Methadone

Methadone is a synthetic opioid used in medical practice for the treatment of chronic pain and for substitution therapy for dependence on opioids, including heroin. It has analgesic properties and is capable of relieving severe pain and reducing withdrawal syndrome in patients suffering from drug dependence.

Here are some key aspects of methadone:

1. Mechanism of Action: Methadone is an m-opioid receptor agonist, which means it interacts with opioid receptors in the body, blocking pain sensitivity and creating an analgesic effect. It can also reduce withdrawal syndrome and the desire to use opioids in addicted individuals.
2. Indications:
   1. Treatment of chronic pain: Methadone can be used to treat moderate to severe pain in patients for whom other opioid medications are ineffective or inappropriate.
   2. Substitution therapy: Methadone is used for opioid substitution therapy for opioid dependence to help patients transition from street opioid use to controlled treatment, which can reduce the risk of transmitting infections such as HIV or hepatitis.
3. Form of release: The drug is available as tablets, oral liquid and solution for injection.
4. Dosage: The dosage of methadone may vary depending on the purpose of use and the individual patient. The initial dose is usually determined by the doctor and may be increased gradually until optimal pain control is achieved or withdrawal syndrome is reduced.
5. Side effects: Some of the possible side effects of methadone include drowsiness, constipation, nausea, vomiting, dizziness, loss of appetite, and the risk of developing tolerance and physical dependence with long-term use.
6. Contraindications: The drug is contraindicated in case of allergy to methadone, in severe respiratory disorders, in the use of MAO (monoamine oxidase) inhibitors and in pregnancy (especially in the first trimester).

Methadone should be used strictly as prescribed by a physician and patients should be supervised by a specialist during treatment, especially in the case of substitution therapy, to prevent possible abuse and the development of dependence.

Indications Methadone

1. Chronic Pain Treatment: Methadone can be used for moderate to severe pain relief in patients suffering from various chronic conditions such as cancer, osteoarthritis, back disease and others.
2. Substitutiontherapy: Methadone is widely used as an opioid receptor agonist for substitution therapy for opioid dependence, including heroin. This allows patients to avoid the use of street purchased drugs and associated risks such as transmission of infections including HIV and hepatitis, and reduces drug-related disruption and crime.
3. Medical pain relief: Methadone can also be used to relieve withdrawal symptoms in patients being treated for opioid dependence.

It is important to emphasize that methadone should only be used with a doctor's prescription and under strict supervision.

Release form

Methadone is available in different forms, including tablets and oral solution. Tablets can contain varying amounts of the active ingredient, such as 5 mg, 10 mg and 25 mg. Oral solution contains methadone hydrochloride in concentrations of 1 mg or 5 mg per 1 ml of solution.

Pharmacodynamics

1. Opioid receptor agonist:

   • Methadone is an agonist of μ-opioid receptors in the central nervous system. It binds to these receptors, causing activation of opioid signaling pathways.
   • Activation of μ-opioid receptors results in decreased transmission of pain signals along nerve fibers and decreased pain perception.

2. Inhibition of neuronal reuptake of norepinephrine and serotonin:

   • Methadone can also inhibit the reuptake of neurotransmitters, such as norepinephrine and serotonin, into synaptic clefts.
   • This leads to an increase in the concentration of these neurotransmitters in synaptic clefts and enhances their action, which may contribute to analgesia and mood enhancement.

3. Prolonged action:

   • Methadone is characterized by its long-lasting effects, making it particularly useful for keeping opioid-dependent patients stable without the onset of severe withdrawal symptoms.

4. Less intense side effects:

   • Unlike some other opioid agonists, methadone generally has less intense respiratory and cardiovascular side effects when used and dosed properly.

5. Tolerance and addiction:

   • Like other opioid agonists, methadone can cause physical and psychological tolerance as well as dependence, especially with prolonged and inappropriate use.

The general mechanism of action of methadone is its ability to activate opioid receptors and alter the functioning of neural systems responsible for pain perception and mood.

