2. Stamp the pharmacopoeia standard 2. 1 name 2. 1. 1 Chinese name stamp.
2. 1.2 Chinese pinyin carbamazepine
2. 1.3 English name carbamazepine
2.2 structural formula
2.3 molecular formula and molecular weight C 15H 12N2O? 236.27
2.4 Source (name) and content (potency) This product is 5H dibenzo [6, f] azalea ether 5 formamide. The content of C 15H 12N2O should be 98.0% ~ 102.0% in terms of dry products.
2.5 Properties This product is white or white-like crystalline powder; There is almost no smell.
This product is soluble in chloroform, slightly soluble in ethanol, and almost insoluble in water or ether.
2.5. 1 melting point the melting point of this product (appendix ⅵ C of Pharmacopoeia II, 20 10) is 189 ~ 193℃.
2.6 Identification (1) Take about 0. 1g of this product, add 2ml of nitric acid, and heat it in a water bath, which is orange-red.
(2) Take this product, dissolve it in ethanol and dilute it to make a solution containing 10μg per 1ml, and determine it by UV-Vis spectrophotometry (Appendix Ⅳ a of Pharmacopoeia II, 20 10 edition). The maximum absorption is at 238nm and 285nm, and the absorption at 285nm is 0.47 ~ 0.50.
(3) The infrared absorption spectrum of this product should be consistent with that of the reference substance (Figure 94 of the infrared spectrum of drugs).
2.7 check 2.7. 1 pH take 1.0g this product, add 20ml of water, stir 15min, filter, take 1.50ml continuous filtrate, add 1 drop phenolphthalein indicator, and use sodium hydroxide (0.0/kloc). Add 3 drops of methyl red indicator and titrate with hydrochloric acid titration solution (0.0 1mol/L), and the consumption of hydrochloric acid titration solution (0.0 1mol/L) shall not exceed 1.0ml.
2.7.2 chloride take this product 1.0g, add water 100ml, boil, let it cool, filter, take 50ml of continuous filtrate, and check it according to law (Appendix VIII A of Pharmacopoeia II, 20 10 edition). Compared with the control solution made of 7.0 ml standard sodium chloride solution, it shall not be thicker (0.06544).
2.7.3 Take about 50mg of related substances of this product, put it in a 50ml volumetric flask, add 25ml of methanol to dissolve it, add water to dilute it to scale, and shake it evenly to serve as the test solution; Accurately measure 1 ml, put it in a 50-ml volumetric flask, dilute it with methanol-water (1: 1), shake well, accurately measure 5 ml, put it in a 50-ml volumetric flask, and use methanol-water (1: 1). According to the chromatographic conditions under the content determination, take 20μl of reference solution, inject it into the liquid chromatograph, adjust the detection sensitivity so that the peak height of the main component chromatographic peak is about 25% of the full scale, accurately measure 20μl of test solution and reference solution, inject them into the liquid chromatograph respectively, and record the chromatogram until the retention time of the main component peak reaches 6 times. If there are impurity peaks in the chromatogram of the test sample, the area of a single impurity peak shall not be greater than the main peak area of the reference solution (0.2%), and the sum of the impurity peak areas shall not be greater than 2.5 times (0.5%) of the main peak area of the reference solution.
2.7.4 loss on drying takes this product and dries it at 105℃ for 2 hours, and the weight loss shall not exceed 0.5% (Appendix VIII L of Pharmacopoeia II, 20 10).
2.7.5 Take this product 1.0g as residue on ignition, and check it according to law (Appendix VIII N of Pharmacopoeia II, 20 10), and the residue shall not exceed 0. 1%.
2.7.6 Take the residue left under the heavy metal residue on ignition and check it according to law (the second method in Appendix VIII H of Pharmacopoeia 20 10), and the content of heavy metals shall not exceed 10 parts per million.
2.8 the content was determined by high performance liquid chromatography (appendix ⅴ D, part 2, pharmacopoeia 20 10).
2.8. 1 chromatographic conditions and system applicability test with cyanopropyl silane bonded silica gel as filler; Using methanol-tetrahydrofuran-water (120: 30: 850) as the mobile phase (1000ml contains 0.2ml formic acid and 0.5ml triethylamine); The detection wavelength is 230 nm. Take about 25mg of capped reference substance, put it in a 100ml volumetric flask, dissolve it in methanol-water (1: 1) solution, dilute it to scale, shake it evenly, and take 20μl and inject it into a liquid chromatograph. The theoretical number of trays shall be no less than 5000 according to the sealing peak, and the separation degree between the sealing peak and the adjacent impurity peak shall meet the requirements [65438
2.8.2 Determination method Take about 50mg of this product, weigh it accurately, put it in a 50ml volumetric flask, add 25ml methanol, shake it evenly to dissolve it, dilute it to scale with water, shake it evenly, accurately measure 5ml, put it in a 25ml volumetric flask, dilute it to scale with methanol-water solution (1: 1), shake it evenly, and measure it accurately. Use the same method to determine another reference substance-capping. According to the external standard method, calculate the peak area.
