The P-I-E-N-O Parkinsn's List Drug Database
meperidine, pethidine / DemerolTM
PAIN RELIEVER, Analgesic,
HIGH RISK! NOT TO BE TAKEN WITH EldeprylTM , selegeline
Description: Meperidine hydrochloride is an oral and parenteral opiate agonist. In foreign countries, it is known as pethidine. Meperidine is not a natural opiate like morphine or codeine, but is a synthetic compound belonging to the phenylpiperidine class. Other members of this group include diphenoxylate and loperamide, agents commonly used to treat diarrhea, as well as the extremely potent analgesics fentanyl, alfentanil, and sufentanil. Meperidine is recommended for relief of moderate to severe pain but also has the unique ability to interrupt postoperative shivering and shaking chills induced by amphotericin B. Meperidine is metabolized to normeperidine, a compound capable of inducing seizures if it accumulates. Unlike morphine, which was in use long before the passage of the 1938 FD&C act, meperidine was first approved by the FDA and marketed in 1942. It is a schedule C-II controlled substance and is available in both oral and parenteral forms.
Mechanism of action: Despite being structurally distinct from morphine and related opiates, meperidine's effects on opiate receptors are similar to those of morphine; both are agonists at æ-and -receptors. Meperidine alters the perception of pain in the spinal cord and CNS but has no effect on afferent nerve endings. Although the exact physiologic action of opiates is not known, stimulation of opiate receptors ultimately reduces neurotransmitter release. This effect is mediated by any or all of the following three mechanisms: changes in calcium ion mobilization; inhibition of adenylate cyclase; or changes in potassium ion conductance.
Respiration is depressed by a direct effect on the brain stem respiratory center, and the cough center is also suppressed by meperidine. Nausea and vomiting may be induced from direct stimulation of the chemoreceptor trigger zone. Opiate agonists increase smooth muscle tone, which can affect the intestinal, urinary, and biliary tracts. Digestion is delayed by a decrease in gastrointestinal secretions. Some references state that meperidine causes less biliary tract spasm than does morphine. Vasopressin output is stimulated, which can decrease urine output in conjunction with increased tone of the detrusor muscle. Miosis is another characteristic of the opioid analgesics. Compared with morphine, meperidine causes fewer of these effects.
Pharmacokinetics: Meperidine, when administered orally, undergoes extensive first-pass metabolism. As a result, oral bioavailability increases to 80-90% in patients with hepatic impairment, compared with 50-60% in patients with normal hepatic function. Following oral, subcutaneous, or IM administration, onset of analgesia occurs within 10-15 minutes. Peak effects occur within 1 hour, declining gradually over 2-4 hours. Protein binding is 65-75%, primarily to albumin and ›-1-acid glycoprotein. Meperidine is distributed widely, and it crosses the placenta and distributes into breast milk.
In patients with normal hepatic and renal function, meperidine half-life is 3-5 hours; in patients with hepatic dysfunction, it is extended to 7-11 hours. Normeperidine, an active metabolite of meperidine, is about half as potent as meperidine, but it has twice the ability to stimulate the CNS. Half-life of normeperidine is substantially longer (15-30 hours). Accumulation after repeated or high doses, especially in patients with hepatic or renal impairment, should be considered. Patients with normal urine pH excrete about 30% as the active metabolite and about 5% as unchanged parent drug. Acidification of the urine greatly enhances excretion of both meperidine and normeperidine.
CONTRAINDICATIONS/PRECAUTIONS: Due to the effects of opiate agonists on the gastrointestinal tract, meperidine should be used cautiously in patients with GI disease including GI obstruction, ulcerative colitis, or pre-existing constipation. Patients with acute ulcerative colitis (UC) may have toxic dilation of the colon, whereas those with chronic UC may have stimulation of motility of the colon. Also, opiate agonists are contraindicated for use in patients with diarrhea secondary to poisoning or in patients with infectious diarrhea. Meperidine can slow the removal of the infecting organism or toxic material and should not be given until the condition has been treated.
Meperidine should be used cautiously in patients with pulmonary depression or pulmonary disease such as acute bronchial asthma or upper airway obstruction.
