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Chemistry – A synthetic opiate analgesic, meperidine HCl is a fine, white, crystalline, odorless powder that is very soluble in water, sparingly soluble in ether and soluble in alcohol. It has a pKa of 7.7 – 8.15 and a melting range of 186 – 189°. The pH of the commercially available injectable preparation 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 the injectable solution and protect from light during storage. Meperidine has not exhibited significant sorption 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 – 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 can cause histamine release. It does not have antitussive activity at doses lower than those causing analgesia. Meperidine is the only used opioid that has vagolytic and negative inotropic properties at clinically used doses. One study in ponies demonstrated changes in jejunal activity after meperidine administration, but no effects on transit time or colonic electrical activity were noted.
Pharmacokinetics – Although generally well absorbed orally, a marked first-pass effect limits the oral effectiveness of these agents (codeine and oxycodone are exceptions). After injection by IM or subcutaneous routes the peak analgesic effects occur between 30 minutes and one hour, with the IM route having a slightly faster onset. Duration of action is variable with effects generally lasting from 1-6 hours in most species. In dogs and cats a duration of action of only 1-2 hours is generally seen at clinically used doses. The drug is metabolized primarily in the liver (mostly hydrolysis with some conjugation) and approximately 5% is excreted unchanged in the urine.
Uses/Indications – Although no product is licensed in the United States for veterinary use, this agent 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 acute pancreatitis and thermal burns. It is occasionally used in equine medicine in the treatment of colic and 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 in geriatric or severely debilitated patients. Meperidine is contraindicated in cases where the patient is hypersensitive to narcotic analgesics, or in patients taking monamine oxidase inhibitors (MAOIs). It is also contraindicated in patients with diarrhea caused by a toxic ingestion until the toxin is eliminated from the GI tract.
Meperidine should be used with caution in patients with head injuries or increased intracranial pressure and acute abdominal conditions (e.g., colic) as it may obscure the diagnosis or clinical course 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 smoke inhalation).
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 and must be given very slowly IV or it may cause severe hypotension. At usual doses, the primary concern is the effect the opioids have on respiratory function. Decreased tidal volume, depressed cough reflex and the drying of respiratory secretions may all have a detrimental effect on a susceptible patient. Bronchoconstriction following IV doses has been noted in dogs. The CNS depressant 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 the buccal mucosa and cause salivation; this is of particular concern in cats. Chronic administration can lead to physical dependence.
In horses undergoing general anesthesia, meperidine has been associated with a reaction that manifests as tachycardia with PVC’s, profuse sweating, and hyperpnea.
Overdosage – Overdosage may produce profound respiratory and/or CNS depression in most species. 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 respiratory depression. In massive overdoses, naloxone doses may need to be repeated, and animals should be closely observed as naloxone’s effects may diminish before subtoxic levels of meperidine are attained. Mechanical respiratory support should also be considered in cases of severe respiratory depression.
Pentobarbital has been suggested as a treatment for CNS excitement and seizures in cats. Caution must 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 of meperidine while on these agents.
Laboratory Interactions– Plasma amylase and lipase values may be increased for up to 24 hours following administration of opiate analgesics as they may increase biliary tract pressure.
As an analgesic:
a) 2.2 – 4 mg/kg IM or 0.2-0.4 mg/kg IV (may cause excitement) (Robinson 1987)
b) 2 – 4 mg/kg IM or IV (may cause excitement and hypotension with IV use) (Jenkins 1987)
c) 500 mg IV (slowly, CNS excitement may occur) or 1000 mg IM (Booth 1988a)
d) 0.2 – 0.4 mg/kg IV (Muir 1987)
Note: Narcotics (meperidine included) may cause CNS excitement in the horse. Some recommend pretreatment with acepromazine (0.02 – 0.04 mg/kg IV), or xylazine (0.3 – 0.5 mg/kg IV) to reduce the behavioral changes these drugs can cause.
Warning: Narcotic analgesics can mask the behavioral and cardiovascular symptoms associated with mild colic.
a) For analgesia and sedation: 75-150 mg/100 kg body weight four times a day (Schmidt, 1996).
a) Schmidt,M.J., 1986. Proboscidea (Elephants). In: Fowler,M.E. (Editor), Zoo and wild animal medicine. W.B. Saunders, Philadelphia,PA, USA pp. 884-923
Monitoring Parameters -1) Respiratory rate/depth; 2) CNS level of depression/excitation;
3) Blood pressure if possible and indicated (especially with IV use); 4) Analgesic activity
Client Information – Oral dosage forms may cause mouth irritation. When given parenterally, this agent should be used in an inpatient setting or with direct professional supervision.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times –
Veterinary-Approved Products: None
Meperidine HCl for Injection: 50 mg/ml in 30 ml multi-dose vials (MDV); 100 mg/ml in 20 ml MDV; 10 mg/ml in 5 & 10 ml single-dose vial & 30 ml vials for IV infusion only; 25 mg, 50 mg, 75 mg & 100 mg in 1 ml amps and vials, 1 ml fill in 2 ml Tubex, 0.5 ml Uni-Nest amps, 0.5 ml Uni-Amps and 2 ml Carpuject
Meperidine HCl for oral use: 50 mg, 100 mg tablets, 10 mg/ml oral syrup in 500 ml and pt.
A common trade name is: Demerol HCl® (Winthrop-Breon)
Note: Meperidine is listed as a Class-II controlled substance and all products require a prescription. Very accurate record keeping is required as to use and disposition of stock.