Class 2.9 anticonvulsants and analgesics.
2. 10 storage and shading, sealed preservation.
2. 1 1 preparation (1) cover? (2) capping the capsule
2. 12 Edition People's Republic of China (PRC) Pharmacopoeia 20 10 Edition
3. Stamping instructions 3. 1 drug name stamping
3.2 English names are carbamazepine, carpine, finlepsin, macrepan, stazepan, tegretol and Tempord.
3.3 Capin alias carbamoyl benzoxazole; Carbamoyl carbamazepine; Miscellaneous point ning; Delido; Get more benefits; Pershing Finland; Formyl benzoxazole; Carbazole; Carbamazepine; Carbamazepine; Litongding; Tongjingning; Pain and shock; Pain can be effective; Relieve pain; Amidimidazole; Amidinoimipramine; Benzyl carbamate; Ureazine; Salmatin; Tongjingning; Delido
3.4 classification of nervous system drugs >: antiepileptic drugs > others
3.5 dosage form 1. Tablets: 100mg, 200mg, 400mg；;
2. Sustained release tablets: 200mg, 400mg；;
3. Chewable tablets: 100mg, 200mg；;
4. Capsule: 200mg；;
5. Syrup: 20mg (1ml);
6. Suppository: 125mg, 250mg.
3.6 pharmacological action of carbopol 1 Anticonvulsive effect: It may be through enhancing the inactivation efficiency of sodium channels, limiting the release of high-frequency action potentials of postsynaptic neurons, and blocking the release of neurotransmitters by blocking the release of presynaptic sodium channels and action potentials, thus regulating nerve excitability and producing anticonvulsant effect.
2. Anti-peripheral neuropathic effect: It may have analgesic effect by acting on γ -aminobutyric acid (GABA)B receptor, which is related to the regulation of Ca2 ++ channel.
3. Antidiuretic effect: It may be related to the release of antidiuretic hormone (ADH) and the enhancement of water reabsorption in distal renal tubules.
4. Anti-personality disorder and manic-depressive effect: It may be related to inhibiting the accumulation of dopamine and adrenaline.
5. Anti-arrhythmia effect: capping can slightly prolong atrioventricular conduction, reduce 4-phase automatic depolarization potential and prolong the action potential time of Purkinje fiber. In addition, capping can also stabilize the membrane, which is effective for ventricular or supraventricular premature beats and can eliminate symptoms, especially for patients with chronic cardiac insufficiency.
3.7 Pharmacokinetics of Glands Oral absorption is slow and varies from person to person. 4 ~ 5 hours after taking 400 mg carbofuran orally, the plasma concentration reached the peak of 8 ~ 65438 00 μ g/ml, but there was a great difference among individuals, ranging from 0.5 to 25 μ g/ml. The onset time of the antiepileptic effect of carpin varies greatly, and it can relieve trigeminal neuralgia after about 8 ~ 72 hours. It takes 40 hours (8 ~ 55 hours) to reach the steady-state blood drug concentration, and the adult therapeutic blood drug concentration is 4 ~ 12μ g/ml. The bioavailability of carboline is 58% ~ 85%, and the protein binding rate is about 76%. After liver metabolism, it can induce self-metabolism, and the average half-life is 12 ~ 17h. The protein binding rate of the main metabolites 10 and 1 1 is 48% ~ 53%, and the half-life is 5 ~ 8h. 72% is excreted by kidney, and 28% is excreted with feces.
3.8 indications of carpin1. Complex partial seizures (psychomotor seizures or temporal lobe seizures), generalized tonic-clonic seizures, mixed seizures of the above two or other partial or systemic seizures.
2. Relieve neuropathic pain, such as trigeminal neuralgia, glossopharyngeal neuralgia, lightning-like pain of spinal tuberculosis, diabetic peripheral neuralgia, limb pain, post-traumatic neuralgia and some post-herpetic neuralgia.
3. Prevention or treatment of bipolar disorder; Treating affective schizophrenia, refractory schizophrenia and out-of-control syndrome related to limbic system dysfunction.
4. Neurogenic diabetes insipidus.
5. restless legs syndrome (Ekbom syndrome) and hemifacial spasm.
