MEPIVACARIN-BINERGIY - instructions for use. MEPIVACAINE (MEPIVACARE) - instructions for use, description, pharmacological effect, testimony for use, dosage and method of use, contraindications, side effects MEPIVACAIN in dentistry

A. V. Kuzin

k. m. n., doctor dentist-surgeon of the FSU "Tsniis and Chlx" Ministry of Health of the Russian Federation, 3M ESPE Consultant Consultant for Assistance in Dentistry

M. V. Stapleev

doctor Dentist-Therapist, Private Practice (Moscow)

V. V. Voronkova

k. m. n., doctor dentist-therapist branch therapeutic dentistry Clinical and diagnostic center of GBOU VPO "First MGMU them. I. M. Sechenov "Ministry of Health of Russia

Often in clinical practice there is a need for anesthetics short action. There are many low-pass dental interventions that require anneasiating. The use of lengthwise active anesthetics is not entirely legitimate, since the patient leaves the dentist with numbness of a certain area of \u200b\u200bthe oral cavity lasting from 2 to 6 hours.

Taking into account the labor and social burden on the patient, the use of short-acting anesthetics, which make it possible to reduce the duration of the numbness of soft tissues up to 30-45 minutes. Today, local anesthetics based on MEPIivacaines in dentistry today.

MEPIVACARIN is the only anesthetic amide row, which can be used without adding a vasoconstrictor. Most amide anesthetics (articians, lidocaine) expand blood vessels At the injection site, which leads to their rapid absorption in the bloodstream. This reduces the duration of their action, so medicinal forms Anesthetics are produced with epinephrine. In the Russian Federation, Lidocaine is produced without vasoconstrictors in ampoules, which requires its breeding with epinephrine before use. According to modern standards of anesthesia in dentistry, the preparation of the staff of the local prevailing solution is a violation of the anesthesia techniques. 3% MEPIOVACINA has a less pronounced local vasodilator, which makes it possible to effectively apply it to the aim of pain relief and soft oral tissues (Table No. 1).

The duration of the action of mepivakin-containing anesthetics (MEPIOVASIN) is different in certain areas of the oral cavity. This is due to some features of his pharmacological action and features of the anatomy of the oral cavity. According to the instructions of the local anesthetic, the duration of the tooth pulp anesthesia is an average of 45 minutes, the anesthesia of soft tissues is up to 90 minutes. These data were obtained as a result of experimental research in practically healthy patients in the anesthesia of single-darned teeth mainly on upper jaw. Naturally, such studies do not reflect the real clinical conditions under which the dentist is facing inflammatory phenomena in tissues, chronic neuropathic pain, individual characteristics of the patient's anatomy. According to domestic scientists, it was revealed that the average duration of the anesthesia of the teeth pulp using 3% MEPIOVACINA is 20-25 minutes, and the duration of the anesthesia of soft tissues depends on the volume of the anesthetic and the anesthesia (infiltration, conductor) and is 45-60 min.

It is important to the question of the speed of the onset of local anesthesia. Thus, when using 3% MEPIOVACINA, the rate of adhesion of anesthesia pulp the tooth is 5-7 minutes. Therapeutic treatment of teeth will be most painless for the patient from the 5th to 20th after anesthesia. Surgery It will be painless from the 7th to 20th after local anesthesia.

There are some features in the anesthesia of individual teeth groups with 3% pepivacaine. Numerous studies have been proven that it is most effective in anesthesia of single-darkened teeth. The cutters of the upper and lower jaws are anesthetized by infiltration anesthesia with a 3% pepivacine in a volume of 0.6 ml. It is important to take into account the topography of the tops of the roots of the teeth and, accordingly, the depth of promotion of the carpool needle in the tissue. For anesthesia of the fangs, premolars and molars of the upper jaw, the authors are recommended to create anesthetic depot 0.8-1.2 ml. Premolars lower jaw Anesthetia is well anesthetic: a peer anesthesia is carried out in various modifications, which creates anesthetic depot to 0.8 ml. IMPORTANT After chiny anesthesia finger pressed Soft fabrics over chin holes for better diffusion anesthetic. Infiltration anesthesia in the field of molars of the lower jaw with 3% patterns is inefficient in comparison with the artician. The anesthesia of the molars of the lower jaw with a 3% pepivacine is advisable only in patients with contraindications to the use of arthriti-containing anesthetics with epinephrin: in these cases, it is necessary to carry out mandibular anesthesia (1.7 ml of 3% MEPIOVACAIN). Lower jaw fangs are also anesthetized with chin or mandibular anesthesia in patients with contraindications described above.

As a result of many years of experience clinical application MEPIVACAINA was developed and clinical recommendations to its use. Of course, MEPIVACAIN is not anesthetic "for every day", nevertheless there are a number of clinical cases when its use is most appropriate.

Patients with chronic general general diseases.First of all, the use of MEPIOVACAIN in patients with cardiovascular pathology and restrictions on the use of vasoconstrictor is most justified. If there is a small-acting intervention with a duration of less than 20-25 minutes, there is an indication for the use of 3% MEPIOVACAIN, which does not affect the hemodynamic parameters of the patient (Hell, CSS). If a longer treatment or intervention in the field of molars of the lower jaw, from a clinical point of view, the use of only arthikini-containing anesthetics with a Vasoconstrictor 1: 200000 is justified.

Patients with burdened allergic.There is a group of bronchial asthma patients who, who use artician with a vasoconstrictor is contraindicated due to the risk of developing asthmatic status on preservatives contained in the carpool. MEPIVACARIN does not contain preservatives (sodium bisulfite), so it can be used for short-term interventions in this group of patients. With longer interventions, this group of patients with dental treatment is advisable to conduct in specialized agencies under the guidance of a anesthesiologist. MEPIVACAIN can be used in patients with polyvalent allergies and with allergies to a well-known anesthetic. An outpatient dental treatment of such patients is carried out after the conclusion of an allergist's doctor about the tolerance of the drug. According to the clinical experience of the authors of this article, the frequency of a positive allergation on 3% MEPIOVACAIN is significantly lower in comparison with other carpool anesthetics.

