ORAMORPH - PACKAGE LEAFLET - LEAFLETS

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Oramorph - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Unwanted Effects Shelf Life

Active ingredients: Morphine (Morphine sulfate)

ORAMORPH 2 mg / ml syrup

Oramorph package inserts are available for pack sizes:

ORAMORPH 2 mg / ml syrup
ORAMORPH 10 mg / 5 ml oral solution, ORAMORPH 30 mg / 5 ml oral solution, ORAMORPH 100 mg / 5 ml oral solution

Why is Oramorph used? What is it for?

PHARMACOTHERAPEUTIC CATEGORY

ORAMORPH is a syrup based on morphine, a pain reliever belonging to the class of opioids

THERAPEUTIC INDICATIONS

Intense chronic pain and / or pain resistant to other painkillers, in particular pain of cancerous origin

Contraindications When Oramorph should not be used

Hypersensitivity to the active substance or to other closely related substances from a chemical point of view and / or to any of the excipients. Hypersensitivity to morphine is characterized by facial flushing, itching and bronchospasm (administration could cause the appearance of anaphylactic reactions)
In all forms of acute abdomen and paralytic ileus
In children under 1 year
In respiratory depression
In "respiratory insufficiency and" severe hepatocellular insufficiency
In bronchial asthma attacks
In case of heart failure secondary to chronic lung diseases
In head injuries and in case of intracranial hypertension
After biliary tract surgery
In convulsive states
In uncontrolled epilepsy
In acute alcoholism and delirium tremens
In states of central nervous system depression, especially those induced by other drugs such as hypnotics, sedatives, tranquilizers, etc.
In combination with MAOIs, including furazolidone, or less than 2-3 weeks after stopping the previous treatment
In case of treatment with Naltrexone

Oramorph is also generally contraindicated during pregnancy and breastfeeding.

Precautions for use What you need to know before taking Oramorph

Morphine should be administered with caution in elderly and very elderly or debilitated subjects and in patients with:

organic cerebral affections
respiratory insufficiency and chronic lung diseases (particularly if accompanied by bronchial hypersecretion) and in any case in all obstructive conditions of the respiratory tract and in case of reduced ventilatory reserve (such as, for example, in the case of kyphoscoliosis and obesity)
renal and biliary colic
prostatic hypertrophy
myxedema and hyperthyroidism
acute hepatitis and acute liver disease
chronic kidney and liver diseases
adrenocortical insufficiency
shock and severe hypotensive states
slowing of gastrointestinal transit and intestinal diseases of an inflammatory or obstructive type
addiction to opioids
cardiovascular diseases and cardiac arrhythmias

and also:

following urinary duct surgery

Interactions Which drugs or foods may change the effect of Oramorph

Tell your doctor if you are taking or have recently taken any other medicines, even those without a prescription.

The concomitant administration of morphine and other agents that depress the central nervous system, such as other morphine (pain relievers, antitussives and replacement drugs), tricyclic antidepressants, neuroleptics (including phenothiazines), barbiturates, benzodiazepines and other anxiolytics other than benzodiazepines (e.g. meprobamate), hypnotics, sedative antidepressants (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine), sedative H1 antihistamines, central antihypertensives, baclofen, thalidomide and alcohol can potentiate the undesirable effects of morphine, and, in particular, that of inhibition of function respiratory. Drugs that inhibit the cytochrome-P450 system, such as cimetidine, slow down the degradation of morphine, resulting in an increase in plasma concentration.

Morphine can enhance the effects of neuromuscular blocking agents and muscle relaxants in general, dicumarol and other oral anticoagulants. The action of diuretics can be reduced.

Contraindicated associations

Monoamine oxidase inhibitor drugs

Due to inhibition of the central nervous system, co-administration may cause hypotension and respiratory depression (see section "Contraindications").

Naltrexone.

In case of co-administration, the patient may be insensitive to the analgesic effect of morphine.

