Side effects typical of lithium salts are. Side effects of lithium preparations

Lithium salt

In the USSR to medical use lithium carbonate and lithium oxybutyrate are allowed. The action of lithium salts on c.s.s. characterized mainly by their ability to stop acute manic and prevent attacks of affective disorders. Unlike many other psychotropic drugs, HP even with long-term use do not affect intelligence. Lithium oxybutyrate also has sedative and antihypoxic properties, which is due to the presence of a γ-hydroxybutyric acid molecule residue in its molecule. IN therapeutic doses HP have a positive inotropic and negative on the heart and, in this regard, increase the strength and slow down the rhythm of heart contractions, and also prevent the development of arrhythmias, increase the volumetric velocity of coronary blood flow, increase the glycogen content in the conduction system of the heart and cardiomyocytes. Excreted in the urine, lithium ions increase the solubility of uric acid and its salts in it. In addition, L.S. stimulate.

Mechanisms of psychotropic action HP little studied. It is only known that lithium ions are antagonists of sodium ions in the processes of transport of the latter through the cell membranes of nerve and muscle cells. Under the influence of HP there are also changes in bioenergetic, carbohydrate, lipid and protein metabolism and metabolism of some neurotransmitters (norepinephrine, serotonin, enkephalins) and the sensitivity to them of the corresponding receptors on the membranes of neurons.

After the introduction of HP. in lithium ions are unevenly distributed in tissues, as well as structures of the brain. They are found in the highest concentrations in the kidneys and further (in decreasing order of content) in the blood, liver, diencephalon, midbrain and cerebral cortex. When using lithium oxybutyrate, lithium ions are absorbed faster into and penetrate into c.ns. than when other salts are used. lithium ions from the body occurs through. About 50% of the administered dose is excreted in the urine per day. Renal eccentration in the blood, as well as on the body's sodium and potassium content. With a low sodium content in urine, lithium ions undergo reabsorption in the renal tubules, which leads to an increase in the lithium content in the blood. An increase in the excretion of lithium ions in the urine and a decrease in their concentration in the blood is facilitated by the introduction of sodium into the body.

As psychotropic drugs HP used mainly for manic and hypomanic states, for the prevention and elimination of affective disorders (for example, with manic-depressive, schizoaffective and other psychoses), as well as for eliminating behavioral disorders characterized by impulsivity, aggressiveness and agitation (for example, in organic psychosis, and etc.). As a means for the elimination of affective disorders HP used in complex therapy alcoholism. In psychiatric practice, L.S. often used with antipsychotics (see table Antipsychotics) , tranquilizers (tranquilizers) and antidepressants (Antidepressants) , which increases the effectiveness of treatment.

Therapeutic efficacy of HP depends on the level of concentration of lithium ions in the blood, which should be at least 0.6, but not higher than 1.2-1.6 meq / l, since when these concentrations are exceeded, signs of lithium intoxication develop.

Side effect of HP manifested by impaired renal function, as well as water-salt metabolism with the development of a diabetes-like syndrome, dyspeptic disorders and diarrhea. As a result of the depressing effect of lithium ions on the function thyroid gland with prolonged use of its salts, development of diffuse goiter and temporary weight gain. Side and toxic effects of HP. on the cardiovascular system is manifested by sinus tachycardia, extrasystole, a decrease in the value of the T wave by, and a toxic effect on the c.s. - muscle weakness, tremors, ataxia, fascicular muscle twitching, choreatetoid hyperkinesis and epileptaform seizures. As a rule, the occurrence of these effects is associated with an overdose of the drug in the absence of proper control of the therapeutic level of lithium ions in the blood. Given this, it is advisable to determine the concentration of lithium ions in the blood at the beginning of treatment at least 1 time per week, and subsequently - 1 time in 2-4 weeks. If carried out without monitoring the content of lithium ions in the blood, its preparations should be prescribed in a daily dose not exceeding 2 r... Side effects disappear after temporary withdrawal or dose reduction. In the event of side and toxic effects, sodium bicarbonate, aminophylline, diacarb, urea are prescribed.

Methods of application, dosage, form of release and storage conditions for basic lithium preparations are given below.

Lithium carbonate (Lithii carbonas) is administered orally on the first day at a daily dose of 0.6-0.9 r... With good tolerance, starting from the 2nd day of treatment, it is increased by 0.3 rdaily up to a daily dose of 1.5-2.1 r(sometimes up to 2.4 r). The daily dose is divided equally into 3-4 doses during the day. After the disappearance of the manic state, the daily dose is gradually reduced to 1.2-0.6 r... For prophylactic purposes, it is prescribed in a daily dose of 0.3-0.6 r, increasing it to 0.9-1.2 r... Release form: tablets of 0.3 r, coated. Storage: in a dry place. Abroad, lithium carbonate is also produced in the form of tablets (Lithionite-durel, Lithium-durulose, etc.), providing a prolonged action of the drug. In the USSR, a similar dosage form lithium carbonate is the drug "Micalit" (Micalitum) - capsules containing 0.4 rmicroencapsulated lithium carbonate.

