Morphine Sulfate - Dosage, Indications, Side effects, and Pharmacology

Overview

Morphine is a pain reliever used to treat moderate to severe pain. Morphine extended-release capsules and tablets are only used to treat uncontrollable pain with other pain medications. Avoid using Morphine extended-release capsules and tablets to treat pain that can be controlled with as-needed medication.

How Does Morphine Sulfate Work?

Morphine Sulfate comes in the form of a fine white powder. When exposed to air, it gradually loses hydration and darkens when exposed to light for an extended period. At room temperature, it is soluble in ethanol and water. Its chemical name is 7,8-Didehydro-4,5-epoxy-17-methyl-(5,6)-morphinan-3,6 diol sulfate, pentahydrate.

Uses

Morphine Sulfate injection is used to treat moderate to severe pain. Morphine Sulfate injection is used to treat pain caused by cancer, a heart attack, or surgery. Morphine also helps to alleviate the anxiety and insomnia that can accompany severe pain.

Dosage

Loading doses of Morphine Sulfate ranging from one milligram to ten milligrams (maximum 15 mg) can be administered intravenously over four or five minutes. The patient's diagnosis and condition will determine the loading dose. Dosages may vary depending on the patient's tolerance, loading dose, condition, and whether a Morphine background infusion is administered.

Warnings

Morphine Sulfate injection should be used carefully in patients who are debilitated or have hypopituitarism, adrenocortical insufficiency, shock, prostatic hypertrophy, diabetes mellitus, biliary tract diseases, cardiac arrhythmias, myasthenia gravis, excessive obesity, hypotension, and severe cardiac failure. It should also be used cautiously following total joint arthroplasty. In addition, concurrent use of other opioid analgesics, such as Codeine, whether administered orally or by another route, increases the central nervous system depressant effect of Morphine.

For Patients

What Does One Need to Know About Severe Pain?

Severe pain is pain that lasts for at least 12 weeks. The pain could be sharp or dull, with an aching or burning sensation in the affected areas. It could be continuous or intermittent, coming and going for no apparent reason. Severe pain can affect almost any part of the body. The pain can vary depending on the affected area. Common types of severe pain include:

• Post-surgical pain.

• Post-trauma pain.

• Lower back pain.

• Cancer pain.

• Arthritis pain.

• Neurogenic pain.

• Psychogenic pain.

Learn More about Morphine Sulfate

Morphine Sulfate injection USP is a nonpyrogenic, sterile injection solution that is free of antioxidants and preservatives. For intravenous administration with single-use CarpujectTM and iSecureTM syringes. Each ml of the solution includes 2 mg, 4 mg, 8 mg, 10 mg, or 15 mg of Morphine Sulfate. The inactive ingredients are 0.4 mg citric acid, 0.2 mg edetate disodium, and 0.8 mg citric acid sodium chloride; to adjust water and isotonicity for injection to adjust the pH, add hydrochloric acid and sodium hydroxide. The pH scale runs from 2.5 to 4.0.

When and How Often to Take Morphine Sulfate?

Morphine Sulfate injection is available as a liquid solution to be injected intramuscularly or intravenously. It is typically injected every four hours as needed. Use Morphine Sulfate injections at the same times each day. Follow the instructions on the prescription label exactly, and ask the doctor for help. Follow the directions on the Morphine Sulfate injection exactly.

Things To Inform the Doctor before They Prescribe Morphine Sulfate

• Inform the doctor in case of Morphine allergy.

• Inform the doctor about any medications, nutritional supplements, vitamins, and herbal products one takes or plans to take.

• If one has or has had a paralytic ileus.

• If one has had a blockage in the intestines, difficulty swallowing, seizures, prostatic hypertrophy, urinary problems, low blood pressure, Addison's disease, liver, kidney, pancreas, thyroid, or gallbladder disease.

• If a woman is breastfeeding or undergoing dental surgery.

Starting Morphine Sulfate:

Start the treatment with 15 mg Morphine Sulfate extended-release tablets orally every eight or 12 hours. Higher starting doses may cause fatal respiratory depression in patients who are not opioid-tolerant. Morphine Sulfate extended-release tablets of 15 mg orally every 12 hours.

Things to Do After Starting Morphine Sulfate

• Inform the doctor and pathologist if one is taking Morphine Sulfate before having any laboratory tests. The doctor may order certain laboratory tests to assess the body's response to Morphine Sulfate.

