Dosage form: solution for intravenous and intramuscular injection Compound:

1 ml of solution contains:

active substance : ketamine hydrochloride (equivalent to 50 mg ketamine) 57.6 mg;

Excipients: benzethonium chloride 0.1 mg, sodium chloride 1.6 mg, water for injection up to 1 ml.

Description: Transparent colorless or slightly colored liquid. Pharmacotherapeutic group:means for non-inhalation general anesthesia ATX:  

N.01.A.X.03 Ketamine

Pharmacodynamics:

Ketamine causes dissociative anesthesia - a condition in which some areas of the brain are excited and others are inhibited, which explains the manifestation of the analgesic effect with incomplete depression of consciousness and preservation of spontaneous breathing, pharyngeal, laryngeal and cough reflexes (the dose of the drug that causes apnea is 8 times higher than hypnotic). The surgical stage of general anesthesia does not develop when using ketamine (the visceral analgesic activity of ketamine is insufficient, which should be taken into account during abdominal operations).

Causes a specific set of symptoms: somatic analgesia, a condition reminiscent of neuroleptanalgesia, increases blood pressure, myocardial contractility, minute blood volume and myocardial oxygen demand, relaxes the smooth muscles of the bronchi. It practically does not reduce the tone of skeletal muscles and can cause involuntary muscle twitching.

In adults, the minimum dose that causes a hypnotic effect with a single dose intravenous administration, is 0.5 mg/kg body weight (depression of consciousness lasts one and a half minutes). At a dose of 1 mg/kg, it depresses consciousness for 6 minutes, at a dose of 1.5 mg/kg - for 9 minutes, at a dose of 2 mg/kg - for 10-15 minutes. With intramuscular administration of 4-8 mg/kg, the effect occurs within 2-4 minutes (6-8 minutes) and lasts on average 12-25 minutes (up to 30-40 minutes).

In children, with intramuscular administration, general anesthesia occurs after 2-6 minutes, with intravenous administration - after 15-60 s, the duration of action is 15-30 minutes and 5-15 minutes, respectively.

During the period of recovery of consciousness, drowsiness is noted, against the background of which reactions often occur in the form of hallucinations, delusions, and vivid imaginative dreams. After awakening, patients may remain disoriented, sometimes for 6-8 hours. The frequency and severity of these reactions, as well as the cardiac stimulating effect, are reduced when ketamine is combined with antipsychotics (neuroleptics) and anxiolytics medicines(tranquilizers) - droperidol, diazepam.

The analgesic effect of ketamine for somatic pain is manifested when prescribing subnarcotic doses. The maximum analgesic effect occurs 10 minutes after injection into a vein and lasts for 2-3 hours; with intramuscular administration, the effect is longer.

Pharmacokinetics:

Ketamine has a high lipid solubility, which ensures its rapid penetration into the central nervous system. nervous system, easily penetrates histohematic barriers, including the blood-brain barrier. It also stimulates blood circulation. Plasma protein binding reaches 12%.

The volume of distribution is 1.8-2 l/kg, the half-life is 2-3 hours. The main part of the metabolic products is excreted within 2 hours in the urine. Main reason for termination central action ketamine is the rapid redistribution of the drug from the brain to other tissues.

Biotransformation of ketamine is carried out by demethylation by hepatic microsomal enzymes with the formation of several metabolites, some of which retain 1/5-1/3 of the anesthetic activity of ketamine. Elimination of ketamine depends on the oxidase system of the smooth endoplasmic reticulum. The main metabolite, norketamine, has some hypnotic activity that is weaker than that of ketamine. In the process of further metabolism, norketamine is converted into hydroxylated derivatives (hydroxylation of the aromatic cyclohexylamine ring occurs in two different positions and “conjugation”), which form conjugates with glucuronic acid and are eliminated from the body.

A small amount of metabolites can remain in the body for several days; accumulation is not observed with repeated administration. With repeated anesthesia with ketamine, tolerance to the drug may occur, which is partly explained by the induction of liver enzymes.

Indications:

Introductory and basic general anesthesia (especially in patients with low blood pressure or when it is necessary to maintain spontaneous breathing, or when performing artificial ventilation of the lungs with breathing mixtures that do not contain (nitrous oxide)).

Emergency surgical interventions(including at the stages of evacuation, in particular in patients with traumatic shock and blood loss).

Various surgical operations with multicomponent intravenous anesthesia.

Painful diagnostic procedures(endoscopy, catheterization of cardiac chambers), minor surgical procedures for burns, dressings and similar procedures.

Contraindications:

Hypersensitivity to the drug.

Arterial hypertension and conditions accompanied by high blood pressure.

Angina pectoris, myocardial infarction (including in the last 6 months).

Chronic renal failure.

Violation cerebral circulation(including history).

Preeclampsia.

Epilepsy, epilepsy in childhood, eclampsia and other convulsive conditions.

Alcoholism.

Carefully:

Kidney diseases, decompensated chronic heart failure, operations on the larynx and pharynx.

Pregnancy and lactation:

Ketamine crosses the placental barrier. The safety of ketamine during pregnancy has not been established. Use in this category of patients is not recommended.

Directions for use and dosage:

Ketamine is administered intravenously (simultaneously as a stream or fractionally and drip) or intramuscularly.

For adults the drug is administered intravenously at a rate of 2-3 mg/kg, intramuscularly at a rate of 4-8 mg/kg body weight. To maintain anesthesia, the drug is administered at 0.5 mg/kg intravenously or 3 mg/kg intramuscularly or intravenously drip at a rate of 2 mg/kg/h (using an infusion pump or by drip administration of a solution with a concentration of 1 mg/ml (in 5 % dextrose solution (glucose) or 0.9% sodium chloride solution) at a rate of 20-50 drops/min.

