Valocordin

Pharmacological properties

Valocordin is a combined preparation containing phenobarbital and ethyl bromisovalerianate (ethyl ester of α-bromisovalerianic acid). depending on the dose, both of these substances have a sedative, hypnotic effect, and in high doses, a narcotic effect. like other derivatives of barbituric acid, phenobarbital inhibits the reticular formation inhibitor system. ethyl bromisovalerianate has both antispasmodic and sedative effects. at the concentration contained in valocordin, ethyl bromisovalerianate acts as a synergist of phenobarbital (rapid manifestation of the effect).

Pharmacokinetics Phenobarbital is absorbed rapidly (directly in the stomach). About 35% binds to blood plasma proteins, the part that is not bound to proteins is filtered in the kidneys. Reabsorption occurs at low pH. Reverse diffusion does not occur due to alkalinity of urine. About 30% of phenobarbital is excreted unchanged in the urine, and only a small part of it is oxidized in the liver. With prolonged use, there is an accumulation of the active substance in the blood plasma, as well as the induction of liver enzymes. As a result of this induction, the oxidation of phenobarbital and other drugs is accelerated.

Bromine from ethyl bromosovalerianate is released very slowly from the body. If the drug is used for a long time, it accumulates in the central nervous system, which leads to chronic bromine intoxication.

Indications

Functional disorders of the cardiovascular system; neurosis, accompanied by increased irritability and a sense of fear; psychosomatically caused anxiety; excitement states with pronounced autonomic manifestations; violation of falling asleep.

Application

Assign to adults. apply inside with meals with a small amount of liquid. the usual dose is 15-20 drops 3 times a day, with insomnia, you can increase up to 30 drops. the duration of the drug is determined by the doctor.

Contraindications

Hypersensitivity to active substances or to any other component of the drug, acute hepatic porphyria, severe impaired liver and kidney function, diabetes mellitus, depression, myasthenia gravis. medicines containing phenobarbital are contraindicated in cases of alcoholism, drug and drug dependence (including medical history), for respiratory diseases with shortness of breath, obstructive syndrome, severe arterial hypotension, for acute myocardial infarction, and for depressive disorders with a tendency for the patient to suicidal.

Side effects

From the nervous system: asthenia, weakness, impaired coordination of movements, nystagmus, ataxia, hallucinations, paradoxical agitation, insomnia (in elderly patients), decreased concentration, fatigue, inhibition of reactions, headache, cognitive impairment. in some cases, drowsiness and slight dizziness, confusion can be noted.

From the musculoskeletal system: with prolonged use of drugs containing phenobarbital, there is a risk of violation of osteogenesis and the development of rickets. A decrease in bone mineral density, osteopenia, osteoporosis, and fractures have been reported in patients receiving long-term phenobarbital therapy. The mechanism by which phenobarbital affects bone metabolism has not been established.

From the digestive tract: nausea, vomiting, constipation, heaviness in the epigastric region, with prolonged use - impaired liver function.

From the hemopoietic organs: agranulocytosis, megaloblastic anemia, thrombocytopenia, anemia.

From the cardiovascular system: lowering blood pressure, bradycardia.

Very rare: allergic reactions, including angioedema, difficulty breathing, swelling of the face, rash, itching.

Severe skin adverse reactions that have been reported with phenobarbital: Stevens-Johnson syndrome and toxic epidermal necrolysis, urticaria, Lyells syndrome, rhinitis, conjunctivitis, acne, purpura, lacrimation.

special instructions

Life-threatening skin reactions in Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported with phenobarbital.

Patients should be warned of signs and symptoms and closely monitor skin reactions. The highest risk of developing Stevens-Johnson syndrome or toxic epidermal necrolysis is noted during the first weeks of treatment.

If symptoms of Stevens-Johnson syndrome or toxic epidermal necrolysis occur (for example, progressive skin rash, often with blisters and damage to the mucous membranes), then treatment should be discontinued.

The best results in the treatment of Stevens-Johnson syndrome or toxic epidermal necrolysis were noted in the case of early diagnosis and immediate cessation of the use of any drug with suspected occurrence of these symptoms.

If the patient developed Stevens-Johnson syndrome or toxic epidermal necrolysis when applying Valocordin, the drug should not be used in these patients in the future.

