What Is Phenobarbital?

Phenobarbital is used for: sedation: such as anxiety, irritability, hyperthyroidism, hypertension, functional nausea, pyloric spasm in children; hypnosis: occasionally used for refractory insomnia, but often after waking Aftereffects such as fatigue and drowsiness; anticonvulsant: commonly used to fight convulsions caused by central stimulant poisoning or fever, tetanus, encephalitis, cerebral hemorrhage and other diseases; antiepileptic: used for major epilepsy and partial seizures Treatment, the effect is rapid, can also be used for the status of epilepsy; administration before anesthesia; compatible with antipyretic analgesics to enhance its effect; treatment of neonatal hyperbilirubinemia.

On October 27, 2017, the list of carcinogens published by the International Agency for Research on Cancer of the World Health Organization has initially compiled and referenced phenobarbital in the list of 2B carcinogens. ^[1]

Drug type: Essential medicines
Drug name: Phenobarbital

English name: Phenobarbital
Chinese alias: Gadina, Rumina, Frona
English alias: Phenobarbitone;

Phenobarbital chemical name

5-ethyl-5-phenyl-2,4,6 (1H, 3H, 5H) -pyrimidinetrione

Phenobarbital molecular structure

Phenobarbital molecular formula

C12H12N203

Phenobarbital molecular weight

232

Phenobarbital physicochemical properties

It is a white shiny crystalline powder; odorless and slightly bitter. Saturated aqueous solution was acidic. Soluble in ethanol or ether, slightly soluble in chloroform, very slightly soluble in water, and soluble in sodium hydroxide or carbonate solution. Melting point is 174.5-178 ° C.

Phenobarbital Pharmacology

For long-acting barbiturates, the central inhibitory effect varies with dose. It has sedative, hypnotic and anticonvulsant effects. And anti-epilepsy, good for large epileptic seizures and localized seizures and persistent state of epilepsy; poor efficacy for small epileptic seizures; and often not effective for psychomotor seizures, and the seizures may be aggravated when treated with this drug alone . This product also has the effect of enhancing antipyretic and analgesics, and can induce liver microsomal glucuronyltransferase activity, promote the combination of bilirubin and glucuronic acid, reduce plasma bilirubin concentration, and treat neonatal bilirubin Anemia (cerebral nuclear jaundice). Its sodium salt is easily absorbed by oral and injection. Can be distributed in various tissues and body fluids, although the slow entry into human brain tissue, but the highest concentration in brain tissue. It takes 0.5 ~ 1 hour for oral administration and 15 minutes for intravenous injection to take effect. Peak plasma concentration was reached in 2-18 hours. Effective blood medicine is 10 40µg / ml. The average duration of action was 10-12 hours, the average plasma protein binding rate was 40%, t1 / 2 was 50-144 hours in adults, and 40-70 hours in children. 65% are metabolized in the liver, and metabolites and some prototypes (about 30%) are excreted by the kidneys. The renal tubules have a reabsorption effect, which prolongs the duration of the effect.

Phenobarbital indications

Used for: sedation: such as anxiety, irritability, hyperthyroidism, hypertension, functional nausea, pyloric spasm in children; hypnosis: occasionally used for refractory insomnia, but often wake up with fatigue, lethargy, etc. Anticonvulsant effects: anticonvulsants: commonly used to fight convulsions caused by central stimulant poisoning or high fever, tetanus, encephalitis, cerebral hemorrhage and other diseases; antiepileptics: used for the treatment of major epileptic seizures and partial seizures, with rapid effects , Can also be used for the status of epilepsy; administered before anesthesia; compatible with antipyretic and analgesics to enhance its effect; treatment of neonatal hyperbilirubinemia.

Phenobarbital usage and dosage

Due to different dosage forms and specifications, please read the drug instructions carefully or follow the doctor's advice.

Phenobarbital adverse reactions

(1) After effects, dizziness, drowsiness and other after effects can occur. Long-term use can produce tolerance and dependence. Repeated use should be alert to accumulation of poisoning. (2) A few patients may develop allergic reactions such as rash, drug fever, and exfoliative dermatitis.

Phenobarbital contraindications

Prohibited in patients with allergies to this product, severe liver and kidney dysfunction, bronchial asthma, respiratory depression and porphyria.

Phenobarbital precautions

(1) Do not abruptly stop taking medicine for long-term use in the treatment of epilepsy, so as not to cause seizures, or even a state of sustained epilepsy. (2) Normal application of 5 to 10 times the amount of hypnosis can cause moderate poisoning, and 10 to 15 times of severe poisoning. When the blood concentration is higher than 8 to 10 mg / 100ml, it is life-threatening. The symptoms of acute poisoning are drowsiness, which leads to superficial breathing, greatly reduced ventilation, and death from respiratory failure. (3) Be used with caution in severe anemia, heart disease, diabetes, hypertension, hyperthyroidism, the elderly, pregnant women and lactating women. (4) The speed of intravenous injection should not exceed 60mg per minute, too fast can cause respiratory depression. (5) Taking this product during pregnancy can cause hypothrombinemia and bleeding in newborns. Vitamin K has a therapeutic or preventive effect. (6) First aid for poisoning of this product or other barbiturates: If the product is taken orally for less than 3 hours, the stomach can be lavaged with a large amount of warm physiological saline or 1: 2000 potassium permanganate solution (be careful to prevent liquid from flowing into the trachea So as not to cause aspiration pneumonia). After washing, use 10 to 15 g of sodium sulfate (do not use magnesium sulfate) to relieve diarrhea. And sodium bicarbonate or sodium lactate is used to alkalize the urine, reduce reabsorption in the renal tubules, and accelerate drug excretion. Diuretics such as mannitol can also be used to increase urine output and promote drug excretion. In the case of respiratory acidosis caused by respiratory depression, the drug can be promoted into the center and the poisoning reaction is aggravated. Therefore, it is particularly important to ensure that the airway is unobstructed. If necessary, perform tracheotomy or tracheal intubation, oxygen or artificial breathing. Central and central stimulants can also be given appropriately. When the blood pressure is low, glucose saline or low-molecular dextran can be administered intravenously.

