Barbital, chemical name: 5,5-diethylpyrimidine-2,4,6 (1H, 3H, 5H) - trione, molecular formula: CeightHtwelveNtwoOthree, is the first commercializedBarbiturates, white crystalline powder, odorless, slightly bitter taste.
Barbital was oncehypnoticorSedativesIt is used in clinic, but it is eliminated because of its weak effect, many adverse reactions, insecurity and dependence.
Solubility: 1g is soluble in about 130mL cold water, 13mL boiling water, 14mL ethanol, 75mL chloroform and 25mL ether, and in acetone, ethyl acetate, petroleum ether, acetic acid, pentanol, pyridine, aniline, nitrobenzene and alkaline solution.[1]
Molecular structure data
Molar refractive index: 44.09
Molar volume (cmthree/mol）：161.5
Isotonic specific volume (90.2K): 389.1
Surface tension (dyne/cm): 33.6
Polarization (10-24cmthree）：17.47[1]
Calculate chemical data
Reference value for drainage parameter calculation (XlogP): None
Number of hydrogen bond donors: 2
Number of hydrogen bond receptors: 3
Number of rotatable chemical bonds: 2
Number of tautomers: 5
Topological molecular polar surface area: 75.3
Number of heavy atoms: 13
Surface charge: 0
Complexity: 247
Number of isotope atoms: 0
Determine the number of atomic structure centers: 0
Number of uncertain atomic structure centers: 0
Determine the number of chemical bond structure centers: 0
Number of uncertain chemical bond structure centers: 0
Number of covalent bond units: 1[1]
purpose
Prepare buffer solution.Protein electrophoresis.Liver function test.Hydrogen peroxide stabilizer.
Pharmacopoeia standard
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Main active ingredients
5,5-Diethylmalonylurea.Calculated as dry product, including CsixHtwelveNtwoOthreeNot less than 98.5%.[2]
character
White crystal or crystalline powder;Odorless, slightly bitter;The saturated aqueous solution is acidic.
Soluble in boiling water or ethanol, slightly soluble in chloroform or ether, slightly soluble in water;Dissolve in alkali hydroxide or alkali carbonate solution.
The melting point is 189-192 ℃.[2]
identify
Identification reaction of propanylurea[2]
inspect
Clarity: Take 1g of this product and add 10mL of sodium hydroxide solution (1mol/L) to dissolve it. The solution should be clear.
Loss on drying: Take this product and dry it at 105 ℃ to constant weight, and the weight loss shall not exceed 1.0%.
Residue on ignition: not more than 0.1%.[2]
Assay
Take about 0.2g of this product, weigh it accurately, add 40mL of methanol to dissolve it, add 15mL of newly prepared 3% anhydrous sodium carbonate solution, titrate it with silver nitrate solution (0.1mol/L) according to the potentiometric titration method, and get it.Every 1mL of silver nitrate solution (0.1mol/L) is equivalent to 18.42mg of CeightHtwelveNtwoOthree。[2]
pharmacological action
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It is a long-acting barbital hypnotic drug used earlier, which has central inhibitory effects of sedation, hypnosis, anticonvulsant, anesthesia and other different degrees.Its advantages are slow action and long maintenance time.30~60 min after oral administration, the effect was significant and maintained for 6~8 h.In addition, barbital can enhance the analgesic effect of antipyretic analgesics when used together.[3]
Pharmacokinetics
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Sedation and hypnosis;Large dose can resist convulsion and anesthesia.The effect appears slowly and lasts for a long time.[3]
indication
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1. Sedation: such as anxiety, irritability, hyperthyroidism, hypertension, functional nausea, children's pyloric spasm, etc.
2. Sleep well: occasionally used for intractable insomnia, but after waking up, there are often residual effects such as fatigue and sleepiness.
3. Anti convulsion: It is commonly used to fight against convulsions caused by central stimulant poisoning or high fever, tetanus, encephalitis, cerebral hemorrhage and other diseases.
4. Anti epilepsy: It is used for the prevention and treatment of grand mal epilepsy, with rapid effect, and can also be used for status epilepticus.