IN therapeutic dentistrymEPIVACAIN is used in the treatment of uncomplicated caries: Caries enamel, Caries Dentin. It is important to take into account that the necessary duration of anesthesia is limited to the phase of the preparation of solid tooth tissues. After coating the formed cavity, the adhesive material further restoration will be painless. Accordingly, any planned invasive treatment method should not exceed 15 minutes after the onset of anesthesia. Also, when planning treatment, low-efficiency of MEPIOVACAIN should be taken into account with the anesthesia of the fangs and molars of the lower jaw infiltration anesthesia and the intraly genuine anesthesia of the lower jaw teeth.

IN surgical dentistry MEPIVACAINS is used for short-term surgical interventions. The greatest efficiency was detected when removing teeth with chronic periodontitis and when removing intact teeth in orthodontic testimony. It is important, the role of MEPIVACAIN in anesthesia during surgical dressings. Often the seam removal procedure, the change of the wound coating in the bowl of the tooth, the change of iodoform bandage is painful for patients. The use of long-acting anesthetics is unnecessarily due to the subsequent long-term numbness of soft tissues, which can lead to self-separating the field of operation when receiving food. In these cases, infiltration anesthesia is used in a volume of 0.2-0.4 ml of 3% MEPIOVACAIN, and when dubbeds after extensive surgical interventions (cystectomy, excision of soft-wanted formations, removal of the retinated third molar) is carried out conductive anesthesia. The use of MEPIVACAIN with outpatient surgical dressings allows to reduce discomfort and stress in the patient.

Dentistry of children's age.Shorty anesthetics have proven themselves when used in children's dentistry. Using MEPIVACAIN, should take into account the dosage of this drug during local anesthesia in children. MEPIOVACINA is toxic than artician in relation to the central nervous system, since it is quickly absorbed into the bloodstream. Also, MEPIOVACAIN clearance is higher than the artician clearance for several hours. The maximum dosage of the 3% MEPIOVACAIN is 4 mg / kg of the child weight over 4 years old (Table No. 2). However, in the dentistry of children's age is not indications for the use of such high volumes of anesthetic. According to modern standards of security, the dosage of the introduced 3% MEPIOVACAIN should not exceed half of the maximum dose For all dental treatment. With this application of cases of overdose of local anesthetic (weakness, drowsiness, headaches) in children's practice are excluded.

When using MEPIOVACIN, there are practically excluded cases of self-separation by a child of soft tissues of the oral cavity after treatment at the dentist. According to statistics, up to 25-35% of children preschool age injured the lower lip after the treatment of lower teeth, and in most cases it is associated with the use of anesthetics long action Based on artician with a vasoconstrictor. Local anesthetics of short action can be used when tighting the fissure of teeth, the treatment of initial forms of caries, the removal of temporary teeth. Especially justified the use of MEPIOVACAIN in children with polyvalent allergies, bronchial asthma, as the drug does not contain preservatives (EDTA, sodium bisulfite).

Pregnancy and breastfeeding.MEPIVACAIN can be safely used in pregnant women when planned rehabilitation of the oral cavity at the dentist on the indications described above. In most cases, 3% MEPIVACAIN is used with short-term and minimally invasive interventions for up to 20 minutes. The most favorable for the treatment of the second trimester of pregnancy.

MEPIVACAIN can be used in nursing breasts, it is found in the breast milk of the mother in a slight concentration for a child. Nevertheless, the patient is recommended to refrain from feeding a child by 10-12 hours after anesthesia with 3% MEPIOVACINA and 2 hours after anesthesia 4% artician with epinephrine, which completely eliminates the effect of anesthetic on the child.

conclusions

Thus, mepivakin-containing anesthetics (Mepivastezin) found their use in different areas Dentistry. For a separate group of patients, these anesthetics are the only drugs for local anesthesia by virtue of general comprehensive features. As anesthetic short action, the drug can be well used in minimally invasive short-term interventions.

Table # 1. Features of the clinical use of 3% MEETOVACAIN (MEPIVASTEZIN)

Table # 2. Dosage of 3% MEPIOVACAIN at the rate of patient weight (adult / child)

Weight	Mg.	Ml	Carpula
		1.5	0.8
		2.2	1.2
		2.8	1.4
	110	3.6	1.7
	132	4.4	2.4
	154	5.1	2.9
	176	5.9	3.2
	198	6.6	3.6
	220	7.3	4.0
MEPIOLKAIN 3% without a vasoconstrictor. Maximum dose 4.4 mg / kg; 3% solution in 1 karpule 1.8 ml (54 mg)

It has a local escair effect. Acts on sensitive nervous endings or conductors, interrupting pulses from the scene of painful manipulations in the central nervous system, causes a reversible temporary loss pain sensitivity.

It is used in the form of a salt-oxid salt, which is subjected to hydrolysis in a weakly alkaline fabric medium. The released lipophilic base of the anesthetic penetrates through the membrane of the nerve fiber, goes into an active cationic form that interacts with the membrane receptors. The permeability of the membrane for sodium ions is disturbed, and the pulse of the nerve fiber is blocked.

MEPIVACARIN, unlike most local anesthetics, does not have a pronounced vasodilator, which causes a greater duration of its effect and the ability to use without a vasoconstrictor.

Application of MEPIOVASIN during pregnancy and breastfeeding

The optimal choice for dental interventions during pregnancy, as well as breastfeeding - It is "ultrakin DS" (with an epinephrine 1: 200000), or "Killing 1: 200,000". Clearing during pregnancy is as safe as ultrakain. The epinephrine concentration is 1: 200,000, which is present in these anesthetics does not affect the fruit, does not penetrate the placenta, and is also not determined in breast milk.

Fully abandon the content of adrenaline in anesthetic in pregnant women and nursing patients in no case, because Adrenaline narrows vessels in the injection area and therefore slows down the suction of the anesthetic itself into blood, and this in turn leads to a noticeable decrease in the concentration of anesthetic in the blood. But the higher the anesthetic in the blood will be the concentration, the greater the chances of the anesthetic to penetrate the placenta.

Some doctors use for anesthesia in pregnant anesthetics Skandonest or MEPIOVASIN (they do not contain either adrenaline, nor epinephrine). However, as you already understood - to apply such anesthetics in pregnant women and nursing is undesirable, because Due to the lack of a vesseloring component, they are absorbed into the blood very quickly, which means that there will be a high concentration of anesthetic in the blood, which will allow the drug to penetrate the placenta. In addition, Skandonest, and toxicity mepivasin exceeds novocaine 2 times.

No pregnancy clinical researches Using MEPIOVACINing hydrochloride during pregnancy. Animal tests did not give adequate data regarding possible action Mepivacaine hydrochloride for pregnancy, development of embryo / fetus, childbirth and postpartum development.