In children the drug is used for induction of anesthesia for various types combined anesthesia (administered intramuscularly once at a rate of 4-5 mg/kg in the form of a solution with a concentration of 50 mg/ml after appropriate premedication). For basic anesthesia, it is administered intramuscularly (a solution with a concentration of 50 mg/ml) or intravenously (a solution with a concentration of 10 mg/ml in a stream at once or a solution with a concentration of 1 mg/ml dropwise at a speed of 50-60 drops/min); when administered intramuscularly, the dose depends on the body weight and age of the children: newborns and infants - 8-12 mg/kg, children from 1 year to 6 years - 6-10 mg/kg, 7-14 years - 4-8 mg/kg. It is administered intravenously at a dose of 2-3 mg/kg. Anesthesia is maintained with repeated injections of ketamine (3-5 mg/kg intramuscularly or 0.5-1 mg/kg intravenously by bolus or drip injection of a solution with a concentration of 1 mg/ml at a rate of 30-60 drops/min).

To enhance the effect of ketamine, it is usually used in combination with antipsychotics () and narcotic analgesics (fentanyl, and others), and the dose of ketamine should be reduced.

Side effects:

From the nervous system: oppression respiratory center, muscle rigidity, involuntary muscle activity (for prevention, you should pre-administer); during the period of recovery from general anesthesia - psychomotor agitation, hallucinations, prolonged disorientation, psychosis.

From the side of the organ of vision: diplopia, nystagmus, increased intraocular pressure.

From the outside respiratory system : shortness of breath, obstruction of the upper respiratory tract due to spasm of the masticatory muscles and retraction of the tongue, increased bronchial secretion and salivation.

From the cardiovascular system: increased blood pressure, tachycardia.

From the outside digestive system : hypersalivation, nausea.

Local reactions : pain and hyperemia along the vein at the injection site. Overdose:

When ketamine is administered into high doses intravenously (3 mg/kg), in some cases respiratory depression may occur. In these cases, artificial ventilation is indicated. If hallucinations occur, it is advisable to use antipsychotics(), at convulsive syndrome- diazepam. If necessary, carry out symptomatic therapy.

Interaction:

Ketamine enhances the effect of drugs for general anesthesia, narcotic analgesics, antipsychotics (neuroleptics), anxiolytics (tranquilizers) and other drugs that depress the central nervous system.

Before using ketamine, it is necessary to discontinue lithium preparations (1-2 days before), monoamine oxidase inhibitors (15 days before). Do not mix with barbiturates in the same syringe (pharmaceutically incompatible - formation of sediment).

Droperidol and benzodiazepines, including, reduce the risk of psychotomimetic and motor activity, as well as the occurrence of tachycardia and increased blood pressure.

It is not recommended to prescribe with sympathomimetics and drugs that have a stimulating effect on the cardiovascular system (increased hypertensive and arrhythmogenic effects, increased myocardial oxygen demand).

The cardiac stimulating effect of ketamine is weakened when combined with antipsychotics and anxiolytics.

Ketamine enhances the muscle relaxant effect of tubocurarine chloride and suxamethonium iodide, but does not change the effect of pancuronium bromide.

During general anesthesia in patients taking iodine-containing drugs and hormones thyroid gland, there is a high probability of increased blood pressure and tachycardia (can be eliminated with beta-blockers).

Special instructions:

Ketamine is used only in hospital or emergency settings.

To prevent increased secretion of the mucous membranes and salivary glands, the premedication should include or, and the main dose of the drug should be slowly administered (not exceeding 3 mg/kg). During ketamine anesthesia, inhale with a mixture of oxygen and air in a ratio of 1:2.

When using ketamine, it is necessary to monitor the function of external respiration, especially the patency of the upper respiratory tract (spasm of the masticatory muscles and retraction of the tongue are possible).

Caution should be exercised during operations on the larynx and pharynx (muscle relaxants are used).

To prevent muscle rigidity and involuntary twitching during premedication, diazepam is administered intramuscularly or intravenously.

To prevent the development of psychotomimetic effects, the composition of premedications should include,.

Increased intracranial pressure may occur after ketamine use.

The use of the drug may provoke the development of acute mental disorders upon recovery from anesthesia. Caution should be exercised in patients with acute disorders mental health (also if there are such indications in the anamnesis), patients with alcohol intoxication.

Ketamine addiction may develop in patients with drug addiction or who have previously abused drugs.

Impact on the ability to drive vehicles. Wed and fur.:After using ketamine, patients should refrain from driving and other potentially dangerous activities for at least 24 hours. dangerous species activities. Release form/dosage:

Solution for intravenous and intramuscular administration 50 mg/ml.

Package:

In ampoules of 2 ml and 5 ml, in bottles of 5 ml.

5 ampoules in a blister pack.

1 or 2 blister packs with instructions for use, a knife or an ampoule scarifier in a cardboard pack.

20, 50 or 100 blister packs, respectively, with 20, 50 or 100 instructions for use, knives or ampoule scarifiers in a cardboard box or corrugated cardboard box.

A coupon with the packer's number is placed in a cardboard box or corrugated cardboard box.

When packaging ampoules with notches, rings and break points, do not use knives or ampoule scarifiers.

5 bottles in a blister pack.

1 blister pack with instructions for use in a cardboard pack.

30 or 50 contour strip packs, respectively, with 30 or 50 instructions for use in a cardboard box or corrugated cardboard box.

