Meperidine Hydrochloride - Indication, Dosage, Precautions, and Pharmacological Aspects

Overview:

Meperidine was introduced in the 1930s, and since then, it has been widely used to treat moderate to severe pain. The drug was approved by the United States Food and Drug Administration (USFDA) in 1942. However, the medication is not regarded as a first-line analgesic.

Drug Group:

Meperidine is a member of the group of drugs known as opiate (narcotic) analgesics. It functions by altering how the nervous system and brain react to pain.

Available Doses and Dosage Forms:

• Meperidine hydrochloride is usually available as tablets and syrups. The drug is also supplied parenterally (intravenous, intramuscular, or subcutaneous).

• Adult - The normal dosage ranges from 50 mg (milligrams) to 150 mg, taken orally as needed every three or four hours.

• Pediatric - The typical dosage is 1.1 mg/kg (milligrams per kilogram) to 1.8 mg/kg, taken orally every three to four hours as needed, up to the adult dose.

For Patients:

What Is Pain?

Pain is the term used to describe unpleasant body sensations. The nervous system uses pain as a warning indication when something is wrong. It feels unpleasant, like a prick, tickle, sting, burn, or pain. Pain can be sharp or dull. It could be continuous or intermittent. One might experience pain only in one part or throughout the body. Acute and chronic pain are the two different types of pain. An illness, injury, or inflammation is the most common cause of acute pain, which manifests rapidly. It is usually treatable and diagnoseable. Occasionally, it can result in chronic pain. Long-lasting chronic discomfort might lead to serious issues.

The presence of pain can aid in the diagnosis of a condition. If a person has never experienced pain, they could gravely damage themselves without realizing it, or they may not be aware that they have a medical condition that requires attention.

How Does Meperidine Hydrochloride Work?

Meperidine hydrochloride is a painkiller used to treat moderate to severe pain. It is comparable to Morphine and belongs to the group of medications known as opioid analgesics. It alters how the body senses and responds to pain by acting on the brain. Meperidine should not be given for chronic or recurrent pain. Only unexpected episodes of moderate to severe pain should be treated with it.

How Effective Is Meperidine Hydrochloride?

Meperidine is used to treat moderate to severe pain. Meperidine belongs to the group of drugs known as opiate (narcotic) analgesics. The brain and nerve system's response to pain is altered.

What Are the Things to Inform the Doctor Before Taking the Drug?

The doctor should be informed about any prescribed or over-the-counter medication the patient is taking or planning to take. They should also inform the doctor about any allergic reaction they have. Pregnancy, breastfeeding, and any plans to conceive should be reported to the doctor. Mention any medical condition (both in the past and ongoing) to the doctor. Talk to them about fertility, as Meperidine tends to decrease fertility in both men and women. Inform the doctor about the profession the patient is tending to, as driving and operating heavy machines are not recommended during treatment.

How Is Meperidine Hydrochloride Administered?

Meperidine hydrochloride is available as a liquid (syrup) and tablet for oral use. It is mainly used to treat pain. It is often given every three to four hours with or without food. Ask the doctor or pharmacist to explain any instructions on the prescription label that need clarification or are easier to understand. It is important to swallow Meperidine tablets whole, without chewing or crushing them. Each tablet should be swallowed right away after being put in the mouth.

Use a dose-measuring spoon or cup while using Meperidine syrup to ensure the right dosage is administered. Do not use a common household spoon to measure the drug dosage. Consume the prescribed dosage after combining it with half a glass of water. Ensure not to ingest undiluted Meperidine hydrochloride syrup because it could numb the mouth.

The doctor can make dose adjustments during treatment; hence, any side effects that occur need to be reported to the doctor. A patient should not stop taking Meperidine if they have been taking it for more than a few weeks without first consulting the doctor. The doctor will gradually reduce the dose. One can suffer withdrawal symptoms if they stop taking Meperidine abruptly. Sweating, stuffy nose, irritability, back pain, muscle pain, rapid heartbeat, rapid breathing, stomach discomfort, vomiting, restlessness, chills, loss of appetite, watery eyes, upset stomach, yawning, anxiousness, and diarrhea are just a few withdrawal symptoms.

What Are the Side Effects of Meperidine?