5. Administration before anesthesia.
6. It is used in combination with antipyretic and analgesic drugs to enhance its effect.
7. Treat neonatal nuclear jaundice.Long term use may lead to pathological dependence.[3]
purpose
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This product is a long-term hypnotic drug with sedative, hypnotic, anticonvulsant and antiepileptic effects.It can also be used as a pre anesthetic drug, which can enhance the analgesic effect of antipyretic and analgesic drugs when used together.These years, it has been reported that this product can be used to prevent neonatal hyperbilirubinemia and brain nuclear jaundice, and can also treat cholestasis.After adding phenobarbital to patients with brain edema, the brain edema and hernia improved quickly, the blood pressure was easy to stabilize, and the cerebral vasospasm and rebleeding were also reduced.Oral administration of this product combined with intramuscular injection of chorionic gonadotropin in the treatment of primary infertility.It can also treat polycystic egg syndrome and reduce the incidence of intracranial hemorrhage in premature infants.Oral administration of this product can also increase the efficacy of papaverine on cerebrovascular spasm and other diseases.[3]
Specifications
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Tablets: 0.01g, 0.015g, 0.03g, 0.1g per tablet.Sodium phenobarbital for injection: 0.1g each.Barbiturates are a group of central inhibitory drugs obtained by replacing barbituric acid at C5 position.If the substituent is long and has branches (such as isopentabarbital) or double bonds (such as secobarbital), the effect is strong and short;Substitution of benzene ring (such as phenobarbital) has strong anticonvulsant effect;If O at position C2 is replaced by S (such as thiopental), the fat solubility will increase, and intravenous injection will take effect immediately, but the maintenance time is very short.
Comparison of functions and uses of barbiturates
Subclass
medicine
Effective time (hours)
Duration of action (hours)
Main purpose
Long term effect
Phenobarbital
0.5～1 0.5～1
6～8 6～8
Anticonvulsant sedative hypnosis
Medium effect
Pentobarbital Isopentobarbital
0.25～0.5 0.25～0.5
3～6 3～6
Anticonvulsant sedative hypnosis
Short term effect
Secobarbital
zero point two five
2~3
Anticonvulsant sedative hypnosis
Ultra short effect
Thiopental sodium
Iv Immediately
zero point two five
Intravenous anesthesia
Usage and dosage
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1. 0.3-0.6g, taken 0.5 hour before bed.
2. Sedation: 0.3~0.9g per day, 2~3 times.
3. Administration before anesthesia: 0.3g, 40~60min before operation.
4. Anti convulsion: intramuscular injection of sodium barbital, 0.2g each time.Or use 5% solution enema, 0.5g each time.[3]
Adverse reactions
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Similar to phenobarbital, the next morning after hypnosis will have mental depression, dizziness and other reactions;A few have skin rash and fever.Long term use can lead to tolerance and dependence.Large doses can inhibit the respiratory center, and in severe cases, respiratory paralysis may occur and death may occur.It is forbidden for patients with serious damage to liver, lung and kidney functions.[3]
matters needing attention
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Long term use can lead to tolerance and addiction. Repeated use should be alert to accumulated poisoning.A few patients may have allergic reactions such as rash, exfoliative dermatitis and fever.When used for anti epilepsy, do not stop the drug suddenly to avoid rebound phenomenon.During medication, alcohol should be forbidden, and those with poor liver and kidney function should be cautious.Its sodium salt solution is unstable and is not suitable for storage. The solution Ph value is 9.7. There is often precipitation when it is mixed with drugs with low pH value, so it should not be mixed with other drugs for injection.Sealed and protected from light.
1. After medication, dizziness, drowsiness and other sequelae may occur. Long term use may lead to tolerance and addiction.Repeated use should be alert to accumulated poisoning.
2. A few patients may have allergic reactions such as rash, drug heat, exfoliative dermatitis, etc.
3. When it is used to treat epilepsy for a long time, the drug cannot be stopped suddenly, so as not to cause seizures, or even epileptic status.
4. Generally, 5~10 times of hypnotic dose can cause moderate poisoning, and 10~15 times can cause severe poisoning. When the blood concentration is higher than 8~10mg/100mL, life is in danger.The symptoms of acute poisoning are lethargy, then shallow breathing, greatly reduced ventilation, and finally death due to respiratory failure.
5. It should be used with caution or forbidden for patients with severe pulmonary insufficiency (such as emphysema), bronchial asthma and brain injury whose respiratory center is inhibited;It should be used with caution in patients with poor liver and kidney function, and should not be used in patients with cirrhosis or severe liver dysfunction.