A coupon with the packer's number is placed in a cardboard box or corrugated cardboard box.

Storage conditions:

List II. "List narcotic drugs, psychotropic substances and their precursors subject to control in Russian Federation", in specially equipped premises if there is a license for the specified type of activity.

In a place protected from light at a temperature not exceeding 25 ° C.

Best before date: Do not use after the expiration date stated on the packaging. Conditions for dispensing from pharmacies: For hospitals Registration number: P N000298/01 Registration date: 17.10.2011 Owner of the Registration Certificate:MOSCOW ENDOCRINE PLANT, FSUE Russia Manufacturer:   Representative office:  MOSCOW ENDOCRINE PLANT FSUE Russia Information update date:   17.10.2011 Illustrated instructions

IN modern medicine Ketamine has been actively used for a long time. Veterinarians do not refuse it either. This medication is an effective pain reliever used in anesthesia (if necessary emergency help or there are a number of contraindications to other analgesics). Sometimes Ketamine comes to the rescue with bronchospasms.

But for about 60 years, there have been active discussions regarding this medication. Too many side effects the drug has, and its properties are ambiguous. Ketamine is a medicine recognized as a narcotic in the Russian Federation. Sales and production are strictly controlled, and you cannot buy the drug at a pharmacy without a prescription. But why is this medicine classified as a narcotic?

Ketamine is used as an anesthetic

The drug belongs to the psychoactive synthetic substances. More often this medication used during anesthesia. But this is far from its unique use. For example, Western doctors successfully treat depressive states and include the medicine in complex therapy alcohol addiction.

The main feature of Ketamine is the fact that it is suitable for all people and does not provoke allergic reactions.

Thanks to this talent, it is widely used during emergency medical care, when there is simply no time to find out all the nuances of the victim’s health. Also, this drug very quickly puts a person into a state of anesthesia, but does not cause depression of the respiratory system. Ketamine is sometimes used during caesarean sections.

What is ketamine

Indications for use

Ketamine is used as an intravenous anesthetic. It is actively used in the following cases:

1. If there is a traumatic, painful shock.
2. When transporting a victim with serious burns.
3. When a person experiences significant blood loss.
4. If medical procedures are performed that do not require fixation of the patient.

Ketamine can be used by gynecologists, otolaryngologists, and dentists when performing minor surgical procedures. When fast-acting anesthesia is needed (for a period of up to 3 hours).

Benefits of the medication

Anesthesia produced using Ketamine has a number of advantages in comparison with other types of analogues. Besides that this remedy is not allergic, its advantages include the following factors:

1. Does not accumulate in the body.
2. Ketamine does not suppress the cough center.
3. Can be used by intramuscular/intravenous infusion.
4. Stimulates the functioning of the bronchi, leading to their expansion. That is, this anesthesia is allowed to be used by people suffering from bronchial asthma and obstructive bronchitis.

Ketamine is used in medicine for anesthesia

The drug has the form of a light-colored crystalline powder. It is highly soluble in water, alcohol or fat. The drug has narcotic and hallucinogenic effects. There are drug taxes. This:

• Ketalar;
• Ketanest;
• Calypsol.

Ketamine is supplied to pharmaceutical retail in vials/ampoules filled with a clear liquid. You can also see it in powder or tablet form. Due to its excellent ability to dissolve in liquid media, this drug instantly penetrates into parts of the brain, bypassing the blood-brain barrier.

Why is the product dangerous?

If you ask some people what Ketamine is, the answer we will hear is clear - it is a drug that causes hallucinations. It is precisely thanks to this ability that active debates about the advisability of its use do not subside in relation to the drug.

Effects of Ketamine

Patients, after using Ketamine as an anesthetic, complained of the following symptoms:

• sensations of “losing the body”;
• the appearance of vivid illusions;
• frightening dreams;
• the occurrence of hallucinations.

But the mechanism of action of Ketamine is such that all unpleasant and unwanted sensations disappear without a trace as soon as its effect ends. Doctors have also learned to block the hallucinogenic effects of the drug using benzodiazepine medications.

Hallucinations after using Ketamine as an anesthetic were experienced by 5-25% of patients.

After recovering from anesthesia, these patients experienced psychomotor agitation for some time with short-term disorientation in space. Ketamine also has a number of other side effects:

1. Tachycardia and slight increase in blood pressure.
2. Nausea that occurs after a person comes out of anesthesia.
3. Local burning sensation. Appears at the site of drug administration.

But it is worth noting that all similar symptoms are observed after the use of other anesthetic drugs. Almost all patients experience these symptoms.

Ketamine causes vivid hallucinations, it's a psychedelic

Contraindications for use

Ketamine cannot always be used under general anesthesia. It is prohibited to work with it in the following situations:

• glaucoma;
• angina pectoris;
• eye injury;
• traumatic brain injuries;
• arterial hypertension;
• heart failure;
• diagnosed schizophrenia;
• problems with blood circulation in the brain;
• stroke and ischemic condition;
• pathologies accompanied by convulsive activity.

Ketamine as a narcotic drug

Unfortunately, the ubiquitous youth actively began to use Ketamine to obtain hallucinogenic effects. Increased interest in this drug as a drug is promoted by:

• low cost of medicine;
• easily obtainable desired psychedelic effect.

But this drug, especially with prolonged and regular use, has very serious consequences for the body. Its effects disappear without a trace only with a one-time use of the medicine (for anesthesia).

Consequences of use

The medication causes a significant blow to the central nervous system and reproductive organs. The first thing a person encounters is cognitive level disorders. Memory impairment occurs (short-term and long-term). If you do not stop using the drug to obtain hallucinogenic effects, the person begins to suffer mental destruction.

