Pharmacological properties of the drug Arduan
Pipecuronium bromide (2β, 16β-bis(4-dimethylpiperazine)-3α-17β-diacetoxy-5α-androstane dibromide) is a non-depolarizing muscle relaxant with a peripheral mechanism of action due to its effect on the motor end plates of striated muscles. The effect of pipecuronium bromide during intubation in the case of the use of suxamethonium chloride after the cessation of the depolarizing blockade develops after 2-3 minutes, when using only pipecuronium bromide - after 4-5 minutes. The duration of action of the drug is 40–60 minutes, depending on the dose used and the individual sensitivity of the patient. It is excreted unchanged, mainly in urine and in minimal quantities in bile. After repeated administrations of the drug, slight accumulation is possible.
Use of the drug Arduan
Adults For surgical interventions of medium and long duration, the drug is used intravenously:
- for endotracheal intubation and for complete muscle relaxation during surgery, 0.06–0.08 mg/kg body weight is administered;
- for patients intubated with suxamethonium chloride, Arduan is administered at an initial dose of 0.04–0.06 mg/kg;
- in patients with impaired renal function, it is not recommended to exceed a dose of 0.04 mg/kg;
- repeated doses of the drug are 1/4–1/3 of the initial dose. When administered at a higher dose, the effect may be prolonged.
Children and newborns When using combined anesthesia, the initial dose of Arduan is 0.08–0.09 mg/kg. For newborns, lower doses are recommended - 0.05–0.06 mg/kg. The indicated doses of the drug provide muscle relaxation during a 25-35 minute surgical intervention. If it is necessary to increase the period of muscle relaxation for the next 25–35 minutes, the drug is re-administered at a dose of 1/3 of the initial one. Reversal of effect At 80–85% blockade as measured by peripheral neuromuscular stimulator, or partial blockade as determined by clinical symptoms, the Ardoin effect in adults can be reversed by administration of neostigmine bromide at a dose of 1–3 mg in combination with atropine or galantamine at a dose of 10–30 mg. Elimination of the effect is determined using a peripheral neurostimulator or by observing characteristic clinical symptoms.
Publications in the media
(Pipecuronii bromidum) INN
Synonyms. Ardoin.
Composition and release form. Ampoules containing 4 mg of the drug, with the addition of a solvent.
Indications. For muscle relaxation during various types of surgical interventions.
Pharmachologic effect. Pipecuronium bromide is a non-depolarizing muscle relaxant. Blocks n-cholinergic receptors of skeletal muscles, reducing their sensitivity to acetylcholine, and thereby eliminates the possibility of depolarization of the end plate and excitation of the muscle fiber. The curare-like effect is associated with the presence of quaternary ammonium (onium) groups with an optical distance between them approximately equal to the distance between the onium groups in d-tubocurarine. In normal doses it does not cause significant changes in the activity of the cardiovascular system. In large doses it has a ganglion-blocking effect; does not cause histamine release. Myorelaxation occurs after 1 minute, the peak effect occurs after 3-4.5 minutes and lasts 35-45 minutes. Muscle tone stops after 60 minutes. The muscle relaxant effect of pipecuronium bromide is removed by proserin.
Pharmacokinetics. It practically does not bind to plasma proteins. Metabolized in the liver in small quantities. T1/2 is 114-116 minutes, excreted by the kidneys (80% unchanged) and 10% with bile.
Side effects. Increased blood pressure, salivation, skin rash, itching.
Contraindications. Myasthenia gravis, early pregnancy, renal dysfunction, tachycardia, hypersensitivity to the drug.
Adverse reactions when interacting with other drugs. Pipecuronium bromide enhances the inhibitory effect of narcotic analgesics on the respiratory center. Drugs that disrupt neuromuscular transmission (aminoglycoside antibiotics, clindamycin, lincomycin, polymyxin, lidocaine, novocaine, as well as novocainamide, quinidine, magnesium sulfate, etc.) enhance the muscle relaxant effect of pipecuronium bromide. Cardiac glycosides of the digitalis group against the background of the action of pipecuronium bromide can cause cardiac arrhythmias. Drugs that cause hypokalemia (thiazide diuretics, furosemide, corticosteroids, ACTH, etc.) increase the neuromuscular blockade caused by pipecuronium bromide.