6. First aid for poisoning caused by this product or other barbiturates: For those who take this product orally for less than 3 hours, a large amount of warm isotonic saline or 1:2000 potassium permanganate solution can be used for gastric lavage.[3]
inhibition
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Barbiturates are universal central depressants.The sedative, hypnotic, anticonvulsant and anesthetic effects appeared successively with the increase of the dosage.10 times the hypnotic amount can inhibit breathing, or even kill.
Barbiturates mainly inhibit polysynaptic response, weaken facilitation and enhance inhibition in non anesthetic dosage.This effect is mainly seen in GABAergic synapses.It enhances GABA mediated Cl influx and weakens glutamate mediated depolarization.But unlike benzodiazepines, barbiturates increase Cl influx by prolonging the opening time of the chloride channel, causing hyperpolarization.At higher concentrations, it inhibits Ca dependent action potential, inhibits Ca dependent neurotransmitter release, and presents a quasi GABA effect, that is, it can directly increase Cl influx in the absence of GABA.
These drugs need to be used to sedative dosage before they show anti anxiety effect.Because the safety of this kind of drugs is far less than that of benzodiazepines, and they are prone to dependence, they are rarely used for sedation and hypnosis at present.Only phenobarbital and pentobarbital are still used to control status epilepticus;Thiopental is occasionally used for intravenous anesthesia during minor surgery or endoscopy.
Drug addiction
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Barbiturates inhibit the pontine reticular structure and reduce REM sleep. Even if taken for a short time, withdrawal of barbiturates will cause rebound of REM sleep, which is manifested by continuous nightmares and uncomfortable feelings.Therefore, once taking barbiturates, it is often difficult to stop, so it is easy to form dependence.Most of the dependent people take short-term drugs, such as Sukemian, Amital, Pentobarbital, etc.Generally, the dosage of addiction is 4~50 times of the therapeutic dosage. This kind of drug has cross resistance with alcohol. Taking barbiturates with alcohol can accelerate addiction.Sometimes you can become addicted after taking a large amount of drugs.
1. Addiction effects.After taking medicine, it can relieve tension and anxiety, and produce a feeling of delirium and oblivion, which leads to a strong desire to continue taking medicine, even to the point of not taking medicine, forming a strong psychological dependence.At the same time, patients often have symptoms of chronic poisoning.
2. Chronic poisoning.
The main manifestations are: ① ataxia, unstable gait, unclear enunciation, clumsy movements, poor distance discrimination, and nystagmus; ②Slow understanding, difficult thinking, poor memory, wrong judgment; ③Unstable, irritable, moody, stubborn, and prone to conflict with others; ④Irregular living, untidy clothes, dissolute behavior, high sexual desire and poor moral concept; ⑤Toxic psychosis may occur.
(3) Withdrawal symptoms.
① Awakening period: a few hours to 24 hours after drug withdrawal.The symptoms include fatigue, anxiety, decreased blood pressure, orthostatic collapse, absence attack, tachycardia, insomnia, etc.
② Spastic period: It is usually seen about 1~3 days after drug withdrawal, especially on the second day. Spastic attacks are common and even persistent.At the same time, there are insomnia, gross tremor, hyperkinesia, etc.There were abnormal findings in EEG examination.
③ Delirium period: often occurs immediately after the convulsion period.Delirium is mainly nocturnal, mainly manifested as disturbance of consciousness and uncoordinated psychomotor excitement. If accompanied by high fever, it can endanger life.Delirium usually disappears after 5 days, and convulsions can still occur on the 7th day.Sometimes this period lasts about 2 weeks.
④ Hallucination and delusion period: schizophrenic hallucinations and delusions can occur, accompanied by terror, and can last for a long time, up to about two months.
⑤ Emotional instability period: Emotional instability, variability, irritability, and reduced endurance can last for weeks to months.
Related drugs
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Barbiturates: These drugs are all derivatives of barbiturates.Its function is to inhibit the function of the central nervous system, mainly to block the conduction of the upward activation system of the brainstem reticular structure, reduce the impact of afferent impulses on the cerebral cortex, and thus have sedative and hypnotic effects.Barbiturates have the same effect.However, the effect is different in strength and duration. Those with high fat solubility are easy to penetrate the blood-brain barrier into human brain tissue, and the effect is fast and strong. Those with low fat solubility enter human brain tissue slowly, and the effect is also slow.
