Morphine

General characteristics. Structure:

Active ingredient: 8,56 mg of morphine of a hydrochloride in terms of anhydrous substance.

Excipients: dinatrium эдетат (disodium salt of ethylene diamine tetraacetic acid), глицерол (the glycerin distilled), acid solution of hydrochloric 0,1 M, water for injections.

Pharmacological properties:

Pharmacodynamics. Is an agonist of opioid receptors (a mu - a kappa - delta). Activates endogenous anti-nociceptive system and thus breaks interneural transfer of painful impulses at various levels of the central nervous system, and also changes emotional coloring of pain, influencing the highest departments of a brain.

Morphine raises a threshold of painful sensitivity at incentives of various modality, brakes conditioned reflexes, possesses eyforiziruyushchy and moderate somnolent action, raises a tone of the center of a vagus nerve, the center of vomiting oppresses, can stimulate chemoceptors of a starting zone of the emetic center, the respiratory center oppresses, causes narrowing of a pupil due to activation of the center of a third cranial nerve, raises a tone of bronchial tubes and smooth muscle sphincters of internals (intestines, biliary tract, a bladder), increases sokratitelny activity of a myometrium, weakens an intestines peristaltics, brakes secretory activity of glands of digestive tract. Reduces standard metabolism and body temperature a little, stimulates release of antidiuretic hormone. Causes expansion of peripheral blood vessels and release of a histamine that can lead to a lowering of arterial pressure, erubescence, sweating strengthening, reddening of a fibrous casing of eyes. At hypodermic introduction the effect develops in 10-20 minutes and proceeds within 3-5 hours.
Causes accustoming and medicinal (opioid) dependence (morphinism).

Pharmacokinetics. The volume of distribution makes 4 l/kg. 30-35% of drug contact proteins of a blood plasma. Stakh 50-90 min. Elimination half-life 2-4 hours.

About 10% of parenterally administered drug are removed with urine within 24 hours in not changed look, 80% - in the form of glyukuronidny metabolites, the rest is excreted with bile and removed by intestines. Gets through a blood-brain barrier and a placental barrier and it is found in breast milk.

Indications to use:

Morphine is applied as anesthetic at the expressed pain syndrome of a traumatic origin, in the preoperative, operational and postoperative periods, at a myocardial infarction, heavy attacks of stenocardia, pains at the malignancies and other states which are followed by severe pains.

Route of administration and doses:

Morphine is entered subcutaneously. Doses select individually depending on age and a condition of the patient.

Adults: usual doses for adults under skin - on 1 ml of solution of 10 mg/ml. The anesthetizing action develops in 10-15 minutes, reaches a maximum in 1-2 hours and remains within 8-12 and more hours.

The highest doses for adults under skin: one-time - 0,02 g, daily - 0,05 g.

To children from the moment of the birth up to 2 years. Subcutaneously 100 - 200 mkg/kg of weight (0,1-0,2 mg/kg) if necessary each 4-6 hours so that the total dose did not exceed 15 mg.

Children are more senior than 2 years. Subcutaneously 100-200 mkg/kg of weight (0,1-0,2 mg/kg) if necessary each 4-6 hours so that the total dose did not exceed 1,5 mg/kg of body weight.

Features of use:

Use at pregnancy and a lactation. At pregnancy, childbirth and the period of breastfeeding use of morphine is admissible only according to vital indications (possibly development of medicinal dependence in a fruit and the newborn).

With care apply morphine at patients of advanced age, at the general exhaustion, at diseases of a liver and kidneys, insufficiency of a bast layer of adrenal glands. Under careful observation and in the reduced doses it is necessary to apply morphine against the background of effect of the drugs operating on the central nervous system (anesthetics, somnolent drugs, anxiolytics, antidepressants, neuroleptics, antihistaminic, other non-narcotic anesthetics of drugs) in order to avoid excessive oppression of the central nervous system and suppression of activity of a respiratory center.

Drug should not be combined with narcotic analgetics from group of partial agonists (buprenorphine) and agonists - antagonists (налбуфин, буторфанол, трамадол) opioid receptors because of danger of weakening of an analgesia and a possibility of provoking of a withdrawal at patients with dependence to opioids. The anesthetizing action and undesirable effects of opioid agonists (trimeperidine, fentanyl) in the therapeutic range of doses are summed up with effects of morphine. During treatment it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed psychomotor reactions, not to allow the ethanol use.

