Gross formula
Li 2 CO 3Pharmacological group of the substance Lithium carbonate
Nosological classification (ICD-10)
CAS code
554-13-2Characteristics of the substance Lithium carbonate
White granular powder, odorless. Slightly soluble in water, practically insoluble in alcohol.
Pharmacology
pharmachologic effect- antipsychotic, normothymic, sedative.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 of various origins, 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 side nervous system and sense organs: hand tremor, drowsiness, weakness.
From the side of the cardiovascular system and blood (hematopoiesis, hemostasis): cardiac arrhythmia, leukocytosis, inhibition of hematopoiesis.
From the digestive tract: diarrhea, nausea, vomiting, dry mouth.
From the 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 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%. medicines containing sodium or food products 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 in diabetes mellitus (the concentration of insulin in the blood serum may increase), hypothyroidism.
lithium salt- dissociating lithium compounds, which are used as psychotropic drugs with an anti-manic spectrum of action.
In the USSR, lithium carbonate and lithium hydroxybutyrate are allowed for medical use. The effect of lithium salts on the central nervous system characterized mainly by their ability to stop acute manic arousal and prevent attacks of affective disorders. Unlike many other psychotropic drugs, L.s. even with prolonged use, they do not affect memory and intelligence. Lithium hydroxybutyrate also has sedative and antihypoxic properties, due to the presence in its molecule of the residue of the g-hydroxybutyric acid molecule. In therapeutic doses HP have a positive inotropic and negative chronotropic effect on the heart and, therefore, increase the strength and slow down the rhythm of heart contractions, as well as prevent the development of arrhythmias, increase the volumetric rate of coronary blood flow, increase the content of glycogen and RNA 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 leukopoiesis.
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 the bioenergetic, carbohydrate, lipid and protein metabolism and metabolism of certain neurotransmitters (norepinephrine, serotonin, enkephalins) and the sensitivity of the corresponding receptors on the membranes of neurons to them.
After the introduction of HP. lithium ions in the body are unevenly distributed in the tissues, as well as in the structures of the brain. They are found in the highest concentrations in the kidneys and further (in order of decreasing content) in the blood, liver, diencephalon, midbrain and cerebral cortex. When using lithium oxybutyrate, lithium ions are absorbed into the blood faster and penetrate into the central nervous system than when using its other salts. The excretion of lithium ions from the body occurs through the kidneys. About 50% of the administered dose is excreted in the urine per day. Renal excretion in the blood, as well as on the content of sodium and potassium in the body. With a low sodium content in the urine, lithium ions are reabsorbed in the renal tubules, which leads to an increase in the lithium content in the blood. Increasing the excretion of lithium ions in the urine and reducing their concentration in the blood contributes to the introduction of sodium into the body.
How psychotropic drugs HP used mainly in manic and hypomanic states,
for the prevention and elimination of affective disorders (for example, with manic-depressive, schizoaffective and other ah), as well as for the elimination of behavioral disorders characterized by impulsivity, aggressiveness and arousal (for example, with organic ah, psychopathy, etc.). As a means to eliminate affective disorders HP. used in complex therapy a. In psychiatric practice, L.s. often used together with neuroleptics, tranquilizers And antidepressants, which increases the effectiveness of treatment.Therapeutic efficacy HP depends on the level of lithium ion concentration in the blood, which should not be lower than 0.6, but not higher than 1.2-1.6 meq/l, because when these concentrations are exceeded, signs of lithium intoxication develop.
Side effect HP manifested by impaired renal function, as well as water-salt metabolism with the development of a similar syndrome, dyspeptic disorders and diarrhea. As a result of the inhibitory effect of lithium ions on the function of the thyroid gland, with prolonged use of its salts, diffuse a and a temporary increase in body weight may develop.