Information for the patient. Pipecuronium bromide is administered intravenously. The dose for intubation is 0.04-0.08 mg/kg. For muscle relaxation during anesthesia, the drug is used in doses of 0.02 to 0.08 mg/kg. The effect of pipecuronium bromide is stopped by introducing 1-3 mg of proserine after preliminary intravenous administration of 0.25-0.5 mg of atropine. The drug is used only in a hospital.
Special instructions for the use of the drug Arduan
The use of Ardoin is possible only in a specialized hospital with equipment for endotracheal intubation, mechanical ventilation, oxygen therapy, as well as specific antidotes. Use only freshly prepared solution. It is necessary to reduce the dose of the drug in patients with neuromuscular conduction disorders, with a history of indications of poliomyelitis, as well as in obesity (due to the possibility of a relative overdose of Arduan). It should be taken into account that in patients with renal failure, the duration of action of the drug increases. Hypothermia may prolong the effect of the drug. It is recommended to reduce the initial dose of Arduan for diseases of the liver and/or bile ducts. Before starting anesthesia, water-electrolyte imbalance and blood pH disturbances should be compensated. Hypokalemia, hypocalcemia (for example after blood transfusions), hypermagnesemia, hypoproteinemia, dehydration, acidosis, hypercapnia, cachexia, the use of cardiac glycosides, diuretics enhance the effect or increase the duration of action of the drug. The use of Ardoin during cesarean section does not affect the Apgar score, muscle tone and cardiovascular adaptation of the newborn. Only a minimal amount of the active substance penetrates the placental barrier. In pregnant women who were prescribed magnesium salts (which can potentiate neuromuscular blockade) during the treatment of toxicosis, Ardoin should be used with caution and in lower doses.
Arduan
Release form, composition and packaging
Lyophilisate for the preparation of a solution for intravenous administration, white or almost white; the attached solvent is colorless and transparent.
1 fl. pipecuronium bromide 4 mg.
Excipients: mannitol. Solvent: sodium chloride solution 0.9% - 2 ml.
Clinical and pharmacological group: Peripheral muscle relaxant of non-depolarizing competitive type.
pharmachologic effect
Long-acting peripheral muscle relaxant. Due to competitive binding with n-cholinergic receptors located in the motor endings of striated muscle fibers, it blocks signal transmission from nerve endings to muscle fibers.
Does not cause muscle twitching, does not have a hormonal effect, does not stimulate the release of histamine. In average doses it does not cause significant hemodynamic changes. A dose equal to 5 mcg/kg body weight provides 40-50 minutes of muscle relaxation during surgery. The maximum effect develops after 2.5-5 minutes, the effect occurs most quickly at doses equal to 70-80 mcg/kg. Further increase in the dose of the drug shortens the time required for the manifestation of the effect and significantly lengthens the duration of action of the drug.
Pharmacokinetics
Distribution
With intravenous administration, the initial Vd is 110 ml/kg. Vd in the equilibrium state reaches 300±78 ml/kg. The cumulative effect is insignificant or absent when repeated in doses of 10-20 mcg/kg at the time of restoration of the initial contractility by 25%. Penetrates through the placental barrier.
Metabolism and excretion
Plasma clearance is approximately 2.4±0.5 ml/min/kg. T1/2 of pipecuronium averages 121±45 minutes. It is excreted mainly in the urine, with 56% of the active substance in the first 24 hours, 1/3 of the active substance is excreted unchanged, the rest in the form of 3-desacetyl-pipecuronium.
Indications
- endotracheal intubation and relaxation of skeletal muscles during general anesthesia for surgical interventions requiring more than 20-30 minutes of muscle relaxation.