6. Alcohol withdrawal syndrome.
7. arrhythmia.
3.9 Contraindications of capping 1. Patients with atrioventricular block.
2. Platelets, blood routine and serum iron are seriously abnormal.
3. People with a history of bone marrow suppression.
4. People with heart, liver and renal insufficiency.
5. Pregnant and lactating women.
6. People who are allergic to carbofuran and tricyclic antidepressants.
3. 10 Precautions 1. (1) alcoholics; (2) Patients with heart disease (including organic heart disease and congestive heart disease); (3) patients with coronary heart disease; (4) diabetic patients; (5) patients with glaucoma; (6) Those who have a history of adverse blood reactions of other drugs (the risk of bone marrow suppression caused by carboplatin is increased); (7) urinary retention.
2. Effects of drugs on the elderly: Elderly patients are sensitive to carvedilol, which can cause insanity, agitation, anxiety, atrioventricular block or bradycardia.
3. Effect of drugs on pregnancy: Carbohydrate can cross the placental barrier, and FDA classifies pregnancy as D-grade. ..
4. Effect of drugs on lactation: gland can be secreted by milk, and its concentration in milk is about 60% of the blood drug concentration.
5. Effects of drugs on test values or diagnosis: (1) The test values of blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, serum bilirubin, urine sugar and urine protein increased; (2) The value of thyroid function examination decreased; (3) Blood calcium concentration decreased.
6. Check or monitor: (1) whole blood cell count (including platelets and reticulocytes) and serum iron check before and after medication. Check once before administration, and check frequently 2 ~ 3 years after treatment: (2) Urine routine; (3) blood urea nitrogen; (4) liver function examination; (5) Determination of Capone plasma concentration; (6) Ophthalmic examination (including slit lamp, ophthalmoscope and tonometer examination).
7. capping is ineffective for typical or atypical absence seizures, myoclonic seizures or catatonic seizures of epilepsy, and effective for manic depression that lithium, antipsychotics or antidepressants are ineffective or intolerable.
8. The analgesic effect of capping is limited to neuropathic pain.
9. Taking medicine immediately after meals can reduce gastrointestinal reactions.
10. Drink plenty of water to prevent water poisoning.
1 1. Thirst may occur during medication, and diabetic patients may cause increased urine sugar.
12. Start with a small dose, and then gradually increase it until the curative effect is good or there are adverse reactions. Patients who have received other antiepileptic drugs should be given carboplatin, and the dose should be gradually increased. It may be necessary to increase the dose about 4 weeks after the start of treatment to avoid the decrease of blood drug concentration caused by self-induction. Sudden withdrawal of drugs from epileptic patients can cause convulsions or status epilepticus.
13. Stop taking medicine in the following situations: (1) Stop taking medicine immediately when there are symptoms of hepatotoxicity or active liver disease. (2) Stop taking medicine immediately when there are obvious signs of bone marrow suppression. However, if epilepsy symptoms can only be controlled by carboplatin, the dose can be reduced and the white blood cell count should be closely followed up. If the white blood cell count increases gradually, the dose can be increased to control the seizure. (3) When adverse cardiovascular reactions or rashes occur, the drug should be stopped immediately. (4) When used as an analgesic for specific pain syndrome, if the pain is completely relieved, the dosage should be reduced or stopped every month.
14. In case of drowsiness, dizziness, muscle weakness or ataxia, it is necessary to pay attention to whether it is a precursor of poisoning. Symptoms of overdose include anuria, oliguria, urinary retention, cardiovascular reaction (including conduction block, arrhythmia, hypertension, hypotension and shock), nausea, vomiting, ataxia, limb peristalsis and convulsion. , more common in children; Hyperreflexia, decreased activity, dilated pupils, tremor and respiratory depression may also occur. The above symptoms of overdose can appear within 1 ~ 3h after overdose.
15. Overtreatment: (1) Vomiting or gastric lavage; Administer charcoal or laxatives to prevent absorption; Take measures to accelerate excretion, such as diuresis. Dialysis is only necessary when severe poisoning and renal failure occur. (2) Children with severe poisoning may need to exchange blood, and their breathing, heart function, blood pressure, body temperature, pupillary reaction, kidney and bladder functions should be continuously observed for several days. If there is respiratory depression, oxygen should be given, mechanical assisted breathing should be carried out, and tracheal intubation should be carried out if necessary. When blood pressure drops and shock occurs, you can raise both lower limbs and use blood volume dilator and pressor. Diazepam or barbiturates should be used when convulsions occur, but these two drugs may aggravate respiratory depression, hypotension and coma. If the patient has used monoamine oxidase inhibitors in the past week, phenobarbital should not be used.