Associations not recommended

Alcohol

Alcohol increases the sedative effect of morphine. Impaired alertness can make driving and using machines dangerous. The intake of alcoholic beverages and drugs containing alcohol is not recommended.

Associations requiring special precautions for use

Rifampicin

Co-administration causes a decrease in the concentration and activity of morphine and its active metabolite. During and at the end of rifampicin therapy, the patient should be kept under observation, and possibly a modification of the morphine dosage should be made.

Cimetidine and other inhibitors of the cytochrome-P450 system

These drugs slow down the degradation of morphine, resulting in an increase in plasma concentration.

Associations to be taken into consideration

Other agonist morphine analgesics (alfentanil, codeine, dextromoramide, dextropropoxyphene, dihydrocodeine, fentanyl, oxycodone, pethidine, phenoperidine, remifentanil, sufentanil, tramadol)
Morphine-like antitussives (dextromethorphan, noscapine, pholcodine)
Morphine antitussives (codeine, ethylmorphine)
Barbiturates
Benzodiazepines and other anxiolytics

In case of co-administration, there is an increased risk of respiratory depression, even fatal in case of overdose.

Other sedative drugs (neuroleptics, sedative antidepressants, muscle relaxants, sedative H1 antihistamines)

Co-administration may cause an increase in central depression, with an increased risk of impaired alertness, which can make driving and use of machinery dangerous.

Oral anticoagulants (including dicumarol)

Morphine can enhance its effects.

Diuretics

The diuretic action may be reduced.

Warnings It is important to know that:

The administration of morphine, especially if prolonged, determines the onset of tolerance and dependence. Due to its analgesic effect and its action on the level of consciousness, pupil diameter and respiratory dynamics, Oramorph can make the clinical evaluation of the patient difficult and hinder the diagnosis of acute abdominal pictures.

There tolerance it is the condition for which to reach the same level of analgesia the patient needs higher doses of morphine and at more frequent intervals of administration. Tolerance to most of the effects of morphine normally develops over 2-3 weeks of therapy at medium doses, faster if higher doses are used. After the suspension of the treatment the phenomenon subsides and disappears within 2 weeks.

There dependence from morphine can be both physical and psychological and is a condition that arises with repeated administration of the drug. It is characterized by an invincible need to continue taking the drug or other substance with similar properties and can develop after 1 or 2 weeks of treatment at therapeutic doses. Abrupt discontinuation of morphine by a patient who has developed physical dependence results in a withdrawal syndrome, the severity of which depends on the subject, the dose taken, the frequency of administration and the duration of treatment. Withdrawal symptoms occur. they usually manifest within a few hours, reaching maximum intensity within 36-72 hours, then gradually diminish. Symptoms include: yawning, mydriasis, watery eyes, runny nose, sneezing, horrifying, muscle tremor, headache, weakness, sweating, anxiety, irritability, sleep disturbances or insomnia, restlessness, agitation, anorexia, nausea, vomiting, weight loss, diarrhea , dehydration, bone pain, abdominal and muscle cramps, tachycardia, tachypnea, hypertension, increased body temperature and vasomotor disturbances.

Without treatment, the most obvious withdrawal symptoms disappear in 5-14 days. For this reason Oramorph should not be used in painful states sensitive to less potent analgesics or in patients who are not under close medical supervision.

Pregnancy and breastfeeding

The safety of the use of Oramorph during pregnancy is not established. The use of the product, like all narcotic analgesics, is not recommended during pregnancy, as it can cause respiratory depression and withdrawal syndrome in the newborn. In any case, administration should be avoided in premature births or during the second phase of labor, when the dilation of the uterine neck reaches 4-5 centimeters.

Morphine salts are excreted in breast milk. Therefore, in women who are breastfeeding it is necessary to carefully evaluate the risk / benefit ratio and decide on the advisability of administering the drug without breastfeeding the infant or, vice versa, continue breastfeeding avoiding the administration of the drug.