Pharmacokinetics

1. Absorption: Methadone can be administered orally, intravenously, subcutaneously or rectally. After oral administration, it is usually absorbed from the gastrointestinal tract, but the absorption process may be slow and incomplete.
2. Distribution: Methadone has a high volume of distribution, which means that it is rapidly distributed to body tissues, including the central nervous system and adipose tissue.
3. Metabolism: Methadone is metabolized in the liver to form active and inactive metabolites. The main metabolite is methadone eddicarboxylate (EDDP). Methadone metabolism can occur with or without cytochrome P450 involvement.
4. Excretion: Methadone and its metabolites are excreted primarily in the urine, although small amounts may also be excreted through the intestines and in sweat.
5. Half-life: Thehalf-life of methadone from the body varies from 15 to 60 hours. This can depend on many factors including dosage, frequency of administration, individual patient characteristics, etc.
6. Pharmacokinetics in special cases: In patients with impaired hepatic or renal function and in elderly patients, the pharmacokinetics of methadone may be altered, requiring cautious prescribing and dosage monitoring.

Dosing and administration

Methadone dosage can vary widely depending on the individual patient's needs, severity of pain, or degree of opioid dependence. Here are general recommendations for route of administration and dosage:

1. Initial dose for the treatment of chronic pain:

   • The usual starting dose is 2.5-10 mg of methadone taken every 8-12 hours. This may vary depending on the severity of the pain syndrome and the patient's response to the medicine.
   • After initial administration, the dosage may be gradually increased by 5-10 mg every 3-7 days until the optimal effect of pain relief is achieved.

2. Dosage to maintain opioid-dependent patients:

   • For the treatment of opioid dependence, the methadone dosage can be much higher.
   • The usual starting dose is 20 to 30 mg of methadone taken daily.
   • Dosage may be adjusted based on individual patient needs, withdrawal symptoms, and physician recommendations.
   • In most cases, patients take methadone daily in specialized centers under medical supervision.

3. Adherence to doctor's recommendations:

   • Methadone dosage should be individualized according to the needs and response of each individual patient.
   • It is important to follow your doctor's recommendations and not exceed the recommended dosage to avoid side effects and the development of tolerance or dependence.

4. Use with caution:

   • Methadone can cause drowsiness and respiratory depression, so it should be used with caution, especially when first prescribed and when adjusting the dosage.

5. Maintaining a proper admission regimen:

   • It is important to take methadone on a strict schedule to ensure stable levels of the drug in the body and avoid withdrawal symptoms or relapses of pain.

Use Methadone during pregnancy

Methadone use during pregnancy can cause certain problems and risks for both mother and fetus.

Here are some considerations regarding the use of methadone during pregnancy:

1. Fetal exposure: Methadone can cross the placental barrier and affect fetal development. Methadone use during pregnancy may be associated with a risk of fetal problems such as preterm labor, low birth weight, and withdrawal syndrome in the newborn.
2. Risk of dependence in the child: Methadone use by the mother during pregnancy can lead to dependence in the child. Newborns may be born with opioid withdrawal syndrome, which requires medical intervention and treatment.
3. Need for medical supervision: Women taking methadone during pregnancy should be under close medical supervision. Doctors should carefully assess the risks and benefits of methadone and may decide to prescribe it only if absolutely necessary.
4. Alternative treatments: In some cases, when possible, doctors may recommend alternative treatments to manage pain symptoms or treat opioid dependence in pregnant women to minimize risks to the fetus.

In general, the use of methadone during pregnancy should be closely monitored and conducted under the supervision of a physician.

Contraindications

1. Allergic reaction: A known allergy to methadone or any of its components is a contraindication.
2. Severe respiratory disorders: The drug should be avoided in acute or severe respiratory failure, as methadone may depress the respiratory center and aggravate this condition.
3. Use of MAO inhibitors: Methadone is not recommended in concomitant use of monoamine oxidase inhibitors (MAOIs), as this may lead to serious interactions and increased risk of adverse effects, including hypertensive crisis.
4. Pregnancy: The use of methadone, particularly in the first trimester of pregnancy, may be contraindicated due to the potential risk to the fetus. However, in some cases, the indications for prescribing may outweigh the risks and the decision to use should be made by a physician, taking into account the individual characteristics of the patient.
5. Severe hepatic impairment: In severe hepatic impairment, methadone may accumulate in the body and cause toxic effects; therefore, its use may be contraindicated or require special caution and supervision.
6. Severe re nal impairment: In severe renal impairment, methadone may be eliminated more slowly from the body, which may lead to accumulation and toxic effects.

