Lithium salt preparations. Lithium preparations for health and longevity

Before modern medicine There are many difficult tasks, including the treatment of affective disorders of the human psyche.

Lithium preparations were discovered in 1949 and are still widely used in the suppression, prevention and prevention of affective mood disorders, as well as depressive-manic illnesses to this day.

What group do lithium preparations belong to?

History of formation

Even in antiquity, healers noticed the calming effect of alkaline waters from some mineral springs. Scientific medicine discovered lithium salts as a remedy for gout in 1859. It has been found that when taking lithium, the solubility of uric acid crystals increases, but the use has toxic consequences.

Australian scientist John Cade in 1949 introduced guinea pigs in abdominal cavity urine of psychotics with lithium salts and unexpectedly found a sharp decrease in toxic effects. He extended this experiment on some of his patients with mental disorders and received good effect. This experience led him to believe that lithium deficiency was the cause of the manic states.

Salts "Li" began to be used as food salt substitutes for hypertensive patients. Side effects metal on human body yet led to the death of four patients. The United States immediately banned lithium products and began to use them again only in 1970.

What are lithium salts

Lithium salts are organic compounds of a dissociating (decaying) nature with a psychotropic spectrum of action. At In therapeutic use, lithium cations and anions accumulate in the blood up to a certain concentration. They do not bind to proteins and retain their physiological properties in the body. The level of lithium ions is necessarily monitored and maintained under the strict supervision of a physician.

The alkaline element "Li" is naturally found in some mineral springs and in sea salt. Lithium compounds are, as a rule, colorless substances of a crystalline structure that are poorly soluble in water. When lithium salts enter the body, they are concentrated in the brain and tissues and excreted through the kidneys. Metal ions stimulate the sensitivity of brain neurons and dynamically influence the course of neurochemical processes.

Mechanism of action

Main pharmacological action salts of lithium is the activation of reuptake by adrenergic endings in the central nervous system of free norepinephrine and serotonin, which form the development of affective states. The therapeutic effect reduces the number of b-adrenergic receptors and suppresses noradrenergic activity.

Lithium ions inhibit sodium ions in nerve and muscle cells, thereby interfering with the transfer of monovalent cations through membranes and weakening nerve impulses.

"Li" blocks the activity of neuronal dehydrogenase enzymes that synthesize inositol, which regulates the sensitivity and cellular respiration of neurons.

Drug therapy "Li" shows the best results in the treatment of mixed affect, when patients have the presence of a manic syndrome. At the same time, there should be a sufficiently large light gap between the phases of the cycle, then lithium salts exhibit a stabilizing effect on the patient's psyche.

Classification of drugs: what is used and what is not

In pharmacology, only some lithium preparations are used:

The following lithium salts are not used in the Russian Federation: citrate, sulfate, chloride, orotate. These drugs have the same properties as carbonate, but are prohibited for use. Previously, citrate (a compound with citric acid) was part of the Seven Up drink as an anti-hangover component.

Scope and purposes

Indications for the use of basic lithium preparations:

1. lithium carbonate(Lithii carbonas) has a prolonged action and is widely used in the psychiatric industry for such diagnoses: manic phase and exacerbation prevention, schizoaffective disorders, chronic alcoholism, some forms of drug addiction, sexual deviations,. The practice of lithium carbonate therapy for progressive muscular dystrophy is known. Also, the drug is used to treat various (including) - clinical picture after the therapeutic course, it was noted by an increase in muscle strength and an increase in motor activity.
2. Lithium oxybate(Lithii oxybutyras) has a pronounced effect at the same clinical conditions, as in the appointment of carbonate. Lithium and sodium hydroxybutyrate are similar in properties and treat recurrent nervous disorders with manic episodes. Lithium hydroxybutyric acid salt is administered intramuscularly and has less toxicity.
3. lithium nicotinate(Lithium nicotinate) reduces the craving for alcohol and is prescribed for the treatment of chronic alcoholism, acute intoxication, withdrawal symptoms. The therapeutic effect is expressed both against the background of the formation of alcohol motivation, and against the background of alcohol dependence that has already arisen.
4. Lithium succinate used for external use in skin dermatitis, seborrhea and fungal diseases.