Lithium oxybutyras and butyrate are prescribed orally or intramuscularly in daily doses up to 3 r, which are divided into 2-3 receptions. Method of production: tablets of 0.5 rand ampoules of 2 ml 20% solution. Storage: List B: in a dry place.

Bibliography: New data on pharmacology and clinical use lithium salts, ed. E.I. Lyubimova, M., 1984, bibliogr.

1. Small Medical Encyclopedia. - M .: Medical encyclopedia... 1991-96 2. First aid. - M .: Great Russian Encyclopedia. 1994 3. encyclopedic Dictionary medical terms... - M .: Soviet encyclopedia. - 1982-1984.

See what "Lithium salt" is in other dictionaries:

LITHIUM (SALT) - Usually they belong to antipsychotics, lithium compounds are used primarily for the treatment of bipolar disorders, especially the manic aspect. The mode of action of lithium in the body is unknown. He, however, competes ... Dictionary in psychology

Lithium salt - lithium preparations (lithium carbonate, lithium oxybutyrate, lithium nicotinate, lithium oxybate, lithium citrate), which have a normotimic effect (that is, normalizing mood), as well as an anti-manic effect. Mainly used for ... ... Encyclopedic Dictionary of Psychology and Pedagogy

Active ingredient ›› Lithium carbonate Latin name Tabulettae Lithii carbonas obductae 0.3 g ATC: ›› N05AN01 Lithium salts Pharmacological group: Normotimics Nosological classification (ICD 10) ›› F30 Manic ... ...

- (Lithii carbonas). Synonyms: Contemnol, Camcolit, Carbopax, Contemnol, Eskalith, Licarb, Lithane, Lithicarb, Lithium carbonicum, Lithizine, Lithobid, Lithomyl, Lithonate, Liticar, Lito, Neurolepsin, Plenur, Priadel, Teralithe, etc. White ... Dictionary medical supplies

- (shenite) double complex salts of the general formula M2I MII (SO4) 2 6H2O. Cs, K, NH4, Rb, Tl can act as MI metal, Cd, Co, Cr, Cu, Fe, Mg, Mn, Ni, V, Zn as MII metal. The name "shenita" comes from the mineral ... ... Wikipedia

Li2CO3, colorless crystals with a monoclinic lattice (a \u003d 0.839 nm, b \u003d 0.500 nm, c \u003d 0.621 nm, b \u003d 114.5 °, z \u003d 4, space group C2 / c); t. pl. 732 ° C, above this temperature it dissociates into Li2O and CO 2; dense 2.111 g / cm 3; С ° р98.32 J / (mol ... Chemical encyclopedia