Side and toxic effects HP on the cardiovascular system is manifested by sinus tachycardia, extrasystole, a decrease in the size of the T wave on the ECG, and the toxic effect on the central nervous system. - muscle weakness, om, 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 over 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 once a week, and subsequently - once every 2-4 weeks. If the treatment is carried out without monitoring the content of lithium ions in the blood, its preparations should be prescribed in a daily dose not exceeding 2 G. Side effects disappear after a temporary withdrawal or reduction in the dose of drugs. If side effects and toxic effects occur, sodium bicarbonate, eufillin, diacarb, urea are prescribed.Methods of application, doses, formulations and storage conditions of the main 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 G. With good tolerance, starting from the 2nd day of treatment, it is increased by 0,
Drugs that affect kidney function can affect serum lithium concentrations, and even a small increase in its 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, they are excreted from the body unchanged.
Interaction with certain classes of drugs:
Antipsychotics. Lithium, if necessary, can be administered simultaneously with antipsychotics. There is evidence that when it is combined with antipsychotics in middle-aged and elderly people, reversible neurotoxicity sometimes occurs. However, this drug combination is reasonably safe and effective when antipsychotics and lithium are used in moderate doses and the patient is closely monitored; however, this drug combination should be discontinued as soon as the therapeutic effect of lithium is achieved. With a combination of antipsychotics and lithium, tremor may become generalized; some patients also have a peculiar deterioration in their mental state, internal tension, agitation, irritability, explosiveness, emotional lability, impulsivity, memory impairment for current events. Extrapyramidal side effects and hyperkinesia are possible; there have been cases of a clinical picture resembling neuroleptic malignant syndrome. Severe neuroxic reactions occur extremely rarely: for example, acute toxic encephalopathy can develop with deep clouding of consciousness, cerebral, cerebellar and stem neurological symptoms, and signs of cerebral edema. Most often, encephalopathy was noted when lithium was combined with haloperidol, but it was also 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 weight gain.
Carbamazepine ("Finlepsin"). The combination of lithium with carbamazepine is used for persistent TIR, however, according to some data, 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 a neurotoxic effect of lithium or with a history of neurological diseases), symptoms of a neurotoxic effect are possible even against the background of moderate drug concentrations in the blood. Both drugs cause hypothyroidism, so during therapy it is necessary to monitor the function of the thyroid gland. Lithium can reduce leukopenia and neutropenia caused by carbamazepine, but lithium is not a means of preventing hematopoietic depression. It may also reduce hyponatremia caused by carbamazepine.
Valproic acid. Sometimes it can increase the effectiveness of lithium in persistent TIR.
Tricyclic antidepressants (amitriptyline). Lithium can enhance the therapeutic effect of antidepressants, but the risk of intoxication also increases. Rare cases of seizures have been described with a combination of high-dose amitriptyline and lithium, as well as cardiovascular complications and hypothyroidism while taking lithium and tricyclic antidepressants for more than six months. There is evidence of the occurrence of signs of a neurotoxic effect in the form of tremor, memory impairment, distractibility, disorganization of thinking, even with normal lithium concentrations in the blood and moderate doses of amitriptyline. Serotonin syndrome was diagnosed in a number of patients on the background of a combination of lithium and clomipramine.
Antidepressants are selective serotonin reuptake inhibitors (fluoxetine). The combination of lithium with antidepressants of this group, as a rule, is well tolerated, but can also cause adverse effects: CNS intoxication and arterial hypertension or hypotension. In general, lithium may enhance the serotonergic effects of SSRIs, thereby causing characteristic neurological and gastrointestinal side effects. Occasionally, cases of serotonin syndrome have been reported. Antidepressants in this group may increase the side effects of lithium.
Antidepressants are monoamine oxidase inhibitors. The combination of lithium with drugs of 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. May cause cardiotoxic and other side effects 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. It is not recommended to combine due to a pronounced side effect on thyroid function.
Antihypertensive drugs. ACE inhibitors and type 1 angiotensin receptor antagonists can increase serum lithium levels, leading to 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, tremor, dysarthria, blurred vision, lethargy, dysphoria. Lithium reduces the hypotensive effect of clonidine.
