Grindeks bupivacaine

General characteristics. Structure:

Active ingredient: 5 mg of bupivacaine of a hydrochloride of monohydrate in terms of hydrochloride bupivacaine.

Excipients: sodium chloride, 0,1 M acid solution hydrochloric or 0,1 M solution of sodium of hydroxide to pH 4,0-6,5, water for injections.

Local anesthetic.

Pharmacological properties:

Pharmacodynamics. Bupivacaine is anesthetic of amide type of long action. Reversibly blocks carrying out impulses on nerve fibril due to influence on natrium channels, has hypotensive effect, slows down heart rate. Approach and duration of local anesthesia depends on a medicine injection site.

Pharmacokinetics. Concentration of bupivacaine in plasma depends on a dose, a way of introduction and the number of veins in the place of an injection. The bupivacaine elimination half-life after the general and two-phase absorption respectively makes 7 minutes and 6 hours of an epidural space. The slow phase of absorption is a factor which limits bupivacaine removal speed. Therefore the bupivacaine elimination half-life at epidural introduction is longer, than after an intravenous injection.

The general clearance in/in an injection makes later of plasma 580 ml/min., distribution volume – 73 l, an elimination half-life – 2,7 h, an indicator of hepatic extraction – 0,4. Linkng with proteins of plasma makes 96 %. Bupivacaine is well dissolved in fats.

Bupivacaine is metabolized in a liver, by a hydroxylation in 4-hydroxy-bupivacaine and by N-dealkylation in 2,6-pipekoloksilidin (RRH), a mediator of both processes is P4503A4 cytochrome.

After epidural introduction in urine about 0,2% of not changed bupivacaine, 1% of a pipekoloksilidin and about 0,1% 4 hydroxybupivacaines are found.

Bupivacaine gets through a placenta. Linkng with proteins of plasma in an organism of a fruit is lower, than in mother's organism, concentration of untied fraction in an organism of a fruit and mother is identical. Cosecretes with mother's milk. It is removed mainly by kidneys, only 5-6% of bupivacaine are removed in not changed view with urine.

 

Indications to use:

- long blockade of nerves;

- epidural anesthesia if addition of adrenaline is contraindicated or strong relaxation of muscles is undesirable (for example, anesthesia after operations or anesthesia at the time of delivery).

Route of administration and doses:

The way of introduction – intramusculary, subcutaneously or epiduralno – depends on a type of anesthesia.

At appointment to the patient of a certain dose of drug the doctor has to estimate a physical condition of the patient. Applying continuous blockade of nerves in the form of long infusion or at repeated in introduction, it is necessary to consider risk of toxic concentration of drug in plasma and risk of local injury of a nerve.

The dose depends on a type of anesthesia. In surgery (diagnostic and medical manipulations) apply 2.5-100 mg to anesthesia. For carrying out blockade of a trifacial - 2.5-12.5 mg; a star-shaped node - 25-50 mg; a sacral, brachial plexus - 75-150 mg; intercostal blockade - 10-25 mg; blockade of peripheral nerves - 25-150 mg.

For carrying out long epidural spinal anesthesia an initial dose - 50 mg, supporting - 15-25-40 mg each 4-6 h.

When carrying out epidural and caudal anesthesia in obstetric practice the dose makes 15-50 mg. Epidural anesthesia at Cesarean section - 75-150 mg. At blockade of a pudental nerve - 12.5-25 mg from each party.

The maximum dose makes 2 mg/kg.

Usually big concentration of drug is necessary for a total block of all nerve terminations of large nerves. Smaller concentration of solution of bupivacaine is necessary for anesthesia or pain relief.

Aspiration needs to be carried out before introduction of the main dose. The general dose is entered slowly, with a speed of 25-50 mg/min., under constant control of the doctor, or in the form of repeated doses. When carrying out epidural anesthesia it is necessary to carry out a test dose from 3-5 ml of solution of bupivacaine which contains adrenaline solution. During a test dose it is necessary to support verbal contact with the patient and to regularly determine heart rate. At emergence of the minimum toxic effects further introduction is stopped.

Features of use:

Spinal anesthesia should be carried out only under observation of the experienced anesthesiologist.

When carrying out spinal anesthesia at patients with a hypovolemia the risk of development of sudden and heavy arterial hypotension is increased.

With care apply at patients who receive antiarrhytmic drugs with mestnoanesteziruyushchy activity.

It is necessary to observe strictly compliance of the used dosage form of bupivacaine to indications to use.

There are no proofs that solution of bupivacaine influences pregnancy course, and also reproductive process.

There are no proofs that bupivacaine influences a lactation. It is allocated with breast milk in insignificant quantities. At purpose of bupivacaine it is recommended to stop breastfeeding.

Long blockade of nerves minimum influence reaction and coordination and only temporarily break motive function.

At use of bupivacaine it is impossible to manage the vehicle and potentially dangerous mechanisms.