Dosage regimen
The drug should be used only intravenously. Immediately before administration, 4 mg of dry substance is diluted with the supplied solvent.
With balanced anesthesia, Ardoin's ED50 and ED90 are 30 mcg/kg and 50 mcg/kg body weight, respectively. The minimum time required for the onset of effect is observed at doses of 70-80 mcg/kg. The dose should be selected individually for each patient, taking into account the type of anesthesia, the expected duration of surgery, possible interactions with other drugs used before or during anesthesia, concomitant diseases and the general condition of the patient. The use of a peripheral nerve stimulator is recommended to control neuromuscular blockade.
The drug should be used under the supervision of a qualified physician with clinical experience in the use of peripheral muscle relaxants.
Recommended Doses
The initial dose for intubation and subsequent surgery - 80-100 mcg/kg body weight - provides good or excellent conditions for intubation for 150-180 seconds, while the duration of muscle relaxation is 60-90 minutes;
The initial dose for muscle relaxation during surgery after intubation with succinylcholine is 50 mcg/kg body weight, which provides 30-60 minutes of muscle relaxation;
A maintenance dose of 10-20 mcg/kg provides 30-60 minutes of muscle relaxation. In chronic renal failure, the dose of the drug should be calculated depending on the QC.
Children aged 3 months to 1 year should be prescribed the drug at the rate of 40 mcg/kg body weight (which provides muscle relaxation lasting from 10 to 44 minutes), from 1 year to 14 years - 57 mcg/kg (providing muscle relaxation lasting from 18 to 44 minutes). 52 min).
Eliminating the effect of the drug
When implementing a neuromuscular block of 80-85%, determined using a peripheral nerve fiber stimulator, or at the time of partial blockade, determined by clinical signs, the use of atropine (0.5-1.25 mg) in combination with neostigmine (1-3 mg) or galantamine (10-30 mg) stops the neuromuscular effect of Ardoin.
Side effect
- From the central nervous system and peripheral nervous system: rarely (less than 1%) - central nervous system depression, hypoesthesia.
- From the musculoskeletal system: rarely - weakness of skeletal muscles after cessation of muscle relaxation, muscle atrophy.
- From the respiratory system: rarely - hypnea, apnea, pulmonary atelectasis, respiratory depression, laryngospasm as a result of an allergic reaction.
- From the cardiovascular system: rarely - myocardial ischemia (up to myocardial infarction) and brain, atrial fibrillation, ventricular extrasystole, bradycardia, decreased blood pressure.
- From the blood coagulation system: rarely - thrombosis, decrease in aPTT and prothrombin time.
- From the urinary system: rarely - hypercreatininemia, anuria.
- Metabolic disorders: rarely - hypoglycemia, hyperkalemia.
Allergic reactions: rarely - skin rash, hypersensitivity reactions, Quincke's edema.
Contraindications
- children up to 3 months;
- hypersensitivity to pipecuronium and/or bromine.
Use with caution in cases of biliary tract obstruction, edema syndrome, dehydration, impaired water-electrolyte metabolism, hypothermia, myasthenia gravis, respiratory failure, heart failure in the stage of decompensation, renal and/or liver failure, pregnancy, and during breastfeeding.
Pregnancy and lactation
The use of the drug during pregnancy is possible only if the expected benefit to the mother outweighs the potential risk to the fetus. Pipecuronium bromide penetrates the placental barrier. Pregnant women who took magnesium salts (which can enhance neuromuscular blockade) for toxicosis as palliative therapy are prescribed pipecuronium bromide in reduced doses. The drug should be used with caution during breastfeeding.
special instructions
The drug should be used exclusively in a specialized hospital with appropriate equipment for artificial respiration and in the presence of a specialist in artificial respiration. Careful monitoring of the maintenance of vital functions is necessary during surgery and in the early postoperative period until adequate vital tone is fully restored.