Diuretics ("diuretics"). When combined with thiazide diuretics (for example, hydrochlorothiazide), the excretion of lithium decreases and its serum concentration increases, 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 contradictory. Lithium is sometimes combined with a potassium-sparing or thiazide diuretic to reduce lithium-induced polyuria or nephrogenic diabetes insipidus. Osmotic diuretics reduce the concentration of lithium in the blood, which can lead to a decrease in the effectiveness of therapy and the occurrence 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. The serum concentration of lithium increases. Cases of severe renal intoxication have been described with the combined use of lithium and metronidazole.
Theophylline, aminophylline. The serum concentration of lithium decreases, which may 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 increased toxic effects of lithium and the development of arrhythmias.
Muscle relaxants. Lithium can potentiate their action. If surgical treatment with the use of muscle relaxants is necessary, it is necessary to warn the anesthetist about taking lithium and stop taking it 48-72 hours before the operation.
inhalation anesthetics. It is necessary to cancel the lithium preparation 1-2 days before the operation.
Caffeine. Lithium-induced tremor may be exacerbated.
Ethanol. Lithium relieves alcoholic euphoria, reduces cravings for alcohol and cognitive impairment caused by alcoholism. With alcohol withdrawal, lithium is ineffective. As with other CNS depressants, ethanol interacting with lithium can cause sedation or confusion.
Included in medications
ATH:N.05.A.N.01 Lithium
Pharmacodynamics:Normothymic agent (normalizes the mental state without causing general lethargy). It also has antidepressant, sedative and antimanic effects. The effect is due to lithium ions, which, being antagonists of sodium ions, displace them from cells and thereby reduce the bioelectrical activity of brain neurons. Accelerates the metabolism of biogenic amines (the concentration of norepinephrine and serotonin in brain tissues decreases). Increases the sensitivity of neurons in the hippocampus and other areas of the brain to the action of dopamine. Interacts with lipids formed during the metabolism of inositol.
At therapeutic concentrations, it blocks the activity of inosyl-1-phosphatase and reduces the concentration of neuronal inositol, which is involved in the regulation of neuronal sensitivity.
The beneficial effect of lithium in migraine may be due to changes in the concentrations of serotonin and histamine in platelets. The antidepressant effect may be associated with an increase in serotonergic activity and a decrease in the regulation of the function of β-adrenergic receptors.
Pharmacokinetics:When taken orally, it is absorbed from the gastrointestinal tract. Cmax of the active substance in plasma is reached after approximately 9 hours. Does not bind to plasma proteins. Penetrates through the placental barrier, excreted with breast milk. Not metabolized.
The kidneys excrete 95%, with feces - less than 1%, with sweating - 4-5%.
Indications:Manic and hypomanic states of various origins, prevention and treatment of affective psychoses, prevention and treatment of affective disorders in patients with chronic alcoholism. Migraine, Meniere's syndrome, sexual disorders, drug addiction.
XXI.Z70-Z76.Z72.1 Alcohol consumption
V.F30-F39.F30 manic episode
V.F30-F39.F31 bipolar affective disorder
VI.G40-G47.G43 Migraine
VIII.H80-H83.H81.0 Meniere's disease
Contraindications:Hypersensitivity, severe surgery, leukemia, pregnancy, breastfeeding.
Carefully:Diseases of the cardiovascular system (including atrioventricular blockade), diseases of the central nervous system (epilepsy, parkinsonism), diabetes, thyrotoxicosis, hyperparathyroidism, infections, psoriasis, renal failure, urinary retention, impaired water and electrolyte metabolism (dehydration, diuretic treatment, salt-free diet, ion retention
sodium, vomiting, diarrhea) Pregnancy and lactation:Contraindicated for use during pregnancy and lactation (breastfeeding).
Dosage and administration:The dose is determined by the level of lithium concentration in the blood plasma. Taken inside. For adults, the dose is 300-600 mg 3-4 times a day. Therapeutic concentration of lithium in plasma - 0.6-1 mmol / l.