Drugs that affect kidney function can affect serum lithium concentrations, and even a small increase in lithium concentration can be dangerous, since the therapeutic range of lithium is narrow.
Lithium ions do not affect the activity of liver enzymes and do not undergo biotransformation themselves; they are excreted from the body unchanged.
Interacting with individual classes medicines:
Antipsychotics. Lithium, if necessary, can be administered simultaneously with antipsychotics. There is evidence that, when combined with antipsychotics, reversible neurotoxicity sometimes occurs in middle-aged and elderly people. Nevertheless, this drug combination is quite safe and effective if antipsychotics and lithium are used in moderate doses and the patient is closely monitored; however, the use of this combination of drugs should be discontinued immediately upon reaching therapeutic effect lithium. With a combination of neuroleptics and lithium, tremor can become generalized; some patients also experience a kind of deterioration mental state, internal tension, agitation, irritability, explosiveness, emotional lability, impulsivity, impaired memory for current events. Extrapyramidal side effects and hyperkinesias are possible; there have been cases of clinical picture, resembling neuroleptic malignant syndrome. Severe neuroxic reactions occur extremely rarely: for example, acute toxic encephalopathy with deep dullness, cerebral, cerebellar and brainstem neurological symptoms, signs of cerebral edema can develop. Most often, encephalopathy was observed when lithium was combined with haloperidol, but it has also been described when combined with thioridazine, perphenazine and thiothixene. Such factors as high doses of drugs, organic pathology of the central nervous system, the presence of infection, fever, and dehydration predispose to neurotoxic reactions with this combination of drugs. The use of lithium in conjunction with antipsychotics can also lead to an increase in body weight.
Carbamazepine (Finlepsin). The combination of lithium with carbamazepine is used for persistent MDP, however, according to some reports, carbamazepine can increase the side effects of lithium.
In most cases, the combination of carbamazepine and lithium is well tolerated, but in patients at risk (with signs of the neurotoxic effect of lithium or with neurological diseases history), symptoms of a neurotoxic effect are possible even against the background of medium concentrations of drugs in the blood. Both drugs cause hypothyroidism, so thyroid function must be monitored during therapy. Lithium can reduce leukopenia and neutropenia caused by carbamazepine, but lithium is not a means of preventing hematopoietic suppression. It can also reduce carbamazepine-induced hyponatremia.
Valproic acid. Sometimes it can increase the efficiency of lithium when the TIR is resistant.
Tricyclic antidepressants (amitriptyline). Lithium can enhance the therapeutic effect of antidepressants, but the risk of intoxication also increases. Rare cases of seizures with a combination of amitriptyline in a high dose and lithium, as well as cardiovascular complications and hypothyroidism with the simultaneous administration of lithium and tricyclic antidepressants for more than six months have been described. There is evidence of the appearance of signs of a neurotoxic effect in the form of tremor, memory impairment, distraction, disorganization of thinking, even with normal blood lithium concentration and moderate doses of amitriptyline. Serotonin syndrome was diagnosed in a number of patients against the background of a combination of lithium and clomipramine.
Antidepressants - selective inhibitors reuptake of serotonin (fluoxetine). The combination of lithium with antidepressants of this group, as a rule, is well tolerated, but it can also cause adverse consequences: intoxication of the central nervous system and arterial hypertension or hypotension. In general, lithium can enhance the serotonergic effect of SSRIs, thereby causing characteristic neurological and gastrointestinal side effects. Cases of serotonin syndrome have sometimes been reported. Antidepressants in this group can increase the side effects of lithium.
Antidepressants are monoamine oxidase inhibitors. The combination of lithium with drugs in this group can cause serotonin syndrome.
Dopaminergic drugs. Against the background of a combination of lithium and levodopa, the development of dyskinesias and hallucinations is possible; when combined with methyldopa, neurotoxic side effects may develop disproportionately to the concentration of lithium in the blood plasma.
Verapamil. The appearance of cardiotoxic and other side effects is possible in patients with neoplastic processes complicated by cardiovascular diseases.
Thyroid hormones. When lithium is combined with thyroxine or liothyronine, the release of thyroid hormone decreases.
Iodine preparations. Combining is not recommended due to pronounced side effects on the function of the thyroid gland.
Antihypertensive drugs. ACE inhibitors and angiotensin type 1 receptor antagonists can increase serum lithium concentration, resulting in lithium toxicity; therefore, it is better for patients taking lithium to prescribe antihypertensive drugs of other groups (beta-blockers, prazosin). Methyldopa in combination with lithium can cause confusion, tremors, dysarthria, blurred vision, lethargy, and dysphoria. Lithium reduces the hypotensive effect of clonidine.
Diuretics ("diuretics"). When combined with thiazide diuretics (for example, hydrochlorothiazide), lithium excretion decreases and increases serum concentration, which can lead to lithium intoxication. Potassium-sparing diuretics are safer; data on the combination of lithium with loop diuretics and carbonic anhydrase inhibitors are controversial. Sometimes lithium is combined with a potassium-sparing or thiazide diuretic to reduce lithium-induced polyuria or nephrogenic diabetes insipidus... Osmotic diuretics decrease the concentration of lithium in the blood, which can lead to a decrease in the effectiveness of therapy and the emergence of "breakthrough" mania or depression.
Some non-steroidal anti-inflammatory drugs (indomethacin, phenylbutazone) increase the reabsorption of lithium in the kidneys and, as a result, its concentration in the blood, which can lead to intoxication. Ketorolac is incompatible with lithium preparations.
Metronidazole, tetracyclines. Serum lithium concentration increases. Cases of severe renal intoxication with the combined use of lithium and metronidazole have been described.
Theophylline, aminophylline. The serum concentration of lithium decreases, which can lead to a decrease in the effectiveness of therapy, the occurrence of mania or depression.
Cardiac glycosides (digitoxin). This combination is not recommended due to the increased toxic effects of lithium and the development of arrhythmias.
Muscle relaxants. Lithium can potentiate their action. If necessary surgical treatment with the use of muscle relaxants, it is necessary to warn the anesthesiologist about taking lithium and stop taking it 48-72 hours before the operation.
Inhalation anesthetics. It is necessary to cancel the lithium drug 1-2 days before the operation.
Caffeine. Lithium-induced tremors may increase.
Ethanol. Lithium relieves alcohol euphoria, reduces alcohol cravings and cognitive impairments caused by alcoholism. Lithium is ineffective for alcohol withdrawal. Like other CNS depressants, ethanol interacts with lithium and can cause sedation or confusion.

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

Blocks sodium channels in neurons and muscle cells, causes a shift in the intra-neuronal metabolism of catecholamines.

It is quite fully absorbed in the digestive tract, T max 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, placental barrier, enters breast milk.

Application of the substance Lithium carbonate

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

Contraindications

Hypersensitivity, severe surgical intervention, severe cardiovascular diseases (may exacerbate, possibly impaired lithium excretion), epilepsy and parkinsonism (may exacerbate, the neurotoxic effect of lithium may be masked), a history of leukemia (lithium may exacerbate leukemia), renal failure, severe dehydration (the risk of toxicity increases lithium), pregnancy, breastfeeding.