According to doctors, long-term use psychedelics lead to massive destruction of neurons (brain cells).

Doctors consider the following to be emerging urological problems:

• formation of ulcerative colitis;
• the appearance of enuresis (urinary incontinence);
• pain when urinating (blood clots are visible in the urine).

The drug Ketamine (if used not as prescribed by doctors) very often leads to a serious overdose. In this case (if timely assistance is not provided), the psychedelic can provoke depression respiratory functions and subsequent death.

How is the drug used?

Powder. Drug addicts mainly use Ketamine as a snorting mixture. This form of the drug is the least dangerous. And to obtain the desired effect, small doses of the psychedelic are needed.

Ketamine, used as a narcotic, is safest when used as a snorting mixture (powder)

Pills. The effect of Ketamine will become stronger if you use this drug in tablet form. This drug is distributed underground under the guise of Ecstasy pills and in the slang of drug addicts it has the names “vitamin K”, “Ket”, “Nastya”.

Injections. One of the most hazardous applications narcotic substance. After administration of the drug by intravenous injection, the effect of the drug comes instantly (sometimes the person does not even have time to remove the needle). It is in this case that the danger of an overdose of the drug will increase many times.

How does the drug work?

This psychedelic actively affects the thalamus (the area of ​​the brain responsible for the redistribution of information coming from the senses). The drug also disorganizes the associative area of ​​the cerebral cortex. Under the influence of Ketamine, a person loses the ability to process received sensory information for some time, but reflexes important for human life are preserved:

• cough;
• laryngeal;
• muscular;
• respiratory;
• swallowing.

The elimination period of the drug is about 2-3 hours. But when laboratory research blood serum, and especially in chronic drug addiction, traces of Ketamine will be detected within 20-25 days.

After administering the drug, a person feels the following effects:

1. There is numbness in the limbs.
2. There is a desire to lie down and relax.
3. Severe dizziness occurs.
4. Consciousness is distorted (a person cannot name a name, ceases to be aware of himself).
5. There is a feeling of moving in space, but at the same time the person sees himself as if from the outside.
6. A person can feel like a certain object moving along communication lines and power lines. IN delirious he even imagines himself as a traveler to the past/future.

Fortunately, Ketamine does not have a euphoric effect, so this type drugs are not common. When taking it, a drug addict has no excitement, no desire to laugh, sing, the feeling of complete delight and joy will disappear.

Narcologists, studying the specificity of the effects of Ketamine on a person, note that the hallucination scenario is mainly associated with the person’s previous activities. That is, variants of illusions arise from those recent memories that are stored in the brain. Ketamine also enhances the state of the addict, which he had at the time of taking the drug.

Ketamine most actively affects the thalamus, causing hallucinations

If a person was in good mood, then the effect of the drug is optimistic. But with gloomy, sad thoughts, Ketamine “gives” hallucinations filled with terrible nightmares. But such nuances are noted only at the first stages of use.

Over time, taking Ketamine no longer brings these effects. The addict gets only constant anxiety and influxes of panic. This side effects Ketamine, which develop after 1-1.5 months of regular use of the drug.

The source of such manifestations is the breakdown product of Ketamine, norketamine. This drug metabolite has a powerful sedative effect.

Coming out of drug intoxication

After the end of the psychedelic effect, the person begins to come to his senses from the moment of awareness own body and personality. Sobering up is accompanied by the following symptoms:

• tingling sensation;
• strange sensations when moving the body;
• muscle discomfort (minor soreness).

A person gradually regains the ability to focus his gaze on various objects, and memory comes back. Coordination is the last thing to wake up. After the psychedelic drug wears off, the addict still has a feeling of “rubbery” in his movements for some time. This is quite noticeable to others, but the drug user himself does not notice anything.

Withdrawal syndrome

Ketamine is addictive, like any drug. In the absence of the usual dose, a person experiences withdrawal symptoms that occur against the background of:

• fears;
• sweating;
• insomnia;
• headache;
• dizziness;
• trembling all over the body;
• general weakness and lethargy.

Very painful incoming pain in muscles and joints. They are difficult to bear and very depressing for addicts. The drug addict tries in every possible way to find funds to buy the next, now necessary dose. The withdrawal state can last up to two weeks.

Ketamine is a drug that has long been used in medicine, but is increasingly being considered as a medicinal drug for adolescents. IN Western Europe Ketamine is currently the most popular club drug. Probably because it is stimulating and hallucinatory - like ecstasy, but much cheaper. Unfortunately, many do not understand the harmful effects and the possibility of addiction to it.

Ketamine is a general anesthetic synthesized in 1963 to replace phencyclidine to produce a type of anesthesia called dissociative anesthesia. Ketamine is initially distributed in the brain, where it reaches concentrations 3-5 times higher than plasma levels, and is then redistributed to less vascularized tissues. Ketamine has been reported to be abused in the US, used in the country as a anesthetic in veterinary medicine. These alarm signals forced US authorities to add ketamine to the list of controlled substances starting in 1999.
Slang names for ketamine include: “K”, “Kay”, “Super acid”, “Green”, “Super C”, “Purple”, vitamin K. Typically, ketamine users are those who for a long time uses MDMA. The drug is used, in particular, at parties or in gay clubs. In "closed" groups in Europe, initiating ketamine use is a real ritual. The most vulnerable group are those who are used to taking MDMA or other stimulant drugs.