Mepivacaine hydrochloride penetrates through a placental barrier. Compared to other local anesthetics, with the use of MEPIOVACINing, the course of the first trimester of pregnancy can not be excluded by the increased risk of developing malformations from the fetus, early timing MEPIOVACINA pregnancy can be used only if it is impossible to use other local anesthetics.

Lactation (breastfeeding) is unknown, in which MEPIOVACINing hydrochloride falls into breast milk. If the introduction of MEPIOLKAIN required during the lactation period, feeding can be continued after 24 and odia after its introduction.

Children remove children aged 4 years. Special measures Safety. It is necessary to take into account that in patients taking blood coagulation inhibitors (for example, heparin or aspirin), unintentional puncture of the vessel with the introduction of a local anesthetic can lead to serious bleeding and increasing the bleeding centenary

Local anesthesia when removing the tooth, teeth treatment -

For local anesthesia, carpill syringes and carpulas are used to be used in which anesthetic solution is concluded (Fig.4-5). The quality of anesthesia is significantly higher than the usual one-time syringe. In addition, the needles for carpool anesthesia are many times thinner than the usual disposable syringes (Fig. 6), which means that the injection will not be so painful.

The cost of anesthetics and anesthesia is anesthetic-one anesthetic carpula (whether it is ultrakin, kilifable, septant or others) is about 30 rubles. The cost of one anesthesia in dental clinic will be on average 250 rubles.

Indeed, the injection of anesthetic can be painful. The pain will depend on both the patient's pain sensitivity threshold and the technique of anesthesia by a doctor. According to the rules, one kampule anesthetic (1.7 ml) must be administered within 40-45 seconds. If the doctor saves time and introduces anesthetic quickly, it is logical that it will cause pain.

To reduce the discomfort from the injection of anesthetic, you can ask the doctor to pre-use anesthetic spray (Fig. 7), for the suspension of the mucous membrane at the injection site (the lidocaine-spray is most often used). You can also ask the doctor to enter anesthetic slowly.

Preparations for removing fear and anxiety - Also there are drugs that allow reduce fear and anxiety before the upcoming campaign to the dentist. Of the non-prescription drugs, the drug Afobazol can be distinguished, which is especially convenient for those who need to make several trips to the dentist, because

You can also take advantage of valerian, mother-in-law, kivalol, rollerine. However, it is also desirable to take these drugs, starting a few days before the visit to the doctor. Plus, these drugs in addition to the sedative effect have a sleeping pill effect, which is not very good for motorists and working people.

Cautions, therapy control

To eliminate the intravascular input of MEPIOVACAIN solution with epinephrine, it is necessary to carry out an aspiration sample before entering the entire dose of LS.

With caution to assign:
■ with severe cardiovascular diseases;
■ with diabetes;
■ during pregnancy and lactation;
■ children and older patients;
■ All MEPIOVACAIN solutions containing vasoconstrictors should be cautious to prescribe patients with cardiovascular and endocrine diseases (thyrotoxicosis, diabetes, heart patterns, arterial hypertension, etc.), as well as receiving in-adrenoblastors, tricyclic antidepressants and Mao inhibitors.

Similar medication

In situations where patients have individual intolerance to the components of the drug, the analogues of the tools are selected, so MEPIOVASIN can be replaced with the following anesthetics:

• Isocaine;
• MEPIVACARIN;
• MEPIDONT;
• Mepicaton;
• Scandinibs;
• Skandonest.

The price of MEPIVASIN starts from 1500 rubles and higher.

Method of application and dose

In dentistry, the drug is used to conduct anesthesia of the following species:

• conductor - injection of the drug is introduced into the location of the nerve barrel from the jaw;
• infiltration - Injection anesthetic is introduced into the place of dental treatment, the sensitivity of which must be removed;
• internally Pacific - a non-attractive method in which the drug is applied to an open pulp;
• intracitial - the preparation is introduced into the periodontal slots, the effect of anesthetic occurs after a minute of injection.

MEPIOVACINA use is advisable for any surgical interventions in the oral cavity requiring local anesthesia. Use anesthetic is possible at:

• carrying out operation on the mucosa of the mouth;
• treating medium and deep caries, pulpitis, periodontitis and other dental diseases;
• periodontal treatment: operations on gingivoplasty, elimination of the recession of the gums, culesage of periodontal pockets;
• installation of non-removable prostheses (crowns, bridges) on non-pressed teeth;
• the governing of dental implants and carrying out related operations (for example, bone plastic);
• dental removal;
• excision of a gumper hood over the teeth of wisdom under the pericoronite;
• carrying out resection of the top of the dental root;
• removing cyst, tumors and other neoplasms in the oral cavity.

To obtain anesthetizing effect, the drug is introduced subcutaneously, subbelicist or intradermally in the location of the nerves and ganglia.

Instructions for use of MEPIVacaine indicate that its use is possible only with professional dental treatment. It is not necessary to calculate the dose to count the dose, so this information is unlikely to be useful.

The amount of solution used depends on the type of intervention and the method of introducing anesthesia. With infiltration anesthesia, adult patients introduces 1.8 ml of a solution with concentration active substance 3%. The volume of 9 ml is sufficient for full anesthesia oral cavity In an adult patient. Maximum dose of anesthetic introduced by adults and children whose weight exceeds 30 kg, can reach 5.4 ml.

• in the presence of allergic reactions to the components of the means (including other preparations of the amide group);
• severe liver diseases;
• miasti;
• porphyry.

With caution, the means is used in cardiovascular disorders, in childhood and old age, in pregnant women, in nursing mothers.

When non-compliance with the dosing mode, the following may appear side Effects:

• violation of swallowing function;
• non-linked speech;
• convulsions;
• impairment;
• violation of the respiratory function;
• swelling quinque;
• hives;
• reduced arterial pressure.

In addition, due to the lack of vasoconstrictors in the preparation (Adrinalin narrows vessels), bleeding may occur at the injection site. When taking drugs that dilute blood should be informed about this to the doctor.

The price of MEPIVACARION depends on the manufacturer's company, the pharmacy pricing policy, which sells the drug. It can vary within 1000-1500 rubles per pack.

The drug is intended exclusively for professional use by doctors. Instructions for anesthetic can only be used to familiarize yourself with the features of the means.

