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Neuromuscular blocking agents and the physiology of the neuromuscular junction.

Neuromuscular blocking agents (NMBA) are drugs that cause skeletal muscle weakness or paralysis and therefore prevent movement. These agents produce this effect at the neuromuscular junction by interfering with the action of the neurotransmitter acetylcholine (Ach). NMBAs either depolarize the per-and post-synaptic membrane receptors or compete with acetylcholine for binding of the acetylcholine receptors at the neuromuscular junction.

The NMBAs are divided into two types: depolarizing and non-depolarizing agents. The depolarizing agents bind to acetylcholine receptors and cause a sustained postsynaptic membrane depolarization. By preventing repolarization of the nerve ending, the postsynaptic ending becomes refractory and unexcitable, resulting in flaccid muscles.

At present, succinylcholine is the only available agent in this class. The non-depolarizing agents produce paralysis and muscle weakness by competing with acetylcholine for binding at the acetylcholine receptors. By preventing the binding of acetylcholine, the nondepolarizing agents block the depolarizing effects of acetylcholine, thereby preventing muscle contraction.

Uses for Neuromuscular Blocking Agents

The clinical uses of NMBAs important to respiratory therapist are to facilitate endotracheal intubation, to enhance patient, ventilator synchrony, and to reduce oxygen consumption. Other uses include muscle relaxation during surgery, reduction of intracranial pressure in intubated patients with uncontrolled intracranial pressure, and termination of convulsive status epilepticus and tetanus in patients' refractory to other therapies.

It also can be used to facilitate procedures or diagnostic studies for selected patients who must remain immobile such as trauma patients. It must be noted that any paralysis will need the assistance of a respiratory therapist since the use of these agents will affect breathing.

The NMBAs are usually given intravenously and exhibit a dose-related response on muscles. The primary use of NMBAs in the operating room is for anesthesia induction before endotracheal intubation. In an intensive care unit setting, NMBAs are used primarily for management of mechanical ventilation.

The Neuromuscular Junction

The autonomic nervous system consists of the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS consists of the brain and the spinal cord, and the PNS includes all the nerves outside of the CNS. The skeletal muscle system includes all the peripheral nerves that control voluntary movement.

Examples of skeletal muscles include the quadriceps, biceps and diaphragm, which are responsible for motor functions such as movement, lifting, and breathing. The autonomic nervous system includes peripheral nerves that control involuntary movement. These nerves stimulate visceral organs such as the heart muscles and other smooth muscles found in bronchioles, arteries and veins.

The basic nerve cell, or neuron, consists of a cell body. The cell bodies of these neurons, located in the brain and spinal cord, stimulate skeletal muscles via the axons of the peripheral nerves. These axons are large nerve fibers extending from the peripheral nerve cell bodies to the muscle fibers. The area between the nerve and muscle, or synapse, is specialized into a motor end plate.

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The area between the axon and the skeletal muscle fiber is also called the neuromuscular junction. This is the area in which the chemicals are transferred to elicit an act of movement. In this case, NMBAs stop [he attachment of the chemical to the site and movement is stopped.

The transmission of nerve conduction in skeletal muscle is chemically mediated by the neurotransmitter ACh. When a nerve impulse reaches the end of the motor neuron, ACh is released from the presynaptic nerve ending into the synaptic cleft. Ach diffuses across the synaptic space and interacts with specific acetylcholine receptors on the postsynaptic muscle fiber membrane, resulting in a response by the muscle fiber.

During the short period that ACh is in contact with the muscle fiber membrane, a nerve action potential, or nerve impulse, is initiated in the postsynaptic cell. Ach is then broken down and inactivated by the enzyme acetylcholinesterase (AChE), allowing the muscle fiber to depolarize.

In the depolarization phase, the muscle membrane becomes permeable to sodium ions. As the concentration of sodium ions increases within the postsynaptic cell, a rise in membrane potential occurs. If enough receptors are activated at the same time, a critical threshold is reached and a muscle contraction occurs.

On the basis of the neuromuscular physiology described, muscle contraction may be blocked in the following two ways--competitive inhibition, the binding and blocking of the acetylcholine receptors without depolarization; and prolonged occupation and persistent binding of the Ach receptors, resulting in sustained depolarization of the neuromuscular junction. Both depolarizing and nondepolarizing agents resemble the neurotransmitter acetylcholine.

Agents

As mentioned previously, the only depolarizing agent on the market is succinylcholine (Anectine), which is an ultra short-acting agent that is typically only used for rapid intubation scenarios. The agent has onset of about one minute and lasts about 10 to 15 minutes.

Unlike depolarizing agents, non-depolarizing agents provide many more choices. Common agents include pancuronium, rocuronium and vencuronium all have an onset of a few minutes and can last up to a couple hours. Other agents include cistracurium, doxacurium and mivacurium, all of which have onsets within a few minutes and can last for about an hour.

In the next issue, an in-depth discussion on mode of action and how each agent (depolarizing and non-depolarizing) is utilized in the body will be covered. Hazards associated with the use of NMBAs, including the use of these agents with mechanically ventilated patients, will be discussed.

Neuromuscular blocking agents are often a therapist's best friend

Doug Gardenhire MS, RRT-NPS

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Douglas Gardenhire is a veteran therapist, author, educator and the Director of Clinical Education in the RC Program at GA State University.
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Title Annotation:RESPIRATORY PHARMACOLOGY
Author:Gardenhire, Doug
Publication:FOCUS: Journal for Respiratory Care & Sleep Medicine
Date:Mar 1, 2010
Words:920
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