Side effects Methadone

1. Drowsiness and fatigue: Methadone may cause drowsiness or fatigue in some people, especially when starting or changing dosage.
2. Constipation or digestive disorders: This is a common side effect that may occur in some patients taking methadone.
3. Headache: Some people may experience headaches while taking methadone.
4. Dizziness or loss of balance: These symptoms may also be observed.
5. Changes in appetite: Some people may experience a loss or increase in appetite when taking methadone.
6. Sleep disorders: Insomnia or changes in sleep quality may occur.
7. Dry mouth: Some patients may experience dry mouth when taking methadone.
8. Loss of libido: Some people may experience a decrease in sex drive.
9. Rare but serious side effects: Include allergic reactions, heart problems, breathing problems, etc.

Overdose

1. Respiratory depression: One of the most dangerous consequences of methadone overdose is respiratory depression, which can lead to hypoxia (lack of oxygen) and arterial hypotension (low blood pressure). In severe cases, this can lead to respiratory arrest and cardiac arrest.
2. Decreased consciousness and coma: Methadone overdose can cause severe sedation leading to loss of consciousness and even coma.
3. Pupillary miosis: This is a constriction of the pupils that is one of the characteristic signs of overdose from opioids, including methadone.
4. Muscle weakness and atonia: Patients with methadone overdose may experience severe muscle weakness and atonia (loss of muscle tone), which can lead to difficulty maintaining upright posture and movement.
5. Cardiovascular disorders: This may include tachycardia (accelerated heart rate), arrhythmias (irregular heart rhythm), and arterial hypotension.
6. Seizures and shaking: Some patients may develop seizures or shaking as a result of methadone overdose.

Interactions with other drugs

1. Central depressants: The use of methadone with other central depressants such as alcohol, benzodiazepines, barbiturates or sleeping pills may increase the depressant effect on the central nervous system, which may result in severe respiratory and circulatory depression.
2. Antianemic drugs: The use of methadone with iron-containing preparations such as Ferum preparations may reduce iron absorption in the GI tract due to decreased acidity of gastric juice, which may result in reduced efficacy of the preparations.
3. Antiepileptic drugs: The use of methadone with antiepileptic drugs such as carbamazepine, phenytoin or phenobarbital may accelerate the metabolism of methadone in the liver and reduce its effectiveness.
4. Antidepressants and anxiolytics: The use of methadone with antidepressants such as selective serotonin reuptake inhibitors (SSRIs) or anxiolytics such as benzodiazepines may increase the depressant effect on the central nervous system and lead to an increased risk of respiratory depression.
5. Antifungal drugs: The use of methadone with antifungal drugs such as ketoconazole or fluconazole may alter the metabolism of methadone and increase its concentration in the blood, which may increase its effects and risk of overdose.

Storage conditions

1. Storage temperature: Methadone should normally be stored at a controlled temperature of 15°C to 30°C (59°F to 86°F). This means that it should be stored in a cool and dry place, protected from direct sunlight and humidity.
2. Protection from light: Methadone is sensitive to light, so it should be stored in its original packaging or in a dark container that protects it from direct exposure to light.
3. Child protection: Like any other medication, methadone should be stored out of the reach of children to prevent accidental ingestion.
4. Special requirements: In some cases there may be additional storage requirements depending on the form of methadone (e.g. Tablets, injectable solution, syrup, etc.). It is important to follow the recommendations on the package or in the instructions for use.
5. Observing expiration dates: The expiration date of methadone should be monitored and the drug should not be used after it has expired, as this can lead to deterioration and loss of efficacy.