• Side Effects - Lightheadedness, weakness, vomiting, mood swings, vision changes, dryness of the mouth, pain in the head, feeling of extreme calmness, sweating, flushing, and pain in the stomach.

• Serious Side Effects - Rashes, decrease in sexual drive and erection loss, confusion, stiffness in the muscles, diarrhea, heartbeat, coordination loss, slow breathing, difficulty in urinating, seizures, menstruation cycle becomes irregular, loss of appetite, hallucination, shivers, and tremors.

Dietary Considerations: A regular diet is followed unless instructed by the doctor.

Missed Dose: This drug is consumed as needed. Take the missed dose right away if the doctor has prescribed Meperidine regularly. To continue with the regular dosing plan, skip the missed dose if it is almost time for the next one. If a dose is missed, the second one should not be taken to compensate for it.

Overdose:

Meperidine overdose that is serious is marked by respiratory depression, extreme drowsiness that progresses to unconsciousness or coma, skeletal muscle weakness or paralysis, decrease in body temperature, cold and clammy skin, and occasionally decrease in heart rate and blood pressure decrease. A substantial overdose may result in apnea (breathing stops while sleeping), circulatory collapse, cardiac arrest, and death, especially if it is administered intravenously.

Restoring adequate respiratory exchange through a patent airway and aided or regulated breathing should get the most attention. The specific antidote for respiratory depression is Naloxone hydrochloride, a narcotic antagonist. Therefore, a suitable dose of this antagonist should be given as needed, ideally by intravenous (IV) administration, in addition to efforts to revive the patient's breathing.

In the absence of clinically notable respiratory or cardiovascular depression, Naloxone should not be given. Supporting measures such as oxygen, intravenous fluids, vasopressors, and others should always be used. The stomach should be emptied using emesis (forcing the stomach's contents out of the mouth) or gastric lavage (emptying stomach content via nasogastric tube).

A normal dosage of a narcotic antagonist will cause an abrupt withdrawal syndrome in a person who is physically dependent on narcotics. The amount of physical dependability and antagonist dose will determine the severity of the syndrome. When feasible, it is safer to avoid using narcotic antagonists on people like this. Suppose a narcotic antagonist must be used to treat severe respiratory depression in a physically dependent patient. In that case, it should be provided with extreme caution and at a dose that is only one-fifth to one-tenth of the starting dose.

Storage and Disposal: The drug should be kept away from children and minors and keep it adequately packed in its original container. Avoid keeping it in the bathroom. Keep it at ambient temperature and away from extreme heat and moisture sources. Be sure to use a drug take-back program to promptly dispose of any unwanted or old medications. Any expired or unnecessary Meperidine tablets or solutions can be flushed down the toilet to safely dispose of in case of no access to a nearby take-back program.

For Doctors:

Indication: Meperidine hydrochloride is prescribed to treat moderate to severe pain.

Dose: Meperidine dosage needs to be adjusted based on the patient's pain level and response. Meperidine hydrochloride is typically less effective when administered parenterally than when it is taken orally. The dose of Meperidine hydrochloride should normally be reduced appropriately, frequently by 25 % to 50 %, if given with Phenothiazines or some other tranquilizers, which potentiate the effects of Meperidine.

Dosing Considerations:

• Adult - The normal dosage ranges from 50 mg (milligrams) to 150 mg, taken orally as needed every three or four hours.

• Pediatric - The typical dosage is 1.1 mg/kg (milligrams per kilogram) to 1.8 mg/kg, taken orally every three to four hours as needed, up to the adult dose.

What Are the Pharmacological Aspects of Meperidine Hydrochloride?

• Description

  • Appearance - Crystalline and white.

  • Melting Point - 186 degrees Celsius to 189 degrees Celsius.

  • Solubility - Soluble in water but does not decompose upon boiling for a short period.

  • Chemical Name - 4-Piperidinecarboxylic acid, 1-methyl-4-phenyl-, ethyl ester, hydrochloride.

  • Inactive Ingredient - Calcium Sulfate, Stearic Acid, Starch, Talc, and Dibasic Calcium Phosphate.

