Dithylinum

General characteristics. Structure:

Active ingredient: 20 mg of Dithylinum in 1 ml of solution.

Pharmacological properties:

Pharmacodynamics. Has myorelaxation effect. Is the depolarizing muscle relaxant of short action. Breaks carrying out neuromuscular excitement and causes relaxation of skeletal muscles. Competes with acetylcholine for N-holinoretseptory, causes permanent depolarization of a trailer plate owing to high affinity to cholinergic receptors and acetylcholinesterase resistance. In the beginning development of depolarization is shown by fastsikulyation (the generalized disorganized reduction of myofibrils) owing to short-term simplification of neuromuscular transmission, then the depolarized membranes cease to react to additional impulses and the mioparalitichesky effect occurs (there is spastic paralysis). Drug quickly collapses blood pseudo-cholinesterase that limits intensity and duration of neuromuscular blockade.

After intravenous administration muscle relaxation develops in the following sequence: circular muscle of an eye, masseters, muscles of extremities, muscles of an abdominal wall, throat, intercostal muscles, diaphragm. Causes increase in a brain blood-groove and intracranial pressure in the conditions of weak general anesthesia. After intramuscular introduction action develops in 2-4 min., later in introductions — through 54-60 with; the maximum effect develops in 2-3 min. and remains in full 3 min. Duration of action is 5-10 min.

Expressiveness of effect depends on a dose: 0,1 mg/kg — relaxation of skeletal muscles without considerable influence on respiratory system, 0,2-1 mg/kg — full relaxation of muscles of an abdominal wall and respiratory muscles (considerable restriction or a full stop of spontaneous breath). Has bystry and short-term effect. Does not kumulirut. Long muscle relaxation requires repeated introduction. Bystry approach of effect and the subsequent bystry recovery of neuromuscular conductivity allow to create the controlled and managed muscle relaxation.

At the repeated or prolonged use there is a transition to "the double block" (the antidepolyarizatsionny block) to development of long respiratory depression and an apnoea.

Pharmacokinetics. After intravenous administration it is distributed in plasma and extracellular liquid. In blood and fabrics is exposed to two-stage hydrolysis by pseudo-cholinesterase: in the beginning it is formed сукцинилмонохолин which slowly degrades to succinic acid and sincaline. It is allocated with kidneys in the form of active and inactive metabolites; about 10% of the entered dose of Dithylinum are allocated in not changed look. Linkng with proteins makes 30%. In 30 min. after administration of drug in a dose of 1 mg/kg Dithylinum metabolites in urine are not defined. Plasma elimination half-life of blood (Т½) is equal to 1,5-4 min. At a heavy liver failure or genetic insufficiency of T½ pseudo-cholinesterase it is extended till several o'clock. Т½ does not depend on a renal failure. Drug does not get through intact GEB, badly passes through a placenta.

Indications to use:

Dithylinum is used only in the conditions of the general anesthesia for relaxation of skeletal muscles for the purpose of a trachea intubation, for example, at intestinal impassability, "acute abdomen", the emergency Cesarean section, at urgent operations at patients with "not released stomach", and also for easing of expressiveness of spasms at a countershock.

Route of administration and doses:

Dithylinum can be applied only in the conditions of a specialized hospital in the presence of the corresponding equipment to carrying out an endotracheal intubation and an artificial respiration, an oxygenotherapy. The mode of dosing is set individually, taking into account the required degree of a relaxation, body weight and reaction of the patient. It is recommended to check by the beginning of operation sensitivity of the patient by intravenous administration of Dithylinum in a dose of 0,075 mg/kg.

Adults and teenagers since 12 years: intravenously slowly, struyno or kapelno (for long drop infusion use 0,1% solution). Depending on a clinical situation at intravenous administration the single dose varies from 0,1 to 1,0-1,5 mg/kg. A single dose for an intubation from 1 to 1,5 mg/kg of body weight. For long relaxation of muscles during all operation it is possible to enter fractionally, in 5-7 min., 0,5-1 mg/kg. Repeated doses work more for a long time.

Dosage at children from 1 to 12 years: At babies and children aged up to 12 years: 1 mg/kg of body weight.

At newborns and babies: 1-2 mg/kg of body weight. Newborns need a high dose of succinylcholine in body weight mg/kg (more than the volume of distribution). Equivalent therapeutic doses of succinylcholine have similar time of action in all age groups. In all cases administration of drug in high doses is allowed only after transfer of the patient into artificial ventilation of the lungs.

Patients with obesity. Dosing at patients with obesity has to be calculated, proceeding from ideal, but not the actual body weight.

Special groups of the population. A dosage at a liver failure. The dose of drug has to be lowered at patients with a serious illness of a liver or cirrhosis as at them activity of cholinesterase of plasma is reduced.

