SUCCINYLCHOLINE CHLORIDE
Chemistry - A depolarizing neuromuscular blocking agent, succinylcholine chloride occurs as anodorless, white, crystalline powder. The dihydrate form melts at 190°C and the anhydrous form at160°C. Aqueous solutions are acidic with a pH of approximately 4. One gram is soluble in about 1ml of water and about 350 ml of alcohol. Commercially available injections have a pH from 3-4.5.
Succinylcholine may also be known as suxemethonium chloride.
The powder forms of the drug are stable indefinitely when stored unopened at room temperature.
After reconstitution with either D5W or normal saline, they are stable for 4 weeks at 5°C or 1 weekat room temperature, but because they contain no preservative, it is recommended they be usedwithin 24 hours.
Succinylcholine chloride is compatible with all commonly used IV solutions, amikacin sulfate, cephapirin sodium, isoproterenol HCl, meperidine HCl, norepinephrine bitartrate, scopolamine HBr.
It may not be compatible with pentobarbital sodium and is incompatible with sodium bicarbonateand thiopental sodium.
The neuromuscular block remains as long as sufficient quantities of succinylcholine remain, and ischaracterized by a flaccid paralysis. Other pharmacologic effects are discussed in the precautionsand adverse effects sections.
Succinylcholine is metabolized by plasma pseudocholinesterases to succinylmonocholine andcholine and 10% of it is excreted unchanged in the urine. Succinylmonocholine is partially excretedin the urine and may accumulate in patients with impaired renal function. Succinylmonocholine hasapproximately 1/20th the neuromuscular blocking activity of succinylcholine, but if it accumulates, prolonged periods of apnea may result.
Contraindications/Precautions - Succinylcholine is contraindicated in patients with severe liverdisease, chronic anemias, malnourishment (chronic), glaucoma or penetrating eye injuries, predisposition to malignant hyperthermia, and increased CPK values with resultant myopathies. Assuccinylcholine can exacerbate the effects of hyperkalemia, it should be used with extreme cautionin patients who have suffered traumatic wounds or burns, are receiving quinidine or digitalistherapy, have preexisting hyperkalemia or electrolyte imbalances, as arrhythmias or cardiac arrestmay occur. It should also be used with caution in patients with pulmonary, renal, cardiovascular, metabolic or hepatic dysfunction.
It is unknown if succinylcholine can cause fetal harm. The drug does cross the placenta in lowconcentrations and a newly delivered neonate may show signs of neuromuscular blockade if themother received high doses or prolonged administration of the drug prior to delivery.
Succinylcholine should not be used if organophosphate agents have been given or applied recently.
Succinylcholine chloride does not have analgesic effects; and should be used with appropriateanalgesic/sedative/anesthetic agents.
In horses, the following additional recommendations have been made by the American Associationof Equine Practitioners:1) Inform the owner that succinylcholine chloride is to be used as a restraining agent, not asan anesthetic. 2) Obtain history before use; do not use in horses if within 30 days they have received, anantibiotic ending in "mycin", organophosphate insecticides or anthelmintics, any othercholinesterase inhibitor, or procaine. 3) Do not use in debilitated, excited, or exhausted horses. 4) If possible, withhold food for 4-6 hours before use. 5) Dosage of 0.088mg/kg IV may be used to paralyze skeletal muscles without causingrespiratory depression. Higher doses may cause apnea and death without respiratorysupport. Lower doses may be possible if animal is used with a preanesthetic agent. 6) After administration, have someone hold the horse that is familiar with the actions ofsuccinylcholine chloride so that the animal does not fall forward on its nose. Be preparedto administer oxygen and artificial respiration. 7) If death occurs, a necropsy should be performed.
Overdosage - Inadvertent overdoses, or patients deficient in pseudocholinesterase may result inprolonged apnea. Mechanical ventilation with O2 should be used until recovery.
Repeated or prolonged high dosages may cause patients to convert from a phase I to a phase IIblock.
Diazepam may reduce the duration of action of succinylcholine.
Succinylcholine may cause a sudden outflux of potassium from muscle cells, thus causing arrhythmias in digitilized patients.
Drugs such as neostigmine or organophosphates, which can inhibit pseudocholinesterases, should not be used with succinylcholine.
Intravenous procaine (competes for the pseudocholinesterase enzyme) and cyclophosphamide(decreases plasma pseudocholinesterase) may prolong succinylcholine's effects.
Thiazide diuretics and Amphotericin B may increase succinylcholine's effects by causingelectrolyte imbalances.
Increased incidences of bradycardia and sinus arrest may occur if used concurrently with narcoticanalgesics.
Concomitant administration with inhalation anesthetics (halothane, cyclopropane, nitrousoxide, diethyl ether) may induce increased incidences of cardiac effects (bradycardia, arrhythmias, sinus arrest and apnea) and in susceptible patients, malignant hyperthermia.
Succinylcholine may also be known as suxemethonium chloride.
Storage, Stability, Compatibility
Commercial injectable solutions should be stored refrigerated(2°-8°C). One manufacturer (Glaxo Wellcome - Anectine®) states that multiple dose vials are stablefor up to 2 weeks at room temperature with no significant loss of potency.The powder forms of the drug are stable indefinitely when stored unopened at room temperature.