• Clinical Pharmacology - Meperidine hydrochloride is a narcotic painkiller that is qualitatively comparable to Morphine in several ways. They function most effectively in the central nervous system and in organs with smooth muscles. The main therapeutic effects include drowsiness and analgesia, which reduce pain. Some research suggests that Meperidine, when used at equianalgesic (equal pain-relieving) doses, may be preferable to Morphine in terms of causing fewer problems with smooth muscle spasms, constipation, and suppression of the cough reflex. According to some research, Meperidine may be preferable to Morphine when it comes to causing fewer side effects such as constipation, smooth muscle spasms, and cough suppression when used in equianalgesic (equivalent pain-relief) doses.

• Mechanism of Action -

  • In addition to acting as a local anesthetic, Meperidine acts as a kappa-opiate receptor agonist. Compared to Morphine, Meperidine has higher kappa-receptor-affinity. When linked with G-protein receptors, opiate receptors control synaptic transmission positively and negatively by activating effector proteins through G-proteins. When an opiate is bound, the G-protein complex is stimulated to exchange GTP (Guanosine triphosphate) for GDP (Guanosine diphosphate).

  • Meperidine lowers the activity of a chemical called cAMP (cyclic adenosine monophosphate), which is typically located inside the cells close to the cell surface. Opioids limit the release of several molecules in the body that carry pain signals when they diminish cAMP. Substance P, GABA, dopamine, acetylcholine, and noradrenaline are a few of these substances. The release of hormones like vasopressin, somatostatin, insulin, and glucagon is also slowed down by opioids.

  • Opioids also affect the nerve cells in the body. They allow potassium to enter the cells by opening other channels while closing others that let calcium into them. This reduces the likelihood of nerve cells firing and transmitting pain signals, which lessens discomfort and reduces nerve activity.

  • Opioids can, therefore, aid in pain relief, but they also carry the risk of addiction and other negative effects.

• Pharmacokinetics:

  • Absorption - Due to substantial first-pass metabolism, Meperidine has a 50 % to 60 % oral bioavailability in patients with normal hepatic function. Patients with hepatic impairment (such as liver cirrhosis) have an increase in bioavailability of 80 % to 90 %. Compared to parenteral treatment, Meperidine is less than half as effective when taken orally. In healthy adults, one study found that 80 % to 85 % of the medication given intramuscularly was absorbed within six hours of the intragluteal injection. However, inter-individual variance and patient-specific variables cause significant variability in absorption following intramuscular injection.

  • Metabolism - The hydrolysis of Meperidine to meperidinic acid and partial conjugation with glucuronic acid are the steps in the metabolism of the drug in the liver. Additionally, normeperidine is formed from Meperidine via N-demethylation, after which it is partially conjugated and hydrolyzed. The CNS-stimulating effects of normeperidine are twice as much as those of Meperidine, although they have around half the potency of Meperidine.

  • Elimination - The drug is excreted out in the urine. pH of the urine affects how much of a medicine is eliminated, either intact or as metabolites. When urine pH is not under control, 5 % to 30 % of the Meperidine dose is excreted as normeperidine and roughly 5 % is excreted unmodified. Meperidine and normeperidine are detected in acidic urine, whereas the free and conjugated forms of Meperidine and normeperidine acids are found in alkaline urine.

Toxicity: Studies not conducted for carcinogenesis, mutagenesis, and impact on fertility.

What Are the Contraindications of Meperidine Hydrochloride?

• People known to be allergic or hypersensitive to Meperidine or any of its ingredients should not use it.

• Patients with significant respiratory impairment should not take Meperidine Hydrochloride.

• Patients who are on monoamine oxidase (MAO) inhibitors or who have recently taken such medications should not use Meperidine. Patients who have received such medications within 14 days have occasionally experienced unexpected, severe, and even fatal responses following therapeutic doses of Meperidine. Although the exact mechanism of these reactions is unknown, pre-existing hyperphenylalaninemia may play a role. Some have exhibited symptoms similar to the syndrome of acute opioid overdose, including severe respiratory depression, hypotension, coma, and cyanosis.