Application during pregnancy and lactation

Contraindicated in pregnancy.

Discontinue during treatment breast-feeding.

Side effects of the substance Lithium carbonate

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

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

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

From the side genitourinary system: polyuria, kidney dysfunction.

Others: myasthenia gravis, 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 enhance 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 the plasma. CCBs increase the incidence of neurotoxic complications (caution should be exercised). With simultaneous use with methyldopa, the risk of lithium toxicity may increase, even if its serum concentrations 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 lengthen the blockade of neuromuscular transmission when used together with atracuria besylate, 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 preparations or food products reduce the effectiveness of lithium preparations (high sodium intake enhances the excretion of lithium).

When administered simultaneously with antipsychotics and antidepressants, an increase in body weight is possible. Incompatible with ethanol-containing drinks.

Overdose

Symptoms: speech impairment, hyperreflexia, tonic and epileptic seizures, oliguria, loss of consciousness, collapse, coma.

Treatment: symptomatic.

Route of administration

Inside.

Substance Precautions Lithium Carbonate

Cannot be used for violations of the water-salt balance (salt-free diet, sodium deficiency, diarrhea, vomiting). Use with caution when diabetes mellitus (the concentration of insulin in the serum may increase), hypothyroidism.

The side effects of lithium salts have been known since the first years of their use. These are dyspeptic disorders, especially in the first weeks of admission, tremors of the fingers, dizziness, drowsiness, fatigue, muscle weakness, thirst and polyuria, decreased thyroid function, eCG changes... Less common are skin reactions, weight gain, and tooth loss.

Renal dysfunction has been thoroughly studied over the past 10 years. They are clinically expressed as polyuria and polydipsia. We observed several patients whose daily fluid intake was close to 10 liters. At the beginning of the use of lithium, these phenomena were treated as factors that complicate life, disrupt night sleep (awakening from thirst, from the urge to urinate). However, the low density of urine in these patients made it necessary to investigate the concentration capacity of the kidneys. Observations were carried out with the study of the daily amount of excreted urine, its microscopic composition, creatinine clearance, concentration of electrolytes and blood creatinine, tubular function. In some patients, violations were not found, in others, some pathological changes were noted.

One of the causes of renal impairment is a decrease in sensitivity to antidiuretic hormone. The function of the glomeruli suffers little, although there is evidence that biopsy reveals histological changes: fibrosis, inflammation of the interstitial tissue. The mechanism of action of lithium is unclear. To date, published data on 150 biopsies, but the same changes were found in patients with MDP, not treated with lithium. Despite these morphological changes, the filtration function of the glomeruli decreases extremely rarely. Thus, in 180 patients who received lithium carbonate for 17 years, the creatinine clearance was 100 ml / min on average (the study was conducted within 24 hours); in 19 patients - from 70 to 50 ml / min, in 4 - from 50 to 30 ml / min. Another indicator of the nephron's filtration capacity - the concentration of creatinine in the blood plasma - changes with the duration of lithium treatment, but insignificantly: an increase of 1 mg / l over 10 years of treatment.

Thus, the question that psychiatrists have been asking themselves is: "Do patients treated with lithium receive mental health at the cost of kidney damage?" - dropped. However, another function of the kidneys - the ability to concentrate urine - suffers in many. Over the years, the distal tubules of the nephron and collecting ducts react less and less to antidiuretic hormone (the mechanism of this action is influenced by the effect of lithium ion on cAMP of cell membranes). The reabsorption of water in these areas is sharply reduced, which leads to a condition similar to diabetes insipidus.

Polyuria leads to thirst, polydipsia, nocturia, and weight gain. After the abolition of lithium, the concentration function of the kidneys is gradually restored, however, normalization is slow, and for many months it may be defective.

We observed three patients with particularly severe polyuria. One of them is a doctor who is interested in the problem of electrolyte shifts in the body during lithium treatment. After the acute, difficult dual phase of his illness was over, he willingly began prophylactic treatment with lithium. In those years, it was not yet established what was primary - thirst or polyuria, and we advised patients to refrain from heavy drinking. As a result, muscle weakness and hand tremors appeared - the lithium dose had to be reduced. Measurements of the concentration of potassium and sodium in blood plasma and erythrocytes in this patient showed extreme variability, in addition, ECG changes appeared. All this was interpreted as a sharp violation of water-salt metabolism. Two years later, in spite of the fact that the patient's mental state was still unstable (the disease continued to manifest itself in short depressive and manic attacks), he, worn out mainly by nick-turia, refused to take lithium. At the height of the treatment with lithium carbonate, he drank up to 10 liters a day, 2 years after the cancellation - 5 ... 7 liters. Polyuria and sharp fluctuations in the concentration of potassium, sodium, and calcium persisted.