Phenobarbital drug interactions

(1) Combination with paracetamol can cause liver toxicity. (2) with paracetamol, dicoumarin, hydrocortisone, dexamethasone, testosterone, estrogen, progestin, oral contraceptives, chlorpromazine, chloramphenicol, doxycycline, gray yellow When combined with mycin, digoxin, digoxigenin, phenytoin, and cyclosporine, phenobarbital accelerates their metabolism and reduces the efficacy. (3) The drug effect of activating cyclophosphamide in the body when combined is increased. (4) When used in combination, the plasma concentrations of ethosuccin and carbamazepine are reduced, and t1 / 2 is shortened. (5) When used in combination, the sodium valproate is shortened, the liver toxicity is increased, and the concentration of phenobarbital is increased. (6) Enhance the hypotensive effect of calcium antagonists when combined.

Phenobarbital

Tablet: 15mg, 30mg, 100mg; injection: 1ml: 0.1g, 2ml: 0.2g; sterile powder for injection: 0.1g.

Phenobarbital Pharmacopeia Introduction

[Identification] (1) Take about 10mg of this product, add 2 drops of sulfuric acid and about 5mg of sodium nitrite, mix, it is orange-yellow, and then turns orange-red. (2) Take about 50mg of this product, put 1ml of formaldehyde test solution in a test tube, heat and boil, cool, slowly add 0.5ml of sulfuric acid along the tube wall to make two liquid layers, and heat in a water bath. The interface is rose red. (3) The infrared light absorption spectrum of this product should be consistent with the control spectrum (spectrum set 227). (4) This product shows the identification reaction of malonyl ureas (Appendix III). [Check] For acidity, take 0.20g of this product, add 10ml of water, stir and boil for 1 minute, let cool, filter, take 5ml of filtrate, add 1 drop of methyl orange indicator liquid, and it should not be red. Clarity of ethanol solution Take 1.0g of this product, add 5ml of ethanol, heat to reflux for 3 minutes, the solution should be clear. Relevant substances are taken from this product, and the mobile phase is dissolved and diluted to make a solution containing 1 mg per 1 ml as the test solution; 1 ml is precisely measured, placed in a 200 ml measuring flask, diluted with mobile phase to the mark, and shaken as Control solution. According to the high performance liquid chromatography (Appendix VD) test, octylsilane-bonded silica gel was used as the filler; acetonitrile-water (25:75) was used as the mobile phase, and the detection wavelength was 220nm; the theoretical plate number was based on phenobarbital The peak calculation is not less than 2500, and the resolution of the phenobarbital peak and the adjacent impurity peaks should meet the requirements. Take 5µl of the control solution and inject it into the liquid chromatograph, adjust the detection sensitivity so that the peak height of the main component chromatographic peak is about 15% of the full range; accurately measure 5µl each of the test solution and the control solution, and inject them into the liquid chromatograph respectively. Record the retention time of the chromatogram to the main component peak three times. If there is an impurity peak in the chromatogram of the test solution, the area of the single impurity peak must not be greater than the area of the main peak of the control solution (0.5%), and the sum of the area of each impurity peak must not be greater than the control solution. Double the main peak area (1.0%). Take 1.0g of this product for neutral or alkaline materials, place it in a separating funnel, add 10ml of sodium hydroxide test solution to dissolve, add 5ml of water and 25ml of ether, shake for 1 minute, separate the ether layer and wash with water. 3 Each time, 5ml, take the ether solution and filter through dry filter paper. The filtrate is placed in a constant-temperature evaporation dish at 105 ° C, evaporated to dryness, and dried at 105 ° C for 1 hour. The residual residue should not exceed 3mg. Loss on drying: Take this product and dry it at 105 to constant weight. Loss of weight should not exceed 1.0% (Appendix L). The ignition residue shall not exceed 0.1% (Appendix N). [Content determination] Take about 0.2g of this product, accurately weigh, add 40ml of methanol to dissolve, and then add 15ml of a new 3% anhydrous sodium carbonate solution, according to potentiometric titration (Appendix A), using silver nitrate titration solution ( 0.1 mol / L) titration. Each 1ml of silver nitrate titration solution (0.1mol / L) is equivalent to 23.22mg of C12H12N2O3. [Category] Sedative hypnotics, anticonvulsants. [Storage] Keep sealed.

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