There are two main classes of natural and synthetic drugs used as neuromuscular blockers—nondepolarizing and depolarizing.
Nondepolarizing blocking drugs, also called competitive or stabi-lizing drugs, are derived from curare alkaloids and syntheticallysimilar compounds. They include:
Because nondepolarizing blockers are absorbed poorly from the GI tract, they’re administered parenterally. The I.V. route is pre-ferred because the action is more predictable.
These drugs are distributed rapidly throughout the body.
A variable but large proportion of the nondepolarizing drugs is ex-creted unchanged in urine. Some drugs, such as atracurium, pan-curonium, and vecuronium, are partially metabolized in the liver.
Nondepolarizing blockers compete with acetylcholine at the cholinergic receptor sites of the skeletal muscle membrane. This blocks acetylcholine’s neurotransmitter action, preventing the muscle from contracting.
The effect can be counteracted by anticholinesterase drugs, such as neostigmine and pyridostigmine, which inhibit the action of acetylcholinesterase, the enzyme that destroys acetylcholine.
The initial muscle weakness produced by these drugs quickly changes to a flaccid (loss of muscle tone) paralysis that affects the muscles in a specific sequence. The first muscles to exhibit flaccid paralysis are those of the eyes, face, and neck. Next, the limb, ab-domen, and trunk muscles become flaccid.
Lastly, the intercostal muscles (between the ribs) and diaphragm (the breathing muscle) are paralyzed. Recovery from the paralysis usually occurs in the reverse order.
Because these drugs don’t cross the blood-brain barrier, the patient remains conscious and can feel pain. Even though the patient is paralyzed, he’s aware of what’s happening to him and can experience extreme anxi-ety but can’t communicate his feelings.
For this reason, an analgesic or antianxi-ety drug should be administered along with a neuromuscular blocker. (See Us-ing a neuromuscular blocker safely.)
Nondepolarizing blockers are used for intermediate or prolonged muscle relaxation to:
· ease the passage of an endotracheal (ET) tube
· decrease the amount of anesthetic required during surgery
· facilitate realignment of broken bones and dislocated joints
· paralyze patients who need ventilatory support but who fight the ET tube and ventilation
· prevent muscle injury during electroconvulsive therapy (ECT) (passing an electric current through the brain to treat depression) by reducing the intensity of muscle spasms.
These drugs alter the effects of nondepolarizing neuromuscular blockers:
o Aminoglycoside antibiotics and anesthetics potentiate or exag-gerate the neuromuscular blockade.
· Drugs that alter the serum levels of the electrolytes calcium, magnesium, or potassium also alter the effects of the nondepolar-izing blockers.
· The anticholinesterases (neostigmine, pyridostigmine, and edro-phonium) antagonize nondepolarizing blockers and are used as antidotes to them.
· Drugs that can increase the intensity and duration of paralysis when taken with a nondepolarizing blocker include inhalation anesthetics, aminoglycosides, clindamycin, polymyxin, verapamil, quinine derivatives, ketamine, lithium, nitrates, thiazide diuretics, tetracyclines, and magnesium salts.
· Drugs that can cause decreased neuromuscular blockade when taken with a nondepolarizing blocker include carbamazepine, hy-dantoins, ranitidine, and theophylline. (See Adverse reactions tonondepolarizing blockers.)
o Concurrent use of corticosteroids may result in prolonged mus-cle weakness.