3. 1 1 Adverse reaction of capping 1. Common blurred vision, diplopia, nystagmus and lethargy. Capping may also stimulate potential mental illness, causing mental disorders or agitation in the elderly, and the incidence of adverse reactions increases with the increase of blood drug concentration. Rare toxic reactions of the central nervous system, such as speech difficulties, slurred speech, depression, restlessness, rigidity, unexplained auditory hallucinations, uncontrollable limb movements, hallucinations, etc.
2. Digestive system: common thirst, nausea and vomiting; Rare severe diarrhea; Rare allergic hepatitis, manifested as dark urine, pale stool, yellow skin and sclera, etc.
3. Respiratory system: rare allergic pneumonia.
4. Cardiovascular system: rare arrhythmia, atrioventricular block, bradycardia, congestive heart failure, edema, hypertension or hypotension, thrombophlebitis, syncope, etc.
5. Blood system: rare aplastic anemia, granulocytopenia, pancytopenia, thrombocytopenic purpura, myelosuppression, lymphadenoma.
6. Endocrine metabolism: hyponatremia can be seen, showing weakness, nausea, vomiting, insanity, abnormal nervous system, trance and increased seizures; Rare hypocalcemia, characterized by increased seizure frequency and muscle or abdominal spasm; Rare osteoporosis and acute intermittent porphyria.
7. Urogenital system: rare nephrotoxicity and acute renal failure. There are reports of sexual dysfunction abroad.
8. Skin: StevensJohnson syndrome, toxic epidermal necrolysis or lupus erythematosus-like syndrome are rare, characterized by rash, urticaria, itching, fever, joint pain, fatigue or weakness.
9. Others: rare adenoma, paresthesia and peripheral neuritis.
3. Usage and dosage of 1 2 capping1. Anticonvulsive: at the beginning 100mg, 2 ~ 3 times a day; After the second day, it was increased by 100mg every day until the curative effect appeared. When maintaining, it should be adjusted to the minimum effective amount according to the situation and taken several times. Attention should be paid to the individualization of dosage, and the maximum daily dosage should not exceed 1200mg.
2. Analgesia: initial 100mg, twice a day; After the second day, the dose 100 ~ 200mg was increased every other day until the pain was relieved. The maintenance dose is 400 ~ 800 mg per day, and the maximum dose does not exceed100 ~ 200 mg per day.
3. Pain caused by diabetic neuropathy: 200mg each time, 2 ~ 4 times a day.
4. Antidiuretic: 300 ~ 600mg； per day when used alone; Combined with other antidiuretic drugs, 200 ~ 400 mg daily, divided into 3 ~ 4 times.
5. Anti-mania or anti-psychosis: 200 ~ 400 mg per day at first, and then gradually increase the dose every week. Usually, the adult's * * * is 1200mg, which is usually taken in 3-4 times. A few used 1600mg per day.
6. Alcoholism syndrome: an average of 200mg each time, 3 to 4 times a day. In severe cases, the dose can be increased to 400mg each time in the first few days, three times a day.
7. Arrhythmia: 300 ~ 600 mg daily, divided into 2 ~ 3 times.
3. 13 drug interaction 1. When carboine is combined with chlorpromazine, clofibrate (atropine), desmopressin, lysine vasopressin, pituitrin and vasopressin, the antidiuretic effect can be enhanced.
2. Loxapine, maprotiline, thioton, tricyclic antidepressants, erythromycin, hypocrellin, isoniazid, verapamil, diltiazem? Dexpropoxyphene, weizine, fluoxetine, cimetidine, acetazolamide, danazol, desipramine and other drugs can increase the concentration of capped blood drugs and produce toxic reactions.
3. When it is used together with acetaminophen (especially in single overdose or long-term massive use), it can increase the risk of liver poisoning and reduce the curative effect of acetaminophen.
4. Combined with adenosine can aggravate the degree of heart block.
5. When combined with carbonic anhydrase inhibitors, the risk of osteoporosis increases, so when early symptoms appear, carbonic anhydrase inhibitors should be stopped immediately, and corresponding treatment should be given if necessary.
6. Combined with lithium salt, metoclopramide or antipsychotic drugs (such as haloperidol and thioridazine), it can increase the side effects of nervous system.
7. When combined with coumarin anticoagulants, estrogen, contraceptives containing estrogen, cyclosporine, digitalis (except digoxin), doxycycline, levothyroxine or quinidine, the curative effect of the latter can be reduced.