Tolerance and physiological dependence can occur with meperidine and other opiate agonists. Abrupt discontinuation of prolonged opiate agonist therapy can result in withdrawal symptoms (see Adverse Reactions). Also, meperidine should be used cautiously in patients with a history of substance abuse.
Patients with head trauma or with increased intracranial pressure should not be given meperidine because it can make it difficult to evaluate neurologic parameters. Hypoventilation can produce cerebral hypoxia and raise CSF pressure, unrelated to and exaggerating the injury.
Opiate analgesics should be used cautiously in patients with cardiac disease causing supraventricular dysrhythmias or hypotension. Opiate agonists can induce vasovagal syncope or orthostatic hypotension.
Because meperidine has atropine-like effects, it should be used with caution in patients with glaucoma.
Meperidine should be prescribed extremely cautiously, if at all, to patients with renal disease. Drug accumulation or prolonged duration of action can occur in patients with renal impairment or hepatic disease. Convulsions can be precipitated during use of meperidine in patients with a preexisting seizure disorder or in patients with renal failure. Patients with renal disease may be more prone to urinary retention and oliguria during therapy with meperidine.
Meperidine should be prescribed cautiously to patients undergoing biliary tract surgery, although meperidine reportedly causes less biliary tract spasm than does morphine.
Meperidine readily crosses the placenta and normally should not be given during pregnancy. Premature infants are especially sensitive to respiratory depression. Narcotic analgesics generally are not recommended for use in children.
The elderly are more susceptible to adverse reactions from meperidine and should be carefully monitored; lower doses may be indicated.
Any patient receiving an opiate analgesic should be warned about the possibility of sedation and the need to use caution when performing any hazardous tasks.
DRUG INTERACTIONS: Respiratory and/or CNS depression can be additive if meperidine is used concomitantly with other drugs that cause CNS depression. These drugs include: anxiolytics, sedatives, and hypnotics; barbiturates; benzodiazepines; ethanol; general anesthetics; HA-blockers; phenothiazines; tricyclic antidepressants; or other opiate agonists. The effects of meperidine on respiration, CNS, and blood pressure can be potentiated. Concomitant use of meperidine and chlorpromazine can lead to significant lethargy and/or orthostatic hypotension. A dose reduction of one or both drugs may be warranted.
Concurrent use of opiate analgesics with either antidiarrheals or other drugs with anticholinergic properties can lead to severe constipation and/or additive CNS depression. An exaggerated hypotensive response may be seen if antihypertensive agents are administered to patients receiving opiate analgesics.
Barbiturates have been shown to increase the generation of the neurotoxic metabolite, normeperidine; it is possible that other hepatic enzyme-inducing drugs may produce the same effect. Caution should also be observed when using meperidine with carbamazepine, phenytoin, or rifampin. Despite changes in meperidine pharmacokinetics, however, phenytoin did not affect the analgesic action of meperidine.
Opiate antagonists, such as naloxone, naltrexone, and nalmefene, are pharmacologic opposites of meperidine. These drugs can block the actions of meperidine and, if administered to patients who are opiate-dependent, can produce acute withdrawal and/or allow pain to recur.
There is some in vitro data that suggest cimetidine can inhibit the hepatic metabolism of meperidine, however, the clinical implications of this pharmacokinetic interaction have not been determined.
Meperidine appears to block the neuronal reuptake of serotonin. Accumulation of serotonin can cause cardiovascular and/or neurologic adverse reactions. Meperidine should be used cautiously, if at all, in patients receiving MAOIs, especially selegeline. Clomipramine, fluoxetine, paroxetine, sertraline, and sumatriptan are other drugs that can potentiate the effects of serotonin. Although no reports of interactions with meperidine are known, these drugs should nevertheless be used carefully with meperidine.
ADVERSE REACTIONS: The most significant adverse effect associated with opiate agonist use is the potential for respiratory depression. When used in therapeutic doses, the risk is generally small. Caution needs to be employed in patients receiving opiates via IV injection, in patients with preexisting respiratory or cardiovascular disease, or in patients who are receiving other CNS depressants.