We have made attempts to reduce polyuria, especially nocturia. Some influence was exerted by taking amitriptyline, finlepsin or nootropil before bedtime. Polyuria and polydipsia are not life threatening by themselves. However, a decrease in the concentration capacity of the kidneys leads to the risk of dehydration if fluid loss is difficult to replace or if additional fluid loss occurs (eg, repeated profuse vomiting, bleeding). Dehydration reduces lithium clearance and can lead to toxicity.

It has long been known that a normal salt diet is required for safe lithium treatment; it has now been established that the normal human intake of fluid is also necessary. Even a one-day "dry eating" is dangerous. In whatever conditions a patient who takes lithium may find himself, he must ensure himself the opportunity to drink. This should be taken into account during long trips in transport, with profuse sweating, with diarrhea. In patients with severe polyuria, dehydration occurs very quickly. This also applies when patients undergo anesthetic surgery. Not only the period of unconsciousness, but also the subsequent period, if the patient is forbidden to drink, is dangerous; on these days we advise discontinuing lithium and administering as much parenteral fluid as possible.

In order not to miss the gradually developing impairment of the concentration ability of the kidneys, we demand that all patients, regardless of clinical manifestations, twice a year undergo a general urinalysis and be examined for the content of blood urea (or residual nitrogen). For 16 years, in 15 out of 350 patients, residual nitrogen exceeded 40 mmol / l (maximum - 70) - without a visible clinical picture of kidney disease. These patients were prescribed a course of Lespinephril, some of them took 5-NOC. At the same time, the analytical data normalized. Low relative density (1000 ... ... 1005) was constantly recorded. Only in one patient, suffering from concomitant heart disease, hypertension and nephritis, after taking lithium, an increase in hematuria was found, protein in the urine and, at the insistence of nephrologists, lithium intake was temporarily canceled. Practice shows that polyuria - polydipsia develops more often at high concentrations of lithium in the blood plasma, therefore, when this side effect appears, an attempt should be made to reduce the dose of lithium. According to our data, polyuria occurred in 25 people at a concentration above 0.7 mmol / l and in 4 - below this limit (out of 250 patients).

Effect on the heart. Soon after the widespread introduction of lithium into practice, asymptomatic ECG changes were noted in patients. We, together with the cardiologist L.G. Gepstein, analyzed the ECG of 95 patients who had been taking lithium carbonate for many years. The disturbances we found coincided with those given in the literature: flattening of the T wave before merging with the isoline, negative T wave, biphasic T. Sometimes the ECG indicates a violation of conduction in the atrioventricular bundle (His), while the rhythm of heart contractions is disturbed. Organic, structural myocardial lesions are also described. ECG changes without appropriate clinic are not considered a reason for discontinuation of lithium treatment. Perhaps they are associated with hypokalemia.

Arrhythmia and conduction disturbances are often transient. Lithium inhibits the heart rate in the sinus, and therefore it was used to stop paroxysmal tachycardia. Obstruction of the impulse from the atria to the ventricles can lead to a transient atrioventricular block. This causes patients (often unaware of their heart failure) fainting or short-term periods of clouding. Previously, these obscurations were attributed to the feeling of weakness and fatigue caused by lithium. In fact, this is the result of a short interruption in the supply of oxygen to the brain during arrhythmias. If the patient complains of short episodes of "turbidity in the head", "clouding of consciousness", it is necessary first of all to make an ECG. Less commonly, there is an increase in ventricular excitability. It is dangerous for patients with coronary atherosclerosis.

Myocardial infarctions have been reported in patients taking lithium, but there is no strong evidence that lithium played a role in the origin of these infarctions. Among our 250 patients, 6 suffered myocardial infarction, each of them took lithium for at least 5 years. Age: 45, 48, 59, 60, 62, 78 Five are men, one is a woman. All by nature are restless, anxious, with great responsibility related to their work, having chosen difficult professions, four - they did their job well, but lived in constant anxiety for the correctness of their actions (surgeon, psychiatrist, literature teacher in the senior classes of an English school , polar explorer) and two - gifted design engineers who, after the very first bouts of illness, had to retire from creative work, which then became a constant cause for feelings and regrets. Long before the heart attack and treatment with lithium, all had hypertension of one severity or another, five had angina attacks, and only one patient had a heart attack accidentally, during examination during the flu. This characteristic of the group of patients with myocardial infarction does not reveal any etiopathogenetic relationship with lithium intake. 3 out of 6 patients continued to take lithium carbonate in the acute period and, since drinking was limited to them, the concentration of lithium in the blood was determined often, and the doses were reduced.