Driving and using machines

Even when administered as prescribed, Oramorph can affect the degree of the reaction in such a way that the ability to drive and use machines is impaired.

These effects may be more pronounced if the product is taken in combination with alcohol or other sedative drugs.

For those who carry out sporting activities: the use of the drug without therapeutic necessity constitutes doping and can in any case determine positive anti-doping tests.

Important information about some of the ingredients of ORAMORPH

The medicine contains sucrose and syrup of glucose: if you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

The medicine contains 10% of ethanol (alcohol), and eg. up to 400 mg for a 5 ml dose, equivalent to 10 ml of beer or 4 ml of wine per dose.

It can be harmful to alcoholics, children and high-risk groups such as people with liver disease or epilepsy.

The medicine also contains parahydroxybenzoates. It can cause allergic reactions, even delayed ones.

Dosage and method of use How to use Oramorph: Dosage

Adults:

The starting dose is 10-20 mg (5-10 ml) every 4 hours.

Children:

Children between 6 and 12 years: the maximum dose is 5-10 mg (2.5-5 ml) every 4 hours

Children between 1 and 5 years: the maximum dose is 5 mg (2.5 ml) every 4 hours

Use in children under the age of 1 year is not recommended.

The dose may be increased on medical advice based on pain intensity and previous analgesic treatments.

A dose reduction may be appropriate in elderly and debilitated patients.

The duration of the treatment is necessarily variable in relation to the intensity of the painful symptoms and the type of pathology.

When patients switch from a different morphine preparation to Oramorph, a re-definition of the dosage is appropriate.

Orally administered morphine sulfate is rapidly absorbed from the gastrointestinal tract, however, when Oramorph is substituted for injectable morphine, a 50% to 100% increase in dosage is usually required to achieve the same analgesic level.

Overdose What to do if you have taken too much Oramorph

In case of accidental ingestion / intake of an excessive dose of Oramorph, notify your doctor immediately or go to the nearest hospital.

Symptoms

The signs of overdose and morphine toxicity are: miosis, respiratory depression and hypotension. In severe cases, circulatory failure and deep coma can occur.

Therapy

Treatment of morphine overdose consists of general supportive measures, together with the administration of 400 µg of naloxone intravenously. This treatment can be repeated at 2-3 minute intervals, if necessary, or replaced by an infusion of 2 mg in 500 ml of normal saline or 5% dextrose (5 µg / ml). The stomach should be emptied and a 0.02% aqueous solution of potassium permanganate must be used for this purpose.

Artificial respiration may be necessary. Fluid and electrolyte levels must be kept within normal values.

WHAT TO DO IF YOU HAVE FORGOTTEN ONE OR MORE DOSES

Do not take a double dose to make up for a forgotten prescribed dose.

EFFECTS DUE TO THE SUSPENSION OF THE TREATMENT

Do not stop treatment without first consulting your doctor. In case of prolonged treatment, an abrupt interruption may lead to a withdrawal syndrome, characterized by the following symptoms: anxiety, irritability, chills, dilated pupils, hot flashes, sweating, tearing, runny nose, nausea, vomiting, abdominal pain, diarrhea , articolar pains.

Treatment of a withdrawal syndrome should be carried out under the direct supervision of the physician.

Side Effects What are the side effects of Oramorph

Like all medicines, Oramorph can cause side effects, although not everybody gets them.

The most frequent side effects at the start of treatment are: drowsiness, confusion, nausea and vomiting. They are usually transient, so their persistence should lead to suspicion of an associated cause or an overdose. Constipation, on the other hand, does not decrease with the progress of treatment.

