2 English reference lithium carbonate [Landau Chinese-English Dictionary]
Lithium carbonate bromide [Xiangya Medical Dictionary]
3 Overview Lithium carbonate is an antimanic drug. White crystalline powder; Odorless and tasteless; Alkaline reaction of aqueous solution. It can obviously inhibit mania and improve the emotional disorder of schizophrenia. It can inhibit the release of neurotransmitters from noradrenergic and dopaminergic nerve endings, increase the reuptake of neurotransmitters by presynaptic membrane, reduce the sensitivity of postsynaptic membrane receptors, and increase the synthesis of serotonin in the brain. It is easily absorbed by oral administration and does not combine with plasma protein. The excretion rate in the body varies greatly from person to person. When treating mania, the therapeutic dose is close to the toxic dose. 1.5mmol/L or more, with mild toxic reaction; If it exceeds 2mmol/L, there is a serious reaction. It must be used under the monitoring of blood drug concentration. All elderly patients or patients with renal insufficiency should be regarded as contraindications.
4 Lithium Carbonate Pharmacopoeia Standard 4. 1 Name 4. 1. 1 Chinese Name Lithium Carbonate
4. 1.2 Computing power of Chinese Pinyin
4. 1.3 English name lithium carbonate
4.2 molecular formula and molecular weight Li2CO3 73.89
4.3 The content or titer stipulates that the content of Li2CO3 in this product shall not be less than 98.5%.
4.4 Characteristics This product is white crystalline powder; Odorless and tasteless; Alkaline reaction of aqueous solution.
This product is slightly soluble in water and almost insoluble in ethanol.
4.5 Identification (1) Take platinum wire, moisten it with hydrochloric acid, dip it in this product, and burn it in a colorless flame, the flame is rouge red.
(2) Identification reaction of carbonate in aqueous solution of this product (Appendix III of Pharmacopoeia II, 20 10 edition).
4.6 Check 4.6. 1 chloride Take 0. 10g of this product, and check it according to law (Appendix VIII A of Pharmacopoeia Part II, 20 10). Compared with the control solution made of 7.0ml standard sodium chloride solution, it should not be thicker (0.07%).
4.6.2 Take 0.20g of this product as sulfate radical, and check it according to law (Appendix VIII B of Pharmacopoeia II, 20 10 edition). Compared with the control solution made of 2.0ml standard potassium sulfate solution, it should not be more concentrated (0. 1%).
4.6.3 Take 0.5g of aluminum salt and iron salt, add 10ml of water, drop hydrochloric acid and stir to dissolve, boil, cool, take 5ml of solution, and add ammonia test solution to make it alkaline without turbidity.
4.6.4 Take the insoluble matter in 10g acid, put it in a beaker, add 50ml water, slowly add 70ml hydrochloric acid solution (1 → 2), cover with watch glasses, boil 1h, and vertically melt the glass crucible in11with constant weight.
4.6.5 Take 5.0g of calcium salt, add 50ml of water, mix well, add excessive dilute hydrochloric acid, boil to remove carbon dioxide, cool, add 5ml of ammonium oxalate test solution, add ammonia water test solution to make it neutral, stand for 4 hours, filter with a vertical molten glass crucible, and wash with water until the washing solution has no reaction to calcium chloride test solution. Put the vertical molten glass crucible into a beaker, cover it with water, add 3ml of sulfuric acid and heat it to 70℃. Titrate with potassium permanganate titrant (0.02mol/L) until the solution turns pale red and lasts for 30 seconds. The consumption of potassium permanganate titration solution (0.02mol/L) shall not exceed 3.8ml(0. 15%).
4.6.6 Weigh 1.0g magnesium salt, add 3ml water, add about 2ml nitric acid to make it just dissolve, adjust the pH value to neutrality with sodium hydroxide solution, dilute it to 10ml with water, shake well, take out 0.25ml, add water to 9ml, and add glycerol 1ml, 0.0/kl.
