Caffeine-sodium benzoate

General characteristics. Structure:

Active ingredients: 80 mg of caffeine, 120 mg of Natrium benzoicum in 1 ml of solution.

Excipients: sodium hydroxide, water for injections.

Pharmacological properties:

Pharmacodynamics. Has psychogogic and analeptical properties. The mechanism of action is connected with ability of caffeine to act as the competitive antagonist of purine A1 and A2A-receptors. As a result of blockade of receptors processes of braking in the central nervous system decrease, secretion of neurotransmitters (serotonin, noradrenaline and dopamine) in motor zones of a cerebral cortex, a hypothalamus and a myelencephalon is facilitated and stabilized. In doses of relatives to toxic caffeine is capable to block activity of phosphodiesterases (III, IV types are preferential) and to slow down disintegration of tsAMF and tsGMF that stimulates activity of neurons and accelerates a metabolism in a cell.

Strengthening of dofaminergichesky transfer in synapses of a cerebral cortex makes psychogogic impact. Activation of adrenergic transfer in synapses of a hypothalamus and a myelencephalon activates cortical functions, increases physical activity, causes anorexia, makes tonic impact on a vasomotor center. Strengthening of cholinergic transfer in synapses of bark and a myelencephalon activates cortical functions, increases activity of a respiratory center.

Caffeine exerts direct exciting impact on TsNS: stimulates mental activity, increases intellectual and physical effeciency, shortens reaction time, activates positive conditioned reflexes. After administration of caffeine cheerfulness appears, the exhaustion and drowsiness temporarily decrease or eliminated. At elderly people influence on a dream is more expressed: approach of a dream is slowed down, the general time of a dream decreases and the frequency of night awakenings increases.

Against the background of oppression of a respiratory center causes increase and deepening of breath. Influences cardiovascular system: increases the frequency and force of cordial reductions, at hypotension raises the ABP (does not influence the ABP normal level). At premature children eliminates periodic breathing due to decrease in partial pressure of carbon dioxide in blood, increases ventilation volume, without influencing significantly function of cardiovascular system.

Relaxes smooth muscles of bronchial tubes, bilious ways, causes dilatation of vessels of skeletal muscles, heart and kidneys, narrows vessels of abdominal organs (especially at their initial dilatation). Has weak diuretic effect due to expansion of renal vessels and braking of a reabsorption of electrolytes in renal tubules.

Reduces aggregation of thrombocytes. Stimulates secretion of glands of a stomach. Raises standard metabolism, strengthens a glycogenolysis, causing a hyperglycemia.

Pharmacokinetics. After hypodermic introduction it is soaked up quickly and fully. Well gets through all gistogematichesky barriers, being distributed on bodies and fabrics. Gets through GEB and a gematoplatsentrany barrier. Concentration in liquor and amniotic liquid are comparable to concentration of caffeine in a blood plasma. In saliva concentration of caffeine makes 65-85% of its concentration in plasma.

After introduction is exposed to intensive metabolism in a liver with education dimetil-and monomethylxanthines, dimetil-and monomethyl-uric acid, trimetil-and dimethylcordianine, uridine derivatives. The main way of metabolism – education under the influence of an isoform of P450 CYP1A2 cytochrome of dimethylxantines (theophylline, paraxanthine) having pharmacological activity (72 – 80% of the entered dose).

The period of semi-elimination (T½) of caffeine makes 2,5-4,5 h, at newborns in connection with low enzymatic activity of microsomal enzymes elimination of caffeine is slowed down, T½ makes 80 23 h, at the age of 3-5 months it decreases to 14,4 h and in 5-6 months becomes to equal indicators of the adult. The general clearance of caffeine at the adult makes 155 ml/kg/h, at the newborn child it is equal to 31 ml/kg/h.

At the smoking persons reduction of the period of semi-elimination of caffeine by 30 - 50% in comparison with non-smoking persons is observed.

Caffeine preferential with urine in the form of metabolites is emitted. 10% of the entered dose are allocated in not changed look.

Indications to use:

Supportive application at respiratory depression (including at slight poisonings with narcotic analgetics and HP hypnotic drugs, carbon oxide) and recovery of lung ventilation after use of the general anesthesia.

Route of administration and doses:

2 - 3 times a day are entered by the adult subcutaneously on 200 mg (1 ml of solution), children on 25 - 100 mg (0,1-0,5 ml of solution).

Intramuscular administration of solution of caffeine Natrium benzoicum is not recommended in connection with a possibility of development of painful spastic reduction of muscles in the place of an injection.

Features of use:

Influence on TsNS depends on type of a nervous system and can be shown both by excitement, and braking of higher nervous activity.

Because effect of caffeine on arterial pressure consists of vascular and cardial components, both the effect of cardiac activation, and oppression (weak) of its activity as a result can develop.

