Methylmorphine

Uses

Methylmorphine is an opioid analgesic used to treat moderate to severe pain when the use of an opioid is indicated.

Methylmorphine sulfate is a form of this drug that is commonly used. It is available in tablet form and indicated for the relief of mild to moderately severe pain, where the use of an opioid analgesic is appropriate .

The solution form is used by itself or combined in a syrup with other drugs and is used as a cough suppressant in adults aged 18 and above , .

Methylmorphine is also used to associated treatment for these conditions: Common Cold, Cough, Flu caused by Influenza, Mild pain, Pain, Severe Pain, Dry cough, Moderate Pain, Upper respiratory symptoms, Airway secretion clearance therapy

How Methylmorphine works

Methylmorphine is a selective agonist for the mu opioid receptor, but with a much weaker affinity to this receptor than morphine, a more potent opioid drug. Methylmorphine binds to mu-opioid receptors, which are involved in the transmission of pain throughout the body and central nervous system , . The analgesic properties of codeine are thought to arise from its conversion to Morphine, although the exact mechanism of analgesic action is unknown at this time , .

Toxicity

Oral LD50: 427 mg kg-1 (rat) .

Overdose/toxicity

Symptoms of opioid toxicity may include confusion, somnolence, shallow breathing, constricted pupils, nausea, vomiting, constipation and a lack of appetite. In severe cases, symptoms of circulatory and respiratory depression may ensue, which may be life-threatening or fatal , .

Teratogenic effects

This drug is classified as a pregnancy Category C drug. There are no adequate and well-controlled studies completed in pregnant women. Methylmorphine should only be used during pregnancy if the potential benefit outweighs the potential risk of the drug to the fetus .

Methylmorphine has shown embryolethal and fetotoxic effects in the hamster, rat as well as mouse models at about 2-4 times the maximum recommended human dose . Maternally toxic doses that were about 7 times the maximum recommended human dose of 360 mg/day, were associated with evidence of bone resorption and incomplete bone ossification. Methylmorphine did not demonstrate evidence of embrytoxicity or fetotoxicity in the rabbit model at doses up to 2 times the maximum recommended human dose of 360 mg/day based on a body surface area comparison .

Nonteratogenic effects

Neonatal codeine withdrawal has been observed in infants born to addicted and non-addicted mothers who ingested codeine-containing medications in the days before delivery. Common symptoms of narcotic withdrawal include irritability, excessive crying, tremors, hyperreflexia, seizures, fever, vomiting, diarrhea, and poor feeding. These signs may be observed shortly following birth and may require specific treatment .

Methylmorphine (30 mg/kg) given subcutaneously to pregnant rats during gestation and for 25 days after delivery increased the rate of neonatal mortality at birth. The dose given was 0.8 times the maximum recommended human dose of 360 mg/day .

The use in breastfeeding/nursing

Methylmorphine is secreted into human milk. The maternal use of codeine can potentially lead to serious adverse reactions, including death, in nursing infants .

Food Interaction

• Avoid alcohol.
• Take with food. Food reduces irritation.

Methylmorphine Alcohol interaction

[Moderate] GENERALLY AVOID:

Ethanol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics.

Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills.

In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

Concomitant use of opioid analgesics with ethanol should be avoided.

Methylmorphine Drug Interaction

Major: pregabalin, pregabalin, quetiapine, quetiapine, diazepam, diazepam, alprazolam, alprazolamModerate: contained in alcoholic beverages , contained in alcoholic beverages Unknown: acetaminophen, acetaminophen, acetaminophen, acetaminophen, albuterol, albuterol, cyanocobalamin, cyanocobalamin, cholecalciferol, cholecalciferol

Methylmorphine Disease Interaction

Major: impaired GI motility, infectious diarrhea, liver disease, prematurity, acute alcohol intoxication, drug dependence, gastrointestinal obstruction, hypotension, intracranial pressure, respiratory depressionModerate: adrenal insufficiency, biliary spasm, hypothyroidism, renal dysfunction, seizure disorders, urinary retention, arrhythmias

Volume of Distribution

Apparent volume of distribution: about 3-6 L/kg, showing an extensive distribution of the drug into tissues .

Elimination Route

Absorption

Methylmorphine is absorbed from the gastrointestinal tract. The maximum plasma concentration occurs 60 minutes after administration .

Food Effects

When 60 mg codeine sulfate was given 30 minutes post-ingestion of a high high-calorie meal, there was no significant change in the absorption of codeine .

Steady-state concentration

The administration of 15 mg codeine sulfate every 4 hours for 5 days lead to steady-state concentrations of codeine, morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) within 48 hours .

Half Life

Plasma half-lives of codeine and its metabolites have been reported to be approximately 3 hours .

Clearance

Renal clearance of codeine was 183 +/- 59 ml min-1 in a clinical study .

Renal impairment may decrease codeine clearance .

Elimination Route

About 90% of the total dose of codeine is excreted by the kidneys. Approximately 10% of the drug excreted by the kidneys is unchanged codeine .

The majority of the excretion products can be found in the urine within 6 hours of ingestion, and 40-60 % of the codeine is excreted free or conjugated, approximately 5 to 15 percent as free and conjugated morphine, and approximately 10-20% free and conjugated norcodeine .

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