For children under the age of 12 - 15-20 mg 2-3 times a day.
The maximum daily dose for adults when taken orally is 2.4 g.
Side effects:From the side of the central nervous system and peripheral nervous system: muscle weakness, hand tremor, adynamia, drowsiness, with prolonged use, articulation disorders, hyperreflexia are possible.
From the side of the cardiovascular system: cardiac arrhythmias.
From the digestive system: dyspepsia.
From the side of the endocrine system: rarely - thyroid dysfunction.
Other: increased thirst, impaired hematopoiesis, leukocytosis, weight gain.
Overdose:Symptoms: early - diarrhea, drowsiness, loss of appetite, muscle weakness, nausea, vomiting, dysarthria, tremor; late - dizziness, blurred vision, impaired coordination of movement, polyuria, confusion, convulsions.
Treatment: as a first aid it is advisable to inject a large number fluids and salt, in severe cases, inpatient treatment is required.
Interaction:With simultaneous use with thiazide diuretics, indapamide, a rapid increase in the concentration of lithium in the blood plasma and the development of toxic effects are possible.
With simultaneous use with ACE inhibitors, an increase in the concentration of lithium in the blood plasma and the development of toxic effects are possible; with non-steroidal anti-inflammatory drugs - it is possible to increase the toxic effects of lithium; with iodine preparations - an increase in the risk of thyroid dysfunction is possible; with xanthine derivatives - it is possible to increase the excretion of lithium in the urine, which can lead to a decrease in its effectiveness.
With simultaneous use with alprazolam, a clinically significant increase in the concentration of lithium in the blood plasma is possible; with acyclovir - a case of increased toxic effect of lithium is described; with baclofen - cases of increased hyperkinetic symptoms in patients with Huntington's chorea are described.
With the simultaneous use of lithium carbonate with verapamil drug interaction is unpredictable. With the simultaneous use of lithium carbonate with diltiazem, a case of psychosis has been described.
With simultaneous use with haloperidol, extrapyramidal symptoms may increase; with carbamazepine, clonazepam - neurotoxicity may develop.
With simultaneous use with methyldopa, the development of the toxic effect of lithium is possible; with metronidazole - it is possible to increase the concentration of lithium in the blood plasma.
When used simultaneously with sodium chloride, sodium bicarbonate, high sodium intake increases the excretion of lithium, which can lead to a decrease in its effectiveness.
With simultaneous use with norepinephrine, a decrease in the vasoconstrictive effect of norepinephrine is possible; with phenytoin - cases of the development of symptoms of the toxic effects of lithium are described; with fluoxetine - it is possible to increase the concentration of lithium in the blood plasma and the development of toxic effects; with furosemide, bumetanide, cases of increased toxic effects of lithium are described.
With simultaneous use with chlorpromazine and other phenothiazines, it is possible to reduce the absorption of phenothiazines from the gastrointestinal tract and reduce their concentration in blood plasma by 40%, increase the intracellular concentration of lithium and the rate of its excretion in the urine, increase the risk of developing extrapyramidal reactions, delirium, impaired cerebellar function (especially in elderly people).
Special instructions:It is used with caution in cardiovascular diseases (including AV blockade, intraventricular blockade), central nervous system diseases (including epilepsy, parkinsonism, organic lesions, schizophrenia), severe dehydration, infectious diseases, urinary retention, renal failure, as well as diabetes mellitus, hyperparathyroidism, thyrotoxicosis, psoriasis, in debilitated patients and hyponatremia of any etiology.
Elderly patients and debilitated patients require correction of the dosing regimen.
Nausea and vomiting like early signs lithium toxicity may be masked by the antiemetic effect of some phenothiazines.
During the first month of therapy, the concentration of lithium in the blood plasma should be monitored weekly. When a stable concentration is reached, the control is carried out monthly, then 1 time in 2-3 months.
Avoid drinking alcohol during treatment.
Dosage forms prolonged action should not be used in children under the age of 12 years, do not alternate with other dosage forms.