• The use of Meperidine is contraindicated in patients who exhibit serotonin syndrome. Agitation, diarrhea, heat, tachycardia, sweating, tremors, and diminished consciousness are the symptoms of serotonin syndrome. In other reactions, tachycardia, hyperpyrexia, hypertension, and hyperexcitability have been the most common signs. Suppose Meperidine or other narcotic is required for these patients. In that case, a sensitivity test should be carried out in which several low and incremental doses of Morphine are given over several hours while the patient's state and vital signs are being closely monitored.

Warnings and Precautions:

• Meperidine should not be used to manage pain that lasts over a lengthy period. It works well for treating sudden onset of moderate to severe pain. Due to the accumulation of Meperidine's metabolite, normeperidine, prolonged usage of the drug can increase the risk of toxicity, including seizures. As a result, its use should be restricted to short-term pain management and not advised for illnesses associated with persistent pain.

• Similar to other opioid agonists, Meperidine hydrochloride also has the potential to be abused whether used for legitimate or illegal purposes. In circumstances where the doctor or pharmacist is worried about a greater likelihood of misuse, abuse, or diversion, this should be taken into account when prescribing or dispensing Meperidine hydrochloride. To reduce these dangers and guarantee the safe and proper use of the drug, careful observation and responsible prescribing techniques are needed.

• In some patient populations, opioid analgesics like Meperidine, especially when taken in combination with Central Nervous System (CNS) depressants, can have a limited and narrow therapeutic index. These medications should only be taken when the advantages of opioid analgesia outweigh the known hazards, which include postural hypotension, respiratory depression, and altered mental status. In the below-mentioned conditions, using Meperidine hydrochloride may be associated with increased risks, so it should be used with caution:

  • Pheochromocytoma.

  • Adrenocortical insufficiency (e.g., Addison's disease).

  • Sickle cell anemia.

  • Acute alcoholism.

  • Prostatic hypertrophy or urethral stricture.

  • Coma.

  • Delirium.

  • Kyphoscoliosis is associated with respiratory depression.

  • Toxic psychosis.

  • Myxedema or hypothyroidism.

  • Impairment of hepatic, pulmonary, or renal function.

  • Debilitated patients.

• Labor and Delivery - Meperidine is capable of crossing the placental barrier, which raises the risk of respiratory and psychophysiological depression in the infant and may call for resuscitation. As a result, it is typically not advised to use meperidine during childbirth.

• Convulsion - Meperidine may make previous convulsions worse in patients with convulsive disorders. In addition, persons without a history of convulsive disorders may experience seizures if the dosage is significantly increased above the advised levels as a result of the development of tolerance.

• Supraventricular Tachycardias - Meperidine should be taken cautiously in people with disorders such as atrial flutter and other supraventricular tachycardias. This is due to the possibility of vagolytic activity in Meperidine, which could significantly raise the pace of ventricular response.

• Acute Abdominal Conditions - Meperidine or other narcotics may be used to treat individuals who have acute abdominal illnesses, which could conceal the diagnosis or clinical development of those disorders.

What Are the Drug Interactions of Meperidine Hydrochloride?

• Acyclovir - Acyclovir may raise plasma concentrations of Meperidine and its metabolite, Normeperidine. Hence, caution should be exercised when taking the two medications simultaneously.

• Cimetidine - Cimetidine decreased Meperidine's clearance and volume of distribution and the production of its metabolite, Normeperidine, in healthy persons. As a result, caution should be exercised when the two medications are administered concurrently.

• Phenytoin - Phenytoin may have an impact on Meperidine's hepatic metabolism. When given concurrently, it may cause Meperidine's half-life to be shortened, its bioavailability to be decreased, and its clearance to increase in healthy persons. The levels of Normeperidine in the blood, however, rise. Consequently, it is advised to use caution when combining Phenytoin and Meperidine.

• Ritonavir - Ritonavir may raise plasma concentrations of the active metabolite normeperidine; hence, simultaneous dosing should be avoided.

• Interaction With Alcohol - Combining Meperidine with alcohol, other opioids, or illegal drugs that additionally depress the central nervous system may have negative consequences. The chance of enhanced central nervous system depression, which can cause increased drowsiness, respiratory depression, and other potentially harmful side effects, is thus raised when these drugs are administered together. Meperidine should not be taken with any medications that depress the central nervous system, similarly to Meperidine, to reduce the risk of side effects or overdose.