4.6.7 Take 0. 10g of potassium, put them in 50ml volumetric flasks respectively, add 10ml hydrochloric acid solution (1 → 2) to dissolve, dilute one part with water to scale, and shake well to serve as test solution; Add standard potassium chloride solution (accurately weigh 19 1mg 150℃ drying 1 hour, put it in a 1000ml volumetric flask, dilute it to scale with water, shake well, and accurately measure 10ml. According to atomic absorption spectrophotometry (the second method in Appendix Ⅳ D of Pharmacopoeia Part II, 20 10), it should meet the requirements (0.030%) when measured at the wavelength of 766.5nm.
4.6.8 Take 0.50g of this product in two portions of sodium, put them in 50ml volumetric flasks respectively, add 10 ml hydrochloric acid solution (1 → 2) to dissolve, dilute one portion with water to scale, and shake well as the test solution; Add 23ml standard sodium chloride solution to the other part, dilute it to scale with water, and shake it evenly as control solution. According to atomic absorption spectrophotometry (the second method in Appendix IV D of Pharmacopoeia Part II, 20 10), it should meet the requirements (0.030%) when measured at the wavelength of 589nm.
4.6.9 Take this product 1.0g for heavy metals, dissolve it in appropriate amount of hydrochloric acid, add appropriate amount of water, adjust the pH value to 3 ~ 4 with dilute acetic acid or ammonia solution, add water to 25ml, and check it according to law (the first method in Appendix VIII H, Part II of Pharmacopoeia 20 10). The content of heavy metals shall not exceed 20 parts per million.
4.6. 10 Arsenic Salt Take this product 1.0g, add 22ml of water and 5ml of hydrochloric acid, and check it according to law (Appendix VIII J of Pharmacopoeia II, 20 10 Edition), which should meet the requirements (0.0002%).
4.7 Content determination: take about 65438±0g of this product, weigh it accurately, add 50ml of water and 50ml of sulfuric acid titration solution (0.5mol/L), slowly boil to remove all carbon dioxide, cool, add phenolphthalein indicator, titrate with sodium hydroxide titration solution (65438 0mol/L), and correct the titration result with blank test. Every 1ml sulfuric acid titration solution (0.5mol/L) is equivalent to 36.95 mg of li2co3.
Category 4.8 Antimanic drugs.
4.9 Store in a sealed and dry place.
4. 10 Preparation of (1) lithium carbonate tablets? (2) Lithium carbonate sustained-release tablets
4. 1 1 Edition People's Republic of China (PRC) Pharmacopoeia 20 10/Edition.
5 lithium carbonate instructions 5. 1 drug name lithium carbonate
5.2 English name lithium carbonate
5.3 Alias lithium salt of lithium carbonate; ns 16895； CamcolitLithobid
5.4 classification of nervous system drugs >: antimanic drugs
5.5 dosage form 1. Tablets: 0. 125g, 0.25g, 0.5g；;
2. Sustained release tablets: 0.3g；;
3. Capsule: 0.25g, 0.5g. ..
5.6 Pharmacological Effects of Lithium Carbonate Lithium Carbonate is an antimanic drug, which can obviously inhibit mania and improve the emotional disorder of schizophrenia. Its mechanism of action has not yet been determined. It is speculated that lithium carbonate has the effect of stabilizing mood, which may be due to the influence of lithium ion on the activity of potassium sodium triphosphatase and the decrease of the content of catecholamine neurotransmitters. Some people think that lithium salt can inhibit adenylate cyclase and reduce the content of cyclic adenosine monophosphate, thus reducing the sensitivity of dopamine receptor and producing drug effect. In addition, lithium carbonate can also promote the synthesis of serotonin, increase the content of serotonin, and also contribute to emotional stability. According to literature reports, lithium carbonate has a certain effect on hematopoietic system, can increase peripheral white blood cells, and has a certain effect on pathological and iatrogenic leukopenia such as aplastic anemia and neutropenia caused by radiotherapy and chemotherapy.