After reconstitution with either D5W or normal saline, they are stable for 4 weeks at 5°C or 1 weekat room temperature, but because they contain no preservative, it is recommended they be usedwithin 24 hours.
Succinylcholine chloride is compatible with all commonly used IV solutions, amikacin sulfate, cephapirin sodium, isoproterenol HCl, meperidine HCl, norepinephrine bitartrate, scopolamine HBr.
It may not be compatible with pentobarbital sodium and is incompatible with sodium bicarbonateand thiopental sodium.
Pharmacology - SUCCINYLCHOLINE CHLORIDE
An ultrashort-acting depolarizing skeletal muscle relaxant, succinylcholine bondswith motor endplate cholinergic receptors to produce depolarization (perceived as fasiculations).The neuromuscular block remains as long as sufficient quantities of succinylcholine remain, and ischaracterized by a flaccid paralysis. Other pharmacologic effects are discussed in the precautionsand adverse effects sections.
Uses, Indications
Succinylcholine chloride is indicated for short-term muscle relaxation neededfor surgical or diagnostic procedures, to facilitate endotracheal intubation in some species, and toreduce the intensity of muscle contractions associated with electro- or pharmacological- inducedconvulsions. Dogs, cats, and horses are the primary veterinary species where succinylcholinechloride has been used.Pharmacokinetics - SUCCINYLCHOLINE CHLORIDE
The onset of action, with complete muscle relaxation, after IV administrationis usually within 30 seconds to 1 minute. In humans this effect lasts for 2-3 minutes and thengradually diminishes within 10 minutes. The very short duration of action after a single IV dose isthought to occur because the drug diffuses away from the motor end-plate. If multiple injections ora continuous infusion is performed, the brief activity is a result of rapid hydrolysis bypseudocholinesterases at the site of action. After IM injection, the onset of action is generally within2-3 minutes and may persist for 10-30 minutes. Dogs exhibit a prolonged duration of action (ยป 20minutes); this species appears unique in this idiosyncratic response.Succinylcholine is metabolized by plasma pseudocholinesterases to succinylmonocholine andcholine and 10% of it is excreted unchanged in the urine. Succinylmonocholine is partially excretedin the urine and may accumulate in patients with impaired renal function. Succinylmonocholine hasapproximately 1/20th the neuromuscular blocking activity of succinylcholine, but if it accumulates, prolonged periods of apnea may result.
Contraindications/Precautions - Succinylcholine is contraindicated in patients with severe liverdisease, chronic anemias, malnourishment (chronic), glaucoma or penetrating eye injuries, predisposition to malignant hyperthermia, and increased CPK values with resultant myopathies. Assuccinylcholine can exacerbate the effects of hyperkalemia, it should be used with extreme cautionin patients who have suffered traumatic wounds or burns, are receiving quinidine or digitalistherapy, have preexisting hyperkalemia or electrolyte imbalances, as arrhythmias or cardiac arrestmay occur. It should also be used with caution in patients with pulmonary, renal, cardiovascular, metabolic or hepatic dysfunction.
It is unknown if succinylcholine can cause fetal harm. The drug does cross the placenta in lowconcentrations and a newly delivered neonate may show signs of neuromuscular blockade if themother received high doses or prolonged administration of the drug prior to delivery.
Succinylcholine should not be used if organophosphate agents have been given or applied recently.
Succinylcholine chloride does not have analgesic effects; and should be used with appropriateanalgesic/sedative/anesthetic agents.
In horses, the following additional recommendations have been made by the American Associationof Equine Practitioners:
Adverse Effects, Warnings
Succinylcholine chloride can cause muscle soreness, histamine release, malignant hyperthermia, excessive salivation, hyperkalemia, rash, and myoglobinemia/myoglobinuria. Cardiovascular effects can include bradycardia, tachycardia, hypertension, hypotension, or arrhythmias.Overdosage - Inadvertent overdoses, or patients deficient in pseudocholinesterase may result inprolonged apnea. Mechanical ventilation with O2 should be used until recovery.
Repeated or prolonged high dosages may cause patients to convert from a phase I to a phase IIblock.
Drug Interactions
Furosemide, phenothiazines, oxytocin, quinidine, procainamide, betaadrenergic blockers (propranolol), lidocaine, magnesium salts, and isoflurane may enhance the actions of succinylcholine.Diazepam may reduce the duration of action of succinylcholine.
Succinylcholine may cause a sudden outflux of potassium from muscle cells, thus causing arrhythmias in digitilized patients.
Drugs such as neostigmine or organophosphates, which can inhibit pseudocholinesterases, should not be used with succinylcholine.
Intravenous procaine (competes for the pseudocholinesterase enzyme) and cyclophosphamide(decreases plasma pseudocholinesterase) may prolong succinylcholine's effects.
Thiazide diuretics and Amphotericin B may increase succinylcholine's effects by causingelectrolyte imbalances.
Increased incidences of bradycardia and sinus arrest may occur if used concurrently with narcoticanalgesics.
Concomitant administration with inhalation anesthetics (halothane, cyclopropane, nitrousoxide, diethyl ether) may induce increased incidences of cardiac effects (bradycardia, arrhythmias, sinus arrest and apnea) and in susceptible patients, malignant hyperthermia.