Therapeutic and prophylactic doses

In psychiatric practice, for the relief of a manic state, lithium salts are used according to a certain scheme. On the first day, the daily dosage is 0.6-0.9 g. The next day, the dose is increased by 0.3 g and, with good tolerance, increases again every day (daily intake 0.9-2 g).

With such a schedule, the concentration of lithium in the blood is up to 1.2 mmol / l.

Exceeding these indicators is considered toxic and can cause irreparable harm to health.

After obtaining a positive normothymic effect, the dose is gradually reduced to a maintenance dose, and with repeated manifestations of the disease, it increases again.

Depending on the patient's condition, lithium salts can be used preventive treatment. With somatic symptoms of the manic or depressive phase of bipolar disorder, a prophylactic dose of 0.6-0.9 g is prescribed.

Patients in old age are shown lower dosages of therapeutic agents than young people.

Lithium preparations should be taken after meals, absorption occurs mainly in small intestine for 6-8 hours. The half-life and excretion through the kidneys, depending on the age of the patient, ranges from 24-36 hours. With insufficient amounts of sodium and potassium ions in the blood, lithium is reabsorbed by the renal tubules.

Possible side effects

Among the side effects of the use of lithium preparations in psychotherapy, cardiac arrhythmias, thirst, muscle weakness, nausea, frequent urge to urinate, and exacerbation of gastrointestinal diseases are noted.

In the process of treatment, it is necessary to monitor the analyzes for the level of lithium in the body in order to prevent kidney failure in time.

The appointment and intake of any drug should be carried out strictly according to the doctor's prescription. Combination with certain drugs leads to dangerous side effects and an increase in the concentration of lithium.

An overdose of lithium preparations often leads to death.

Contraindications and restrictions

Dysfunction thyroid gland and kidney are the main contraindications to the use of drugs. There is a risk of developing hypothyroidism (rarely hyperthyroidism).

During the reception of funds, doctors advise not to drive a car. Large amounts of salt and liquids should be avoided, but consumed in moderation and regularly. Doctors recommend not to abuse harmful products(smoked meats, pickles and spicy foods).

Medical treatment of nursing mothers is also not recommended, since the effect of lithium on the health of the unborn baby has not been studied.

Lithium salts really expressively cope with the function of stopping acute manic episodes and prevent affective outbursts.

The emotional excitation of the patient gradually fades away, sleep is restored, behavior is streamlined. But a positive psychotropic effect is achieved precisely in the cycle of manic-depressive psychosis, and not during depressive dynamics.

Gross formula

Pharmacological group of the substance Lithium carbonate

Nosological classification (ICD-10)

CAS code

Characteristics of the substance Lithium carbonate

White granular powder, odorless. Slightly soluble in water, practically insoluble in alcohol.

Pharmacology

It blocks sodium channels in neurons and muscle cells, causes a shift in the intraneuronal metabolism of catecholamines.

Sufficiently completely absorbed in the gastrointestinal tract, Tmax is 6-12 hours. T 1/2 increases from 1.3 days after the first dose to 2.4 days after 1 year of regular intake. Passes through the BBB, the placental barrier, penetrates into breast milk.

Application of the substance Lithium carbonate

Manic phase and prevention of exacerbations of bipolar affective disorder, schizoaffective disorders, manic and hypomanic states various genesis, affective disorders in chronic alcoholism, drug dependence (some forms), sexual deviations, Meniere's syndrome, migraine.

Contraindications

Hypersensitivity, major surgery, severe cardiovascular disease (may worsen, lithium excretion may be impaired), epilepsy and parkinsonism (may worsen, the neurotoxic effect of lithium may be masked), a history of leukemia (lithium may cause an exacerbation of leukemia), kidney failure, severe dehydration (increased risk of lithium toxicity), pregnancy, breastfeeding.

Use during pregnancy and lactation

Contraindicated in pregnancy.

Stop during treatment breast-feeding.

Side effects of the substance Lithium carbonate

From the nervous system and sensory organs: hand tremor, drowsiness, weakness.