  • Head Injury and Increased Intracranial Pressure - Meperidine hydrochloride has depressive effects on the respiratory system and increases cerebrospinal fluid pressure. This is noticeably increased in the presence of intracranial lesions, a preexisting rise in intracranial pressure, or a head injury. Meperidine and other narcotic drugs can mask the symptoms in those who have had head trauma, hence making the treatment difficult. Thus, Meperidine must be used in the head injury patients very carefully and only when necessary.

  • Respiratory Conditions - Patients experiencing an acute asthmatic attack, those with COPD or cor pulmonale, those with a significantly reduced respiratory reserve, and those who already have respiratory depression, hypoxia, or hypercapnia should use Meperidine with extreme caution. Even standard therapeutic doses of opioids may reduce respiratory drive in these patients while concurrently raising pulmonary resistance to the point of apnea.

  • Hypotensive Effect - Meperidine administration has the potential to cause a significant drop in blood pressure, particularly in postoperative patients or people whose ability to maintain healthy blood pressure is hampered by things like decreased blood volume, the use of drugs like Phenothiazines, or the use of particular anesthetics.

• Interactions With Mixed Agonist and Antagonist Opioid Analgesics - Pentazocine, Nalbuphine, Butorphanol, and Buprenorphine are examples of antagonist or agonist analgesics that should be delivered with caution to a patient who has already received or is currently undergoing an administration with a pure opioid agonist analgesic like Meperidine. Due to competitive receptor blockage in this condition, mixed agonist or antagonist analgesics may lessen the analgesic effect of Meperidine and may cause withdrawal symptoms in these patients.

• Interactions With Other CNS Depressants - In patients who are already taking other Central Nervous System (CNS) depressants, Meperidine hydrochloride should be used with caution, and it is recommended to start with a lower dosage. Hypnotics, sedatives, phenothiazines, anesthetics, other tranquilizers, and alcohol are a few examples of CNS depressants. When combined with the usual doses of Meperidine hydrochloride, the risk of drug-drug interactions is high. It could result in harmful side effects like respiratory depression, hypotension, profound drowsiness, coma, or even a life-threatening situation.

Specific Considerations:

• Pregnancy - Except in cases when a doctor concludes that the potential advantages outweigh the potential risks, Meperidine hydrochloride should generally be avoided by pregnant women before the start of labor. This is because its safety for usage in pregnancy up until labor has not been shown beyond a reasonable doubt, and there might be worries about potential adverse effects on fetal development.

• Ambulatory Patients - Meperidine hydrochloride can impair the mental and bodily capacities required to safely perform potentially dangerous occupations, such as operating heavy machinery and driving. Patients should be instructed to use caution in these circumstances. Meperidine can also cause orthostatic hypotension in people who are walking or standing, just like other drugs.

• Lactating Mothers - Meperidine is found in the milk of nursing mothers who take the medication. A decision should be made regarding whether to cease breastfeeding or to stop taking the medicine, given the danger of serious adverse effects in nursing infants, while also taking into account any potential benefits the medication may have for the nursing mother.

• Use in Alcohol Addiction - An opioid drug called Meperidine hydrochloride is not allowed to be used to treat pain, which is related to addiction. It is used to treat only pain which are unrelated to addiction. Since these patient populations are more likely to acquire narcotic tolerance, dependence, and the potential for addiction, it should be used with caution when treating patients with alcoholism and other drug dependencies. Meperidine Hydrochloride usage can be quite dangerous for the patient, especially when mixed with other CNS depressants.

• Pediatric Population - It is unknown whether Meperidine is safe and effective for children. According to literature research, Meperidine is eliminated more slowly in neonates and young babies than it is in older kids and adults. They are more vulnerable to respiratory depression and other effects of the drug. If Meperidine use in newborns or young babies is being considered, any potential benefits of the medication must be compared to the relative risk of the patient.

• Geriatric Population - To assess age-related variations in safety or efficacy, not enough patients 65 years or older were enrolled in clinical investigations of Meperidine hydrochloride during the product development. According to literature reports, older adults eliminate medication more slowly than younger patients, which makes them more vulnerable to side effects. In older patients, it is advised to reduce the total daily dose of Meperidine, and the potential advantages of the medication should be compared to the relative danger to an aged patient.