Other changes in the heart muscle have also been described that cannot be unconditionally attributed to the action of lithium. J. Mitchell, Th. Mackenzie (1982) describes a heart biopsy of a 65-year-old woman who died of a heart attack. During long-term treatment with lithium salts, she developed arrhythmias. After death, a slight defeat by atherosclerosis was found, and in the left ventricle - pronounced phenomena of myocarditis. The heart muscle had a higher concentration of lithium than other organs, including brain tissue. This case was discussed in the literature, was analyzed by M. Schou, who proved that the calculated concentration was wrong. However, some tropism of lithium to the tissues of the heart, apparently, is there, as evidenced by the frequency of heart lesions in children born to mothers who took lithium during pregnancy, which will be reported in more detail below.

Conclusion of foreign studies and the result of our observations: heart disease and arrhythmias that appear during the period of lithium treatment are not a reason for stopping treatment. However, the following rules must be followed:

Clinically examine the heart before starting lithium treatment;

People over 40 should have an ECG done before treatment;

During the treatment period, often determine the concentration of lithium in the blood and try to keep it as low as possible;

Avoid the appointment of diuretics and remember the need for a complete diet and adequate drinking;

Sightly interview the patient about the sensations of cardiac arrhythmias and cases of "clouding of consciousness";

In case of heart attack, discuss with cardiologists the possibility of continuing treatment with lithium.

Cancellation of lithium treatment is dangerous because of the possibility of a relapse of the disease.

Twice we observed that patients with MDP develop severe mania immediately after an acute infarction and received intensive treatment. Before that, on the day of the heart attack and for another 1 ... 2 days, while the extent of the heart lesion was unclear, these patients did not take lithium. Then the cardiologists themselves consulted a psychiatrist and suggested continuing the lithium treatment. For example, one patient was constantly agitated, in the intensive care unit of the infarction unit, fun reigned, he shouted at the doctor, reproached him for cowardice, demanded that he be allowed to walk, exchanged with other patients of the intensive care unit, almost did not sleep, etc. lithium in both cases was sufficient to stop the mania. Lithium had a beneficial effect on the pulse rate, and tachycardia decreased.

The possibility of using lithium during pregnancy is another question that is last years has been studied more thoroughly. General rulethat during the ripening of the fetus, the mother should not take any medications, in this case it is not suitable, since the mother is a sick person, the normal prenatal development of the fetus and the regime necessary for the child after birth depend on her mental calmness. In addition, it is well known how severe postpartum depression is and how high the risk of their occurrence is in a patient with TIR.

After ingestion, lithium dissolves in the volume of body fluid, it does not bind to plasma proteins, and does not undergo metabolism. The peak concentration occurs 2 ... 4 hours after administration and can be 2 ... 3 times higher than the constant concentration. 99% of it is excreted by the kidneys, 1% through the rectum. The period of its 50% elimination is from 7 to 24; h and depends on the rate of filtration in the kidneys, individual for each person. During pregnancy, the filtration rate in the glomeruli increases, creatinine clearance increases, lithium is excreted faster, which poses a threat of relapse of the disease. Therefore, the determination of the concentration of lithium in plasma in pregnant women should be carried out frequently. At some overseas lithium treatment centers, determinations are made weekly. After childbirth, the filtration rate quickly returns to normal, which can dramatically increase plasma concentration and lead to intoxication if the dose of lithium remains the same as that taken during pregnancy. Some authors propose to cancel lithium intake a week before childbirth, others - with the onset of labor. Lithium easily passes through the placenta, its concentration in the fetal blood is equal to that of the mother. Therefore, avoiding intoxication in the mother is a way to avoid intoxication in the fetus. Children born with intoxication have a characteristic appearance: muscle hypotonia, drowsiness, cyanosis. They often have heart murmurs, there is no sucking reflex, and an arrhythmic pulse is noted. Intoxication symptoms disappear within 10 days.

S. Linden, Ch. Prich (1983) distinguishes three stages of lithium exposure to a child:

From conception to egg implantation - 17 days; as a rule, the toxicity of lithium at high concentration leads to the death of the embryo;

From the 18th to the 55th day - the period of organogenesis; the toxic effect of lithium can lead to the formation of deformities;

From the 56th day to childbirth: the effect of intoxication affects the size and number of cells in developing tissues; by this time the organs have already been formed, but to some extent the teratogenic effect can be felt.

Toxicity depends on the concentration of lithium in the blood, that is, on the daily dose, and on the frequency of its intake. Peaks in concentration after taking a large dose of lithium are toxic to the fetus, and if the drug is taken in small doses throughout the day, the danger is immeasurably less. Taking lithium preparations of prolonged action also does not give high rises in concentration.

Information about congenital malformations comes from the "International Register of Lithium Babies" organized by the group of countries, which includes the Scandinavian countries, USA, Canada. It was founded in 1968. The Center encourages doctors to provide all information about babies born to mothers who have taken lithium during a certain period of pregnancy. Of course, this information is not very clear, it does not compare with the control group in the population; there is still no data on developmental defects in children whose mothers suffer from TIR but do not take lithium. In addition, some take not only lithium, but also some other medications. The pregnancy itself in some mothers proceeds with complications that have nothing to do with lithium. The register publishes informational messages about registered children.

