SKELETAL 1 Flashcards
Neuromuscular paralysis that results from persistent depolarization of the end plate (eg, by succinylcholine).
Depolarizing blockade
A phase of blockade by a depolarizing blocker during which the end plate repolarizes but is less than normally responsive to agonists (acetylcholine or succinylcholine)
Desensitization
Hyperthermia that results from massive release of calcium from the sarcoplasmic reticulum, leading to uncontrolled contraction and stimulation of metabolism in skeletal muscle.
Malignant hyperthermia
Neuromuscular paralysis that results from pharmacologic antagonism at the acetylcholine receptor of the end plate (eg, by tubocurarine)
Nondepolarizing blockade
A drug that reduces abnormally elevated muscle tone (spasm) without paralysis (eg, baclofen, dantrolene)
Spasmolytic
Synonym for nonpolarizing blockade
Stabilizing blockade
The neuromuscular blocking drugs, which act at the skeletal myoneural junction, are used to produce ____ to facilitate surgery or assisted ventilation.
muscle paralysis
The ___ drugs, most of which act in the CNS, are used to reduce abnormally elevated tone caused by neurologic or muscle end plate disease.
spasmolytic
Skeletal muscle contraction is evoked by a ___ transmission process.
nicotinic cholinergic
One neuromuscular blocker used clinically is an agonist at the nicotinic end plate receptor (depolarizing type).
succinylcholine
- All agents are given parenterally.
- They are highly polar drugs and do not cross the blood-brain barrier.
- Drugs that are metabolized (eg, mivacurium, by plasma cholinesterase) or eliminated in the bile (eg, vecuronium) have shorter durations of action (10–20 min) than those eliminated by the kidney (eg, metocurine, pancuronium, pipecuronium, and tubocurarine), which usually have durations of action of less than 35 min.
Nondepolarizing Neuromuscular Blocking Drug
Nondepolarizing Neuromuscular Blocking Drug that At high blood levels, it may cause seizures.
laudanosine
A stereoisomer of atracurium, is also inactivated spontaneously but forms less laudanosine and currently is one of the most commonly used muscle relaxants in clinical practice.
Cisatracurium
Prototype drug that are neuromuscular blockers that are quaternary amines and structurally related to acetylcholine.
tubocurarine
- Nondepolarizing drugs prevent the action of ACh at the ____
- They act as ___ blockers → the blockade can be overcome by increasing the amount of agonist [ACh] in the synaptic cleft
- They behave as though they compete with ACh at the receptor, and their effect is reversed by ___ inhibitors.
- skeletal muscle end plate
- surmountable
- cholinesterase
Has the most rapid onset of available nondepolarizing drugs.
rocuronium (60-120Ss)
Is composed of 2 Ach molecules linked end to end. It is metabolized by cholinesterase (butyrylcholinesterase or pseudocholinesterase) in the liver and plasma. Acts like a nicotinic agonist and depolarizes the neuromuscular end plate.
Succinylcholine
Because tension cannot be maintained in skeletal muscle without periodic repolarization and depolarization of the end plate, continuous depolarization results in
muscle relaxation and paralysis
When given by continuous infusion, the effect of succinylcholine changes from continuous depolarization ___ to gradual repolarization with resistance to depolarization ____
- (phase I)
- (phase II)
The initial depolarization of succinylcholine is often accompanied by ___ (prevented by pretreatment with small doses of a nondepolarizing blocker).
twitching and fasciculations
This is best accomplished by administration of __ such as neostigmine or pyridostigmine.
cholinesterase inhibitors
The paralysis produced by the depolarizing blocker succinylcholine is __ by cholinesterase inhibitors during phase I. During phase II, the block produced by succinylcholine is usually ____ by cholinesterase inhibitors.
- increased
- reversible
The action of full doses of ___ leads directly to respiratory paralysis. If mechanical ventilation is not provided, the patient will asphyxiate.
neuromuscular blockers
Autonomic ganglia are stimulated by ___ and weakly blocked by ___.