For injection anesthesia, a 3% solution of mepikavaine is used without a vasoconstrictor or 2% solution with epinephrine (1: 100 000). The maximum total dose for injecting administration is 4.4 mg / kg.

Only for professional use in dental practice. After conducting an injection to be carried out skin sample on increased sensitivity to the drug. Anamnesis should be collected relative to the simultaneous use of other medicines.

• The dentistry uses a 3% solution of Skandonest, which is available in 1.8 ml kapulos.
• Apply both infiltration and conductor anesthesia.
• It is a drug selection for patients with contraindications to the introduction of vasoconstrictors.

• This local anesthetic is preferable to others when arterial hypertension, diabetes mellitus, bronchial asthma, pregnancy (in the second trimester, with extreme necessities) and some other diseases and states.
• A single dose for an adult - 3 karpula, for a child - no more than 1 karpula.

The drug is used exclusively for local anesthesia. The following cases are indications:

• surgical interventions in the oral cavity;
• trachea intubation;
• broncho-, esophagoscopy;
• tonsilectomy.

To achieve effective anesthesia enough to use minimal dosage drug. For older patients, a sufficient dose not exceeding 4ml. In childhood, the amount of solution is taken at the calculation of body weight:

• 20-30 kg \u003d 0.25-1ml;
• 30-45 kg \u003d 0.5-2ml.

Elderly people are not recommended to use this drug due to the danger of excess MEPIOVACAIN level in plasma. This contributes to the weak process of metabolism, slow propagation on blood flow. The risk of accumulation of this substance is especially great when conducting repeated injections.

The same effect can provoke total weakness Patient, regardless of his age. With such situations, the dose of the drug should be lowered as much as possible, that is, to introduce a minimum anesthetic dose to have enough for anesthesia. In people with such diseases as atherosclerosis, angina, also requires a decrease in the dosage of the drug.

Indications

■ Infiltration anesthesia interventions on the upper jaw.

■ Explore anesthesia.

■ Introligative anesthesia.

■ Internal anesthesia.

■ MEPIVACAIN is an LC of the choice in patients with increased sensitivity to vasoconstrictors (severe cardiovascular insufficiency, diabetes, thyrotoxicosis, etc.), as well as to preservative vasoconstrictors - bisulfite ( bronchial asthma And Allergies on the LANs containing sulfur).

■ Hypersensitivity.

■ Heavy liver function disorders.

■ Miastration.

■ Porphyry.

• Drug-uncontrollable epilepsy;
• Porphyry;
• Childhood up to 4 years
• Malignant hyperthermia;
• Acute heart failure;
• Severe arterial hypotension;
• Increased sensitivity to any component of the drug or allergic to local anesthetics of amide type;
• Violation of the conductive heart system (AU blocking II and III degree, bradycardia documented), imparation of atrioventricular conductivity, not supported by the pacemaker;

Like any other medicine, Skandonest can cause adverse reactions And has some contraindications to use:

• Allergic reactions to this drug in history
• Peat pathology
• Heavy Miasthenia

Mepivacaine ( international name Mepivacaine) is a local anesthetic amide group derived from xylidine. MEPIVACARIAIN is used in infiltration for peripheral transistor anesthesia and for sympathetic, regional and epidural blockade of nerves in surgical and dental procedures. It is available on sale with and without adrenaline. Compared with MEPIVACARIN produces less vasodilation and has a faster beginning and a longer duration of action.

Commercially known as: Mepivastesin (Jepharm, Palestine), Skandonysta (Septodont, France), Scandicain, Carboyan (Caresteam Health, Inc., USA).

MEPIVACAIN has a faster start of action and a longer period than Lidocaine. The duration of its action is about 2 hours, it is twice as more efficiently. Used for local anesthesia in dentistry and spinal anesthesia. At a concentration of 3%, it is produced without a vasoconstrictor, at 2% with a vasoconstrictor, the branded name Levonordeofrine, a concentration of 1: 20,000. Anesthetic It is recommended to use patients who are contraindicated anesthetics with a vasoconstrictor.

MEPIVACARIN IN STOMATOLOGY

Local anesthetic is used in dentistry for the following types of anesthesia on the bottom and:

MEPIVACARIN IN STOMATOLOGY

Mechanism of action

Like all, Mepivacaine causes reversible blocking of nervous conductivity, reducing the permeability of the nervous membrane for sodium ions (Na +). This reduces the rate of depolarization of the membrane, thereby increasing the threshold of electrical excitability. Blocking affects everything nerve fibers In the following sequence: autonomous, touch and motor, with decreasing effects in the reverse order. Clinically, the loss of nerve function follows the following order: pain, temperature, touch, proprioceptation and skeletal muscle tone. In order for anesthetics to be effective, it is necessary to direct penetration into the nervous membrane, which is achieved by injection of a local anesthetic solution subcutaneously, intracutaneously or subbuilding around nerve or ganglia stems. For MEPIVACINA, the degree of engine blockade depends on the concentration and can be summarized as follows:

• 0.5% is effective for blocking small surface nerves;
• 1% will block sensory and sympathetic conductivity without affecting the operation of the motor system;
• 1.5% will provide extensive and often full blocking of the propulsion system
• 2% will ensure the complete blocking of the motor system by any group of nerves.

Pharmacokinetics

MEPIOVACIN Systemable absorption depends on the dose, concentration, path of administration, vascularization of tissue and the degree of vasodilation. Use of mixtures containing vaconishing meanswill counteract the vasodilation produced by pepivacaine. This reduces the absorption rate, prolongs the duration of the action and supports hemostasis. For dental anesthesia, the beginning of the action for the upper and lower jaw occurs after 0.5-2 minutes and 1-4 minutes, respectively. It is maintained for 10-17 minutes, and the anesthesia of soft tissues lasts about 60-100 minutes after the administration of a dose for an adult. When conducting an epidural method of painting MEPIVACINA has an action of 7-15 minutes and duration of approximately 115-150 minutes.

MEPIVACARIN crosses the placenta of passive diffusion and is distributed over all tissues with high concentration in well perfused organs, such as liver, lungs, heart and brain. MEPIVACARIN is subjected to rapid metabolism in the liver and deactivation by hydroxylation and N-demethylation. In adults, three inactive metabolites were discovered: two - phenols, which are highlighted as glucuronide conjugates, and one is 2 ', 6'-pyloxidin. Approximately 50% of MEPIOVACINA is shown in bile in the form of metabolites, which administer enterogetic circulation and subsequently stand out. Only 5-10% of MEPIOVACINA is displayed unchanged in the urine. Some metabolism can occur in the lungs.