5.7 Rapid and complete pharmacokinetics of lithium carbonate after oral absorption. After a single dose, the plasma concentration reached its peak at 0.5h or 4h (sustained release tablets). According to the routine administration, the steady-state blood drug concentration will be reached in about 6 ~ 7 days. Widely distributed in all tissues of the body. It does not degrade in vivo, has no metabolites, and does not combine with protein. Most of them are excreted by kidney, and 80% can be reabsorbed by renal tubules. The rate at which lithium is excreted by the kidneys varies from person to person, especially sodium ions in plasma. When the concentration of sodium ion in plasma is high, the concentration of lithium salt decreases and the discharge speed is fast, otherwise it is slow. Only a small amount is excreted from milk, tears, * * *, sweat or saliva. The average half-life of lithium carbonate is 24 hours for adults,18 hours for adolescents and 36-48 hours for the elderly.
5.8 indications of lithium carbonate 1. It is mainly used to treat manic state of manic depression, alternating episodes of manic depression and maintenance treatment of manic depression in remission period.
2. It can also be used for neutropenia and aplastic anemia.
3. It can also be used for menorrhagia and acute bacillary dysentery.
5.9 Contraindications of lithium carbonate 1. Patients with cardiovascular diseases;
2. Patients with central nervous system diseases (such as epilepsy or Parkinson's disease);
3. Dehydrator;
4. Diabetic patients;
5. People with hypothyroidism;
6. Renal insufficiency;
7. Severe weakness;
8. Serious infection;
9. Urinary retention and low sodium diet;
10. Pregnant women;
1 1. Lactating women;
12.
5. 10 Precautions 1. Elderly patients.
2. Effects of drugs on children:/kloc-The safety and effectiveness of taking lithium for children under 0/2 years old are not clear, so lithium carbonate is not recommended.
3. Effects of drugs on pregnancy: Do not use lithium carbonate during pregnancy (especially during the first three months of pregnancy). Because lithium carbonate has not ruled out the possibility of fetal teratogenesis. In addition, the blood concentration of general therapeutic dose can affect pregnant women and fetuses before or during labor, which should be paid attention to.
4. Effect of drugs on breastfeeding: Lithium carbonate can be excreted from breast milk, which affects breastfeeding babies. It is best not to breastfeed during taking medicine.
5. Effect of drugs on test value or diagnosis: (1) Lithium carbonate can cause abnormal ECG, such as flattening of T wave or protruding of U wave. (2) It can cause urine sugar positive and proteinuria, and increase the excretion of VMA.
6. Check or monitor: (1) renal function before and after medication and during medication. (2) Determination of blood lithium content: Blood samples must be collected 12h after the last medication. During the treatment, the blood lithium content is generally measured every 2 weeks until the condition is stable. (3) Determination of thyroid function: Lithium carbonate can inhibit thyroid activity, and thyroid preparations can be added during treatment to prevent the recurrence of bipolar disorder. (4) White blood cell count and classification: Lithium can cause reversible white blood cell elevation.
7. The toxicity of lithium increases with the increase of blood concentration, and the commonly used dose is close to the toxic dose. When the plasma concentration of lithium is higher than 1.5meq/L, the possibility of toxic reaction is higher than that when the plasma concentration is lower than1.5meq/L. However, sensitive person, lithium reagent may have poisoning symptoms when its concentration is lower than1.5meq/L. Therefore, there should be blood concentration monitoring and first aid. When there are different degrees of poisoning symptoms, the drug should be stopped or reduced immediately.
8. In acute mania, patients have a high tolerance to lithium carbonate, but with the improvement of manic symptoms, this tolerance will decrease, so it is necessary to adjust the dose in time. Domestic experience suggests that the concentration of lithium carbonate can be controlled at 0.8 ~ 1.2 mmol/L when treating acute mania. The concentration of lithium carbonate can be controlled at 0.6 ~ 0.8 mmol/L during maintenance treatment. For patients with severe acute mania, it is generally advocated to use lithium carbonate combined with chlorpromazine or haloperidol first, and then use lithium carbonate alone to maintain after acute symptoms are controlled.
9. If there is persistent vomiting, diarrhea, high fever, or a large loss of body fluids caused by other reasons (such as sun exposure and sweating) during the treatment, it will easily lead to a gradual increase in blood lithium concentration. Pay attention to adjust the dosage, supplement the intake of body fluids and sodium, and stop taking drugs when necessary.