Ketamine is a powerful and fast-acting anesthetic derivative of phencyclidine, a substance belonging to the group of psychodisleptics, also referred to as a hallucinogen. Ketamine is used in human and veterinary medicine as a drug for preoperative anesthesia. In addition, as an analgesic and for treatment mental illness- heavy bipolar disorder. Sometimes also used to treat addiction to alcohol and heroin because it relieves withdrawal symptoms. It is also used as an antidepressant, because A study by British scientists from the University of Oxford suggests that ketamine relieves symptoms of depression, even those resistant to treatment.

Ketamine is a colorless and odorless substance that dissolves easily in water and alcohol, and produces a state of retrograde amnesia. Thus, (usually for criminal purposes) it is used as a substance that causes a disturbance of consciousness, a blackout (for example, a “rape pill”).

Ketamine is like a drug

Ketamine as a narcotic can be used in the form of a solution, tablets, ampoules or powder, usually by oral and intranasal administration, less by injection. Taken in a dose of 0.5 g or higher, it causes a short-term (about fifteen minutes) feeling of depersonalization, unreality, and detachment from the body (trip). A person who uses ketamine then reports experiencing a trip into himself, visiting other worlds and a distortion of the sense of time (expansion), accompanied by colorful visual effects (ketamine acts as a hallucinogen). The onset of action is 5-10 minutes after administration and persists after 1-3 hours.

The most powerful effect of high doses of ketamine is called K - hole - ketamine hole (K-hole). This is a condition in which there is a loss of contact with the outside world and the presence discomfort, near death and nightmares (psychiatrists compare this condition with severe symptoms schizophrenia).

Ketamine - how to recognize symptoms of use

Signs of taking ketamine include:

• loss of coordination
• speech disorders
• double vision (diplopia)
• nystagmus - horizontal and vertical dilation of the pupils
• hallucinations, delusions
• dizziness
• insomnia
• increased blood pressure and tachycardia;
• respiratory depression

Side effects of ketamine

Side effects of ketamine include numerous injuries and illnesses gastrointestinal tract And urinary tract, including expansion biliary tract, as well as abdominal pain and kidney damage and Bladder(inflammation, fibrosis, and ulceration). In particular, a person with myocardial ischemia should be treated with caution, as the symptoms of the disease may worsen. In addition, British researchers from University College London showed that long-term use Ketamine impairs the process of memorizing and comparing facts. In addition, this most accessible drug on the black market is almost always contaminated with contaminants, including amphetamine, which poses an even greater health threat.

Forms of use and composition

"Special K", "vit Kat", "cat valium" is presented as a solution or white powder (obtained by removing the solvent from the injection forms).

Typically, ketamine is sold in combination with marijuana or tobacco.

Special K is usually used in combination with other drugs such as ecstasy, heroin or cocaine.

The ketamine solution is injected into a vein and applied to foods that can be smoked or eaten.

The powder is added to drinks, cigarettes or dissolved and then administered parenterally.
The only source of ketamine is pharmaceutical products.

Toxic effects of ketamine

Ketamine has effects on the central nervous system that differ from classical general anesthetics. The anesthesia it causes is called “dissociative anesthesia,” characterized by separation from the environment, accompanied by shallow sleep and intense analgesia.

Ketamine works primarily in the cerebral cortex and limbic system as an antagonist of NMDA receptors, preventing their activation by glutamic acid, an excitatory neurotransmitter in the brain. Analgesia is thought to be mediated in part by μ receptors ( parenteral administration ketamine potentiates the antinociceptive effect of fentanyl through μ-receptors). Naloxone has a limited ability to counteract the analgesic effects of ketamine.

It acts at the level of specific opioid receptors at the level of the central nervous system; Ketamine reduces the function of the thalamus, which is the brain's sensing station, resulting in undifferentiated sensations. Ketamine also reduces hypothalamic function, leading to emotional reactions, separated from reality.

Effects occur over a period of time depending on the route of administration, in the following way:

• — intramuscular effects appear in less than 5 minutes;
• - when administered orally, 15-20 minutes after administration;
• - When administered by swallowing, effects occur within 5-10 minutes.

Therapeutic doses of ketamine are produced by:

• - tachycardia;
• - increased blood pressure;
• - increased oxygen consumption by the myocardium.

For these reasons, it is contraindicated as the sole anesthetic in patients with myocardial ischemia (it is usually preferred as an anti-bronchospasm agent to relax the bronchial muscles). Despite the above limitations, ketamine is commonly used due to its simple introduction and short duration of action.

Ketamine is different from most anesthetics because it stimulates cardiovascular system.
Substances that cause respiratory depressants such as ethanol, opioids, barbiturates, benzodiazepines, or cardiovascular drugs(cocaine or amphetamines) increase the acute toxicity of ketamine. The cardiac stimulatory effect of ketamine is due to inhibition of central catecholamine and an increase in the amount of circulating catecholamines.

Hypertension and acute edema lungs is less often associated with taking ketamine, and more often with other drugs (amphetamines and their analogues, ephedrine and cocaine). Intravenous administration of ketamine to cocaine addicts leads to hypertensive crisis and pulmonary edema.

Acute ketamine poisoning

In acute poisoning, ketamine affects cognitive performance and perception of one's body, time, world, and reality.

Manifestations of acute ketamine intoxication:

• - anxiety;
• — agitation;
• - changes in perception;
• — movement disorders and analgesic effects (under such conditions the consumer may suffer from burns, falls or other accidents).

With massive overdoses of ketamine, seizures can occur, and sometimes apnea - stopping breathing.