If pain in the heart does not go away after taking the drug, you must consult a doctor to exclude acute coronary syndrome. It is prescribed with caution in case of hyperkinesis, hyperthyroidism, adrenal gland hypofunction, uncompensated heart failure, severe arterial hypotension and constant pain, acute drug intoxication.

Valocordin contains 55 vol.% Ethanol.

Long-term use of Valocordin is not recommended because of the danger of drug dependence, the possible accumulation of bromine in the body and the development of bromine poisoning.

Children. There is no experience with the use of the drug in children.

During pregnancy and breastfeeding. During pregnancy and lactation, taking the drug is contraindicated.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. Valocordin reduces the reaction rate. Patients taking Valocordin should refrain from potentially dangerous activities that require increased attention and speed of psychomotor reactions.

Interactions

When using the drug with other drugs that inhibit the central nervous system, mutual reinforcement of the action (sedative-hypnotic effect) is possible, which may be accompanied by respiratory depression. alcohol enhances the effect of the drug and may increase its toxicity.

Medicines containing valproic acid enhance the effect of barbiturates.

Phenobarbital induces liver enzymes and, accordingly, can accelerate the metabolism of certain drugs that are metabolized by liver enzymes (for example, coumarin derivatives, antibiotics and sulfonamides). Phenobarbital enhances the effect of analgesics, anesthetics, drugs for anesthesia, antipsychotics, tranquilizers; reduces the effect of paracetamol, indirect anticoagulants, metronidazole, tricyclic antidepressants, salicylates, digitoxin.

Possible effect on the concentration in the blood of phenytoin, as well as carbamazepine and clonazepam. MAO inhibitors prolong the effect of phenobarbital. Rifampicin may decrease the effect of phenobarbital. When used with gold preparations, the risk of kidney damage increases. With prolonged simultaneous use with NSAIDs, there is a risk of gastric ulcer and bleeding. The simultaneous use of drugs containing phenobarbital with zidovudine increases the toxicity of both drugs.The interaction of Valocordin (containing phenobarbital) with lamotrigine, thyroid hormones, doxycycline, chloramphenicol, antifungals (the azole group), griseofulvin, GCS, oral contraceptives is undesirable due to the possible weakening of the effects of these drugs.

Increases the toxicity of methotrexate.

Overdose

Symptoms acute (mild to moderate) barbiturate poisoning: dizziness, fatigue, deep sleep, from which the patient cannot be awakened.

Hypersensitivity reactions may occur: angioedema, urticaria, pruritus, rash.

Acute severe poisoning: deep coma, accompanied by tissue hypoxia, shallow breathing, first accelerated and then slowed, increased heartbeat, arrhythmia, hypotension, bradycardia, vascular collapse, decreased or lost reflexes, nystagmus, headache, nausea, weakness, impaired cardiac activity , decreased body temperature, decreased heart rate, decreased diuresis.

Failure to provide timely medical attention may result in death due to vascular insufficiency, respiratory paralysis or pulmonary edema.

Prolonged use of drugs containing bromine can lead to bromine poisoning, which is characterized by the following symptoms: confusion, ataxia, apathy, depressed mood, conjunctivitis, colds, acne, or purpura.

Treatment. Cases of acute valocordin poisoning should be treated in the same way as poisoning with other sleeping pills and barbiturates, depending on the severity of the poisoning symptoms. The patient must be hospitalized in the intensive care unit. Breathing and blood circulation require stabilization. Respiratory failure requires artificial respiration, the shock is stopped by the introduction of plasma and plasma substitutes. If a lot of time has passed after taking the drug, it is necessary to rinse the stomach (10 g of activated carbon powder and sodium sulfate are injected into the stomach). In order to quickly remove barbiturate from the body, one can perform forced diuresis with alkalis, as well as hemodialysis and / or hemoperfusion.

Treatment of bromine poisoning: elimination of bromine ions from the body can be accelerated by the introduction of a significant amount of p-ra table salt with the simultaneous introduction of saluretics.

If hypersensitivity reactions occur, prescribe desensitizing drugs.

Storage conditions

In the original packaging at a temperature not exceeding 25 ° C.