All opiate agonists can cause CNS depression, including drowsiness, confusion, dizziness, and/or sedation. Headache also can occur, as well as anxiety and restlessness. However, because meperidine is converted to a neurotoxic metabolite, meperidine can cause paradoxical excitation including seizures if administered in excessive doses or to patients with renal failure. Some patients with renal failure who have received prolonged therapy with meperidine have developed altered mental status, somnolence, coma, and/or myoclonic jerks. If seizures or cardiac arrhythmias occur, treatment with meperidine should be discontinued. Meperidine has been shown to be associated with post-operative delirium more than other opiate agonists.
Adverse GI effects of opiate agonists include nausea/vomiting, but nausea or vomiting are usually minimal at therapeutic dosage in most patients. Prolonged use of opiate agonists commonly results in constipation, particularly with codeine, meperidine, methadone, and morphine however meperidine appears to cause less constipation than the others. Hyperamylasemia, secondary to drug-induced spasm of the sphincter of Oddi, has been associated with various opiate agonists. While serum amylase and lipase concentrations can rise as a result of biliary obstruction or spasm, overt pancreatitis is rare with opiate analgesics. Gastritis and hepatotoxicity are also relatively rare with these agents.
Diaphoresis and flushing may be associated with hydrocodone, meperidine, methadone, or morphine.
Opiate agonists can cause cardiovascular adverse reactions. These reactions include sinus bradycardia, sinus tachycardia, palpitations, hypertension, hypotension, orthostatic hypotension, and syncope.
Anticholinergic effects occur with meperidine but are infrequent. Patients can experience xerostomia (dry mouth), blurred vision, or urinary retention.
Opiate agonists present the potential for abuse although the true risk of this phenomenon is extremely low. Patients with chronic pain may be inclined to misuse these drugs. Mild physiological dependence, however, can occur commonly during therapy with opiate agonists and abrupt discontinuation of the drug in these patients can provoke a withdrawal syndrome. Routine use of opiate agonists by an expectant mother can lead to withdrawal symptoms in the newborn. Symptoms of withdrawal include nausea and diarrhea, coughing, lacrimation, rhinorrhea, profuse sweating, twitching muscles, and piloerection. Mild elevations in body temperature, respiratory rate, and blood pressure can also occur. A long acting opiate agonist such as methadone can be administered to minimize opiate withdrawal.
Meperidine and other opiate agonists are known to cause pruritus. Opiate agonist-induced pruritus is thought to be mediated through stimulation of central opiate receptors since opiate antagonists (i.e., nalmefene or naloxone) have been shown to ameliorate pruritus associated with cholestasis.
PATIENT INFORMATION:
What do meperidine tablets do?
Meperidine (DemerolTM ) is a narcotic pain killer (analgesic) It relieves moderate to severe pain. Federal law prohibits the transfer of meperidine to any person other than the patient for whom it was prescribed. Do not share this medicine with anyone else. Generic meperidine tablets are available.
What should my doctor, dentist, or pharmacist know before I take meperidine?
They need to know if you have any of these conditions:
How should I take this medicine??
Take meperidine tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. If meperidine upsets your stomach you can take it with food or milk. Take your doses at regular intervals. Do not take your medicine more often than directed.
Elderly patients over 65 years old may have a stronger reaction and need smaller doses.
What is I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.
What other medicines can interact with merperidine?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects could I notice from taking meperidine?
Those who are bed-ridden or in severe pain seem to have fewer side effects.
Serious side effects with meperidine include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with meperidine include:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for when I take meperidine?
Tell your doctor if your pain does not go away. Use exactly as directed by your doctor to reduce the chance of becoming dependent on meperidine. Meperidine can be habit-forming. If you are being prescribed meperidine continuously around-the-clock for pain, do not stop taking except on your doctor's advice. Your pain could return and get more difficult to relieve.
You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how meperidine affects you. Do not stand or sit up quickly, especially if you are an older patient. This reduces the risk of dizzy or fainting spells. Alcohol can increase possible drowsiness, dizziness, confusion and affect your breathing. Do not take alcoholic drinks.
Your mouth may get dry. Chewing sugarless gum or sucking hard candy, and drinking plenty of water may help. Have regular dental checks.
If you are going to have surgery, tell your doctor or dentist that you are using meperidine.
Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.
Store at room temperature between 15 and 30C (59 and 86F). Protect from light. Keep container tightly closed. Throw away any unused medicine after the expiration date.
WARNING! Not to be used in conjunction with selegiline [DeprenylTM , Eldepryl TM ].
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