Not to use in situations where emergence of paralytic Ilheus is possible. At threat of emergence of paralytic Ilheus use of morphine has to be immediately stopped.

At patients with alleged heart operation or other operation with an intensive pain syndrome, use of morphine should be stopped for 24 h before operation. If afterwards therapy is shown, then the mode of dosing is chosen taking into account weight of operation.

There can sometimes be a tolerance and dependence on drug. When developing nausea and vomiting it is possible to apply a combination with fenotiaziny. For reduction of side effect of drugs of morphine by intestines it is necessary to use purgatives.

It must be kept in mind that children up to 2 years are more sensitive to effects of opioid analgetics and they can have paradoxical reactions.

Side effects:

From the alimentary system: more often - nausea and vomiting (is more often at the beginning of therapy), a lock; less often - dryness in a mouth, anorexia, a spasm of biliary tract, a cholestasia (in the main bilious channel), a gastralgia, spasms in a stomach; seldom - a hepatotoxic (dark urine, a pale chair, hysteria of scleras and integuments), at a serious inflammatory illness of intestines - an intestines atony, paralytic intestinal impassability, toxic megacolon (a lock, a meteorism, nausea, spasms in a stomach, vomiting).

From cardiovascular system: more often - the lowering of arterial pressure, tachycardia, is less frequent - bradycardia, frequency is unknown - increase in arterial pressure.

From respiratory system: more often - oppression of a respiratory center, is less frequent — a bronchospasm, an atelectasis.

From a nervous system: more often - dizziness, a faint, drowsiness, extraordinary fatigue, the general weakness; less often — a headache, a tremor, involuntary muscular twitchings, a diskoordination of muscular movements, paresthesias, nervousness, a depression, confusion of consciousness (hallucinations, depersonalization), increase in intracranial pressure with probability of the subsequent disturbance of cerebral circulation, sleeplessness; seldom - an uneasy dream, oppression of the central nervous system, against the background of high doses - muscle tension (especially respiratory), at children is paradoxical excitement, concern; frequency is unknown - a spasm, dreadful dreams, sedative or exciting action (especially at elderly patients), a delirium, decline in the ability to concentration of attention.

From urinogenital system: less often - decrease in a diuresis, a spasm of ureters (difficulty and an urodynia, frequent desires to an urination), decrease in a libido, decrease in a potentiality; frequency is unknown — a bladder sphincter spasm, disturbance of outflow of urine or aggravation of this state at a hyperplasia of a prostate and a stenosis of an urethra.

Allergic reactions: more often - goose breathing, a hyperemia of the person, face skin rash; less often - skin rash, a small tortoiseshell, a skin itch, a face edema, trachea hypostasis, a laryngospasm, a fever.

Local reactions: a hyperemia, hypostasis, burning in the place of an injection.

Others: more often - the increased sweating, a dysphonia; less often - disturbance of clearness of visual perception (including a diplopia), a miosis, a nystagmus, imaginary feeling of good health, feeling of discomfort; frequency is unknown - a ring in ears, medicinal dependence, tolerance, a syndrome of "cancellation" (muscular pains, diarrhea, tachycardia, a mydriasis, a hyperthermia, rhinitis, sneezing, perspiration, yawning, an aioreksiya, nausea, vomiting, nervousness, fatigue, irritability, a tremor, spasms in a stomach, the general weakness, a hypoxia, muscular contractions, a headache, increase in arterial pressure and other vegetative symptoms).

At repeated use of morphine in techetsy 1-2 weeks (sometimes within 2-3 days accustoming development (weakening of the anesthetizing action) and opioid medicinal dependence is possible.

Interaction with other medicines:

Strengthens effect of somnolent, sedative, mestnoanesteziruyushchy medicines, drugs for the general anesthesia and anxiolytics.

The ethanol, muscle relaxants and medicines oppressing the central system strengthen the depriving of bonuses effect and respiratory depression.

Buprenorphine (including the previous therapy) reduces effect of other opioid analgetics; against the background of use of high doses of agonists of a mu - opioid receptors reduces respiratory depression, and against the background of use of low doses of agonists of a mu - or the kappa - opioid receptors - strengthens; accelerates emergence of symptoms of "withdrawal" at the termination of reception of agonists of a mu - opioid receptors against the background of medicinal dependence, at their sudden cancellation partially reduces expressiveness of these symptoms. At systematic reception of barbiturates, especially phenobarbital, there is a probability of reduction of expressiveness of analgeziruyushchy action of narcotic analgetics, stimulates development of cross tolerance.