Dosage at a renal failure. Patients with a renal failure or a hemodialysis do not need drug dose adjustment if potassium level in blood serum is normal. If the content of potassium in blood serum is higher than 5,5 mmol/l after administration of drug, the risk of fatal cardiovascular complications increases. 

Dosage at heart diseases. There is no need for the special modes of dosing, but it is necessary to consider information which is contained in the sections "Contraindications" and "Precautionary measures".

Dosage at elderly patients. Dose adjustment of drug is not required from elderly patients.

Features of use:

Use during pregnancy and in the period of a lactation. Dithylinum should be applied during pregnancy if the expected advantage for mother exceeds risk for a fruit. Drug does not get through a placenta. Because of decrease in level of cholinesterase of plasma during pregnancy the effect of Dithylinum can increase. Level of cholinesterase of plasma reaches normal values in 6-8 weeks after the delivery. It is not known whether drug in breast milk is emitted. In need of use of Dithylinum in the period of a lactation breastfeeding needs to be stopped.

Precautionary measures. With care apply at diseases of cardiovascular system, diseases of a respiratory organs, neuromuscular diseases, the increased intraocular pressure, at the states which are followed by reduction of activity of cholinesterase, a hypothermia, hypomagnesiemia, hypocalcemia, hypopotassemia, pregnancy.

Parasympathomimetic effects, such as bradycardia and asystolia, arterial hypotension, the increased salivation can be prevented or weakened by administration of atropine. Side effects from heart meet at children more often (at first bradycardia, then tachycardia, are possible, the replacing nodal rhythm, ventricular premature ventricular contraction). Death cases at children and teenagers are registered. Regarding these cases patients had not recognizable neuromuscular diseases. Frequency of a rhythm increases, irrespective of age when the second dose is entered in 15 minutes after the first dose. In this regard and Dithylinum should not the subsequent reasons is entered by continuous infusion.

Succinylcholine is inactivated during hydrolysis under the influence of cholinesterase or pseudo-cholinesterase of plasma. Thus, duration of effect of succinylcholine, first of all, depends on concentration and activity of this enzyme. Insufficiency of cholinesterase or pseudo-cholinesterase can prolong effect of Dithylinum considerably. Insufficiency can be inborn, and also develop against the background of heavy dysfunction of a liver, the renal failure demanding dialysis, a hypothyroidism, a serious illness of various etiology (malignant tumors, heavy disturbance of food), burns or reception of medicines (see the section "Interaction with Other Medicines"). Physiological decrease in cholinesterase exists at newborn, elderly people and at the end of pregnancy. Essential increase in duration of effect of succinylcholine has clinical value, first of all, for patients with genetic insufficiency of cholinesterase. Under certain circumstances such patients have to continue to be on IVL for several hours.

Administration of drug can lead to considerable transition of potassium from intracellular spaces in extracellular. Increase in blood serum of level of potassium can lead to a life-threatening hyperpotassemia with fibrillation of ventricles and an asystolia. Patients with a renal failure, patients with heavy burns and multiple injuries are exposed to extra risk.

After administration of drug there can be temporary muscular fastsikulyation leading to muscle pain, the prekurarezation (introduction of low doses of not depolarizing muscle relaxants) can reduce initial muscular fastsikulyation and muscle pains. Overcooling can cause delay of physical and biochemical processes in membranes and by that to potentiate and extend effect of succinylcholine. Gipermagniyemiya and a hypocalcemia by inhibition of presynaptic release of acetylcholine, and a hypopotassemia, reducing membrane rest potential, can be the cause of strengthening or duration of effect of succinylcholine.

Neostigmina methyl sulfate (Prozerin) or other antikholinesterazny means are not antagonists of succinylcholine of iodide, on the contrary, suppressing activity of cholinesterase, they extend and strengthen action. Preliminary (in 1 min.) introduction of 3-4 mg of d-tubocurarine or 10-15 mg of Diplacinum of dichloride almost completely prevents fastsikulyation and the subsequent muscular pains.

Usually apply not depolarizing muscle relaxants which enter after a preliminary intubation of a trachea against the background of iodide succinylcholine to long operations.

Apply only in the conditions of specialized department, in the presence of the equipment to IVL and personnel owning this equipment.

In high doses or at repeated introduction can call "the double block": if after the last introduction muscle relaxation remains more than 25-30 min. and breath completely is not recovered, in/in methyl sulfate (Prozerin) or Galantaminum — after preliminary administration of atropine (0,5-0,7 ml of 0,1% of solution) enter a neostigmin.

Influence on ability to control of motor transport and other potentially dangerous mechanisms. During treatment by drug patients should not manage vehicles or mechanisms after introduction of Dithylinum, at least 24 hours.

Side effects:

From digestive tract: increase in intragastric pressure with increase in risk of regurgitation pregnant women, at patients with hernias of an esophageal opening have diaphragms, an atony of a stomach and intestines, ascites and tumors of an abdominal cavity, the increased salivation.