• This prescription cannot be renewed. If one is taking Morphine Sulfate to control the pain on a long-term basis, make sure to keep the doctor's appointments so that one does not run out of medication.

• If one is taking Morphine Sulfate on a short-term basis, contact the doctor if one continues to experience pain after the medication has worn off.

Look Out for Side Effects

The side effect of these medications is:

• Dry mouth.

• Stomach pain.

• Cramps.

• Nervousness.

• Headache.

• Mood changes.

• Small pupils.

• Drowsiness.

• Difficulty in urinating.

Dietary Alterations

The systemic bioavailability of Morphine Sulfate in food has not been thoroughly studied for all strengths. However, one study with 30 mg Morphine Sulfate extended-release tablets found no significant differences in Cmax and AUC values when taken fasting or with a high-fat breakfast.

What Should Be Done on Missing a Dose?

If one takes Morphine injections or tablets, the doctor will most likely advise taking the medication only when necessary if the person has been instructed to take the tablets or liquid at regular intervals. In case one is on an extended-release product, take the dose after remembering it and skip the next dose at a regularly scheduled time. Avoid taking a double dose.

What Should Be Done to Treat Morphine Sulfate Overdose?

Even in complete darkness, Morphine Sulfate can cause miosis. The sign of opioid overdose is pinpoint pupils but are not pathognomonic. In overdose situations, marked mydriasis rather than miosis may be observed. Priority should be given to re-establishing adequate respiratory exchange through providing a patent airway and implementing assisted or controlled ventilation. Use supportive measures to treat circulatory shock and pulmonary edema caused by an overdose. Arrhythmias or cardiac arrest may necessitate cardiac massage or defibrillation.

How to Store Morphine Sulfate?

• Until ready to use, store at 20 degrees Celsius to 25 degrees Celsius (68°F to 77°F).

• Do not freeze.

• Protect from sunlight.

• Do not heat-sterilize any unused portion.

• Does not contain any antioxidants or preservatives.

How to Handle Morphine Sulfate?

Any unused pharmaceutical product or waste material should be disposed of according to local regulations.

How to Dispose of Morphine Sulfate?

Keep this medication in its original container, tightly closed, and out of the reach of children. Keep it at room temperature and away from extreme heat and moisture sources. Any outdated or no longer needed medication must be disposed of immediately through a medicine take-back program. If one does not have a nearby or easily accessible take-back program, flush any outdated or no longer needed morphine extended-release tablets, liquids, and capsules down the toilet so that others do not take them.

Avoid Self-medication:

Avoid taking the medication for a condition that was not prescribed. Also, do not suggest the medication to anyone with the same symptoms because the medication may show different effects in different individuals. Instead, consult the physician, discuss with them, and then take medicine.

Staying On Morphine Sulfate

Tips to stay on track with Morphine Sulfate:

• Take the drug as directed by the physician.

• Do not miss a dose or overdose to compensate for a missed dose. If one does so, inform the physician immediately.

• Also, schedule regular appointments with the physician to monitor the disease progression and recommend dose alteration.

For Doctors

Indication

Morphine Sulfate injection is used to treat moderate to severe pain. Morphine Sulfate injection is used to treat pain caused by cancer, surgery, or a heart attack. Morphine also helps to alleviate the anxiety and insomnia that can accompany severe pain.

Pharmacology

Mechanism of Action

Morphine, a full opioid agonist, is relatively selective for the mu receptor, though at higher doses, it can interact with other opioid receptors. Morphine sulfate has a wide range of side effects, including respiratory depression, drowsiness, mood changes, decreased gastrointestinal motility, vomiting, nausea, and changes in the endocrine and autonomic nervous systems.

• Effects on CNS - Morphine's other therapeutic effects include anxiolysis, feelings of relaxation, and euphoria. Although the precise mechanism of the analgesic action is unknown, specific CNS opiate receptors and endogenous morphine-like compounds have been identified throughout the spinal cord and brain and play a role in the perception and expression of analgesic effects.

• Effects on Gastrointestinal Tract - Morphin reduces gastric, biliary, and pancreatic secretions. Morphine reduces motility and causes an increase in tone in the antrum of the duodenum and stomach. There is delayed digestion, and propulsive contractions are reduced.

• Effects on Cardiovascular System - Morphine causes peripheral vasodilation, leading to orthostatic hypotension and fainting. Histamine release may occur, which may contribute to opioid-induced hypotension. Pruritus, flushing, sweating, and red eyes are all symptoms of histamine release and peripheral vasodilation.