10. Lithium can reduce the reabsorption of sodium salt in renal tubules, which can lead to hyponatremia, and sodium salt can promote the excretion of lithium salt through kidneys, so patients should maintain a normal diet, including intake of salt and enough liquid (2500~3000ml) during medication.
1 1. overreaction: Early poisoning symptoms include diarrhea, lethargy, loss of appetite, muscle weakness, dyspnea, nausea, vomiting, slurred speech and tremor. Symptoms of severe poisoning include blurred vision, clumsiness, confusion, convulsion, dizziness, polyuria and severe tremor, and epilepsy, coma and even death may occur.
12. Overtreatment: (1) inducing vomiting or small-volume gastric lavage. (2) Maintain the balance of body fluids and electrolytes and monitor renal function. (3) Measure the plasma lithium concentration every 3 hours until the lithium concentration is lower than1.0 meq/L. (4) For patients with severe poisoning, hemodialysis can be interrupted and/or osmotic diuretics (acetazolamide or mannitol) can be given intravenously at one time. (5) Avoid infection.
5. The adverse reactions of11lithium carbonate can be seen as nausea, vomiting and hand tremor, which may be digestive tract and central nervous system reactions or early poisoning symptoms.
5. 12 Use and dosage of lithium carbonate 1. Acute episode of mania: at the initial stage of treatment, 0.25~0.5g each time, three times a day, and then adjust the dose according to the blood lithium concentration. Maintenance treatment was started at 0.25g each time, three times a day, and then the dose was adjusted according to the blood lithium concentration. Sustained-release tablets: 0.9 ~ 1.5g 1 ~ 2 times per day during the treatment period, and maintained at 0.6~0.9g per day.
2. Granulopenia and aplastic anemia: 0.3g each time, 3 times a day.
3. Hypermenorrhea: take 0.6g on the first day of menstruation, and then take 0.3g every day for three days. 1 .2g is 1 course of treatment. Take it every menstrual cycle 1 course.
4. Acute bacillary dysentery: 0. 1g each time, three times a day, and the first dose is doubled. For a few patients with severe symptoms, the dosage can be doubled every time in the first 1 ~ 3 days, and the original dosage will be maintained for 2 ~ 3 days after the symptoms and feces are obviously improved, and then the dosage will be reduced, and the drug will be stopped in about 3 ~ 4 days. Do not use any other drugs for hyperthermia except antipyretic drugs. The total course of treatment is about 7 ~ 10 days.
5. 13 drug interaction 1. When combined with muscle relaxants (such as succinylcholine, etc.). ), muscle relaxation is enhanced and the time limit is prolonged.
2. When combined with antidiuretic drugs, lithium poisoning is easy to occur because lithium is excluded by the kidney.
3. Care should be taken when lithium is combined with diuretics or angiotensin converting enzyme inhibitors. Because the loss of sodium salt will reduce the clearance rate of lithium in kidney, which will lead to the increase of serum drug concentration of lithium salt and lead to lithium poisoning. When these drugs are used together, the dosage of lithium should be reduced and the plasma drug concentration of lithium should be monitored.
4. Indomethacin and piroxicam can significantly increase the plasma concentration of lithium. There is also evidence that other non-steroidal anti-inflammatory drugs have similar characteristics. When these drugs are combined with lithium salt, the blood concentration of lithium salt should be monitored.
5. Combined with aminophylline, caffeine, theophylline or sodium bicarbonate, it can increase urine output and reduce the blood concentration and curative effect of lithium carbonate.
6. When combined with chlorpromazine and other phenothiazine derivatives, the plasma concentration of chlorpromazine can be reduced by 40%. In addition, lithium poisoning may be a precursor to nausea and vomiting. After compatible application, the gastrointestinal adverse reactions of phenothiazine drugs often affect the observation of lithium poisoning precursors.
7. The hypotensive effect of norepinephrine combined with lithium carbonate is weakened.
8. It has been previously reported that taking lithium and haloperidol at the same time may sometimes lead to encephalopathy syndrome (weakness, lethargy, fever, trembling, confusion, extrapyramidal symptoms, leukocytosis, elevated serum enzymes, elevated urea nitrogen and fasting blood sugar), and then irreversible brain damage. The relationship between the combination of lithium and haloperidol and these symptoms is not clear. However, patients should monitor the early symptoms of neurotoxicity more carefully when receiving such combined therapy, and stop taking the drug immediately if the above symptoms appear. The above situation has not been reported in recent years.