Phenobarbital is also known as Lumina: Phenobarbital has inhibitory effect on the central nervous system, which can produce sedative, hypnotic and anticonvulsant effects with the increase of dosage.Its effect lasts for 6-8 hours, which can shorten people's sleep time and prolong their sleep time, but it is accompanied by dreaminess.It can be used for administration before anxiety, insomnia and anesthesia. When used with antipyretic analgesics, its analgesic effect can be increased. A larger dose has anticonvulsant effect, and it can be used for severe attacks of pain, tetanus, etc.In addition, it can treat neonatal cerebral nuclear jaundice, because it can induce liver microsomal glucuronosyltransferase, promote the combination of bilirubin and glucuronide, and reduce the plasma bilirubin concentration.
Usage and dosage: ① Take 15-30 mg orally by adults outside the town three times a day. ②Hypnotic adults: 30-100 mg per time, take before bed, 250 mg per time at maximum, 500 mg per day.Toxic and side effects: there are often lasting effects such as lethargy, dizziness, and low spirits.Allergic reactions are occasionally seen, such as rash, exfoliative dermatitis, motor dysfunction, jaundice, toxic hepatitis, etc.If the dosage is exceeded, acute poisoning may occur, with symptoms such as lethargy, respiratory depression, tachycardia, blood pressure drop, shock, etc., and finally death due to anesthesia of the respiratory center.Preparation and specification: 30mg/tablet, 100mg/tablet.Precautions: ① Long term use may lead to tolerance and dependence, and repeated use or excessive dose may lead to accumulated poisoning, so use shall be controlled. ②The dosage should be reduced for elderly patients, and it should not be used for patients with liver and kidney dysfunction, respiratory system dysfunction, brain injury and leaf enkephalosis. ③It can enhance the central inhibitory effect of other medium frame inhibitors. ④Sodium valproate can inhibit the metabolism of phenobarbital, and the dosage of the latter should be reduced when used in combination.
2、 Isopentobarbital, also known as Amital: This product is similar to phenobarbital in its role, high in fat solubility, easy to penetrate the blood-brain barrier, and quick in action. It is a medium effect barbital hypnotic. It can be taken orally for 15-30 minutes to sleep, and is used for simple insomnia and sedation in anxiety and tension.The injection is mainly used for anti convulsion, such as the rescue of carbuncle, hyperthermia convulsion, and persistent status of epilepsy and carbuncle.Usage and dosage: ① Take 20-40 mg orally for adults, 2-3 times a day. ②For hypnotic adults, 100-200 mg should be taken before sleep.Toxic and side effects: the same as phenobarbital.Preparation and specification: tablet, 100mg/tablet.Precautions: ① This product is addictive and should not be used for a long time. ②The injection is unstable and should be prepared on the spot. ③Other precautions are the same as phenobarbital.
3、 Pentobarbital sodium: The effect of this product is the same as that of isobarbital, and it is a medium effect drug.It takes effect 15 minutes after oral administration and lasts for 3-6 hours.It is clinically used for hypnosis and is effective for all kinds of insomnia.Administration before anesthesia can prevent convulsion.
Usage and dosage: Hypnosis: adults take 100-200 mg orally each time.Toxic and side effects: the same as phenobarbital.Preparation and specification: 50 mg/tablet.Precautions: the same as isopentabarbital.Sukemian, also known as Scobarbital Sodium, is a short-term barbital drug with similar effect to phenobarbital, but it takes effect quickly. People can sleep 15-20 minutes after taking it, and it lasts for about 3 hours.It is clinically used for insomnia with difficulty in sleeping, as well as for tension, anxiety, overexcitement, and sedation before anesthesia and surgery.Usage and dosage: ① Take 50mg orally for adults to calm down, three times a day. ②For hypnotic adults, 100-200 mg should be taken before sleep.Toxic and side effects: the same as phenobarbital.Preparation and specification: capsule, 100mg/capsule.Precautions: continuous use is easy to produce tolerance. After 1-2 weeks of use, the hypnotic effect is significantly reduced. Long term use can also produce dependence, which should be strictly controlled. Other uses are the same as phenobarbital.
The commonly used drugs for clinical treatment of insomnia and dreaminess include Yangxue Anshen Tablet, Jieyu Anshen Granule, Yening Granule, etc.