From the side of cardio-vascular system and blood (hematopoiesis, hemostasis): violation heart rate, leukocytosis, inhibition of hematopoiesis.

From the digestive tract: diarrhea, nausea, vomiting, dry mouth.

From the genitourinary system: polyuria, kidney dysfunction.

Others: myasthenia, increased thirst, weight gain, hypothyroidism, allergic reactions, alopecia, acne.

Interaction

The combination of carbamazepine with lithium increases the risk of neurotoxic effects. Metronidazole, fluoxetine, diuretics, NSAIDs, ACE inhibitors slow down the excretion of Li + by the kidneys and increase its toxic effects (careful monitoring of the concentration of lithium in the blood serum is recommended). The combined use of lithium with ampicillin and tetracycline can lead to an increase in the concentration of lithium in plasma. CCBs increase the incidence of neurotoxic complications (caution should be exercised). With simultaneous use with methyldopa, the risk of developing lithium toxicity may increase even when its concentrations in the blood serum remain within the recommended therapeutic limits. Urea, aminophylline, caffeine, theophylline increase the excretion of Li + by the kidneys and reduce its pharmacological action.

Lithium preparations reduce the pressor effect of norepinephrine (an increase in the dose of norepinephrine may be required), increase or prolong the blockade of neuromuscular transmission when used together with atracurium besilate, pancuronium bromide, suxamethonium; enhance the neurotoxic effects of haloperidol, reduce the absorption of chlorpromazine (and possibly other phenothiazines) from the gastrointestinal tract, which leads to a decrease in its concentration in the blood serum by 40%. Sodium-containing drugs or foods reduce the effectiveness of lithium preparations (high sodium intake increases the excretion of lithium).

With simultaneous appointment with neuroleptics and antidepressants, an increase in body weight is possible. Incompatible with ethanol-containing drinks.

Overdose

Symptoms: speech disorder, hyperreflexia, tonic and epileptic convulsions, oliguria, loss of consciousness, collapse, coma.

Treatment: symptomatic.

Routes of administration

inside.

Substance Precautions Lithium carbonate

Do not use in case of violations of the water-salt balance (salt-free diet, sodium deficiency, diarrhea, vomiting). Use with caution when diabetes(the concentration of insulin in the blood serum may increase), hypothyroidism.

Lithium carbonate

Chemical properties

Salt formed alkali metal lithium and carbonic acid . The substance is a colorless powder or odorless crystals. The agent is poorly soluble in water (especially in hot water), practically insoluble in alcohols. His molecular mass = 73.9 grams per mole. The melting point is about 618 degrees Celsius.

Lithium carbonate is used in the production of plastics, pyrotechnics, porcelain, glass-ceramics , in the desulfurization of steel, in the glass industry.

For medical purposes, lithium salts began to be used even by ancient physicians. They used alkaline mineral water rich in lithium compounds for the treatment of patients with agitation and other mental disorders accompanied by euphoria.

By 1949, Australian scientist John Cade is injecting ToLithium carbonate to treat, and various mania . Then, due to the high toxicity of such compounds, a ban on their use was introduced until 1970. Nowadays Lithium carbonate is actively used in medicine as normotimic and an antipsychotic.

pharmachologic effect

Sedative, antipsychotic, normothymic.

Pharmacodynamics and pharmacokinetics

The substance acts as an antagonist sodium ions in nerve and muscle cells. Thus, muscle weakness develops, it is difficult to carry out nerve impulse . Lithium has an impact on transport, and other monoamines , in some areas of the brain, sensitivity to increases.

Salts also inhibit enzyme activity. , kinase 3 glycogen synthase , protein kinase C . Substance stimulates shift intraneuronal metabolism of catecholamines .

After penetration into the stomach, the agent is rapidly and completely absorbed. It reaches its maximum concentration within 6-12 hours. The half-life is from one day to 2.5 days (after a year of daily intake). The cure overcomes blood-brain barrier passes into breast milk.

Lithium salts are excreted through the kidneys, depending on the level of sodium and potassium, lithium is either reabsorbed in the renal tubules or maintains its equilibrium concentration in the blood.

