MEPERIDINE HCL

Chemistry - A synthetic opiate analgesic, meperidine HCl is a fine, white, crystalline, odorlesspowder that is very soluble in water, sparingly soluble in ether and soluble in alcohol. It has a pKaof 7.7 - 8.15 and a melting range of 186 - 189°. The pH of the commercially available injectablepreparation is between 3.5 and 6. Meperidine may also be known as: Pethidine HCl; Dolantin,
Dolantol, Eudolat, or Isonipecaine.

Storage, Stability, Compatibility

Meperidine is stable at room temperature. Avoid freezing theinjectable solution and protect from light during storage. Meperidine has not exhibited significantsorption to PVC IV bags or tubing in studies to date.
Meperidine is reported to be physically compatible with the following fluids and drugs: sodium chloride 0.45 & 0.9%, Ringer's injection, lactated Ringers injection, dextrose 2.5, 5 & 10% for injection, dextrose/ saline combinations, dextrose/Ringers lactated solutions, atropine, benzquinamide, butorphanol, chlorpromazine, dimenhydrinate, diphenhydramine HCl, dobutamine, droperidol, fentanyl citrate, glycopyrrolate, metoclopramide, pentazocine lactate, promazine HCl, succinylcholine and verpamil HCl.
Meperidine is reported to be physically incompatible with the following agents: aminophylline, amobarbital sodium, heparin sodium, hydrocortisone sodium succinate, methicillin, methylprednisolone sodium succinate, morphine sulfate, nitrofurantoin sodium, oxytetracycline HCl, pentobarbital sodium, phenobarbital sodium, phenytoin sodium, sodium iodide, tetracycline HCl, thiopental sodium and thiamylal sodium.

Pharmacology - MEPERIDINE HCL

Refer to the monograph: Narcotic (opiate) Analgesic Agonists, Pharmacology of, for more information.
Meperidine is primarily a Mu agonist. It is approximately 1/8th as potent as morphine, but produces equivalent respiratory depression at equi-analgesic doses as morphine. Like morphine, it cancause histamine release. It does not have antitussive activity at doses lower than those causinganalgesia. Meperidine is the only used opioid that has vagolytic and negative inotropic properties atclinically used doses. One study in ponies demonstrated changes in jejunal activity after meperidineadministration, but no effects on transit time or colonic electrical activity were noted.

Pharmacokinetics - MEPERIDINE HCL

Although generally well absorbed orally, a marked first-pass effect limits theoral effectiveness of these agents (codeine and oxycodone are exceptions). After injection by IM orsubcutaneous routes the peak analgesic effects occur between 30 minutes and one hour, with the IMroute having a slightly faster onset. Duration of action is variable with effects generally lasting from1-6 hours in most species. In dogs and cats a duration of action of only 1-2 hours is generally seenat clinically used doses. The drug is metabolized primarily in the liver (mostly hydrolysis with someconjugation) and approximately 5% is excreted unchanged in the urine.

Uses, Indications

Although no product is licensed in the United States for veterinary use, thisagent has been used as an analgesic in several different species. It has been used as sedative/analgesic in small animals for both post-operative pain and for medical conditions such as acutepancreatitis and thermal burns. It is occasionally used in equine medicine in the treatment of colicand in other large animal species for pain control.
Contraindications/Precautions - All opiates should be used with caution in patients with hypothyroidism, severe renal insufficiency, adrenocortical insufficiency (Addison's disease), and ingeriatric or severely debilitated patients. Meperidine is contraindicated in cases where the patient ishypersensitive to narcotic analgesics, or in patients taking monamine oxidase inhibitors (MAOIs). Itis also contraindicated in patients with diarrhea caused by a toxic ingestion until the toxin iseliminated from the GI tract.
Meperidine should be used with caution in patients with head injuries or increased intracranialpressure and acute abdominal conditions (e.g., colic) as it may obscure the diagnosis or clinicalcourse of these conditions. It should be used with extreme caution in patients suffering from respiratory disease or from acute respiratory dysfunction (e.g., pulmonary edema secondary to smokeinhalation).
Opiate analgesics are also contraindicated in patients who have been stung by the scorpion species
Centruroides sculpturatus Ewing and C. gertschi Stahnke as they may potentiate these venoms.

Adverse Effects, Warnings

Meperidine may be irritating when administered subcutaneously andmust be given very slowly IV or it may cause severe hypotension. At usual doses, the primaryconcern is the effect the opioids have on respiratory function. Decreased tidal volume, depressedcough reflex and the drying of respiratory secretions may all have a detrimental effect on asusceptible patient. Bronchoconstriction following IV doses has been noted in dogs. The CNSdepressant effects of the these drugs may encumber the abilities of working animals.
Gastrointestinal effects may include: nausea, vomiting, and decreased intestinal persitalsis. In dogs, meperidine causes mydriasis (unlike morphine). If given orally, the drug may be irritating to thebuccal mucosa and cause salivation; this is of particular concern in cats. Chronic administration canlead to physical dependence.
In horses undergoing general anesthesia, meperidine has been associated with a reaction thatmanifests as tachycardia with PVC's, profuse sweating, and hyperpnea.
Overdosage - Overdosage may produce profound respiratory and/or CNS depression in mostspecies. Other effects can include cardiovascular collapse, hypothermia, and skeletal muscle hypotonia. Some species (especially cats) may demonstrate CNS excitability (hyperreflexia, tremors)and seizures at doses greater than 20 mg/kg. Naloxone is the agent of choice in treating respiratorydepression. In massive overdoses, naloxone doses may need to be repeated, and animals should beclosely observed as naloxone's effects may diminish before subtoxic levels of meperidine areattained. Mechanical respiratory support should also be considered in cases of severe respiratorydepression.
Pentobarbital has been suggested as a treatment for CNS excitement and seizures in cats. Cautionmust be used as barbiturates and narcotics can have additive effects on respiratory depression.

Drug Interactions

Other CNS depressants (e.g., anesthetic agents, antihis tamines, phenothiazines, barbiturates, tranquilizers, alcohol, etc.) may cause increased CNS or respiratory depression when used with meperidine.
Meperidine is contraindicated in patients receiving monamine oxidase (MOA) inhibitors(rarely used in veterinary medicine) for at least 14 days after receiving MOA inhibitors in humans.
Some human patients have exhibited signs of opiate overdose after receiving therapeutic doses ofmeperidine while on these agents.
Laboratory Interactions- Plasma amylase and lipase values may be increased for up to 24hours following administration of opiate analgesics as they may increase biliary tract pressure.