8. Covering can reduce the absorption of nomifenol and accelerate its elimination.
9. Lithium can reduce the antidiuretic effect of carbobase.
10. Combined with oral contraceptives, * * massive bleeding and contraceptive failure may occur.
1 1. Combined with some diuretics (such as hydrochlorothiazide and furosemide) can cause hyponatremia.
12.Carpin has antagonistic effect on non-depolarizing muscle relaxants (such as Pankelin).
13. When combined with monoamine oxidase (MAO) inhibitor, it can cause high fever or/and hypertensive crisis, severe convulsion and even death, and the interval between the two drugs should be at least 14 days. When captopril is used as an anticonvulsant, monoamine oxidase inhibitors can change the types of seizures.
14. It can reduce alcohol tolerance.
15. Grapefruit juice can increase the capped peak blood concentration.
3. 14 expert comments: capping is more and more widely used in the treatment of epilepsy, and has become the first choice for various types of epilepsy. The medicine has good curative effect on generalized tonic-clonic seizure, simple partial seizure, complex partial seizure and mixed seizure. However, it is ineffective for typical and atypical absence seizures, myoclonic or flaccid seizures, and improper application can aggravate epileptic seizures.
The antiepileptic mechanism of 4- carbopentine poisoning carbopentine (amipamine, kanapamine, lidocaine) is not clear. Clinically used for psychomotor seizures and grand mal seizures; Relieve trigeminal neuralgia and glossopharyngeal neuralgia; Prevention and treatment of bipolar manic depression; It can resist arrhythmia caused by digoxin poisoning. Oral absorption is slow and incomplete, and intestinal-hepatic recirculation exists. The binding rate of plasma protein is 76%, and its metabolites 10, 1 1 also have anticonvulsant and neuropathic effects, and its protein binding rate is 48% ~ 53%. The half-life of plasma is 25 ~ 65h, the metabolite is 5 ~ 8h, and the distribution volume is 1.4L/kg, which can reach 3L/kg after overdose. The effective therapeutic blood concentration for adults is 4 ~ 65438 0.2 μ g/ml. The peak plasma concentration can reach 8 ~ 65438 00μ g/ml 4 ~ 5h after oral administration of 400mg. Serum level > 10μg/ml is related to ataxia and nystagmus. The maximum recommended therapeutic dose for adults is1600 mg/d; /d； Children 30mg/(kg? D), the maximum amount of lg/d, taken in batches. [2]
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4. 1 clinical manifestations [2]
1. The incidence of adverse reactions increased with the increase of blood drug concentration (>; 8.5~ 10 μ g/ml):
(1) Gastrointestinal reactions are uncommon and mild. Occasionally, hepatitis and hepatic cholestasis occur.
(2) blurred vision and diplopia are common.
(3) StevensJohnson syndrome with less allergic reaction.
(4) Rare adverse reactions include adenopathy or lymphadenopathy (gland enlargement).
(5) Arrhythmia or atrioventricular block or bradycardia.
(6) Granulopenia and myelosuppression, acute renal failure is rare.
(7) Central nervous system manifestations, language difficulties or unclear, mental depression or nervousness, tinnitus, trembling, hallucinations, uncontrollable body movements, SLE syndrome.
(8) About 65,438 0% of patients who used carboplatin developed proteinuria.
(9) Peripheral neuropathy.
(10) Hypocalcemia: Muscle or abdominal spasm with increased frequency.
(1 1) Acute purpura with dark urine.
(12) thromboangiitis.
2. Syndrome of excessive secretion of antidiuretic hormone: Carboplatin releases antidiuretic hormone, which leads to water retention, increased blood volume and hyponatremia, leading to mental abnormality and convulsion.
3. In case of dizziness, lethargy, dizziness, fatigue, muscle ataxia and other symptoms, be alert to poisoning symptoms.
4. Acute poisoning often occurs after excessive intake 1 ~ 3h. Mainly neuromuscular manifestations; Cardiovascular symptoms such as increased heart rate, blood pressure changes, shock and conduction disorders still exist. Diabetes and abnormal electroencephalogram.
4.2 Laboratory tests show that the concentration of carbopol in blood is generally greater than its therapeutic concentration. [2]
4.3 The diagnostic points of bottle cap poisoning are [2]:
1. has a history of taking or taking Capone by mistake, and has the above clinical manifestations.
2. Eliminate the possibility of poisoning by other drugs.
4.4 The key points of treatment for gland poisoning are [2]:
1. In case of overdose, induce vomiting and gastric lavage immediately.
2. Symptomatic support treatment. Keep the respiratory tract unobstructed and take oxygen. Keep vital signs stable and treat complications.