Influence on the ability to drive vehicles and control mechanisms: during the period of treatment, care should be taken when driving vehicles and engaging in other potentially dangerous species activities that require increased attention and speed of psychomotor reactions.
InstructionsSubstances that prevent the recurrence of future phases of the disease or reduce the severity and/or duration of these phases.
Classification of mood stabilizers:
Lithium salts
Carbamazepine
Lamotrigine
Valproates
In 1941, data appeared on the antimanic effect of lithium, and in the 1970s, information on its preventive effect appeared.
Pharmacology and biochemistry of lithium. Variety of biochemical effects: serotonin-antagonistic effect, affects the cellular signaling system (including through inositol), has a neurotropic effect (increased volume of gray matter/hippocampus, increased BDNF).
Important: Lithium has a small therapeutic spectrum (danger of cumulation, therefore regular monitoring of blood levels is required), excretion from the body is carried out through the kidneys.
Practical applications of lithium:
Assessment of individual risk of relapse: lithium prophylaxis is indicated if 2 phases occur within 4 years or the total number of phases present is three.
Successful outcome: 65-80% of cases either completely avoid recurrence or achieve a significant reduction in the frequency, severity and duration of relapse
The effect of suicide prevention (the number of suicides in Germany decreases by 250 every year)!
Serum lithium control under standard conditions (12 hours after the last dose)
The prophylactic level of lithium in serum is 0.5-0.8 mmol / l
Regular determination of lithium levels has proven to be a good auxiliary method
Additional monitoring of serum lithium levels is recommended in the presence of somatic diseases, loss of salts and fluids, while following a diet for weight loss and when prescribing diuretics
Investigations before and during lithium therapy:
1. Questions about possible side effects:
Increasing thirst, sweating, tremors, nausea, diarrhea, fatigue, weight gain
2. Clinical researches:
Neck coverage: goiter in 50% of patients, neurotoxic side effects: ECG changes are possible, acne, psoriasis are more rare side effects
3. Laboratory research:
- serum lithium concentration: initial stage- weekly, later with an interval of 1-3 months; control 12 + 0.5 hours after the last dose
- Serum creatinine: interval from 6 to 12 months.
- T3, T4, TSH- or TRH-test: annually (hypothyroidism in 5% of patients taking lithium)
- blood picture: annually (leukocytosis is typical with normal ESR)
- electrolytes (sodium, potassium, calcium): annually
- special attention require insulin-dependent diabetes mellitus, hyperparathyroidism
4. ECG: annually (repolarization?)
5. EEG: if there are indications of convulsive readiness
Should be considered:
- in case of intercurrent diseases or severe side effects, more frequent monitoring of serum lithium levels is necessary, as well as appropriate additional studies
- interactions with concomitant drug treatment
Side effects of lithium:
The most common side effects of lithium treatment are tremor, thirst, polyuria, goiter, weight gain, nausea, diarrhea.
Reasons for discontinuing lithium prophylaxis, as reported by patients:
- resistance to long-term therapy (constant reminder of illness, feeling "at the mercy of drugs", no need to continue taking pills due to well-being)
- somatic side effects (primarily weight gain)
- mental side effects ("hypomania deficit", creativity deficit)
Treatment of lithium side effects:
- treatment : beta-blockers
- prevention of goiter: L-thyroxine (suppressive therapy)
Intoxication with lithium salts- starting from 2.0 mmol/l:
- severe tremor, increased reflexes, drowsiness, dysarthria, ataxia, dyskinesias
- EEG: distinct general changes(slowing the rhythm) and lowering the seizure threshold
- the most important causes of intoxication are dehydration and salt deficiency caused by:
diseases accompanied by high body temperature
weight loss/diet
kidney disease
taking diuretics
Contraindications for lithium salts:
Absolute contraindications for taking lithium are acute renal failure, myocardial infarction, psoriasis and the first trimester of pregnancy.
Due to the increased risk of intoxication, lithium should be discontinued 48 hours before anesthesia and surgery.