When calculating the dose, the anesthesia technique used, possible interactions with other drugs administered before or during anesthesia, the condition and individual sensitivity of the patient to the drug should be taken into account. Doses that cause muscle relaxation do not have a significant cardiovascular effect and in the vast majority of cases do not cause bradycardia.
The need to prescribe and dosage regimen of vagolytic drugs for premedication should be carefully analyzed in advance (the stimulating effect on the n. vagus of other drugs used simultaneously, as well as the type of operation, should also be taken into account).
To prevent a relative overdose of the drug and to ensure appropriate control of the restoration of muscle activity, it is recommended to use a peripheral nerve stimulator. Patients with neuromuscular transmission disorders, obesity, renal failure, impaired liver and/or biliary tract function, and also if there is a history of polio, should be prescribed the drug in lower doses.
In case of liver dysfunction, the use of Ardoin is possible only in cases where the expected benefit to the patient outweighs the potential risk.
In this case, the drug should be used in the minimum effective dose. If you are overweight or obese, the duration of action of Arduan may increase, so you should use a dose calculated for your ideal weight. Some conditions (hypokalemia, digitalization, hypermagnesemia, diuretic use, hypocalcemia, hypoproteinemia, dehydration, acidosis, hypercapnia, cachexia, hypothermia) may contribute to a change in the duration of the effect. Before starting anesthesia, it is necessary to normalize the electrolyte balance, blood glucose levels and eliminate dehydration. Increased caution should be exercised when using Arduan if there is a history of anaphylactic reactions caused by muscle relaxants, due to the possible development of cross-hypersensitivity.
Use in pediatrics
Children aged 1 to 14 years are less sensitive to pipecuronium bromide and their duration of therapeutic effect is shorter than in adults and infants (under 1 year). The effectiveness and safety of use in the neonatal period have not been studied. The therapeutic effect in infants from 3 months to 1 year does not differ significantly from that in adults.
Impact on the ability to drive vehicles and operate machinery
In the first 24 hours after the cessation of the muscle relaxant effect of Ardoin, it is forbidden to drive a car or other machinery, the operation of which is associated with an increased risk of injury.
Overdose
Symptoms: prolonged paralysis of skeletal muscles, apnea, marked decrease in blood pressure.
Treatment: in case of overdose or prolonged neuromuscular blockade, perform mechanical ventilation until spontaneous breathing is restored. At the beginning of the restoration of spontaneous breathing, an acetylcholinesterase inhibitor (neostigmine, pyridostigmine, endrophonium) is administered as an antidote: atropine 0.5 - 1.25 mg in combination with neostigmine (1-3 mg) or galantamine (10-30 mg). Respiratory function should be carefully monitored until satisfactory spontaneous breathing is restored.
Interactions of the drug Arduan
Succinylcholine enhances the effect of Ardoin. Inhalation anesthetics (halothane, methoxyflurane, diethyl ether) and barbiturates enhance and increase the duration of action of Arduan. The use of antibiotics such as gentamicin, clindamycin, ampicillin and tetracycline during surgery in usual doses did not affect the effect of Ardoin, assessed by tetanic exhaustion. However, the absence of tetanic exhaustion does not exclude an interaction, so a prolonged effect is rarely possible in the early postoperative period. The simultaneous use of Arduan with aminoglycosides requires special caution and monitoring. Strengthening and/or increasing the duration of the action of Arduan is possible with the simultaneous use of drugs for intravenous anesthesia (ketamine, fentanyl, propanidide, barbiturates); diuretics; β-adrenergic receptor blockers; thiamine; MAO inhibitors; guanidine; protamine; phenytoin; β-adrenergic receptor blockers; calcium antagonists; lidocaine (iv injection). Weakening the effect of Ardoin is possible when using GCS, neostigmine bromide, norepinephrine, theophylline, potassium chloride, sodium chloride, calcium chloride before surgery. Changing (strengthening or weakening) the action of Ardoin is possible with the simultaneous use of depolarizing muscle relaxants (depending on their dose, period of use and individual sensitivity of the patient).