Chronic intoxication

Drug consumption has the following static features:

• — experimental use (for recreational purposes);
• - regular consumption - the consumer begins to leave school/work more and more, fears losing the opportunity to purchase the drug (buys in reserve);
• - daily worries - the consumer loses motivation (school / service becomes indifferent);
• - addiction - the consumer cannot cope with everyday affairs without drugs, denies the problem he has, worsens physical state, after consumption loses control.

Under conditions of abuse, ketamine produces dose-related progressive effects, ranging from a state of sleep to delirium accompanied by immobility, intense analgesia, and amnesia. The state induced by it (“high”) is similar to that caused by LSD or phencyclidine, but only lasts 30-60 minutes.

Ketamine results in a clinically similar neurophysiological and behavioral syndrome to schizophrenic psychosis.

Ketamine trip

Effects reported by ketamine users :

• - At first it seems that everything around is starting to spin, but without dizziness;
• — At some point, the consumer feels that he is outside the body.

Although the descriptions of different consumers vary greatly, most have reported perceiving alternate planes of existence, revelations about the past and future, where communication is very difficult and consumers cannot see or hear people present in the same room.

Tolerance observed in animal experiments occurs rapidly and involves increasing doses.

Its use for recreational purposes leads in some cases to psychological dependence. Psychedelic and psychotic effects have been reported in patients dependent on ketamine. These effects were dose related and included multimodal hallucinatory experiences, paranoid ideation, sensory and musical "gratification". The neuropharmacological mechanisms of this phenomenon are associated with a complex of receptor actions through excitatory amino acids and NMDA receptors.

Withdrawal symptoms have not yet been well characterized, but may include nightmares, disorientation, and loss of sense of reality.

Treatment of acute intoxication

At adverse reactions or acute ketamine vomiting - symptomatic and supportive treatment. Anticonvulsants prescribed when seizures occur. Cardiovascular stimulation is treated with adrenergic blockers. There is no special antidote. Increased elimination measures (forced diuresis, hemoperfusion, hemodialysis) are not useful due to the large volume of distribution and lipid resistance of ketamine.

Mechanism of action

Ketamine has a multifaceted effect on the central nervous system, including blockade of polysynaptic reflexes spinal cord and suppression of the effects of excitatory neurotransmitters in certain areas of the brain. Unlike barbiturates, which cause depression of the reticular activating system, ketamine functionally disconnects, or dissociates, the thalamus (which switches sensory impulses from the reticular activating system to the cerebral cortex) and the limbic cortex (which is involved in the awareness of sensations). While some brain neurons are functionally suppressed, others, on the contrary, are in a state of tonic excitation. Clinical condition dissociative anesthesia characterized by the fact that the patient appears to be awake (he opens his eyes, swallows, muscles contract), but he lacks the ability to analyze and respond to sensory stimuli. The existence of specific ketamine receptors and their interaction with opiate receptors has been proven.

Effect of structure on activity

Ketamine is structural analogue phencyclidine. Ketamine is 10 times weaker than PCP and produces many of its psychomimetic effects. An increase in the potency of the isomer indicates the existence of a stereospecific receptor.

Pharmacokinetics

A. Absorption. Ketamine is used IV or IM (see table below). 10-15 minutes after intramuscular administration, the concentration of ketamine in plasma reaches peak values.

A drug	Indications for use	Route of administration	Dose
Ketamine	Induction	IV, IM	1 -2 mg/kg, 3-5 mg/kg
Etomidate	Induction	IV	0.2-0.5 mg/kg
Propofol (diprivan)	Induction	IV	1-2.5 mg/kg
	Intraoperative anesthesia	IV infusion	50-200 mcg/(kg x min)
	Sedation	IV infusion	25-100 mcg/(kg x min)
Droperidol	Premedication	V/m	0.04-0.07 mg/kg
	Sedation	IV	0.02-0.07 mg/kg
	Elimination of vomiting	IV	0.05 mg/kg 1

TABLE.Indications for use and dosage of ketamine, etomidate, propofol and droperidol
1 The maximum dose in adults that does not delay awakening is 1.25–2.5 mg.

B. Distribution. Ketamine is more lipid soluble than thiopental and less protein bound; at physiological pH, the degree of their ionization is the same. The presence of such properties, along with the increase in cerebral blood flow and cardiac output due to the effect of the drug, leads to rapid absorption of ketamine by the brain and subsequent redistribution (the half-life in the distribution phase is 10-15 minutes). Awakening is due to redistribution of the drug into the peripheral chamber.

B. Biotransformation. Ketamine undergoes biotransformation in the liver, resulting in the formation of several metabolites. Some metabolites (for example, norketamine) retain anesthetic activity. With repeated anesthesia with ketamine, tolerance to the drug may occur, which is partly explained by the induction of liver enzymes. The short half-life of ketamine in the elimination phase is due to significant absorption in the liver (hepatic extraction ratio of 0.9).

D. Excretion. The final products of biotransformation are excreted through the kidneys.

Effect on the body

A. Cardiovascular system.

N.B. Sharply different from all other anesthetics, ketamine increases blood pressure, heart rate and cardiac output. This indirect effect is due to stimulation central departments sympathetic nervous system.

These changes are accompanied by an increase in heart function and an increase in pressure in the pulmonary artery. Due to the stimulation of blood circulation, ketamine is not advisable for use in untreated or improperly treated ischemic heart disease. arterial hypertension, heart failure and arterial aneurysms. On the one hand, ketamine has a direct depressant effect on the myocardium, which manifests itself during sympathetic blockade (for example, in spinal cord rupture) or depletion of catecholamine stores (for example, in the terminal phase of shock). On the other hand, indirect stimulation of blood circulation makes ketamine the drug of choice for acute hypovolemic shock.

