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Succinylcholine Chloride

The Elephant Formulary
© 2003-06 Susan K. Mikota DVM and Donald C. Plumb, Pharm.D.
Published by Elephant Care International -
www.elephantcare.org


Elephant specific information, if available, is in blue.

Chemistry - A depolarizing neuromuscular blocking agent, succinylcholine chloride oc­curs as an odorless, white, crystalline powder. The dihydrate form melts at 190°C and the anhydrous form at 160°C. Aqueous solutions are acidic with a pH of approximately 4. One gram is soluble in about 1 ml 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 .

 

Storage/Stability/Compatibility - Commercial injectable solutions should be stored re­frigerated (2°-8°C). One manufacturer (Glaxo Wellcome - Anectine®) states that multiple dose vials are stable for 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 week at room temperature, but because they contain no preservative, it is recommended they be used within 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 bicarbonate and thiopental sodium.

 

Pharmacology - An ultrashort-acting depolarizing skeletal muscle relaxant, succinyl­choline bonds with motor endplate cholinergic receptors to produce depolarization (perceived as fasiculations). The neuromuscular block remains as long as sufficient quanti­ties of succinylcholine remain, and is characterized by a flaccid paralysis. Other pharma­cologic effects are discussed in the precautions and adverse effects sections.

 

Uses/Indications - Succinylcholine chloride is indicated for short-term muscle relaxation needed for surgical or diagnostic procedures, to facilitate endotracheal intubation in some species, and to reduce the intensity of muscle contractions associated with electro- or pharmacological- induced convulsions. Dogs, cats, and horses are the primary veterinary species where succinylcholine chloride has been used.

 

Pharmacokinetics - The onset of action, with complete muscle relaxation, after IV admin­istration is usually within 30 seconds to 1 minute. In humans this effect lasts for 2-3 min­utes and then gradually diminishes within 10 minutes. The very short duration of action after a single IV dose is thought to occur because the drug diffuses away from the motor end-plate. If multiple injections or a continuous infusion is performed, the brief activity is a result of rapid hydrolysis by pseudocholinesterases at the site of action. After IM injec­tion, the onset of action is generally within 2-3 minutes and may persist for 10-30 minutes. Dogs exhibit a prolonged duration of action (≈ 20 minutes); this species appears unique in this idiosyncratic response.

 

Succinylcholine is metabolized by plasma pseudocholinesterases to succinylmonocholine and choline and 10% of it is excreted unchanged in the urine. Succinylmonocholine is par­tially excreted in the urine and may accumulate in patients with impaired renal function. Succinylmonocholine has approximately 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 liver disease, chronic anemias, malnourishment (chronic), glaucoma or penetrating eye injuries, predisposition to malignant hyperthermia, and increased CPK values with re­sultant myopathies. As succinylcholine can exacerbate the effects of hyperkalemia, it should be used with extreme caution in patients who have suffered traumatic wounds or burns, are receiving quinidine or digitalis therapy, have preexisting hyperkalemia or elec­trolyte imbalances, as arrhythmias or cardiac arrest may 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 low concentrations and a newly delivered neonate may show signs of neuromuscular blockade if the mother 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 appro­priate analgesic/sedative/anesthetic agents.

In horses, the following additional recommendations have been made by the American Association of Equine Practitioners:

1)   Inform the owner that succinylcholine chloride is to be used as a restraining agent, not as an anesthetic.

2)   Obtain history before use; do not use in horses if within 30 days they have re­ceived, an antibiotic ending in “mycin”, organophosphate insecticides or an­thelmintics, any other cholinesterase 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 caus­ing respiratory depression. Higher doses may cause apnea and death without res­piratory support. 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 of succinylcholine chloride so that the animal does not fall forward on its nose. Be prepared to administer oxygen and artificial respiration.

7)   If death occurs, a necropsy should be performed.

 

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 in prolonged 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 II block.