All of these side effects are predictable and need adequate treatment. The product also at therapeutic doses causes respiratory depression and to a lesser extent circulatory depression. Respiratory depression is generally mild or moderate and without significant consequences in subjects with integrity of the respiratory function: however, it can induce serious consequences in patients with broncho-pulmonary diseases such as the formation of areas of atelectasis. However, severe respiratory and circulatory depression up to respiratory arrest and collapse has been reported following oral or parenteral administration of narcotic-analgesics. In case of abrupt discontinuation of therapy, a withdrawal syndrome may occur.

The reported side effects are as follows:

Alterations of the heart and vascular system Bradycardia, lipothymia, syncope, circulatory depression (albeit to a lesser extent to the respiratory one) and hypotension, more marked in the case of hypovolemia. Alterations of the nervous system Respiratory depression, circulatory depression, respiratory arrest, collapse, miosis, visual disturbances, headache, dizziness, increased intracranial pressure which can aggravate pre-existing brain pathologies, excitement, insomnia, irritability, agitation, euphoria and dysphoria, sedation, asthenia and myoclonus (especially in the elderly and in subjects with renal insufficiency, in case of overdose or too rapid increase of the dose) Gastrointestinal alterations Nausea, vomiting, constipation Renal and urinary disorders Oliguria and urinary retention, more severe in case of concomitant urethroprostatic stenosing disease Alterations to the skin and subcutaneous tissue Redness of the face, neck and upper chest regions, itching, hives and other rashes, sweating Alterations of the endocrine system Increase in vasopressin elevation and decrease in ACTH, thyrotropic hormone, 17-hydroxy and 17-ketocorticosteroid Hepatobiliary changes Spasms of the biliary tract, with transient increases in plasma amylase and lipase Psychiatric disorders depression of mood, mental blunting and states of indifference, and, especially in the elderly, nightmares and hallucinations.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

Expiry and Retention

Store in the original package to protect the medicine from light.

Do not store above 30 ° C.

Keep ORAMORPH out of the reach and sight of children.

Do not use ORAMORPH after the expiry date which is stated on the carton after the abbreviation: EXP. The expiry date refers to the last day of the month.

Note the day you opened the bottle and use ORAMORPH within 3 months of the opening date.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.

COMPOSITION

ORAMORPH 2 mg / ml syrup The active ingredient is morphine sulphate.

1 ml of syrup contains 2 mg of morphine sulfate. The other ingredients are: sucrose, glucose syrup, methylparaben, propylparaben, ethyl alcohol and purified water.

It is available in 100ml, 250ml or 500ml packs. Each package comes with a measuring cup.

The medicine is also available as ORAMORPH 20 mg / ml oral solution in multi-dose packs and single-dose containers containing 10 mg / 5 ml, 30 mg / 5 ml and 100 mg / 5 ml respectively.

PHARMACEUTICAL FORM AND CONTENT

ORAMORPH is a practically colorless syrup

Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.

More information about Oramorph can be found in the "Summary of Features" tab. 01.0 NAME OF THE MEDICINAL PRODUCT 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION 03.0 PHARMACEUTICAL FORM 04.0 CLINICAL PARTICULARS 04.1 Therapeutic indications 04.2 Posology and method of administration 04.3 Contraindications 04.4 Special warnings and appropriate precautions for use 04.5 Interactions with other medicinal products and other forms of interaction04.6 Pregnancy and lactation04.7 Effects on ability to drive and use machines04.8 Undesirable effects04.9 Overdose05.0 PHARMACOLOGICAL PROPERTIES05.1 Pharmacodynamic properties05.2 Pharmacokinetic properties05.3 Preclinical safety data06.0 INFORMATION PHARMACEUTICALS 06.1 Excipients 06.2 Incompatibilities 06.3 Shelf life 06.4 Special precautions for storage 06.5 Nature of the immediate packaging and contents of the package 06.6 Instructions for use and handling 07.0 MARKETING AUTHORIZATION HOLDER08 .0 MARKETING AUTHORIZATION NUMBER 09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIOPharmaceuticals, FULL DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON ESTEMPORANEA PREPARATION AND CONTROL

01.0 NAME OF THE MEDICINAL PRODUCT

ORAMORPH

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

1 ml of syrup contains: morphine sulphate 2 mg

(2.5-5.0-10.0 ml of syrup contain 5-10-20 mg of morphine sulfate respectively).