The last publication was in 1978.By this time, there were 217 babies under observation, of which 7 were born dead, 2 had trisomy on chromosome 21 (mothers were over 30 years old), 183 were healthy at birth and 25 (i.e. i.e. 11.5%) had developmental defects. Of these 25, 18 had abnormalities in the development of the cardiovascular system: tortuosity of the aorta, non-closure of the arterial (botallov) duct, defect of the interventricular septum, insufficiency of the mitral and tricuspid valves, anomalies of the umbilical artery and the rare Ebstein anomaly (defect of the tricuspid valve in the right ventricle) ...

After 1978, 7 more cases of Ebstein's anomaly and 1 case of dextrocardia were reported. The remaining 7 children had anomalies in the structure of the outer ear, urethra, central nervous system and endocrine system... When comparing the proportion of heart anomalies with the rest, their predominance is noted to a greater extent than is the case in the population. Therefore, the conclusion of all who studied this issue is unanimous: you should not take lithium salts during the first trimester of pregnancy.

Of those children who were identified as healthy at birth in the "Register of Lithium Children", 83% developed normally in subsequent years. The rest were found to have insufficient weight gain, enuresis, stuttering, dysgraphia, dyslexia, but these are symptoms that are unlikely to be associated with their mothers taking lithium salts.

Among our patients, six took lithium during pregnancy. All these patients (age 20 ... 25 years) before the start of prophylactic therapy with lithium were ill for 3 to 5 years, the disease in all proceeded as bipolar, with frequent phases, with suicidal thoughts during depression, with pronounced excitement during mania, disorganizing family life ...

All of them got married after the beginning of lithium intake, when affective fluctuations were largely smoothed out. At the first suspicion of pregnancy, at our request, the patients stopped taking lithium and did not take until the 4th month. During this time, two developed mild depression, one was in a hypomanic state until the very birth. As soon as lithium intake was resumed, the lithium concentration in the blood was determined every 2 ... 3 weeks. She was small for all, lower than the one that was before pregnancy - 0.4 ... ... 0.5 mmol / l.

Childbirth in one patient was difficult, the child was born in asphyxiation with an umbilical cord entwined with the neck, but later, after six months, he did not lag behind his peers. In another, the child was born lethargic, apparently in a state of intoxication. Unfortunately, childbirth came somewhat prematurely, the patient was out of our control, and after childbirth, the baby's blood was not tested for lithium content. Hypotension and insufficient activity during sucking lasted for about a month, then the patient herself developed depression. The child was brought up in conditions of maternal deprivation and the uneven attitude of the rest of the family, developed unevenly, but by the age of school, these features were smoothed out. The third child (girl) inherited from the mother a pronounced asthenic constitution and later, with a well-developed intellect, revealed nonspecific neurotic features. Three children were healthy, the eldest was 14 years old.

We investigated the concentration of lithium in the milk of nursing mothers, it was about one-third of the level in blood plasma. Is it ok to feed while taking lithium? Since these babies had the same lithium levels in utero as their mothers, breastfeeding means a more gentle lithium regimen for them than before. In the opinion of the majority, to deprive the child of such an important factor for his development as breast feeding, no reason.

Data on incompatibility of lithium salts with other drugs... It has long been known that the combination of lithium with diuretics is undesirable. Since they are saluretics, they change the electrolyte balance in the body, lithium also leads to increased calcium excretion, redistribution of intra- and extracellular potassium and sodium - all this against the background of diuretics can take on pathological dimensions. Against the background of diuretics, the danger of lithium intoxication increases.

For some time, the literature has discussed the dangers of combining lithium salts with haloperidol. When examining 425 patients, it was shown that complications occur with a combination of drugs no more often than in patients taking only lithium or only haloperidol (cited by L. van Knorring et al., 1982). The ratio of lithium concentrations in erythrocytes and blood plasma was examined in patients receiving only lithium and its combination with phenothiazines, butyrophenones, thioxanthenes, in total 59 patients. It turned out that the erythrocyte / plasma index was higher where the combination of drugs was used, and especially when combined with phenothiazines. A high index, according to the author, indicates a passive penetration of lithium into the cell, which may be accompanied by nephrotoxic and neurotoxic effects. Despite this, medical practice often cannot do without a combination of drugs, and if control over the concentration in plasma and erythrocytes is observed, such treatment is justified.

It is unsafe to combine lithium salts with non-steroidal anti-inflammatory drugs (indomethacin, brufen, etc.), as well as when combined with diuretics; in these cases, an increase in the concentration of lithium in plasma is observed. A combination with potentially nephrotoxic antibiotics (tetracyclines) is undesirable. It has been observed that lithium lengthens the action of muscle relaxants, which is dangerous during ECT. M. Schou advises to cancel lithium 2 days before the start of ECT and renew it a day or two after the end of the course. Our experience in ECT treatment with the use of sombrevin anesthesia and the muscle relaxant listenone (21 people) did not reveal an increase in the concentration of lithium immediately after a seizure attack, or complications in the form of a delay in respiratory recovery.