 

Drug Interactions - Furosemide, phenothiazines, oxytocin, quinidine, procainamide, beta-adrenergic 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 caus­ing electrolyte imbalances. Increased incidences of bradycardia and sinus arrest may occur if used concurrently with narcotic analgesics. Concomitant administration with inhalation anesthetics (halothane, cyclopropane, ni­trous oxide, diethyl ether) may induce increased incidences of cardiac effects (bradycardia, arrhythmias, sinus arrest and apnea) and in susceptible patients, malignant hyperthermia.

 

Doses -

Horses: See Precautions above.

a)   0.088 mg/kg (Muir )

b)   0.088 - 0.11 mg/kg IV, IM (Mandsager 1988)

 

Elephants: Succinylcholine is used as a euthanasia agent during culling operations.  Elephant references are listed below.  The reader is referred to the specific articles for further information.

 

Elephant References:

a) Pitts,N.I. and Mitchell,G. 2003. In vitro succinylcholine hydrolysis in plasma of the African elephant (Loxodonta africana) and impala (Aepyceros melampus). Comp Biochem Physiol C Toxicol Pharmacol 134:(1):123-129  Abstract: In elephants the time lapsed from i.m. injection of an overdose of the muscle relaxant succinylcholine (SuCh) until death, is significantly longer than in impala. To determine a difference in the rate of SuCh hydrolysis, once the drug enters the circulation, contributes to this phenomenon we have measured the rate of hydrolysis of SuCh in elephant and impala plasma, and by elephant erythrocytes. Rate of hydrolysis was determined by incubating SuCh in plasma or erythrocyte lysate at 37 degrees C and quantifying the choline produced. Plasma SuCh hydrolytic activity in elephant plasma (12.1+/-1.7 Ul(-1) mean+/-S.D.; n=9) was significantly higher than it was in impala plasma (6.6+/-0.6 Ul(-1); n=5), but were approximately 12 and 21 times lower, respectively, than in human plasma. Elephant erythrocyte lysate had no SuCh hydrolytic activity. Applying this data to previous studies, we can show that the ratio of SuCh absorption to SuCh hydrolysis is expected to be 1.25:1 and 1.41:1 for elephants and impala respectively. It will thus take at least 1.7 times longer for elephant to achieve a plasma SuCh concentration similar to that in impala. We conclude that a more rapid hydrolysis of SuCh in elephant plasma is one factor that contributes to the longer time to death compared to impala.

b) Pitts,N.I. and Mitchell,G. 2002. Pharmacokinetics and effects of succinylcholine in African elephant (Loxodonta africana) and impala (Aepyceros melampus). Eur J Pharm Sci 15:(3):251-260  Abstract: The phenomenon of slow onset of succinylcholine (Sch) effect in elephants was investigated by analyzing blood concentrations of Sch and its metabolite choline in elephant and impala. To assess whether the slow onset phenomenon is related to the pharmacokinetics of Sch following i.m. administration, we analyzed the time course of plasma concentrations of intact drug and its metabolite and determined its pharmacological effects. Blood samples were obtained from anaesthetized elephant (n=6) and impala (n=7) following i.m. administration of a lethal dose of Sch. Time from Sch injection to onset of apnoea and to death was significantly longer for elephant than impala (mean+/-S.D. apnoea 4.4+/-1.5 and 2.3+/-0.9 min, respectively; death 32.6+/-7.3 and 6.2+/-3.4 min, respectively). The C(max) was not different between elephants and impala (20.3+/-7.9 vs. 14.4+/-6.8 nmol ml(-1), respectively) but the t(max) was significantly longer for elephants (23.0+/-7.6 vs. 3.7+/-2.2 min). Analysis of the plasma Sch and choline concentrations over time revealed that the relative amount of Sch entering the circulation within the first 30 s after i.m. injection is greater for impala than elephant. No greater rate in the plasma hydrolysis of Sch in elephant compared to impala was apparent.