1 ml of oral solution contains: morphine sulphate 20 mg

(0.25-0.5-1.0 ml of oral solution contain respectively 5-10-20 mg of morphine sulfate; 4-8-16 drops respectively contain 5-10-20 mg of morphine sulfate).

For the full list of excipients, see 6.1.

03.0 PHARMACEUTICAL FORM

Oral solution.

Syrup.

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

Intense chronic pain and / or pain resistant to other painkillers, in particular pain of cancerous origin.

04.2 Posology and method of administration

Oral solution

Adults:

The starting dose is 10-20 mg every 4 hours, corresponding to 0.5-1 ml or 8-16 drops.

Children:

Children between 6 and 12 years old: the maximum dose is 5-10 mg every 4 hours (equal to 0.25-0.5 ml or 4-8 drops)

Children between 1 and 5 years old: the maximum dose is 5 mg every 4 hours (equal to 0.25 ml or 4 drops)

Use in children under the age of 1 year is not recommended.

Syrup

Adults:

The recommended dose is 10-20 mg (5-10 ml) every 4 hours.

Children:

Children between 6 and 12 years old: The maximum dose is 5-10 mg (2.5-5 ml) every 4 hours

Children between 1 and 5 years old: The maximum dose is 5 mg (2.5 ml) every 4 hours

Use in children under the age of 1 year is not recommended.

The dose may be increased on medical advice based on pain intensity and previous analgesic treatments.

A dose reduction may be appropriate in elderly and debilitated patients.

The duration of the treatment is necessarily variable in relation to the intensity of the painful symptoms and the type of pathology.

When patients switch from a different morphine preparation to Oramorph, a re-definition of the dosage is appropriate.

04.3 Contraindications

Hypersensitivity to the active substance or to other closely related substances from a chemical point of view and / or to any of the excipients. Hypersensitivity to morphine is characterized by facial flushing, itching and bronchospasm (administration could cause the appearance of anaphylactic reactions)

In all forms of acute abdomen and paralytic ileus

In children under 1 year (see section 4.2 Posology and method of administration).

In respiratory depression.

In "respiratory insufficiency and" severe hepatocellular insufficiency.

In bronchial asthma attacks.

In case of heart failure secondary to chronic lung diseases.

In head injuries and in case of intracranial hypertension.

After biliary tract surgery.

In convulsive states.

In uncontrolled epilepsy.

In acute alcoholism and delirium tremens.

In states of central nervous system depression, especially those induced by other drugs such as hypnotics, sedatives, tranquilizers, etc. (see section 4.5 Interaction with other medicinal products and other forms of interaction).

In combination with MAOIs, including furazolidone, or less than 2-3 weeks after discontinuation of previous treatment (see section 4.5 Interactions with other medicinal products and other forms of interaction).

In case of treatment with Naltrexone.

Oramorph is also generally contraindicated in pregnancy and lactation (see section 4.6 Pregnancy and lactation).

04.4 Special warnings and appropriate precautions for use

Special warnings

Due to its analgesic effect and its action on the level of consciousness, pupil diameter and respiratory dynamics, Oramorph can make the clinical evaluation of the patient difficult and hinder the diagnosis of acute abdominal pictures.

The administration of morphine, especially if prolonged, can determine the onset of tolerance and dependence.

Abrupt discontinuation of morphine by a patient who has developed physical dependence results in a withdrawal syndrome, the severity of which depends on the subject, the dose taken, the frequency of administration and the duration of treatment. Withdrawal symptoms occur. they usually manifest within a few hours, reaching maximum intensity within 36-72 hours, then gradually diminish. Symptoms include: yawning, mydriasis, watery eyes, runny nose, sneezing, horrifying, muscle tremor, headache, weakness, sweating, anxiety, irritability, sleep disturbances or insomnia, restlessness, agitation, anorexia, nausea, vomiting, weight loss, diarrhea , dehydration, bone pain, abdominal and muscle cramps, tachycardia, tachypnea, hypertension, increased body temperature and vasomotor disturbances.