B. Respiratory system. Standard induction doses of ketamine have little effect on breathing. With rapid bolus administration or when combined with opioids, apnea may develop. Ketamine is a powerful bronchodilator that bronchial asthma making it an ideal anesthetic for induction. Although upper airway reflexes are usually not depressed, tracheal intubation is indicated if there is an increased risk of aspiration. Ketamine increases salivation, which can be prevented by prior administration of an anticholinergic drug.

B. Central nervous system. In parallel with circulatory stimulation, ketamine increases brain oxygen consumption, cerebral blood flow and intracranial pressure. Therefore, intracranial volumetric formations- contraindication to the use of ketamine. Ketamine can cause myoclonic movements caused by subcortical electrical activity, not detected on EEG. Undesirable psychomimetic effects (for example, illusions, frightening dreams, delirium) during the awakening phase are less likely to occur when benzodiazepines are used as premedication and in children. Ketamine is the most “full-fledged” of non- inhalational anesthetics, because it causes analgesia, amnesia and loss of consciousness.

Drug interactions

Ketamine potentiates the action of non-depolarizing muscle relaxants. The combined use of theophylline and ketamine increases the risk of seizures. Diazepam weakens the stimulation of blood circulation caused by ketamine and lengthens its half-life in the elimination phase. Ketamine causes myocardial depression when administered in conjunction with halothane or, to a lesser extent, other inhaled anesthetics. Lithium preparations may prolong the effects of ketamine.

Registration number:

Trade name of the drug: Ketamine

International (nonproprietary) name: ketamine

Dosage form: solution for intravenous and intramuscular administration

Compound: 1 ml of solution contains:
Active substance: ketamine hydrochloride, equivalent to 50 mg of ketamine - 57.6 mg.
Excipients: benzethonium chloride, sodium chloride, water for injection.

Description: transparent, colorless or slightly colored liquid.

Pharmacotherapeutic group: a means for non-inhalation general anesthesia.

ATX code:

Pharmacological properties
Pharmacodynamics. The drug causes an analgesic effect with incomplete depression of consciousness and preservation of spontaneous breathing, pharyngeal, laryngeal and cough reflexes (the dose of the drug that causes apnea is 8 times higher than the hypnotic dose). The surgical stage of general anesthesia does not develop when using ketamine (the visceral analgesic activity of ketamine is insufficient, which should be taken into account when abdominal operations).
Causes a specific set of symptoms: somatic analgesia, a condition reminiscent of neuroleptanalgesia, increases blood pressure, myocardial contractility, minute blood volume (MBV) and myocardial oxygen demand, relaxes bronchial smooth muscles. Practically does not reduce tone skeletal muscles, may cause involuntary muscle twitching.
In adults, the minimum dose that causes a hypnotic effect with a single intravenous administration is 0.5 mg/kg of body weight (depression of consciousness lasts one and a half minutes). At a dose of 1 mg/kg the drug depresses consciousness for 6 minutes, at a dose of 1.5 mg/kg - for 9 minutes, at a dose of 2 mg/kg - for 10-15 minutes. With intramuscular administration of 4-8 mg/kg, the effect occurs within 2-4 minutes (6-8 minutes) and lasts on average 12-25 minutes (up to 30-40 minutes).
In children, with intramuscular administration, general anesthesia occurs after 2-6 minutes, with intravenous administration - after 15-60 seconds, duration of action - 15-30 and 5-15 minutes, respectively.
During the period of recovery of consciousness, drowsiness is noted, against the background of which reactions often occur in the form of hallucinations, delusions, and vivid imaginative dreams. After awakening, patients may remain disoriented, sometimes for 6-8 hours. The frequency and severity of these reactions, as well as the cardiac stimulating effect, are reduced when ketamine is combined with antipsychotic drugs(neuroleptics) and anxiolytic drugs (tranquilizers) - droperidol, diazepam.
The analgesic effect of ketamine for somatic pain is manifested when prescribing subnarcotic doses. The maximum analgesic effect occurs 10 minutes after injection into a vein and lasts for 2-3 hours; with intramuscular administration, the effect is longer.
Pharmacokinetics. Ketamine, being a lipophilic compound, easily penetrates histohematic barriers, including the blood-brain barrier. Communication with plasma proteins - 12%. The volume of distribution is 1.8-2 l/kg, the half-life is 2.3 hours. Ketamine is metabolized by demethylation; the bulk of metabolic products are excreted within 2 hours in the urine; a small amount of metabolites can remain in the body for several days. Cumulation with repeated administration is not observed.

Indications for use
Introductory and basic general anesthesia (especially in patients with low blood pressure or when it is necessary to maintain spontaneous breathing, or when performing artificial ventilation of the lungs with breathing mixtures that do not contain dinitrogen oxide (nitrous oxide).
Emergency surgical interventions (including at the stages of evacuation, in particular in patients with traumatic shock and blood loss).
Various surgical operations with multicomponent intravenous anesthesia.
Painful diagnostic procedures (endoscopy, cardiac catheterization), minor surgical procedures for burns, dressings, etc. procedures.

Contraindications
Hypersensitivity to the drug, arterial hypertension (and other conditions in which an increase in blood pressure is contraindicated), angina pectoris or myocardial infarction (including in the last 6 months), severe renal failure, cerebrovascular accident (including history), preeclampsia, eclampsia, epilepsy and other convulsive conditions, alcoholism, pregnancy and lactation.
Contraindications to ketamine anesthesia in children are any diseases accompanied by convulsive activity.

Carefully- decompensated chronic heart failure, operations on the larynx and pharynx.