c) Kramer,B. and Hattingh,J. 1995. The neuromuscular junction in the African elephant Loxodonta africana and African buffalo Syncerus caffer. South African Journal of Wildlife Research 25:(1):p14, 3p, 2bw  Abstract: Differences in the physiological response to the drug succinyldicholine occur between the African elephant Loxodonta africana and African buffalo Syncerus caffer, irrespective of the route of administration of the drug. The response in elephants has suggested the presence of unique acetylcholine receptors in their respiratory muscles. In this paper the first observations of the neuromuscular junction in the African elephant and African buffalo are reported. While the basic structure of the junction was found to be typically mammalian in both species, differences were found in the morphology of the postjunctional area where these receptors reside. Elucidation of the structure and function of this junction in these animals is important in the selection of drugs that act as neuromuscular blockers.

d) Hattingh,J., Pitts,N.I., De-Vos,N.I., Moyes,D.G., and Ganhao,M.F. 1991. The response of animals to suxamethonium (succinyldicholine) and succinylmonocholine. Journal of the South African Veterinary Association 62:(3):126-129  Abstract: The time which elapses before cessation of breathing, and blood pressure and blood gas changes after the i.m. administration of suxamethonium, or a mixture of suxamethonium and hexamethonium, was compared in immobilized African elephants (Loxodonta africana) and buffaloes (Synceros caffer). In addition, the respiratory responses of elephants and other animals to i.v. administration of suxamethonium and succinylmonocholine are reported, as are the effects of darting animals with succinylmonocholine. Respiration was affected in a similar fashion in all species investigated. However, the characteristic gradual decrease in respiratory rate seen in elephants during culling, using suxamethonium, resembles the effects observed when succinylmonocholine is administered. It is suggested that elephants are killed by this first breakdown product of suxamethonium during culling and/or that unique acetylcholine receptors may be involved.

e) Hattingh,J., Pitts,N.I., Ganhao,M.F., Moyes,D.G., and de Vos,V. 1990. Blood constituent responses of animals culled with succinyldicholine and hexamethonium. J.S.Afr.Vet.Assoc. 61:117-118  Abstract: Blood constituent responses of elephants and buffaloes culled in the Kruger National Park, using a mixture of succinyldicholine and hexamethonium, were compared to those of animals culled with succinyldicholine only. The results show a decreased physiological response in the animals culled with the mixture, characterized by lower total catecholamine, cortisol and glucose concentrations. Neither a delay of up to 30 min in obtaining blood samples from culled animals, nor a delay of up to 30 min in processing samples obtained immediately after cessation of respiration, gave any significant difference in the blood constituents which were measured.

f) Hattingh,J. 1984. Effects of etorphine and succinyldicholine on blood composition in elephant and buffalo. South African Journal of Zoology 19:286-290

h) Hattingh,J., Wright,P.G., de Vos,V., McNairn,I.S., Ganhao,M.F., Silove,M., Wolverson,G., and Cornelius,S.T. 1984. Blood composition in culled elephants and buffaloes. J.S.Afr.Vet.Assoc. 55:(4):157-164  Abstract: Blood composition of succinyldicholine culled elephants and buffaloes was compared with that of undisturbed animals shot in the brain. The results show statistically significant differences in a number of variables including plasma ACTH and cortisol concentrations. The observed changes are attributed to stress induced by a combination of herding and darting with succinyldicholine and asphyxia. Extrapolation from blood oxygen tensions suggests that this stress may be perceived for an undetermined period which is probably longer in elephants than buffaloes.

Monitoring Parameters -

1)   Level of muscle relaxation

2)   Cardiac rate/rhythm

3)   Respiratory depressant effect

 

Client Information - This drug should only be used by professionals familiar with its use.

 

Dosage Forms/Preparations/FDA Approval Status/Withholding Times -

 

Veterinary-Approved Products: None

 

Human-Approved Products:

Succinylcholine Chloride for Injection 20 mg/ml, 50 mg/ml, 100 mg/ml in 10 ml vials and amps and 5 ml syringes; Anectine® (Glaxo Wellcome); Quelicin®  (Abbott): Succinylcholine Chloride (Organon) (Rx)

 

 

Succinylcholine Chloride Powder for Infusion 500 mg or 1 gram vials; Anectine Flo-Pak® (Glaxo Wellcome); (Rx)

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