• Immune System - Opioids have been shown in vitro and in animal models to affect immune system components. These findings have no clinical significance.

Pharmacodynamics: Morphine concentrations do not predict analgesic response, particularly in patients who have previously been treated with opioids. The minimum effective concentration varies greatly and is influenced by factors, including age, opioid use, age, and general medical condition. Effective doses may be significantly higher in tolerant patients than in opioid-naive patients.

Ingredients

Active Ingredient

Morphine sulfate pentahydrate.

Inactive Ingredients

Lactose monohydrate, povidone, hyetellose, magnesium stearate, purified talc, carnauba wax, polyethylene glycol, polysorbate, stearic acid, and titanium dioxide.

Absorption

Morphine is released more slowly from Morphine Sulfate extended-release tablets than from immediate-release oral preparations. The amount of Morphine absorbed following oral administration of a given dose is essentially the same in extended-release tablets or an immediate-release formulation. Due to presystemic elimination, only 40 % of the administered dose reaches the central compartment.

Distribution

Morphine is distributed to the skeletal muscle, kidneys, spleen, lungs, liver, intestinal tract, and brain after absorption. Morphine has also been found in breast milk and has crossed placental membranes. Morphine has a volume of distribution of three to four liters per kilogram and is 30 to 35 % reversibly bound to plasma proteins.

Metabolism

The major Morphine metabolism pathways are glucuronidation, which produces metabolites such as morphine-3-glucuronide, M3G, and morphine-6-glucuronide, M6G, and sulfation in the liver, which produces morphine-3-ethereal sulfate. Morphine is demethylated to a small extent. M6G has analgesic activity but does not cross the blood-brain barrier well, whereas M3G has no analgesic activity.

Elimination

Morphine is eliminated primarily through renal excretion of M3G. The effective half-life after intravenous administration is typically two to four hours. Approximately ten percent of the dose is excreted in the urine unchanged. Some studies with longer periods of plasma sampling reported a terminal half-life of about 15 hours. A less amount of glucuronide conjugate is excreted in bile, and some enterohepatic recycling occurs.

Toxicity

The reported effects occurred after maternally toxic doses, and the abnormalities observed were typical of those seen when maternal toxicity was present.

Warning and Precaution

• Respiratory Depression - Morphine Sulfate injection USP's primary risk is respiratory depression. Respiratory depression is more common in elderly or debilitated patients and those suffering from hypercapnia, hypoxia, or upper airway obstruction, patients with moderate therapeutic doses, can significantly reduce pulmonary ventilation. Morphine administration should be limited to those who are experienced in the treatment of respiratory depression. Rapid intravenous administration may cause rigidity of the chest wall.

• Cardiovascular Instability - Low doses of Morphine Sulfate have little effect on cardiovascular stability. High doses are excitatory, resulting in sympathetic hyperactivity and increased circulatory catecholamines. Have Naloxone injection and resuscitation equipment on hand in case of side effects and life-threatening and when Morphine therapy is used.

• Central Nervous System (CNS) Depressants - The presence of other CNS depressants, such as alcohol, antihistamines, sedatives, or psychotropic drugs, enhances the depressant effects of Morphine. Morphine increases the risk of respiratory depression, coma, hypotension, profound sedation, or death when combined with other CNS active drugs.

• Central Nervous System (CNS) Toxicity - High doses of Morphine given intravenously may cause central nervous system excitation, resulting in convulsion. Any dose can cause dysphoric reactions, and toxic psychoses have been reported.

• Gastrointestinal Effects - Avoid Morphine Sulfate injection USP in patients with gastrointestinal obstruction, particularly paralytic ileus, because it reduces propulsive peristaltic waves in the GI tract and may prolong the obstruction.

Dosage and Forms

In adults, the usual starting dose is 0.1 mg to 0.2 mg per kg every four hours as needed to manage pain. Slowly administer the injection. Morphine Sulfate injection is administered intravenously. Morphine Sulfate injection USP is available in single-use iSecure and Carpuject syringes with concentrations of 2 mg/mL, 4 mg/mL, 8 mg/mL, 10 mg/mL, and 15 mg/mL.

Administration of the Drug

Before using the product, it should not be diluted. Prior to use, the medicinal product must be visually inspected. Only clear, practically particle-free solutions should be used.