Directions for use and doses
Ketamine is administered intravenously (simultaneously in a stream or fractionally and drip) or intramuscularly.
For adults the drug is administered intravenously at a rate of 2-3 mg/kg, intramuscularly at a rate of 4-8 mg/kg body weight. To maintain anesthesia, the drug is administered at 0.5-1 mg/kg intravenously or 3 mg/kg intramuscularly or intravenously drip at a rate of 2 mg/kg/h (using an infusion pump or by drip administration of a 0.1% ketamine solution (in 5 % dextrose solution (glucose) or 0.9% sodium chloride solution) at a rate of 20-50 drops/min.
In children the drug is used for induction of anesthesia for various types of combined anesthesia (administered intramuscularly once at the rate of 4-5 mg/kg in the form of a 5% solution after appropriate premedication). For basic anesthesia, ketamine is administered intramuscularly (5% solution) or intravenously (1% solution in a stream at once or 0.1% solution in a drip at a rate of 50-60 drops/min); when administered intramuscularly, the dose depends on the body weight and age of the children: newborns and infants - 8-12 mg/kg, children from 1 to 6 years old - 6-10 mg/kg, 7-14 years old - 4-8 mg/kg . It is administered intravenously at a dose of 2-3 mg/kg. Anesthesia is maintained with repeated injections of ketamine (3-5 mg/kg intramuscularly or 0.5-1 mg/kg intravenously by bolus or drip administration of a 0.1% solution of the drug at a rate of 30-60 drops/min).
To enhance the effect of ketamine, it is usually used in combination with antipsychotic drugs (droperidol) and analgesics (fentanyl, promedol, etc.), while the dose of ketamine should be reduced.

Side effect
From the nervous system: depression of the respiratory center, muscle rigidity, involuntary muscle activity (for prevention, diazepam should be pre-administered); during the period of recovery from general anesthesia - psychomotor agitation, hallucinations, prolonged disorientation, psychosis.
From the respiratory system: shortness of breath, obstruction of the upper respiratory tract due to spasm of the masticatory muscles and retraction of the tongue, increased bronchial secretion and salivation.
From the cardiovascular system: increased blood pressure, tachycardia.
From the digestive system: hypersalivation, nausea.
Local reactions: pain and hyperemia along the vein at the injection site.

Overdose
When ketamine is administered in high doses intravenously (3 mg/kg), respiratory depression may occur in some cases. In these cases it is indicated artificial ventilation lungs. When hallucinations occur, it is advisable to use antipsychotic drugs (haloperidol), and for convulsive syndrome - diazepam. If necessary, carry out symptomatic therapy.

Interaction with other drugs
Ketamine enhances the effect of drugs for general anesthesia, narcotic analgesics, antipsychotic drugs (neuroleptics), anxiolytics (tranquilizers) and other drugs that depress the central nervous system.
Before using ketamine, it is necessary to discontinue lincomycin, lithium preparations (1-2 days before), monoamine oxidase inhibitors (15 days before). Do not mix with barbiturates in the same syringe (pharmaceutically incompatible - formation of sediment).
Droperidol and benzodiazepines, incl. sibazon, reduce the risk of psychomimetic and motor activity, as well as the occurrence of tachycardia and arterial hypertension.
It is not recommended to prescribe with sympathomimetics and drugs that have a stimulating effect on the cardiovascular system (increased hypertensive and arrhythmogenic effects, increased myocardial oxygen demand).
The cardiac stimulating effect of ketamine is weakened when combined with antipsychotic drugs and anxiolytics.
Ketamine enhances the muscle relaxant effect of tubocurarine and dithiline, but does not change the effect of pancuronium and suxamethonium.
During general anesthesia in patients taking iodine-containing drugs and thyroid hormones, there is a high likelihood of increased blood pressure and tachycardia (removed by beta-blockers).

special instructions
Ketamine is used only in hospital or emergency settings.
To prevent increased secretion of mucous membranes and salivary glands Premedication should include atropine or methocinium iodide, and the main dose of the drug should be administered slowly (not exceeding 3 mg/kg). During ketamine anesthesia, inhale with a mixture of oxygen and air in a ratio of 1:2.
When using ketamine, you should monitor respiratory function, especially the patency of the upper respiratory tract (spasm of the masticatory muscles and retraction of the tongue are possible).
Caution should be exercised during operations on the larynx and pharynx (muscle relaxants are used).
To prevent muscle rigidity and involuntary twitching during premedication, diazepam is administered intramuscularly or intravenously.
To prevent the development of psychomimetic effects, droperidol and diazepam should be included in premedications.

Release form
Solution for intravenous and intramuscular administration 50 mg/ml. 2 ml and 5 ml in ampoules or 5 ml in bottles. 5 ampoules or bottles in a blister pack.
1 or 2 blister packs (5 ampoules in each) with instructions for use in a cardboard pack; 20, 50 or 100 blister packs, respectively, with 10, 25 and 50 instructions for use in a cardboard box or cardboard box (for hospital use).
1 blister pack (5 bottles) and instructions for use in a cardboard pack; 30-50 blister packs (5 bottles each) with instructions for use (according to the number of packs) in a cardboard box or cardboard box (for a hospital).

Storage conditions
In a place protected from light and out of the reach of children. List II of the “List of narcotic drugs, psychotropic substances and their precursors subject to control in the Russian Federation.”

Best before date
2 years. Do not use after the expiration date indicated on the packaging.

Conditions for dispensing from pharmacies
Use in a hospital setting.

Manufacturer:
Federal State unitary enterprise"Moscow Endocrine Plant"
Moscow, 109052, st. Novokhokhlovskaya, 25.