Actual information

Valocordin is a combined drug with a predominantly sedative effect. also it has some sleeping pills and antispasmodic effect. its therapeutic effect is due to the synergistic action of the components that make up its composition. valocordin - a drug known since the 50s of the twentieth century, when it began to be produced and used in Germany in the treatment of functional and psychosomatic diseases of the cardiovascular system (koll jf, louis a., 1957), in patients with neurosis, neurotic disorders , increased anxiety, agitation, accompanied by severe vegetative reactions, a sense of fear and increased irritability (marshall w., 1956). Valocordin appeared in the USSR in 1963 and soon gained popularity. despite the success of the pharmaceutical industry and the lack of evidence about its effectiveness and safety, the drug is quite common.

Therapeutic effects of the active substances of the drug Valocordin

Phenobarbital

According to the ATC classification, it belongs to antiepileptic drugs from the group of barbiturates. Phenobarbital has previously been widely used to treat neurosis, insomnia, and to alleviate anxiety conditions (Rickels K., Downing R.W., 1974).Barbiturates, in particular phenobarbital, have a wide range of clinical applications, but today they are most often used as anticonvulsant therapy (Suddock J.T., Cain M.D .., 2018). Phenobarbital is also recommended for the treatment of status epilepticus (Falco-Walter J.J., Bleck T., 2016). A study in China found that intravenous phenobarbital showed a better clinical outcome in the treatment of status epilepticus than valproic acid (Su Y. et al., 2016). Despite this, its widespread use is limited by side effects (Hocker S. et al., 2018). Due to its anticonvulsant and sedative properties, phenobarbital is also used in the treatment of alcohol withdrawal syndrome along with benzodiazepines (Oks M. et al., 2018). But still, in the case of alcohol withdrawal syndrome, it is not the drug of choice, since according to numerous studies, benzodiazepines in this case demonstrate better efficacy with fewer side effects (Hammond D.A. et al., 2017). Phenobarbital can be used to treat insomnia, but it is known that the use of this drug as a sleeping pill is addictive (Gupta R.N., 1985). Phenobarbital reduces craniocerebral pressure. However, this drug can cause hypotension, adversely affecting the supply of oxygen to the brain, which is why it is contraindicated in the treatment of head injuries. In this case, the occurring hypoxia of the brain eliminates any clinical benefit of phenobarbital (Roberts I., Sydenham E., 2012).

The mechanism of action of phenobarbital is associated with an increase in the number of open ionic chloride channels in the GABA receptors (the outflow of chlorine ions increases), this leads to an increase in the sensitivity of these receptors to GABA. Thus, phenobarbital has a non-selective inhibitory effect on the central nervous system. It hyperpolarizes the cell membrane, thereby increasing the threshold for the emergence of an action potential. This mechanism explains its anticonvulsant effect (Suddock J.T., Cain M.D., 2018).

Phenobarbital is hydrophilic; its metabolism occurs in the liver. It is secreted mainly by the kidneys (Suddock J.T., Cain M.D., 2018). Phenobarbital induces cytochrome P450, this must be taken into account when combined with oral contraceptives. Due to the induction of cytochrome P450, phenobarbital accelerates the metabolism of estrogens and progestins, which means that it weakens the effect of oral contraceptives, which can lead to an unwanted pregnancy (Sabers A., 2008). Studies have shown that phenobarbital reduces steroids and theophylline through the P450 cytochrome metabolism system (Sayer W.J., 1975). Thus, patients receiving combined oral treatment in connection with lung pathology may experience the ineffectiveness of therapy for pulmonary disease associated with subtherapeutic levels of theophylline and / or corticosteroids in the blood. Patients must be informed of the potential risks of admission. Valocordina before starting therapy.

Ethyl bromisovalerianate

This is the active substance of the drug Valocordin acts as a synergist of phenobarbital. It has a sedative effect, some sleeping pills mainly due to a general decrease in excitability and anxiety (Nosal M.A., Nosal I.M., 1960). Ethyl bromisovalerianate also exhibits an antispasmodic effect (Pastushenkov L.V., 1989).

Peppermint Oil

Peppermint oil as an auxiliary substance that is part of the drug Valocordinhas a mild vasodilator property. It also has a sedative and antispasmodic effect. In addition, in folk medicine it is used as a choleretic and antiemetic agent, it reduces the likelihood of nausea and increased acidity of gastric juice (Nosal M.A., Nosal I.M., 1960).

Hop oil

It has a calming, sedative, anticonvulsant, analgesic and antispasmodic properties (Pastushenkov L.V. et al., 1990). In herbal medicine, it is used not only as a mild sedative, but also for the treatment of insomnia, inflammatory diseases of the stomach, gall bladder and liver (Nosal MA, Nosal IM, 1960), and topically to reduce the severity of itching and pain with skin diseases.