9. Iodide (such as potassium iodide, etc. ) Combined with lithium carbonate can promote hypothyroidism.
5. 14 expert comments lithium carbonate has obvious inhibitory effect on mania, which can stabilize the mood of manic patients and improve the situation of thinking too fast and acting too much. Lithium carbonate can also be used to treat schizophrenia affective psychosis and psychosis with manic symptoms at the same time, and the effect is good. Lithium carbonate can prevent the recurrence of mental illness caused by internal temperament and has a good effect on bipolar disorder.
6 lithium carbonate poisoning lithium carbonate can inhibit the release of neurotransmitters from noradrenergic and dopaminergic nerve endings, increase the reuptake of neurotransmitters by presynaptic membrane, reduce the sensitivity of postsynaptic membrane receptors, and increase the synthesis of serotonin in the brain. It is easily absorbed by oral administration and does not bind to plasma protein, and its half-life is 14 ~ 33h. The excretion rate in the body varies greatly among individuals, so the dosage should be individualized. Can be used for treating mania, schizoid affective psychosis, excitatory schizophrenia and periodic catatonia. In the treatment of mania, the therapeutic dose is close to the toxic dose, and the therapeutic blood lithium concentration is 0.8 ~1.3 mmol/L. It exceeds 1.5mmol/L, with mild toxic reaction. If it exceeds 2mmol/L, there is a serious reaction. It must be used under the monitoring of blood drug concentration. All elderly patients or patients with renal insufficiency should be regarded as contraindications. The initial dose is 0.25g, 1/d, and then gradually increase the dose, not exceeding 2g per day. [ 1]
6. 1 Clinical manifestations [1]
1. During the treatment, patients may have anorexia, abdominal pain, diarrhea, dizziness, fatigue, dry mouth, slight tremor, weight gain and temporary memory loss. Renal diabetes insipidus and polyuria with decreased renal concentration function may occur, which may lead to dehydration and hypernatremia if water is not replenished in time.
2. Nephrotic syndrome occasionally occurs during treatment. During the treatment, some patients also have ECG changes: T wave changes, paroxysmal bundle branch block, atrioventricular block, sinus node dysfunction or arrhythmia.
3. The early symptoms of poisoning are nausea, vomiting, diarrhea and anorexia. Mild to moderate can cause drowsiness, myasthenia, slurred speech, and may appear dyskinesia, muscle spasmodic convulsion, rigidity and extrapyramidal symptoms. In severe poisoning, delirium, coma, convulsion, seizure or excited psychosis, coma and high temperature, increased muscle tone and asymmetric tendon reflexes can be seen. Within the scope of treatment, goiter, hypothyroidism and edema may occur, and acne and psoriasis may occur.
4. Lithium baby refers to the baby born to the mother who took lithium carbonate during pregnancy, and the incidence of developmental malformation is higher than that of the general population 1% ~ 3%.
5. Blood lithium concentration increased.
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6.2 Diagnostic points of lithium carbonate poisoning are [2]:
1. Have a history of taking or taking lithium carbonate by mistake, and have the above clinical manifestations.
2. Eliminate the possibility of poisoning by other drugs.
6.3 The key points of treating lithium carbonate poisoning are [2]:
1. It is effective to induce vomiting within a few minutes after acute ingestion, and gastric lavage and * * * can promote the excretion of lithium carbonate. Medicinal charcoal can't adsorb lithium.
2. There is no specific antidote for lithium carbonate poisoning, and symptomatic support therapy is the main method.
3. Hemodialysis can effectively remove lithium from the body. The indication of hemodialysis is that serum lithium is >: 2.5 ~ 3.5 mmol/L..
4. Indomethacin can be used to treat renal diabetes insipidus.
5. In case of chronic poisoning, lithium carbonate should be stopped immediately, and sodium bicarbonate or theophylline can be used to promote lithium excretion in the body.