Indications for use

The tool is used:

• for treatment manic and hypomanic states of various origins;
• as prophylactic or as a medicine for affective psychoses ;
• with chronic;
• for treatment, Meniere's syndrome , sexual deviations;
• with some forms of drug dependence.

Contraindications

Lithium carbonate should not be prescribed:

• with hypersensitivity to the substance;
• after major operations;
• patients with severe cardiovascular diseases;
• for and ;
• breastfeeding women;
• if the patient, including a history;
• with renal failure;
• persons with severe dehydration and imbalance electrolytes ;
• pregnant women.

Side effects

After taking the medicine, you may experience:

• , nausea , dry mucous oral cavity, vomit, ;
• , decreased muscle tone, ;
• leukocytosis , cardiac arrhythmia, slowing hematopoiesis ;
• kidney failure, polyuria ;
• thirst, weight gain, myasthenia gravis , ;
• and allergic rashes.

Lithium Carbonate, instructions for use (Method and dosage)

The dosage is determined by the attending physician, depending on the initial concentration of lithium in the blood plasma.

Lithium carbonate preparations are taken orally.

The average daily dosage for an adult is about 900-2400 mg, divided into 3-4 doses.

The dosage should be selected in such a way that the equilibrium concentration of the agent in the blood is from 0.6 to 1.2 mmol per liter.

As a rule, when taking 1 gram of a substance per day, the optimal equilibrium concentration is reached within 10-14 days.

If during the course of treatment there are pronounced improvements in the patient's condition, then it is highly recommended not to interrupt therapy in order to avoid relapse.

For children, the optimal concentration of lithium \u003d 0.5-1 mmol per liter.

Overdose

With an overdose of the drug develop: hyperreflexia , speech disorders, epileptic seizures and tonic convulsions , oliguria , loss of consciousness, collapse . Treatment is according to the symptoms.

Interaction

Combination medicinal product With thiazide diuretics , methyldopa , or may lead to rapid growth plasma concentration of lithium in the blood and the development of toxic effects.

ACE inhibitors , non-steroidal anti-inflammatory drugs increase the concentration of lithium in the blood, increase the risk of adverse reactions.

The combined intake of the substance leads to an increase in the level of lithium in the blood.

Derivatives enhance the excretion of lithium from the body with urine, this can lead to a decrease in the effectiveness of the drug.

When combined with this compound, the toxic effect of the drug is enhanced.

It is better not to combine with the drug, drug interaction unpredictable.

With the combined use of the drug, isolated cases of amplification were described hyperkinetic symptoms in patients who are sick chorea of ​​Huntington ., violations in the work of the cerebellum.

Terms of sale

Need a prescription.

Storage conditions

Tablets are stored in a dark, dry place, away from children.

Best before date

special instructions

Some phenothiazines may mask the symptoms of lithium toxicity.

After a month of continuous medication, it is recommended to monitor the concentration of lithium in the blood plasma weekly. Then these indicators can be checked once a month, then once every 2-3 months.

During therapy, you should not drive a car or perform potentially dangerous species activities.

Elderly

The elderly and debilitated patients need dosage adjustment.

With alcohol

During treatment, you can not take alcohol.

Preparations containing (Analogues)

The substance is part of the drugs: Kontemnol, Lithium Carbonate, Lyosan-SR, Lithium Carbonate Coated Tablets .

Lithium- very light and ductile silver-white metal. In industry, it is mainly used to create chemical current sources. But, in a small amount, it is also present in living organisms, performing its rather important role in maintaining health and vitality.

Beneficial features lithium in the human body

The body of an adult contains only about 70 mg of lithium, but when it is deficient, a number of chronic diseases, and in the first place among them - nervous and mental disorders.

Lithium is present in the lymph nodes, adrenal glands, blood plasma, intestines, heart, lungs, liver and thyroid gland. But it plays a special role for the nervous system. Back in the middle of the 20th century, it was noticed that it significantly improves the condition of patients in the treatment of mental illness. Significantly improves general state in Alzheimer's disease and people who have had a stroke.