Peppermint oil and hop oil in the preparation Valocordin contained in small concentrations and are not components that primarily determine its therapeutic effect.

Side effects and possible complications

Side effects and complications when taking Valocordina more often occur with uncontrolled use, exceeding the dose, duration of administration and / or self-medication.

The most common side effects are impaired coordination of movements, drowsiness, loss of appetite, depressive mood, irritability, pain in bones, joints and muscles, less commonly, liver damage, respiratory failure and coma. Both cases of the occurrence of Steven-Johnson syndrome when taking phenobarbital and fixed polymorphic erythema bullosa when taking Valocordina (Savcak V.I., 1987).

Particularly susceptible to the manifestation of side effects are elderly patients. There is information about the treatment of 61 elderly and senile patients in connection with phenobarbital poisoning, which is part of Valocordina. It was found that acute phenobarbital poisoning in elderly and senile patients is more often accompanied by the development of complications from the central nervous system, respiratory (pneumonia) and cardiovascular system than in younger patients. Also, such patients are more likely to have a more severe clinical course and a higher risk of developing an adverse outcome, poisoning (Livanov G.A. et al., 2018).

The risk of complications in patients with COPD is also higher (Suddock J.T., Cain M.D., 2018).

While taking barbiturates and combination preparations containing substances of this group, drinking alcohol is strictly prohibited. This is due to the fact that there is the possibility of inhibition of the respiratory center. Alcohol enhances the inhibitory effect of phenobarbital on the central nervous system. Valocordin It is not recommended for patients with chronic alcoholism or drug addiction.

It is also necessary to warn patients taking Valocordin, about a possible decrease in the rate of reactions and violation of coordination. This is especially important when driving vehicles or working with other mechanisms.

Not recommended Valocordin patients with depression, since phenobarbital can enhance its manifestations.

With uncontrolled administration of the drug, a significant excess of the dose, the toxic effect of phenobarbital may develop.

Symptoms include cognitive impairment, dizziness, muscle weakness, polydipsia, oliguria, hypothermia (decreased body temperature), mydriasis, nausea, vomiting, bradycardia, respiratory depression. The severity of these symptoms can vary significantly (Suddock J.T., Cain M.D., 2018).

The development of coma and death due to severe respiratory depression and hypotension are possible.

Valocordin with prolonged use due to the content of phenobarbital contributes to the progression of osteoporosis. Care must be taken and do not prescribe for a long time. Valocordin patients with osteoporosis.

With prolonged use of the drug in high doses, addiction is possible, as well as the development of withdrawal symptoms when you stop taking this drug.

In this regard, in some countries, for example, in the USA, the United Arab Emirates and Estonia, Valocordin as a drug containing phenobarbital is included in the list of drugs prohibited for import into the country.

In case of overdose - symptomatic treatment.Therapy depends on the symptoms and their severity, and may include respiratory support (intubation and mechanical ventilation), correction of bradycardia and hypotension (administration of vasopressors, colloidal and crystalloid solutions intravenously to restore fluid volume), forced diuresis or hemodialysis (Palmer B.F., 2000).

findings

Valocordin - A drug with more than half a century of history. Today, it is also used as a sedative drug, to relieve cardialgia, insomnia, arousal, anxiety and anxiety. However, patients should be informed of the possibility of serious side effects if this drug is abused. Therefore, it must be remembered that the drug includes phenobarbital, which has a wide range of undesirable side effects, it is also possible to develop addiction, withdrawal symptoms, toxic lesions and even acute phenobarbital poisoning in case of an overdose Valocordina. Patients should be warned about possible drug interactions, since phenobarbital can reduce the therapeutic effect of many drugs, among which are indirect anticoagulants and some antibiotics and antifungal drugs. Women of reproductive age using oral contraceptives should be warned about the weakening of their effect when combined with this drug. It is also necessary to remember that during application Valocordina alcohol consumption is strictly prohibited due to the increased toxic effects of phenobarbital and central nervous system depression. It is not recommended to use the drug in combination with other sedatives, tranquilizers and antipsychotics due to their synergistic inhibitory effect on the central nervous system. Do not use the drug during pregnancy and lactation. In case of compliance with all recommendations, prescribed dose and regimen ValocordinIt is generally well tolerated.