From cardiovascular system: decrease or increase in the ABP, unstable arterial pressure, arrhythmia, tachycardia, bradycardia (is more often at children, at repeated introduction - at children and adults), fibrillation of ventricles and a cardiac standstill, owing to a hyperpotassemia, conductivity disturbance, cardiogenic shock.

Allergic reactions: acute anaphylaxis, bronchospasm, skin rash, small tortoiseshell, anaphylactoid reactions.

Others: the hyperpotassemia, hypercalcemia, the erubescence caused by release of a histamine, increase in the KFK level (generally at the children receiving a halothane), increase in intraocular pressure, change of secretion of sialadens, fever with or without muscular rigidity (masticatory spasm), a porphyria, a mialgiya (in 10-12 h after introduction), muscular fastsikulyation, muscular contractions instead of relaxation (are often connected with inborn myatonias and a dystrophic myatonia), long paralysis as a result of development of the double block and disturbance of neuromuscular transmission that can be at neuromuscular diseases, and also develops owing to an idiosyncrasy (hereditary holinesterazny option), overdose or decrease in level of cholinesterase of plasma, long paralysis of respiratory muscles (it is connected with genetically caused disturbance of formation of serumal cholinesterase), increase in concentration of CO2 at the end of an exhalation, heavy acidosis, a haemoglobinuria, long an apnoea at patients with deficit of cholinesterase of plasma, a laryngospasm, throat hypostasis, a fluid lungs; seldom - рабдомиолиз with development of a myoglobinemia and myoglobinuria (that leads to a renal failure - generally at patients with the diagnosed or latent muscular dystrophy), increase in intracerebral pressure.

Interaction with other medicines:

Strengthens effects of cardiac glycosides. Reduces efficiency of anti-myasthenic medicines. It is incompatible with donor blood (there is a drug hydrolysis), blood preservatives, serumal preservatives, with blood preparations, with solutions of barbiturates (the deposit is formed) and alkaline solutions. Let's combine from 0,9% chloride sodium solution, Ringer's solution, 5% solution of fructose, 5% solution of a dextrose and 6% dextran solution.

The following medicines strengthen and prolong myorelaxation action of Dithylinum: the antikholinesterazny means and drugs having potential ability to reduce activity of cholinesterase of blood (Aprotininum, дифенгидрамин, the eye drops containing cholinesterase inhibitors (an ecothiostalemate, edrofony, pyridostigmine), promethazine, estrogen, oxytocin, glucocorticosteroids in high doses, oral contraceptives), novocaine, Procainum, procaineamide, lidocaine, verapamil, beta adrenoblockers, antiarrhytmic drugs (the I class), blockers of "slow" calcium channels and loopback diuretics, Cimetidinum, MAO inhibitors (фенелзин) and some neuroleptics (Perfenazinum), sympathomimetics, protivo-epileptic drugs, cytostatics (Cyclophosphanum, Thiophosphamidum), alcohol and means, the oppressing central nervous systems, aminoglycosides, Amphotericinum In, clindamycin, cyclopropane, Propanididum, organophosphorous insecticides, salts of magnesium and lithium, quinidine, quinine, chloroquine, a pankuroniya bromide.

Dithylinum is compatible to other muscle relaxants, narcotic analgetics. Galogensoderzhashchy medicines for the general anesthesia strengthen, and thiopental of sodium and atropine reduce undesirable action by cardiovascular system. Atropine reduces effect of drug.

Contraindications:

Hypersensitivity to any of drug components, predisposition to a malignant hyperthermia, the hyperpotassemia and states increasing its risk (a heavy renal failure) because of danger of a cardiac standstill, heavy burns, multiple injuries, heavy infections of abdominal organs, sepsis, a long immobilization, the getting eye wounds with the increased intraocular pressure, the increased intracranial pressure, disturbances of neuromuscular conductivity at a myatonia, poliomyelitis, a side amyotrophic sclerosis, all forms of muscular dystrophy, a heavy myasthenia, the disturbance of an innervation leading to a secondary muscular atrophy (a cross syndrome), inborn insufficiency of cholinesterase, the lactation period.

Overdose:

Symptoms. At overdose respiratory depression, in certain cases - a short-term stop of spontaneous breath is possible.

Treatment. Carrying out artificial ventilation of the lungs. If necessary - transfusion is fresher than the citrated blood, for the purpose of introduction which is contained in it pseudo-cholinesterases. Correction of electrolytic disturbances.

Storage conditions:

In the place protected from light at a temperature from 2 °C to 8 °C. Not to freeze. To store in the place, unavailable to children. Period of validity 1 year 6 months. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

On 5 ml in ampoules in packaging No. 10 or in a blister strip packaging No. 5x1, No. 5x2.