Side effects:

From TsNS and peripheral nervous system: numbness of language, dizziness, sight illegibility, muscular tremor, drowsiness, spasms, loss of consciousness. In the field of anesthesia paresthesias, weakening of a tone of sphincters are possible.

From cardiovascular system: reduction of cordial emission, heart block, arterial hypotension, bradycardia, ventricular arrhythmias, cardiac standstill.

From respiratory system: apnoea.

Allergic reactions: skin manifestations, in hard cases - an acute anaphylaxis.

Side effects are observed seldom, the probability of their development increases at use of an inadequate dose and disturbance of the technology of administration of bupivacaine.

Interaction with other medicines:

Other medicines, for example, other means of local anesthesia and antiarrhytmic means, can influence influence and calculation of the correct dose of solution of bupivacaine, and also to increase risk of the additive toxic action.

At simultaneous use with barbiturates reduction of concentration of bupivacaine in blood is possible.

Use with MAO inhibitors (Procarbazinum, селегелин) increases risk of an excessive lowering of arterial pressure. Local anesthetics strengthen the oppression of TsNS caused by medicines, the oppressing TsNS.

Anticoagulants increase risk of development of bleedings. When processing the place of an injection of bupivacaine the disinfecting solutions containing heavy metals the risk of development of local reaction in the form of morbidity and hypostasis increases.

The combination to the general inhalation anesthesia a halothane increases risk of development of cardiotoxicity of bupivacaine. Bupivacaine strengthens and extends effect of myorelaxation medicines, shows antagonism with anti-myasthenic medicines on action on skeletal muscles, especially when using in high doses that demands additional correction of treatment of a myasthenia.

Inhibitors of cholinesterase reduce metabolism of mestnoanesteziruyushchy medicines.

Contraindications:

- hypersensitivity (to other local anesthetics of amide type);

- when carrying out intravenous regional anesthesia (blockade on Bira) (accidental penetration of bupivacaine into a circulatory bed can cause development of acute system toxic reactions);

- children's age up to 12 years;

 With care it is necessary to appoint in the following cases:

- heavy cardiovascular insufficiency (progressing), heart blocks, co-administration of antiarrhytmic medicines (including beta adrenoblockers is possible);

- inflammatory diseases or infection of the place of an injection;

- deficit of cholinesterase;

- a renal failure, advanced age (65 years), the general serious condition, decrease in a hepatic blood-groove (for example are more senior, at chronic heart failure, liver diseases);

- need of carrying out paracervical anesthesia.

Overdose:

System toxic reactions are mainly shown in work to the central nervous system (CNS) and in cardiovascular system. Similar reactions arise because of high concentration of drug in blood and at accidental overdose of an intra vascular injection, or at especially bystry absorption of a medicine from areas with good blood circulation. Reactions of TsNS are similar at all anesthetics of amide type of long action, and reactions from cardiovascular system more depend on properties of the entered medicine.

Central nervous system. Toxic influence of drug on TsNS is shown by gradual increase in symptoms. The first symptoms are paresthesia around a mouth and numbness of language, an oglushennost, a sharpening of hearing, a sonitus and deterioration in sight. More serious violations are shown in the form of a dysarthtia, a tremor of muscles which appears before spasms. These side effects cannot be mixed with neurotic behavior. Further there can come the loss of consciousness and a big epileptic seizure which can last from several seconds to several minutes. After spasms quickly there comes the hypoxia and a hypercapnia because of the strengthened muscle work. Therefore breath is broken and there is an impassability of respiratory tracts. In hard cases the apnoea is possible. Acidosis, a hypopotassemia and a hypoxia increase toxic reaction even more.

Reduction of toxic reaction depends on the speed of redistribution of medicine from TsNS, and also on his metabolism.

In case of spasms therapy is necessary. The treatment purpose – to provide oxygen access, to stop spasms and to support blood supply. If spasms spontaneously do not stop within 15-20 seconds, in/in 100-150 mg of thiopental ili5-10 are entered by diazepam mg.

Cardiovascular system. Toxic reactions from cardiovascular system can be observed only in hard cases of overdose of medicine. Prodromal symptoms of TsNS can remain unnoticed if the patient is hard paralyzed by sedative medicines or is under the general anesthesia. Toxic reactions are shown in the form of hypotension, bradycardia, arrhythmia, and even the cardiac standstill is possible.

If observe dangerous oppression of cardiovascular system (hypotension, bradycardia), in/in enter 5-10 mg of ephedrine and, in case of need, repeat administration of ephedrine in 2-3 minutes. In case of a blood circulation stop immediately begin kardiopulmonarny resuscitation.

Storage conditions:

To store at a temperature not above 25 °C. Not to freeze! To store in the place, unavailable to children!

Issue conditions:

According to the recipe

Packaging:

Ampoules on 10 ml from colourless glass of a hydrolytic class No. 1 with the line or a point of a break. On 5 ampoules in a strip packaging from a PVC film without covering. On 1 strip packaging in a cardboard box.