Newborn can have a limited ability to make mepivacaine metabolism, but they can eliminate the unmodified drug. Half-exploration period from 1.9 to 3.2 hours - MEPIOVACAIN in adults and 8.7-9 hours in newborns.

The local anesthetics of the ester group are metabolized in plasma enzyme pseudocholinesterase, and one of the main metabolites is para-aminobenzoic acid, which seems to be responsible for allergic reactions. The anesthetics of the amide group are metabolized in the liver and do not form para -aminobenzoic acid.

Indications for use

For cervical block block shoulder plexus, intercostal nerve blocks. Adults: 5-40 ml of 1% solution (50-400 mg) or 5-20 ml of 2% solution (100-400 mg). The increase in the dose should not be carried out more often than every 90 minutes.

For anesthesia peripheral nerves and relief strong pain. Adults: 1-5 ml of 1-2% solution (10-100 mg) or 1.8 ml of 3% solution (54 mg). The increase in the dose should not be carried out more often than every 90 minutes.

For dental anesthesia by infiltration. Adults: 1.8 ml of 3% solution (54 mg). Infiltration should be slowly with frequent aspirations. In adults, 9 ml (270 mg) of a 3% solution is usually sufficient to provide for the entire oral cavity. The total dose should not exceed 400 mg. Incremental doses should not be entered more often than every 90 minutes.
Children: 1.8 ml of 3% solution (54 mg). Infiltration should be slowly with frequent aspirations. The maximum dose should not exceed 9 ml (270 mg) 3% solution. The maximum dose can be calculated according to the following formula based on Clark rule: the maximum dose (mg) \u003d mass (in pounds) / 150 x 400 mg. 1 pound \u003d 0.45 cyllogram.

The dose of local anesthetics is different with the help of anesthetic procedure, anesthetic region, vascularization of tissues and the number of blocked nerves, the intensity of the blockade required by the degree of muscle relaxation, the desired duration of anesthesia, individual indications and physical condition of the patient.

MEPIVACARIN is mainly metabolized in the liver. Lower doses of MEPIVacaine administration may be required for patients with hepatic dysfunction due to long effects and system accumulation. Specific discretions on dosing are not available.

Contraindications for use

Local anesthetics should be appointed only by a doctor who has passed the study of the diagnosis and treatment of toxicity of painkillers, and the relief of serious emergencies that may arise as a result of the introduction of regional anesthetic. Before the introduction of the drug, it is necessary to guarantee the immediate availability of oxygen, equipment for cardiopulmonary resuscitation, appropriate drugs, support staff for the treatment of toxic reactions or emergencies. Any delay in the right provision emergency care It may lead to the development of acidosis, a heart stop and, perhaps, death.

An intravenous or intraarterial administration of MEPIOVACAIN should be avoided. Forced intravenous or intraarterial administration can cause a heart stop and requires long resuscitation. To avoid intravascular administration of MEPIVACAIN during local anesthetic procedures, the aspiration must be performed before the introduction of local anesthetic and after replacing the needle. During epidural administration, the control dose should be administered first, the state of the patient's CNS and cardiovascular toxicity should be monitored, as well as the signs of random intact administration.

With the anesthesia of the head and neck, including ophthalmologic and dental anesthesiaSmall doses of local anesthetics can cause adverse reactions similar to systemic toxicity observed in random intravascular injections of higher doses.

When local anesthetics are used for retrobulbar blockade with ophthalmic surgery, no sensitivity of the cornea should not be perceived as the basis for determining whether the patient is ready to surgery. The absence of the corneal sensitivity is usually preceded by a clinically acceptable akinesia of external eye muscles.

Injection of epidural and nervous anesthesia MEPIOVACINA is contraindicated by patients with the following characteristics: infection or inflammation at the injection site, bacteremia, platelet anomalies, thrombocytopenia<100 000 / мм3, увеличение времени свертывания крови, неконтролируемая коагулопатия и терапия антикоагулянтами. Поясничную анестезию и каудальную анестезию следует использовать с особой осторожностью у пациентов с неврологическими заболеваниями, деформациями позвоночника, сепсисом или тяжелой гипертонией.

Local anesthetics should be used with caution in patients with hypotension, hypovolemia or dehydration, miastenia, shock or heart disease. Patients with impaired heart function, especially the AV block, may be less capable of compensating for functional changes associated with long AV conduction (the extension of the Qt interval) caused by local anesthetics.

MEPIVACINAIN is contraindicated in patients with known hypersensitivity to local anesthetics of amide type. Elderly patients, especially those who receive the treatment of hypertension, can be subject to more risk of hypotensive effects of MEPIOVACAIN.

To evaluate carcinogenic and mutagenic potential in the conditions of fertility, there were no long-term research on animals. According to a person, there is no data indicating that MEPIVACINA is mutagenic or carcinogenic.

• Contraindicated patients with hypersensitivity to local anesthetics of the group of amides or any other component of the formula of the drug
• Serious liver disorders: cirrhosis, porphyrine disease. Patients receiving these blocks should carefully monitor their fan and blood systems, and recommended doses should not be exceeded in these patients.
• Patients with Miastations

General precautions

• Patients under the influence of anesthesia must postpone meals before fully restoring lip sensitivity, cheeks and language
• In pediatric, elderly and patients with malfunction of dose, anesthetic should be reduced
  Patients with epilepsy are prohibited high doses of the drug
• Be extremely careful in patients with liver diseases due to metabolism of amides liver - it can provoke anemia development
• When using any type of local anesthetic, oxygen equipment and resuscitation preparations must be available for immediate use.
• Injecting to the swollen or infected area should be avoided, since it can change the pH and, thus, change the effect of anesthetic.

MEPIVACAIN during pregnancy and lactation

There is a significant transfer of mepivacaine through the placenta of the mother, and the ratio between the concentration of the drug in the fruit and maternal concentrations is about 0.7. Although newborns have a very limited ability to metabolizing MEPIOVACIN, it seems they are able to eliminate this drug. The safety of using MEPIOVACINA hydrochloride for breastfeeding is unknown. Medicine should be prescribed with caution!

MEPIVACARIN quickly crosses the placenta, and when used in epidural, paracerevical, caudal or poudled anesthesia, can cause toxicity for the mother, fetus or newborn. MEPIVACAIN should be used with caution in women who are breastfeeding, as it is not known whether mepivacaine with milk is removed.

