Baclofen

Pharmacodynamics

The pharmacological properties of baclofen are different than that of phenibut and other nootropic drugs . He is an agonist of GABA-B receptors , and the main manifestation of its pharmacological activity is an antispastic effect. It inhibits spinal and visceral reflexes , reduces muscle tension (reduces the tone of skeletal muscles ), clonus . It also has an analgesic effect.

It is assumed that the suppression of mono- and polysynaptic reflexes is due to a decrease in the excretion of excitatory amino acids ( glutamate and aspartate ) from vesicles , which occurs as a result of stimulation of presynaptic GABA receptors . Therefore, the inhibitory effect of the drug, which occurs several hours after administration, can be explained by the release of the accumulated excessive potential of the hamkergetic brake systems.

Pharmacokinetics

Absorption is high. TCmax - 2-3 hours. Communication with plasma proteins - 30%. Penetrates through the placental barrier , excreted in breast milk . It is metabolized by the liver . It is excreted by the kidneys (mainly unchanged).

Indications

Spasticity in multiple sclerosis , strokes , traumatic brain injuries , meningitis , spinal diseases (infectious, degenerative, tumor and traumatic genesis), with cerebral palsy .

Alcoholism

In France, since March 2014, medical authorities (ANSM: Agence nationale de sécurité des médicaments et des produits de santé) have been allowed to prescribe baclofen for the treatment of drug addiction. clinical tests conducted on patients with alcoholism (from 2008 to 2014) showed very good positive results ^[1] . Despite the level of alcohol consumption and the duration of consumption (chronic patients or occasional users who drink excessive doses), the results of treatment with baclofen were amazing. Almost 80% ^{[2] [3] of} patients got rid of alcohol addiction ^{[4] [5]} .

This property of baclofen was noticed in France by Olivier Ameisen, MD, a cardiologist who became an alcoholic and was cured of this medicine. Public opinion was not ready for such an unusually easy cure for alcoholism, since traditional and far from cheap methods of treatment through therapy in rehabilitation centers do not lead to such remarkable results. Dr. Olivier Ameisen, faced with skepticism of doctors to use a neurological drug to treat alcohol dependence. Therefore, he wrote the book “The Last Glass” (Dernier verre, Dr. Oliver Ameisen, Denoel, 2008) ^[6] , in which he described his case in detail and thereby mobilized public opinion. ^[7] After this book, several clinical trials conducted under the supervision of government authorities were organized in France. The above results of these tests forced the French medical authorities to allow the use of baclofen in the treatment of alcohol dependence ^[8] .

To date, the parameters regarding dosage and side effects are not entirely clear. Dosage depends on the degree of dependence and on the physiology of each patient ^[3] .

Contraindications

Hypersensitivity , epilepsy , convulsions ( history ), psychoses , Parkinson's disease , chronic renal failure .

With caution

Cerebrovascular insufficiency , cerebrovascular arteriosclerosis , gastric ulcer and duodenal ulcer , pregnancy , lactation , old age, children's age (up to 12 years)

Inside, during meals: the initial dose is 5 mg 3 times a day, followed by a dose increase of 3 mg every 3 days until the effect is achieved, usually no more than 20-25 mg 3 times a day; the maximum dose is 100 mg / day (for a short time in a hospital). The final dose is set so that a decrease in muscle tone does not lead to excessive myasthenia gravis and does not impair motor function. With increased sensitivity, the initial daily dose is 5-10 mg, followed by a slower increase. In chronic renal failure and during hemodialysis , a daily dose of 5 mg. In children under 10 years old, the daily dose is 0.75-2 mg / kg, older than 10 years - 2.5 mg / kg; the initial dose is 1.5-2 mg / kg 4 times a day, the maintenance dose for children 1-2 years old is 10-20 mg / day, 2-10 years old is 30-60 mg / day. Drug withdrawal is carried out gradually (within 1-2 weeks).

If the initial doses are not observed, as well as an independent increase in the dosage, the drug can cause drug dependence.

Side effects

Nausea , vomiting , drowsiness, dizziness , asthenia , dry mouth, confusion, gait disturbance, urinary retention , constipation or diarrhea , decreased blood pressure , apathy ; euphoria , depression , paresthesia , myalgia , myasthenia gravis , ataxia , tremor , nystagmus , paresis of accommodation , hallucinations , dysuria , enuresis ; cramps , decreased seizure threshold, mydriasis , weight gain. With prolonged use - impaired liver function.

Overdose

Symptoms Muscular hypotension , voluntary urination and defecation , cramps, depression of the respiratory center, confusion, coma , up to a fatal outcome; after regaining consciousness, muscle hypotension may persist for 72 hours.

Treatment. Heavy drinking, diuretics ; with respiratory depression - mechanical ventilation . As an antidote , analeptics can be used - bemegrid , flumazenil niketamide . When hallucinatory conditions occur, antipsychotics and tranquilizers are indicated to facilitate falling asleep.

Abstinence can develop as a result of a sharp discontinuation of the drug after systematic use in small doses for a week or a month. Withdrawal syndrome includes loss of appetite, insomnia , depression , headache, cramping , less often hallucinations. In order to mitigate withdrawal symptoms, gradual withdrawal of the drug with a decrease in each subsequent dose is recommended.

Side effects are often transient in nature, they should be distinguished from the symptoms of the disease for which treatment is carried out: with concomitant epilepsy, treatment is carried out without canceling antiepileptic drugs. In patients with liver diseases and diabetes mellitus, it is necessary to periodically monitor the activity of “liver” transaminases , alkaline phosphatase , and blood glucose . During treatment, one should refrain from potentially hazardous activities associated with the need for increased attention and quick mental and motor reactions. The drug should be used in compliance with the initial doses to avoid drug dependence and withdrawal .

• Dukova O. A. Identification and quantitative determination of baclofen in biological objects by chromatographic and tandem methods: abstract of the dissertation for the degree of candidate of chemical sciences: special. 02.00.02 . - Tomsk, 2017 .-- 24 p.