasons related to its pharmacodynamic profile, but contemporary guidelines emphasize caution due to the risk of neonatal effects and the potential for normeperidine accumulation in the mother. As a controlled substance, meperidine is scheduled under the Controlled Substances Act in the United States, reflecting its potential for dependence and abuse. The drug remains available in some markets and formulations, but prescribers generally favor alternatives with more favorable safety margins for most patients.
Medical uses
Meperidine is indicated for short-term relief of moderate to severe acute pain when other non-opioid therapies are insufficient or contraindicated. Its rapid onset makes it useful in certain perioperative settings or for breakthrough pain in the short term. In practice, however, the use of meperidine has declined in favor of longer-acting or safer-acting opioids, given the risk profile associated with its metabolite normeperidine. The drug has been employed in obstetric analgesia in the past, but this application has diminished due to concerns about fetal exposure and postnatal effects on newborns, including potential withdrawal symptoms after birth. Some clinicians previously cited meperidine's relatively antispasmodic effect on smooth muscle as advantageous in biliary or intestinal colic, but this rationale is less influential in modern practice where alternatives are available.
Pharmacology
Meperidine is a mu-opioid receptor agonist that produces analgesia through classic opioid pathways. It also possesses anticholinergic properties that distinguish it from several other opioids. The analgesic effects are complemented by a less pronounced histamine release compared with morphine, though this varies by dose and individual response. A key differentiator is its metabolism: meperidine is converted in the liver to normeperidine, an active neurotoxic metabolite that is primarily eliminated by the kidneys. In patients with renal impairment or when dosing is prolonged, normeperidine can accumulate and predispose to CNS excitability and seizures. This risk led to recommendations against routine, long-term use of meperidine, particularly in the elderly. Additionally, meperidine exhibits modest serotonergic activity, and there is a risk of serotonin syndrome when it is combined with other serotonergic medications such as selective serotonin reuptake inhibitors or monoamine oxidase inhibitors.
Pharmacokinetics
Onset of action is relatively quick, especially with parenteral administration, and the duration of analgesia is shorter than that of many alternative opioids. Metabolism occurs in the liver, with the formation of normeperidine, which is then excreted renally. Because normeperidine has a longer half-life than meperidine itself, renal function strongly influences overall safety and duration of effect. In older patients or those with kidney disease, accumulation of normeperidine can occur even after short courses, underscoring the importance of careful patient selection and dosing.
Adverse effects and safety
Common opioid-related adverse effects—nausea, vomiting, sedation, constipation, and respiratory depression—can occur with meperidine as with other opioids. Meperidine’s anticholinergic properties can contribute to dry mouth and urinary retention in some individuals. A distinctive safety concern is the neurotoxicity of normeperidine, which can cause tremors, myoclonus, and seizures with high levels or prolonged exposure. This risk is heightened in the elderly and in patients with renal impairment or those receiving repeated doses over a short period. Serotonergic interactions also pose a risk of serotonin syndrome when meperidine is used with other serotonergic drugs. In pregnancy, meperidine crosses the placenta and can affect the fetus; neonatal exposure may contribute to respiratory depression or withdrawal symptoms after birth.
Regulation and contemporary status
Meperidine is a regulated opioid and is classified as a controlled substance in countries that maintain formal scheduling systems. In the United States, it is listed as a Schedule II drug under the Controlled Substances Act, reflecting its potential for dependence and abuse. Due to safety concerns, many clinical guidelines now discourage routine use of meperidine and favor alternative opioids with more favorable safety profiles for most indications. The drug's status varies by country, with some markets continuing to provide it in limited circumstances where other options are unsuitable.
History
Meperidine was developed in the mid-20th century and entered clinical use in the 1940s as an analgesic agent. Its adoption reflected the broader search for synthetic opioids that could offer effective pain relief with certain practical advantages. Over time, accumulating evidence about normeperidine-associated neurotoxicity and broader opioid safety concerns contributed to a reassessment of its role in pain management. The shift toward safer and longer-acting alternatives has shaped contemporary prescribing patterns and regulatory approaches.