Chemical Immobilization Pharmacology: Neuromuscular Blocking Drugs
The San Diego Zoo Wildlife Alliance (SDZWA) is among several organizations that offer education in safe capture chemical immobilization techniques for those who are interested in or who are pursuing careers in veterinary medicine, wildlife management, biology, zoology, animal control and related disciplines. SDZWA currently offers livestream and in-person training sessions that are available in a self-guided e-learning format. Their programs have been approved for continuing education (CE) credits in jurisdictions that recognize RACE approval, as well as by National Animal Care & Control Association (NACA), and The Wildlife Society (TWS).
The purpose of these programs is to provide guidance regarding the safe chemical immobilization of animals. SDZWA also offers selected free online in-depth previews to some of the courses that cover the principles of and techniques relating to chemical immobilization.
Neuromuscular Blocking Drugs
The SDZWA course Chemical Immobilization Pharmacology: Neuromuscular Blocking Drugs, falls into the learning category of Capture Pharmacology. It is one of the courses that goes into detail regarding the drugs commonly used for the chemical immobilization of animals.
Neuromuscular blocking agents (NMBAs) are important role in both human and animal medicine. They are common in surgical situations and rapid sequence intubation, as well as more controversial applications, such as acute respiratory distress syndrome and therapeutic hypothermia.1 It is extremely important to recognize that while neuromuscular blocking drugs prevent muscular movement, they have no effect on an animal’s level of consciousness nor their ability to perceive pain or discomfort.
Neuromuscular blocking drugs’ method of action involves modulating signal transmission in skeletal muscle. There are two classes of NMBAs: depolarizing NMBAs, which act as agonists at nicotinic receptors, and nondepolarizing NMBAs, which act as competitive antagonists at nicotinic receptors to block acetylcholine.1 NMBAs used to induce neuromuscular blockade must be chosen carefully, taking into account clinical indications, the procedure being performed and patient considerations.2
Depolarizing Neuromuscular Blocking Drugs
Currently, succinylcholine is the only depolarizing neuromuscular blocking drug available clinically. Depolarizing NMBAs occupy the postjunctional cholinergic receptors and bring about prolonged depolarization of the endplate region. This prevents the synaptic membrane from completely repolarizing, thus rendering the motor endplate unresponsive to the normal action of acetylcholine.2 The onset of action of succinylcholine is rapid after IV injection, with a duration of 5–10 minutes in most species. It is rapidly hydrolyzed by pseudocholinesterases in the plasma and liver in most species.1
Other pharmacologic effects are associated with the depolarizing NMBAs. After IV administration of succinylcholine, transient muscle fasciculations are usually evident, although general anesthesia tends to attenuate these.2 Cardiac arrhythmias can be many and varied. The indications for the clinical use of succinylcholine are similar to those for the nondepolarizing NMBAs (see below). However, it is considered inhumane to administer succinylcholine as an agent for euthanasia or for immobilization or other procedures without local or general analgesia.2
Nondepolarizing Neuromuscular Blocking Drugs
Nondepolarizing NMBAs are often referred to as “curarizing agents” due to their relationships with the curare alkaloids that were once used for these purposes. These drugs are competitive acetylcholine (ACh) antagonists that directly bind to postsynaptic nicotinic receptors.1 This prevents acetylcholine from binding to the receptor and prevents the motor endplate from depolarizing, resulting in muscle paralysis.3
According to their chemical structure, nondepolarizing NMBAs are classified as:
- Steroidal (e.g., rocuronium, vecuronium, pancuronium), or
- Benzylisoquinolinium (e.g., atracurium, cisatracurium, mivacurium)
Nondepolarizing neuromuscular blocking drugs are not absorbed from the GI tract and must be administered intravenously. Blood-brain and blood-placental barriers are rarely crossed.1 After IV administration of nondepolarizing NMBAs, skeletal muscles become flaccid and nonresponsive to neuronal stimulation. Muscles that are capable of rapid movement (such as those in the eyes) are paralyzed before the larger muscles of the limbs and body. Finally, the diaphragm becomes paralyzed, and respiration ceases.
Some drugs can potentiate the activity of nondepolarizing neuromuscular blocking drugs, including peripherally-acting skeletal muscle relaxants, inhalant anesthetics (e.g., halothane, methoxyflurane), antimicrobials (e.g., aminoglycosides, polymyxins, tetracyclines, and lincosamides), and drugs such as quinidine, procaine, lidocaine, diazepam and barbiturates. Some conditions such as hyper- and hypomagnesemia, hypokalemia, acidosis, and hypothermia, also prolong the effect of these drugs.3
Animals should always be carefully monitored when under the influence of NMBAs, and ventilation support is essential.
Indications for the use of nondepolarizing neuromuscular blocking drugs include:
- Muscle relaxation for orthopedic and intraocular procedures Hypoxemic animals resisting mechanical ventilation
- Tracheal intubation
- Animals with unstable cardiovascular function that require anesthesia but cannot tolerate cardiac depression
- Cesarean section in toxic or high-risk animals
- Convulsions not controllable with usual anticonvulsant agents
- Tetanus
- Strychnine poisoning
- Animals in which the metabolic demand for oxygen should be reduced
- Capture of certain exotic species.1
Calabadion is the most commonly used antagonist for the reversal of neuromuscular blockade using succinylcholine, while neostigmine is typically used to reverse the effects of nondepolarizing neuromuscular blocking drugs.3 Neostigmine has the advantages of broad-spectrum reversal of all nondepolarizing NMBAs, is inexpensive, and a large amount of clinical data to support its use.2 It is typically administered at 0.04 mg/kg, IV. Other reversal agents that may be used are edrophonium and pyridostigmine.
In general, although there are significant benefits to the use of NMBAs in particular situations, there is also the potential for short-term and long-term complications.1 In some settings, the use of neuromuscular blocking drugs can lead to a need for increased postoperative care, prolonged mechanical ventilation, venous thromboembolism, skin tearing and ulcerations, infection, corneal damage, and anaphylaxis.3 Long-term administration can lead to immobility or increased recovery time because of impaired neuromuscular transmission and muscular weakness.1
Interested in learning more about safe capture? The San Diego Zoo now offers courses in safe capture techniques and best practices. Learn reliable, safe, and effective techniques for the species you work with and the scenarios you encounter!
1Murray M.J., et. al. Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient. Critical Care Medicine, 2016;44:2079-2103.
3Naguib M., Lien C.A. Pharmacology of muscle relaxants and their antagonists. In: Miller’s Anesthesia. 7th ed. Miller RD, Eriksson LI, Fleisher LA, et al, eds. Philadelphia, PA: Churchill Livingstone; 2010.
About NexGen Pharmaceuticals
NexGen Pharmaceuticals is an industry-leading veterinary compounding pharmacy, offering sterile and non-sterile compounding services nationwide. Unlike other veterinary compounding pharmacies, NexGen focuses on drugs that are difficult to find or are no longer available due to manufacturer discontinuance or have yet to be offered commercially for veterinary applications, but which still serve a critical need for our customers. We also specialize in wildlife pharmaceuticals, including sedatives and their antagonists, offering many unique options to serve a wide array of zoo animal and wildlife immobilization and anesthesia requirements.
Our pharmacists are also encouraged to develop strong working relationships with our veterinarians in order to better care for veterinary patients. Such relationships foster an ever-increasing knowledge base upon which pharmacists and veterinarians can draw, making both significantly more effective in their professional roles.
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