- succinylcholine
- tubocurarine
Succinylcholine ____ cardiac muscarinic receptors, whereas pancuronium is a moderate blocking agent and causes
- activates
- tachycardia
Specific effects of succinylcholine
- Muscle pain
- hyperkalemia
- regurgitation with possible aspiration of gastric contents
Inhaled anesthetics, especially isoflurane, strongly ___ and ___ neuromuscular blockade.
- potentiate
- prolong
A rare interaction of succinylcholine (and possibly tubocurarine) with inhaled anesthetics can result in
malignant hyperthermia
A very early sign of this potentially life- threatening condition in succinylcholine is
contraction of the jaw muscles (trismus)
Are more sensitive to the actions of the nondepolarizing blockers, and doses should be reduced in these patients.
Older patients (>75 years) and those with myasthenia gravis
The goal of spasmolytic therapy in both chronic and acute conditions is reduction of excessive skeletal muscle tone without
reduction of strength
They act in the CNS and in one case in the skeletal muscle cell rather than at the neuromuscular end plate.
spasmolytic drugs
The spasmolytic drugs used in treatment of the chronic conditions mentioned previously include:
➢ a benzodiazepine
➢ a γ-aminobutyric acid (GABA) agonist
➢ a congener of clonidine
➢ an agent that acts on the sarcoplasmic reticulum of skeletal muscle
➢ diazepam, a benzodiazepine
➢ baclofen, a γ-aminobutyric acid (GABA) agonist
➢ tizanidine, a congener of clonidine
➢ dantrolene, an agent that acts on the sarcoplasmic reticulum of skeletal muscle.
Injected into selected muscles can reduce pain caused by severe spasm and also has application for ophthalmic purposes and in more generalized spastic disorders (eg, cerebral palsy).
Botulinum toxin
Gabapentin and pregabalin antiseizure drugs, have been shown to be effective spasmolytics in patients with
multiple sclerosis
Three of the drugs act in the spinal cord. All 3 drugs reduce the tonic output of the primary spinal motoneurons.
- baclofen,
- diazepam,
- tizanidine
Acts as a GABAB agonist at both presynaptic and postsynaptic receptors, causing membrane hyperpolarization. Presynaptically, by reducing calcium influx, it decreases the release of the excitatory transmitter glutamic acid; at postsynaptic receptors, baclofen facilitates the inhibitory action of GABA.
Baclofen
facilitates GABA-mediated inhibition via its interaction with GABAA receptors.
Diazepam
an imidazoline related to clonidine with significant α2 agonist activity, reinforces presynaptic inhibition in the spinal cord.
Tizanidine
acts in the skeletal muscle cell to reduce the release of activator calcium from the sarcoplasmic reticulum via interaction with the ryanodine receptor (RyR1) channel. Is also effective in the treatment of malignant hyperthermia.
Dantrolene
Causes somewhat less sedation than diazepam, and tolerance occurs with chronic use—withdrawal should be accomplished slowly.
Baclofen
may cause asthenia, drowsiness, dry mouth, and hypotension.
Tizanidine
causes significant muscle weakness but less sedation than either diazepam or baclofen.
Dantrolene
a typical member of this group, is believed to act in the brain stem, possibly by interfering with polysynaptic reflexes that maintain skeletal muscle tone. may cause confusion and visual hallucinations in some patients.
Cyclobenzaprine
Patients with___ often have decreased levels of plasma cholinesterase, thus prolonging the duration of action of mivacurium or succinylcholine.
renal failure
Which of the following drugs is the most effective in the emergency management of malignant hyperthermia?
Dantrolene
The clinical use of succinylcholine, especially in patients with diabetes, is associated with
(A) Antagonism by pyridostigmine during the early phase of blockade
(B) Aspiration of gastric contents
(C) Decreased intragastric pressure
(D) Histamine release in a genetically determined population
(E) Metabolism at the neuromuscular junction by acetylcholinesterase
Aspiration of gastric contents
Myalgias are a common postoperative complaint of patients who receive large doses of succinylcholine, possibly the result of muscle fasciculations caused by depolarization. Which drug administered in the operating room can be used to prevent postoperative pain caused by succinylcholine?
Cisatracurium