We have presented in such detail a number of undesirable effects of lithium salts on physical health only for their correct understanding. The fact is that in the past three decades, many research works, and the complications of its use have been studied much better than with other psychotropic drugs. They are analyzed, explainable, can be measured, there are ways to overcome them (in contrast, for example, from tardive dyskinesia when using antipsychotics). Therefore, despite the fact that we have devoted a significant part of this chapter side effects lithium, we consider the treatment with this drug convenient, affordable for hospitals and outpatients, a fairly safe method of therapy and prevention.

Refusals of some patients from taking lithium partly depend on the lack of supervision of a psychiatrist, partly on the advice of internist doctors who do not know nature side effects with prolonged use of lithium. Sometimes the reason for refusing treatment is excruciating polyuria and thirst, less often - in a small group of patients - mental changes.

Long-term lithium treatment of patients with TIR often leads to a radical change in the lives of these seriously ill people. Mania and depression become weaker and disappear completely. Life becomes stable and safe, the expectation of deterioration, hospitalization disappears. However, some patients find that not all of the effects of lithium on the psyche are positive. Some memory impairment, a constant feeling of fatigue, a decrease in vital energy, initiative are noted. Some patients complain of a feeling that life with lithium has become less colorful and interesting. S. Arnold, describing the subjective sensations of patients, called it "automatic existence". These sensations lead to the fact that patients begin to arbitrarily skip taking pills, treatment is chaotic and ends with hospitalization or suicide.

When carrying out objective examinations of psychological functions, these changes are not detected in all patients, the changes are very insignificant; in addition, it was shown that they can be strengthened and weakened by prescribing a placebo. The results of the examination depend on the motivation for the examination, on the patient's attitude to the very fact of constant medication. In addition, the detected changes, like complaints, may not depend on the side effect of lithium on mental functions, but on the elimination of manic states or its insufficient effect on depression.

M. Schou (1983a) gives vivid illustrations of how some people "suffer" from the complete elimination of affective phases: the statements of a businessman who made the most successful and risky deals at the beginning of a manic state, and a public figure who complained: politician, I should be excited and argue, but I am calm. " More often, complaints about a decrease in activity, that life has become more boring, are associated with an incomplete effect of lithium, with the emergence of very mild, undeveloped depressive phases, when there is no truly depressive melancholy and a decrease in mental activity can be well analyzed and realized by the patient.

Causes fear the influence of lithium on creative activity... It is necessary, considering this issue, to remember that long-term use of lithium is prescribed for patients with severe forms of affective psychoses, with frequent phases, that is, people who, no matter how gifted they are, are constantly out of order due to bouts of illness and spend many months in mental hospitals. When their painful attacks disappear or weaken so much that the patient continues to engage in his work during periods of illness, in some cases he forgets his difficult past and makes demands on himself, focusing on his creative abilities before the onset of the illness.

According to V. Muller-Oerlinghausen (1982), spontaneous creative activity suffers somewhat, but directed, concentrated creative thinking does not change. According to the observations of N. Loo et al. (1981), in the group of patients examined by him (21 people), who received lithium, the intellectual level in several parameters was statistically lower than in the control. The studies were done 1, 2 and 3 years after the administration of lithium. Over time, the marked decline in intelligence did not deepen. N. Loo believes that it is necessary to take into account that the level of intelligence in his group could be influenced by a severe course of a disease such as melancholia gravis with episodes of impaired consciousness; in addition, many received ECT (effect on memory), the duration of the illness was significant, and lithium did not bring complete stabilization of the condition.

M. Schou (1979) reported on a group of artists (24 people) who suffered from TIR. When taking lithium, their affective seizures disappeared altogether or significantly smoothed out. 6 of them complained about a decrease in creative productivity, 6 - did not notice the change, 12 - noted an increase in creative success. Deterioration was noted by those whose creativity was mainly in the period of hypomanic state. Whatever the complaints about the change, the impoverishment of everyday life in patients who have been taking lithium for many years, in general, what the treatment brings is a great benefit.

Patients with frequent and severe manic and depressive phases constitute a special social group in which the patient himself, his family, friends and co-workers - each plays a role in difficult joint attempts to mitigate, minimize the consequences of the patient's continuous mood changes. With a long course of the disease, such a family is unlikely to have periods when fear of impending disaster in the form of a depressive suicide attempt or a manic act with an underestimation of what is permitted does not dominate in its life. The family lives in an atmosphere of constant vigilance, only preliminary plans are made, activities are limited due to the need to subordinate them to the whims of repeated attacks of illness. All this changes with successful prevention with lithium salts. Relapses become less frequent, weaker, or disappear altogether. "The sick or rather the ex-sick becomes the person he was before the disease."