Adverse reactions

Like all local anesthetics, MEPIVACAIN can cause significant CNS and cardiovascular toxicity, especially when high serum concentrations are achieved. The toxicity of the CNS occurs at lower doses and at lower concentrations in plasma than those related to cardiac toxicity. The toxicity caused by the CNS is usually manifested with symptoms of stimulation, such as anxiety, anxiety, nervousness, disorientation, confusion, consciousness, dizziness, vision, nausea / vomiting, tremor and convulsions. Subsequently, depressive symptoms can manifest itself, including drowsiness, unconscious state and respiratory depression (which can lead to a respiratory stop).

In some patients, the symptoms of the TSN toxicity can be soft and short-term. The attacks can be treated by intravenous intravenous benzodiazepines, although it should be done with caution, since these agents are also depressants of the CNS.

Cardiac effects of local anesthetics are due to the interference of conductivity in myocardium. Cardiac effects are observed in very high doses and usually occur after the onset of the TSN toxicity. Adverse Cardiovascular Effects caused by MEPIVACINA include myocardial depression, AV-block, PR lengthening, qt interval lengthening, atrial fibrillation, sinus bradycardia, heart arrhythmias, hypotension, cardiovascular collapse and heart stop.

The seizures of the mother and cardiovascular collapse may occur after the paracervical blockade in the early periods of pregnancy (for example, anesthesia for selective (selective) abortion) due to fast system absorption.

Cardiovascular side effects from MEPIOVACAIN administration should be treated with general physiological support measures, such as oxygen, auxiliary ventilation and intravenous liquids.

There may be a feeling of burning in the injection site. Pre-existing inflammation or infection increases the risk of developing serious skin side effects. Patients should be controlled to detect the reaction at the injection site.

Allergic reactions are characterized by rash, urticaries, edema, itching. These may arise as a result of sensitivity to local anesthesia or meticaben, which are used as a preservative in some drugs.

During the caudal or lumbar epidural blockade of nerves, random penetration into the subarachnoid space can occur.

During objectiveness, local anesthetics can cause various degree of toxicity in mothers, fetus and newborns. The potential of toxicity is associated with the procedure performed by the procedure, type and amount of the drug used and the method of administration. The frequency of heartfrections of the fetus will be constantly monitored, because bradycardia of the fetus may occur, which can be associated with the atherosis of the fetus. Maternal hypotension can be the result of regional anesthesia, which can facilitate this problem.

Despite the fact that anesthetic does not affect the ability to driving a vehicle, the dentist must decide when the patient can control the machine.

Tradename

Mepivastesin

International non-proprietary title

MEPIVACAIN

Dosage form

Solution for submissible injections in dentistry 3% 1.7 ml

Structure

1 ml of solution contains

active substance - MEPIOVACINA hydrochloride 30 mg,

excipients:sodium hydroxide solution 9.0%, sodium chloride, water for injection.

Description

Colorless, transparent not opalescent solution.

Pharmacotherapeutic group

Anesthetics. Local anesthetics. Amides. Mepivacaine.

Code ATH N01BB03.

Pharmacological properties

Pharmacokinetics

Mepivacaine hydrochloride is quickly and largely absorbed. Bonding plasma proteins is 60-78% and semi-elimination period - about 2 hours.

The volume of the distribution is 84 liters. Clearance - 0.78 l / min.

Mostly disintegrates in the liver, metabolic products are removed through the kidneys.

Pharmacodynamics

MEPIVASHIN is used as a local anesthetic in dentistry. Characterized by the rapid beginning of the anesthesia (after 1 to 3 minutes after injection), a pronounced painful effect and good local tolerability. The duration of anesthesia pulp is 20 - 40 minutes, and with the anesthesia of soft tissues - from 45 to 90 minutes. MEPIVASHIN is a local anesthetic of amide type with a rapid beginning of anesthesia, which leads to the reversible braking of the sensitivity of vegetative, sensory and motor nerve fibers. The mechanism of action lies in blocking potential-dependent sodium channels on the nerve fiber membrane.

The drug easily diffuses through the membrane of the nerve fiber in the axoplasm in the form of base. Inside the axon is converted to an ionized cationic form (proton) and causes a block of sodium channels. At low pH values, for example, in conditions of inflammation, the effect of the drug decreases, since the formation of the base of anesthetic is hampered.

Indications for use

Infiltration and conductor anesthesia in dentistry:

With uncomplicated dental removal

With the preparation of carious cavities and teeth under the crown

Method of application and dose

As far as possible, the smallest solution that promotes effective anesthesia should be prescribed.

Adults, as a rule, dose 1-4 ml is sufficient.

Children aged from 4 years with a mass of body 20 - 30 kg, a sufficient dose is 0.25-1 ml; For children with a mass of body 30 - 45 kg - 0.5-2 ml. The amount of injected drug should be determined depending on the age and mass of the body of the child and the duration of the operation. The average dose is 0.75 mg of MEPIOVACAIN / kg of body weight (0.025 ml of meyivasin / kg of body weight).

The plasma mepivacain level can be increased in elderly patients due to reduced metabolic processes and lower distribution of the drug.

The risk of mepivacine cumulation increases with repeated applications. Such effect can be observed with a decrease in the general condition of the patient, also with severe disorders of the liver and kidney function. Thus, in all such cases, a lower dose of the drug is recommended (minimum amount for sufficient anesthesia).

Dose MEPIOVASIN should be reduced in patients suffering from angina, atherosclerosis.

Adults:

For adults, the maximum dose is 4 mg of mepivacaine per kg of body weight and equivalent to 0.133 ml of mepivasin per kg of body weight. This means that 300 mg of MEPIOVACINA or 10 ml of MEPIOVASIN is sufficient for patients with a body weight of 70 kg.

Children aged 4 years:

The amount of injected drug should be determined by the age and mass of the body of the child and the duration of the operation; Do not exceed the value equivalent to 3 mg of mepivacaine per kg of body weight (0.1 ml of meropivasin per kg of body weight).

The drug is intended for injection as a local anesthetic for dental purposes.

In order to eliminate the possibility of intravascular administration, it is necessary to always apply aspiration control in two projections (with the rotation of the needle by 180 °), although its negative result does not always exclude unintentional or unnoticed intravascular administration.