Precautions for use

Morphine should be administered with caution in elderly and very elderly or debilitated subjects (see section 4.2 Posology and method of administration) and in patients with:

organic-cerebral affections;

respiratory insufficiency and chronic lung diseases (particularly if accompanied by bronchial hypersecretion) and in any case in all obstructive conditions of the respiratory tract and in case of reduced ventilatory reserve (such as, for example, in the case of kyphoscoliosis and obesity);

renal and biliary colic;

prostatic hypertrophy;

myxedema and hyperthyroidism;

acute hepatitis and acute liver disease;

kidney disease (see section 4.2 Posology and method of administration) and chronic liver diseases;

adrenocortical insufficiency;

shock and severe hypotensive states;

slowing of gastrointestinal transit and inflammatory or obstructive intestinal diseases;

addiction to opioids;

cardiovascular diseases and cardiac arrhythmias;

and also:

following urinary duct surgery

Oramorph 2 mg / ml syrup contains glucose and sucrose: patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase isomaltase insufficiency should not take the medicine.

04.5 Interactions with other medicinal products and other forms of interaction

Morphine can enhance the effects of neuromuscular blocking agents and muscle relaxants in general, dicumarol and other oral anticoagulants. The action of diuretics can be reduced.

Contraindicated associations

- Monoamine oxidase inhibitor drugs

Due to inhibition of the central nervous system, co-administration may cause hypotension and respiratory depression (see section 4.3 Contraindications).

- Naltrexone

In case of co-administration the patient may be insensitive to the analgesic effect of morphine.

Associations not recommended

- Alcohol

Alcohol increases the sedative effect of morphine. Impaired alertness can make driving and using machines dangerous. The intake of alcoholic beverages and drugs containing alcohol is not recommended.

Associations requiring special precautions for use

- Rifampicin

- Cimetidine and other inhibitors of the cytochrome-P450 system

These drugs slow down the degradation of morphine, resulting in an increase in plasma concentration.

Associations to be taken into consideration

- Other agonist morphinic analgesics (alfentanil, codeine, dextromoramide, dextropropoxyphene, dihydrocodeine, fentanyl, oxycodone, pethidine, phenoperidine, remifentanil, sufentanil, tramadol)

- Morphine-like antitussives (dextromethorphan, noscapine, pholcodine)

- Morphinic antitussives (codeine, ethylmorphine)

- Barbiturates

- Benzodiazepines and other anxiolytics

In case of co-administration, there is an increased risk of respiratory depression, even fatal in case of overdose.

- Other sedative drugs (neuroleptics, sedative antidepressants, muscle relaxants, sedative H1 antihistamines)

Co-administration may cause an increase in central depression, with an increased risk of impaired alertness, which can make driving and use of machinery dangerous.

- Oral anticoagulants (including dicumarol)

Morphine can enhance its effects.

- Diuretics

The diuretic action may be reduced.

04.6 Pregnancy and lactation

04.7 Effects on ability to drive and use machines

Even when administered as prescribed, Oramorph can affect the degree of the reaction in such a way that the ability to drive and use machines is impaired.

These effects may be more pronounced if the product is taken in combination with alcohol or other sedative drugs (see section 4.5 Interactions with other medicinal products and other forms of interaction).

04.8 Undesirable effects

The product also at therapeutic doses causes respiratory depression and to a lesser extent circulatory depression. Respiratory depression is generally mild or moderate and without significant consequences in subjects with integrity of the respiratory function: however, it can induce serious consequences in patients with broncho-pulmonary diseases such as the formation of areas of atelectasis.