At a concomitant use with beta adrenoblockers strengthening of the oppressing action on the central nervous system, with a dopamine - reduction of analgeziruyushchy effect of morphine, with Cimetidinum - strengthening of respiratory depression, with other opioid analgetics - oppression of the central nervous system, breath, a lowering of arterial pressure is possible.

Chlorpromazinum strengthens miotic, sedative and analgeziruyushchy effects of morphine.

Derivatives of a fenotiazin and barbiturates strengthen hypotensive effect and increase risk of emergence of respiratory depression.

Naloxonum reduces effect of opioid analgetics, and also caused by them respiratory depression and the central nervous system; high doses for leveling of effects of a butorfanol, a nalbufin and pentazocine which were appointed for elimination of undesirable effects of other opioids can be required; can accelerate emergence of symptoms of "withdrawal" against the background of drug addiction.

Naltrexone accelerates emergence of symptoms of "withdrawal" against the background of drug addiction (symptoms can appear in 5 min. after administration of drug, proceed during 48 h, are characterized by firmness and difficulty of their elimination); reduces effect of opioid analgetics (analgetic, antidiarrheal, antibechic); does not influence the symptoms caused by histamine reaction. Nalorfinum eliminates the respiratory depression caused by morphine.

Strengthens hypotensive effect of the medicines reducing arterial pressure (including ganglioblokator, diuretics).

Competitively inhibits hepatic metabolism of a zidovudine and reduces its clearance (the risk of their mutual intoxication increases).

Medicines with aptikholinergichesky activity, antidiarrheal medicines (including лоперачид) increase risk of emergence of a lock up to intestinal impassability, an ischuria and oppression of the central nervous system. Reduces effect of Metoclopramidum.

Contraindications:

Hypersensitivity to opiates. The states which are followed by respiratory depression or the expressed oppression of the central nervous system. Convulsive states. The increased intracranial pressure. Head injuries. Acute alcoholic states and alcoholic psychosis. Bronchial asthma. Paralytic intestinal impassability. Heart failure owing to chronic diseases of lungs. Cardiac arrhythmias. Acute surgical diseases of abdominal organs before establishment of the diagnosis. States after surgical interventions on biliary tract. It is not necessary to apply morphine against the background of treatment by monoamine oxidase inhibitors (MAO) and within 14 days after their cancellation.

Use with care. A chronic obstructive pulmonary disease, medicinal dependence (including in the anamnesis), alcoholism, suicide bent, emotional lability, cholelithiasis, surgical interventions on digestive tract, an urinary system, a liver or renal failure, a hypothyroidism, a serious inflammatory illness of intestines, a hyperplasia of a prostate, urethra stricture, an epileptic syndrome. General serious condition of the patient, advanced age, children's age.

Overdose:

At poisoning or overdose develops struporous or coma, a hypothermia, a lowering of arterial pressure, is observed respiratory depression. A characteristic sign is the expressed narrowing of pupils (at a considerable hypoxia pupils can be expanded).

First aid at poisoning - maintenance of adequate lung ventilation Intravenous administration of the specific opioid antagonist of Naloxonum in a dose from 0,4 to 2 mg quickly recovers breath. In the absence of effect in 2-3 minutes introduction of Naloxonum is repeated. An initial dose of Naloxonum for children - 0,01 mg/kg. Use of Nalorfinum is possible: 5-10 mg intramusculary or intravenously each 15 minutes to a total dose of 40 mg. It is necessary to consider a possibility of development of a withdrawal at introduction of Naloxonum and Nalorfinum by the patient with dependence to morphine - in such cases of a dose of antagonists it is necessary to increase gradually.

Storage conditions:

In the place protected from light, at a temperature not above 15 °C. The list II of "The list of the drugs, psychotropic substances and their precursors which are subject to control in the Russian Federation". To store in the place, unavailable to children. A period of validity - 2 years. It is forbidden to use drug after the date specified on упакрвкс.

Issue conditions:

According to the recipe

Packaging:

Solution for hypodermic introduction of 10 mg/ml to the syringe tubes on 1 ml (1 cm3) On 20, 50 or 100 syringe tubes with application instructions in a box from a cardboard.