The injection rate should not exceed 0.5 ml in 15 seconds, i.e. 1 cartridge per minute.

Main system reactions As a result of random intravascular administration, in most cases, it can be avoided using the following technique of administration - after the injection, slowly enter 0.1 - 0.2 ml and in 20-30 seconds slowly enter the remaining solution.

Open cartridges should not be applied in other patients.

The remains must be eliminated.

Side effects

Rarely (\u003e 0.01%)

metal taste in the mouth

nausea, vomiting

noise in ears

dizziness

headache

nervousness, anxiety

excitation, anxiety

• bulk vision

  diplopia

  feeling heat, cold or numbness

  increase the frequency of breathing

  drowsiness, confusion of consciousness, tremor, muscle coupling, tonic-clonic convulsions, loss of consciousness, coma and respiratory paralysis, respiratory stop

  tahipneoe

  bradypunoe

• cardiovascular insufficiency

Heavy cardiovascular attacks are manifested in the form:

fall hell

violations of conductivity

tachycardia

bradycardia

hypotension

• stopping hearts

Rarely (<0,01 %)

allergic reactions, including skin rashes, urticaria, anaphylactoid reactions, anaphylactic shock, angioedema swelling, increasing body temperature.

Contraindications

Hypersensitivity to local anesthetics of amide type or allergies to local anesthetics of amide type

Malignant hyperthermia

Severe disorders of the transmission of nerve impulses and heart conductivity (eg: AV blockade II and III degree, pronounced bradycardia), violations of AV conductivity, which are not supported by the pacemaker

Decompensated heart failure

Heavy hypotension

Medicia and uncontrolled epilepsy

Porphyry

Injection in the inflamed area

Children's age up to 4 years.

Medicinal interactions

β-adrenoblays, calcium channel blockers enhance the inhibition of conductivity and myocardial reductions. If to reduce fear to the patient, apply sedatives, the dose of anesthetic should be reduced, since the latter, like sedatives, is oppressing the central nervous system.

During treatment with anticoagulants, the risk of bleeding is increased (see "Special Instructions" section).

In patients receiving antiarrhythmic drugs, summation of side effects may arise after the use of MEPIOVASIN.

Toxic synergism is observed when co-use with central analgesics, sedatives, chloroform, ether and sodium thiopentle.

special instructions

Only for professional use in dental practice.

Before carrying out an injection, it is necessary to carry out a skin trial for increased sensitivity to the drug. Anamnesis should be collected relative to the simultaneous use of other medicines. If necessary, for premedication, use benzodiazepines. Enter the drug should be slow. The introduction of low doses may cause insufficient anesthesia and lead to an increase in the level of the drug in the blood as a result of the cumulation of the drug or its metabolites.

Athletes should be warned that this drug contains an active ingredient, which can give a positive result during doping control. Since the local anesthetics of amide type are metabolized, mainly in the liver and are removed by the kidneys, it should be used to apply the drug to patients with diseases of the liver and kidney. With liver failure, it is necessary to reduce the dose of MEPIVACAIN. Also reduce dose in cases of hypoxia, hypercalemia or metabolic acidosis. It is necessary to pay increased attention to patients receiving anticoagulants (INR monitoring).

There is a risk of an unintentional injury of the mucous membrane due to biting lips, cheeks, tongue. Patient should be prevented that chewable movements can be carried out during the anesthesia. Erroneous injections and injections in infected or inflamed tissues should be avoided (the efficiency of local anesthesia decreases).

It is necessary to avoid accidental intravascular administration (see section "Method of application and dose".

The drug should be used to use patients with epilepsy in history, diabetes, with cardiovascular diseases, since they have a smaller ability to compensate for functional changes associated with lengthening arteriovenous conductivity that cause drugs.

Precautions

Each time the following drugs / therapy measures should be available when applying local anesthetic.

Anticonvulsant means (preparations for the treatment of seizures, for example, benzodiazepines or barbiturates), muscle relaxants, atropine, vasoconductive agents, adrenaline during acute allergic or anaphylactic reactions;

Resuscitation equipment (especially oxygen sources) for artificial respiration, if necessary;

Careful and constant tracking of cardiovascular and respiratory (respiratory adequacy) indicators of the body's condition and condition of the patient's consciousness after each injection of local anesthetic. Anxiety, anxiety, noise in the ears, dizziness, weakening of vision, trembling, depression or drowsiness are the first signs of the toxicity of the CNS (see the "Overdose" section).

MEPIVASHIN should be applied with extreme caution in cases:

Pronounced disorders of the kidney function

Heavy liver diseases

Angina

Atherosclerosis

Pronounced decrease in blood coagulation

In patients receiving anticoagulants (for example, heparin) or acetylsalicylic acid, random intravascular administration during injection can lead to an increase in the likelihood of serious bleeding and hemorrhages (see the section "Medicinal interaction").

Method of application and dose

Pregnancy and lactation period

Pregnancy

There are no sufficient clinical studies regarding the use of MEPIOVASIN during pregnancy. Animal research did not give an adequate understanding of the consequences when used during pregnancy, intrauterine development, childbirth and postpartum development.

MEPIVASIN penetrates the placental barrier and reaches the fetus in the womb.

When using MEPIOVASIN in the first trimester of pregnancy, the likelihood of the risk of malformations cannot be excluded; In the early periods of pregnancy, MEPIVASHIN should be applied only if it is impossible to use other local anesthetics.

Period lactation

There is no sufficient data, in what doses of meypivastesin penetrate into breast milk. If its use is necessary during lactation, breastfeeding should be stopped and it can be resumed after 24 hours.

Features of the influence of the medicinal product on the ability to control the vehicle or potentially hazardous mechanisms

In sensitive patients, a temporary deterioration of the reaction may occur after the injection of meribasin, for example, during the road. The question of the admission of a patient to driving a vehicle or to work with potentially hazardous mechanisms is solved by a doctor individually in each particular case.

Overdose

Symptoms:may occur immediately, with random intravascular injection or under conditions of pathological absorption (eg: inflamed or vascularized fabric) and in a later period and manifest as symptoms of the dysfunction of the central nervous system (metal taste in the mouth, nausea, vomiting, noise in the ears, Dizziness, excitation, anxiety, increase in respiratory frequency, drowsiness, confusion, tremor, muscle twist, tonic-clonic convulsions, coma and respiratory paralysis) and / or vascular symptoms (drop of blood pressure, conductivity disorders, bradycardia, heart stop).