However, following oral or parenteral administration of analgesic-narcotics, the onset of severe respiratory and circulatory depression up to respiratory arrest and collapse has been reported.

In the event of sudden discontinuation of therapy, a withdrawal syndrome may occur (see section 4.4 Special warnings and precautions for use).

The reported side effects are as follows:

04.9 Overdose

Symptoms

The signs of overdose and morphine toxicity are: miosis, respiratory depression and hypotension. In severe cases, circulatory failure and deep coma can occur.

Therapy

Treatment of morphine overdose consists of general supportive measures, together with the administration of 400 micrograms of naloxone intravenously. This treatment can be repeated at 2-3 minute intervals, if necessary, or replaced by an infusion of 2 mg in 500 ml of normal saline or 5% dextrose (5 mcg / ml). The stomach should be emptied and a 0.02% aqueous solution of potassium permanganate must be used for this purpose.

Artificial respiration may be necessary. Fluid and electrolyte levels must be kept within normal values.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmacotherapeutic group: Opioid analgesics

ATC code: N02AA01

Morphine is a pure agonist opioid, a natural derivative of Papaver somniferum latex, selective for mu receptors. The effects derive from the ability to mimic the action of endogenous ligands such as enkephalins, dinorphins and beta-endorphins.

Morphine binds to specific receptors located at various levels of the central nervous system and in various peripheral organs. The interaction of morphine with the receptors of the central nervous system relieves the sensation of pain and improves the psychological reaction of the subject to pain.

Action on the central nervous system. Morphine has an analgesic action; acts on psychomotor behavior: depending on the dose, causes sedation (> 10 mg) or sometimes excitement (

In high doses, higher than analgesic doses, it causes drowsiness and sleep.

It exercises a "psychodysleptic action, characterized by" the onset of a euphoric or rather dysphoric state. It is a substance that induces drug addiction and causes phenomena of physical and mental tolerance and dependence.

On the respiratory centers, morphine exerts, starting from the therapeutic dose, a depressive action. It depresses the cough centers and acts on the vomiting center (in moderate doses and in subjects who have never taken morphine, it has an emetic effect; stronger doses and with repeated administrations, exerts an "antiemetic action).

Finally, morphine causes a miosis of central origin which is a symptom of chronic intoxication.

Action on smooth muscles.Morphine decreases the tone and peristalticism of the longitudinal fibers and increases the tone of the circular fibers, which causes a spasm of the sphincters (pylorus, ileocecal valve, anal sphincter, sphincter of Oddi, bladder sphincter). This action translates clinically into phenomena of constipation, in an increase in pressure in the biliary channels, in the appearance of spasms in the urinary tract.

05.2 Pharmacokinetic properties

After oral administration, morphine sulfate is readily absorbed from the gastrointestinal tract. It is distributed throughout the body and mainly in the kidneys, liver, lungs and spleen, reaching lower concentrations in the muscles and brain instead. Morphine crosses the placenta by diffusion and traces of the drug are detectable in breast milk.

Since the active ingredient undergoes significant hepatic metabolism (first pass effect), the systemic bioavailability is about 25% (range 15-49%). Metabolization of morphine mainly consists of conjugation to glucuronic derivatives in positions 3 and 6. The substance is metabolised to a lesser extent by N-demethylation and O-methylation. About 10% of the morphine dose is excreted via the faeces. The remainder is excreted in the urine, mainly in the conjugated form. About 90% of a single dose of morphine is excreted in 24 hours.

05.3 Preclinical safety data

LD50 in mice per os: 650 mg / kg; in the rat per os: 460 mg / kg; in the guinea pig per os: 1000 mg / kg.

In humans the toxicity of morphine has been studied in cases of overdose, but due to the great variability in individual sensitivity to opiates it is difficult to determine the exact toxic or lethal dose. The presence of tolerance decreases the toxic effects of morphine.