Pregnancy and lactation. Considering slow elimination of caffeine from a fruit organism, its use during pregnancy is possible only after ratio assessment advantage/risk for mother and a fruit. The excessive use of caffeine during pregnancy can lead to spontaneous abortions, delay of pre-natal fetation, arrhythmia at a fruit; disturbances of a skeletogeny when using high doses and delay of a skeletogeny against the background of smaller doses are possible.

Caffeine and its metabolites get into mother's milk in insignificant quantities, but collect at babies and can cause a hyperactivity and sleeplessness. In need of its use in the period of a lactation it is necessary to estimate a ratio advantage/risk for mother and the child.

Use in a neonatology. And prevention of an apnoea at newborns and at children of chest age in the postoperative period caffeine or caffeine citrate, but not caffeine-sodium benzoate is applied to treatment.

Use for persons with a peptic ulcer of a stomach and duodenum in the anamnesis. It is required to be careful at purpose of caffeine to these groups of patients, in connection with the increased risk of an aggravation at them a peptic ulcer.

Influence on ability to performance of work, connected with need of concentration of attention. At use in high doses caffeine complicates concentration of attention and increases number of the operator mistakes when working interfaced to need of concentration of attention.

Side effects:

From a nervous system: excitement, uneasiness, tremor, concern, headache, dizziness, epileptic seizures, strengthening of reflexes, tachypnea, sleeplessness.

From cardiovascular system: heartbeat, tachycardia, arrhythmias, increase in arterial pressure.

From the alimentary system: nausea, vomiting, aggravation of a peptic ulcer.

Others: a nose congestion, at prolonged use - accustoming, medicinal dependence.

Interaction with other medicines:

Caffeine is an antagonist of adenosine.

At combined use of caffeine and barbiturates, Primidonum, anticonvulsant HP (hydantoin derivatives, especially Phenytoinum) strengthening of metabolism and increase in clearance of caffeine is possible.

At combined use of caffeine and Cimetidinum, peroral contraceptive HP, Disulfiramum, ciprofloxacin, norfloxacin - decrease in metabolism of caffeine in a liver (delay of its removal and increase in concentration in blood).

Meksiletin - reduces removal of caffeine to 50%; nicotine - increases caffeine removal speed.

MAO inhibitors, furasolidone, Procarbazinum and селегилин - high doses of caffeine can cause development of dangerous arrhythmias of heart or the expressed increase in arterial pressure.

Caffeine reduces absorption of drugs of calcium in digestive tract.

Reduces effect of narcotic and somnolent medicines.

Increases removal of drugs of lithium with urine.

Accelerates absorption and strengthens effect of cardiac glycosides, increases their toxicity.

Combined use of caffeine with beta adrenoblockers can lead to mutual suppression of therapeutic effects; with adrenergic bronchodilatory HP - to additional stimulation of the central nervous system, etc. to the additive toxic effects.

At simultaneous use increases bioavailability of acetylsalicylic acid, paracetamol and ergotamine, strengthening that their effect.

Caffeine can reduce clearance of theophylline and, perhaps, other xanthines, increasing a possibility of the additive pharmakodinamichesky and toxic effects.

Antifungal medicines (кетоконазол, флуконазол) slow down metabolism of caffeine and increase its concentration in plasma.

Contraindications:

* hypersensitivity (including to other xanthines);

* alarming frustration (agoraphobia, panic frustration);

* organic diseases of cardiovascular system (including acute myocardial infarction, atherosclerosis);

* Bouveret's disease, frequent ventricular premature ventricular contraction;

* arterial hypertension;

* sleep disorders.

With care. Glaucoma, hyperexcitability, advanced age, epilepsy and tendency to convulsive attacks, pregnancy, lactation period.

Overdose:

Symptoms: a gastralgia, agitation, uneasiness, excitement, motive concern, confusion of consciousness, a delirium, dehydration, tachycardia, arrhythmia, a hyperthermia, the speeded-up urination, a headache, the increased tactile or painful sensitivity, a tremor or muscular twitchings; nausea and vomiting, sometimes with blood; a ring in ears, epileptic seizures (at acute overdose - toniko-clonic).

Caffeine in doses more than 300 mg/days (including against the background of abuse of coffee - more than 4 cups of natural coffee on 150 ml) can cause a condition of alarm, a tremor, a headache, confusion of consciousness, premature ventricular contraction.

At newborns (including premature) at concentration of caffeine in plasma of 50 mg/ml toxic effects are possible: concern, a tachypnea, tachycardia, a tremor, the painful, blown-up stomach or vomiting, increase in a reflex of Moro, at higher concentration - spasms.

The specific antidote does not exist. Measures of the help include the medicine cancellation supporting and the symptomatic therapy directed to elimination of the arisen disturbances, control of level of arterial pressure and stopping of a convulsive syndrome by introduction of tranquilizers of a benzodiazepine row (diazepam).

Storage conditions:

In the place protected from light, at a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 5 years. Not to use medicine after the termination of a period of validity.

Issue conditions:

According to the recipe

Packaging:

On 1 ml in ampoules. On 10 ampoules in packaging No. 10, No. 10 x 1.