Treatment:in case of side effects, immediately stop the introduction of local anesthetic.

Basic general measures

Diagnosis (breathing, blood circulation, consciousness), maintaining / restoring vital respiratory and blood circulation functions, oxygen purposes, intravenous access.

Special measures

Hypertension: lift the upper part of the patient's body, if necessary, give nifedipine sublingual.

Convulsions: Protect patient from related bruises, damage, if necessary, diazepams in / in.

Hypotension: horizontal position of the patient's body, if necessary, intravascular infusion of electrolyte solutions, vasopressors (eg, epinephrine in / c).

Bradycardia: Atropine in / c.

Anaphylactic shock: Contact an emergency doctor. In the meantime, give the patient a horizontal position, lift the lower part of the body. Intensive infusion of electrolyte solutions, if necessary, epinephrine in / in, glucocorticoid in / c.

"MEPIVACAINE (MEPIVACARE)" It is used in the treatment and / or prevention of the following diseases (nosological classification - ICD-10):

Gross formula: C15-H22-N2-O

CAS Code: 22801-44-1

Description

Characteristic: Anesthetic amide type.

Mepivacaine hydrochloride is a white crystalline powder without smell. Water soluble, stable both to acid and alkaline hydrolysis.

pharmachologic effect

Pharmacology: Pharmacological action - topless. Being a weak lipophilic base, passes through the lipid layer of the nervous cell membrane and, turning to the cationic form, is associated with receptors (residues of S6 transmembrane spiral domains) of sodium diaphragm channels located in the end of sensitive nerves. Reversibly blocks potential-dependent sodium channels, prevents the current of sodium ions through the cell membrane, stabilizes the membrane, increases the threshold of the electric stimulation of the nerve, reduces the rate of occurrence of the action potential and lowers its amplitude, ultimately blocks the membrane depolarization, the occurrence and conducting pulse on nerve fibers.

It causes all types of local anesthesia: terminal, infiltration, conductive. It has a fast and strong effect.

If you get into the systemic bloodstream (and the creation of toxic concentrations in the blood), an inhibitory effect on the CNS and myocardium (however, when applying in therapeutic doses, changes in conductivity, excitability, automatism, etc. functions are minimal).

Dissociation constant (PK_A) - 7.6; Solubility in fats average. The degree of systemic absorption and plasma concentration depends on the dose, the method of administration, vascularization of the injection area and the presence or absence of epinephrine in the anesthetic solution. Adding a diluted solution of epinephrine (1: 200000, or 5 μg / ml) to a solution of mepivacine (1: 200,000, or 5 μg / ml) usually reduces the absorption of MEPIOVACINA and its plasma concentration. Binding with plasma proteins is high (about 75%). Penetrates the placenta. Not exposed to plasma esterase. It is rapidly metabolized in the liver, the main pathways of metabolism - hydroxylation and N-demethylation. In adults, 3 metabolites are identified - two phenolic derivatives (excreted in the form of glucuronides) and N-demethylated metabolite (2 ", 6" -pipecole oxyylidide). T_1 / 2 in adults - 1.9-3.2 hours; In newborns - 8.7-9 hours. More than 50% of the dose in the form of metabolites is excreted in bile, then reabsorbed in the intestine (a small percentage is found in the feces) and removed from the urine after 30 hours, incl. unchanged (5-10%). Cumulates in violation of the liver function (cirrhosis, hepatitis).

The loss of sensitivity is observed after 3-20 minutes. Anesthesia lasts 45-180 minutes. The temporal parameters of anesthesia (start and duration) depend on the type of anesthesia, the shadow of its carrying out, the concentration of the solution (dose of the drug) and the individual characteristics of the patient. The addition of vasoconstrictor solutions is accompanied by anesthesia prolongation.

Studies on the assessment of carcinogenicity, mutaging, the influence of fertility in animals and man were not conducted.

Indications for use

Application: Local anesthesia with interventions in the oral cavity (all kinds), trachea intubations, broncho- and esophagoscopy, tonsilctomy, etc.

Contraindications

Contraindications: Hypersensitivity, incl. to other amide anesthetics; Elderly age, severe myasthenia, pronounced liver function (including liver cirrhosis), porphyria.

Restrictions on use: pregnancy, breastfeeding.

Application during pregnancy and breastfeeding: during pregnancy it is possible if the expected effect of therapy exceeds the potential risk to the fetus (may cause a narrowing of the uterine artery and hypocyses of the fetus). With caution during breastfeeding period (there is no data on penetration into breast milk).

Side effects

Side effects: From the side of the nervous system and organs of the senses: arousal and / or depression, headache, ringing in the ears, weakness; violation of speech, swallowing, view; convulsions, coma.

From the side of the cardiovascular system and blood (blood formation, hemostasis): hypotension (or sometimes hypertension), bradycardia, ventricular arrhythmia, is possible to stop the heart.

Allergic reactions: chichanye, urticaria, fruits, erythema, chills, increasing body temperature, swelling quinque.

Others: inhibition of the respiratory center, nausea, vomiting.

Interaction: beta-adrenobloclars, calcium channel blockers, anticircultimical agents enhance the depressing effect on the conductivity and the reduction of myocardium.

Overdose: Symptoms: hypotension, arrhythmia, increase in muscle tone, loss of consciousness, convulsions, hypoxia, hypercupnia, respiratory and metabolic acidosis, dysnae, apnea, heart stop.

Treatment: hyperventilation, maintenance of adequate oxygenation, auxiliary breathing, convulsions and convulsions

(Purpose of Tiopental 50-100 mg V / B or diazepam 5-10 mg V / c), normalization of blood circulation, the correction of acidosis.

Dosage and method of application

Method of use and dose: The amount of solution and total dose depend on the type of anesthesia and the nature of the intervention. For injection injection, a 3% mepivacine solution is used (maximum dose for adults - 4.4 mg / kg, but not more than 300 mg per visit) or 2% solution in combination with epinephrine (1: 80000, 1: 100000) or norepinephrine ( 1: 200000) (maximum dose - 6.6 mg / kg, but not more than 400 mg of MEPIOVACAIN for one visit). Maximum dose of MEPIOVACAIN (in mg) for children is calculated taking into account the mass of the child's body.

Precautions: to caution to prescribe patients with hepatitis, cirrhosis of the liver, hepatic insufficiency, pronounced disorders of the kidney function, acidosis.