Also, it was noted that in those regions where lithium is found in drinking water, mental illness in the population occurs much less frequently, and the character of people is less irritable. Therefore, already in the 70s of the last century, this trace element began to be used in psychotropic drugs for the treatment of depression, aggressiveness, and drug addiction.

In addition to the nervous system, lithium also: takes part in fat and carbohydrate metabolism; reduces the effect allergic reactions; supports work immune system. It has the ability to remove heavy metal salts, radiation from the body, and even neutralize the effects of alcohol on the body.

deficit lithium in the human body

Little is known about lithium deficiency. Perhaps this is because his symptoms overlap or are masked by other associated disorders. It is reliably known that with its deficiency, the nervous system suffers first of all, but what this dependence is, this question has not yet been fully studied. Scientists, at the moment, agree that lithium has the ability to slow down the transmission of nerve impulses, and also takes part in the work of enzymes that carry ions into the brain cells and from the intercellular fluid. After all, it is known that in people with manic states, an increased content of sodium, lithium is usually observed in the brain cells, which helps to balance the balance of microelements, and thus has a positive effect.

It is also noted that reduced content lithium in the body is observed in chronic alcoholics, drug addicts and people prone to suicide. Therefore, it can be assumed that lithium somehow affects not only the nervous system, but also the centers in the brain responsible for pleasure and the ability to rejoice and be happy. More recently, scientists have discovered that all people are able to experience feelings of happiness in different ways. And lithium plays a certain role here. Therefore, the main signs of lithium deficiency include: depression, depression, anxiety, etc.

Not so long ago, it was found that lithium, interacting with other minerals in the body, helps them prevent the development of atherosclerosis, cardiovascular diseases and reduce the risk of developing hypertension and diabetes.

An adult needs about 100 micrograms of lithium per day. Most of it is found in the lymph nodes, lungs and brain. Much less in the liver, blood and muscles.

Excess lithium in the human body

With food, excess lithium is almost impossible to get. A dose starting from 100 mg is considered toxic. Already at this dosage, thirst may appear, sweating and urine output increase, trembling in the hands appears. At high dosages, weakness appears, impaired coordination of movement, nausea, diarrhea, and a person can even fall into a coma.

Sourceslithium

As with many, especially rare, micronutrients, fresh, wild-caught seafood is also a good food source for lithium. Lithium is rich in sea salt, seaweed, and the content in other plants depends very much on the place and conditions of their growth.

Lithium deficiency can be corrected by introducing vitamin-mineral complexes with lithium into the diet, but it is better to do this under the supervision of a doctor.

Lithium absorption

It is clear that organic lithium obtained from food is the best for absorption and safest. It has been established that calcium improves the absorption of lithium, while magnesium, potassium and sodium worsen it.

The most effective psychotropic drug in this group is lithium. Although lithium does have some antidepressant properties, it is not a true antidepressant in the strict sense of the word. The effectiveness of lithium in the treatment of patients with bipolar disorders (see Chapter 360) and other mood disorders has revolutionized psychiatric practice. After the use of lithium was approved by the FDA in 1969, intensive scientific research began in the field of theory, pharmacology and clinical use of this drug.

Mechanism of action of lithium. While some clarity has been achieved regarding the clinical use of lithium, the questions of its mechanisms of action remain largely unknown. Lithium affects the concentration of monoaminergic neurotransmitters in the brain at the level of synapses, and it is believed that this is part of the mechanism of action. In addition, lithium has a strong effect on biological membranes, and this seems to be also included in its mechanism of action on the CNS. Lithium is in some way a unique drug, as it simultaneously alleviates the emotional excitement inherent in manic states, and at the same time controls the state of depression in bipolar disorders. However, the central mechanisms through which clinical effect lithium on polar mood swings remain unexplained.