Considerations for Administration

Morphine Sulfate injection is available in five different concentrations for intravenous administration. Avoid dosing errors caused by confusion between different concentrations and between mg and mL when administering and prescribing Morphine Sulfate injection, which could result in accidental overdose and death. Administration Morphine Sulfate injection should only be used by those familiar with treating respiratory depression. Morphine must be administered gradually; rapid intravenous administration may cause chest wall rigidity. Take care to communicate and dispense the correct dose. Include the total dose in mg and volume when writing prescriptions. The same principles govern the use of similar opioid analgesics. Individualize treatment in each case. In this case, non-opioid analgesics, opioids as needed, combination products, and chronic opioid therapy are used as part of a progressive pain management plan given by WHO.

Contraindications

• Morphine Sulfate is contraindicated in patients with hypercarbia and acute or severe bronchial asthma, as well as in patients suspected of paralytic ileus.

• Morphine Sulfate is not recommended for patients with a history of Morphine hypersensitivity.

• In the absence of resuscitation equipment, Morphine Sulfate is contraindicated in patients with respiratory depression.

Clinical Studies for Morphine Sulfate

Individual patient data analysis from high-quality clinical trials provides important insights into new agent characteristics not immediately apparent from original trials while also informing clinical practice. For example, prophylactic epidural Morphine is more comfortable for the patient than IV PCA alone.

Drug Interactions

• Central Nervous System (CNS) Depressants - Morphine should be used carefully when combined with CNS depressants such as other narcotic analgesics, tricyclic antidepressants, general anesthetics, phenothiazines, tranquilizers, sedatives, alcohol, hypnotics, and antiemetics. Concurrent administration increases the risks of respiratory depression, profound sedation, hypotension, and coma.

• Mixed Agonist - Mixed agonist or antagonist analgesics may reduce analgesia and precipitate withdrawal symptoms in these patients. The patients who have received Morphine Sulfate injection USP should not be given mixed agonist or antagonist analgesics.

• Cimetidine - In one case, the simultaneous administration of Morphine Sulfate injection USP and Cimetidine caused apnea, muscle twitching, and confusion. When Cimetidine is combined with Morphine Sulfate injection USP, patients should be monitored for increased CNS and respiratory depression.

• Muscle Relaxant - Morphine Sulfate enhances the neuromuscular blocking action of skeletal muscle relaxants and causes more respiratory depression.

• Anticholinergics - When combined with opioid analgesics and anticholinergics medications, it may increase the risk of urinary retention, constipation, or paralytic ileus. Morphine Sulfate enhances the neuromuscular blocking of skeletal muscle relaxants and causes more respiratory depression.

• Monoamine Oxidase Inhibitors - Monoamine oxidase inhibitors significantly enhance the action of Morphine Sulfate injection USP. Allow at least 14 days after discontinuing this treatment before starting Morphine Sulfate injection USP.

Other Specifications

Morphine Sulfate in Pregnant Women: It is unknown whether Morphine affects the fetus or affects reproductive capacity when administered to a pregnant woman. Morphine should only be given to a pregnant woman if necessary. No malformations were found in the fetus of a woman who attempted suicide during her first trimester of pregnancy by taking an overdose of Morphine and other medications.

Morphine Sulfate in Lactating Women: Morphine Sulfate injection USP levels in maternal milk are low. The area under the curve (AUC) ratio of milk to plasma Morphine is approximately 2:5:1. The amount of Morphine Sulfate injection USP given to the infant is determined by the mother's plasma concentration, the extent of first-pass metabolism and the amount of milk given to the infant. As there is the possibility of adverse reactions in nursing infants from Morphine Sulfate injection USP, including sedation, respiratory depression, and possible withdrawal symptoms, decide whether to discontinue the drug or nursing.

Morphine Sulfate in Pediatric Patients: Morphine Sulfate injection's effectiveness and safety in pediatric patients under 18 have not been established.

Morphine Sulfate in Geriatric Patients: Morphine Sulfate's pharmacodynamic effects are more variable in older individuals than in the younger population. As the dose increases in older patients, the effective initial dose, rate of tolerance development, and frequency and magnitude of associated adverse effects will vary greatly.

Morphine Sulfate in Renal Impairment Patients: Morphine Sulfate pharmacokinetics are altered in renal failure patients. In patients, clearance is reduced, and the metabolites M6G and M3G may accumulate to much higher plasma levels. Patients with renal failure versus patients with normal renal function. These patients cautiously are started with the low dose of Morphine Sulfate injection USP and carefully monitored for side effects.

Morphine Sulfate in Hepatic Impairment Patients: Morphine Sulfate pharmacokinetics are significantly altered in cirrhotic patients. Clearance was discovered to decrease with an increase in half-life.