Indications for the use of lithium. Lithium is most effective in manic-hypomanic episodes and in preventing recurrent episodes of mania and depression in bipolar disorder. Although some experts classify lithium as a mild antidepressant (especially in cases of depression that occurs on the background of bipolar disorders), it still cannot be considered the drug of choice for depression as such. However, in the prevention of recurrent unipolar depressive disorders lithium may be quite effective. It has been successfully used in combination with neuroleptics in schizoaffective schizophrenia. There may be a subpopulation of schizophrenic patients who respond well to lithium, although many reporters tend to think that such patients should rather be considered as atypical bipolar patients. Finally, there are reports that the use of lithium may be useful in alcoholism. This, of course, is an interesting, but not yet scientifically established fact.

Clinical use of lithium. Lithium is pretty safe medicinal product with an excellent risk/benefit ratio. The only true contraindication for its use is a significant violation of the functional state of the kidneys. Before prescribing lithium to a patient, the physician should have the following information: clinical analysis blood and urine, Zimnitsky's concentration test, data from a study in the blood of total thyroxine (T 4), serum creatinine and electrolytes, and in patients older than 40 years - ECG data.

Lithium reaches its peak serum concentration 1-3 hours after oral administration, the biological half-life of the drug is 24 hours, although this figure varies depending on the age of the patient. In elderly patients, it sometimes exceeds 30 hours (which leads to the use of lower doses), while in adolescents it is less than 20 hours (which, on the contrary, requires the use of higher doses). The content of lithium in the blood serum must be monitored. The most informative for this is a study conducted 10 hours after the last dose. The therapeutic effect in acute manic states is achieved when the concentration of lithium in the blood is 0.8-1.5 meq / l. The need to increase the concentration of lithium in the blood more than 1.5 meq / l is rare. Lithium is administered orally in doses of 600 to 3000 mg 4 times a day. It has been empirically found that each additional 300 mg lithium tablet increases its blood concentration by 0.2 mEq/L. Lithium should be taken until the patient becomes stable. Taking the drug 2-3 times a day allows you to maintain a stable therapeutic concentration in the blood during the day. Full therapeutic effect lithium occurs 7-10 days after the start of therapy, therefore, in early stages In the treatment of manic patients, it may be necessary to additionally use antipsychotic drugs. During acute manic episodes, patients usually tolerate relatively high doses of lithium, but as soon as the manic state can be stopped, the dose of lithium is immediately reduced so as not to cause intoxication. In the case of treatment of an uncomplicated acute manic-hypomanic state, lithium intake is continued for 6-8 months after the symptoms of the disease disappear. Cancel the drug gradually, within 3-4 weeks. Due to various complications long-term treatment doctors are usually very reserved about this lithium regimen, unless, of course, there are very clear indications for it.

Maintenance therapy is indicated in patients with a history of at least three episodes of diagnosed manic and/or depressive states, two of which must occur within a two-year period, and the subsequent episode of exacerbation of the disease - in the next two years. Thus, the doctor must be convinced that exacerbations of the manic-depressive state in the patient occur frequently, proceed quite seriously and significantly disrupt the patient's normal life. At present, they adhere to the tactics of maintaining the minimum concentration of lithium in the blood, which allows avoiding relapses of the disease. Previously, such a concentration in maintenance therapy was considered equal to 0.4-1 meq/l, but recently it has been shown that the frequency of relapses increases significantly only when the concentration of lithium in the blood falls below 0.4 meq/l.

The rate of elimination of lithium from the body in each patient is stable, so that the patient can receive the same maintenance dose of the drug for a long time without a great risk of changing its concentration in the blood. Patients on maintenance therapy should be examined by a doctor every 3-6 months, at the same time they determine the content of lithium, sodium, potassium, T4, TSH and creatinine in the blood, and also examine the concentration function of the kidneys. It should be remembered that the concentration of lithium in the blood is dependent on changes in the content of sodium, therefore, monitoring of patients receiving thiazide diuretics or on a diet low in sodium chloride should be carried out more often.

Side effects when using lithium and its interaction with other drugs. Side effects when taking lithium are varied (Table 364-4). Many of them are very harmless, they appear at the initial stages of treatment and gradually disappear, while others, on the contrary, progress as the treatment continues. As a rule, a rapid increase in the concentration of lithium in the blood portends the occurrence of certain side effects especially from the gastrointestinal tract.

Table 364-4 Side effects of lithium