Chapter_016

Report
Chapter 16
Drugs That Block Nicotinic Cholinergic
Transmission: Neuromuscular Blocking
Agents and Ganglionic Blocking Agents
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Neuromuscular Blockers
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Prevent acetylcholine from activating
nicotinicM
Cause muscle relaxation (paralysis)
No oral forms
Cannot cross


Blood-brain barrier
• No impact on CNS (paralysis, not sedation)
Placenta
• Minimal effects on fetus
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Control of Muscle Contractions
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Basic concepts (see Fig. 16-1)
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Polarization
Depolarization
Repolarization
Steps in muscle contraction (see Fig. 16-2)
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Classification of Neuromuscular
Blocking Agents
Competitive
Competitive
Depolarizing
neuromuscular
blockers I:
tubocurarine
(no longer used)
neuromuscular
blockers II: others
neuromuscular
blockers:
succinylcholine
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Fig. 16-1. The depolarization-repolarization cycle of the motor end-plate and muscle membrane.
(ACh = acetylcholine.)
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Fig. 16-2. Steps in excitation-contraction coupling.
(ACh = acetylcholine.)
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Competitive Neuromuscular
Blockers I: Tubocurarine



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Oldest competitive neuromuscular blocker
(NMB)
No longer used in United States
Replaced by newer NMBs
One of active principles found in curare, a
poison used by primitive arrow hunters
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Competitive Neuromuscular Blockers

Chemistry
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Mechanism of action
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
Quaternary nitrogen atom
Competes with ACh for nicotinicM receptors
Pharmacologic effects



Muscle relaxation: flaccid paralysis
Hypotension
Central nervous system
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Competitive Neuromuscular Blockers

Pharmacokinetics
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Rapid onset of paralysis
Adverse effects


Respiratory arrest
Cardiovascular effects
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Competitive Neuromuscular
Blockers I: Tubocurarine

Precautions and contraindications



Myasthenia gravis
Electrolyte disturbances
Drug interactions



General anesthetics
Antibiotics
Cholinesterase inhibitors
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Competitive Neuromuscular
Blockers I: Tubocurarine

Toxicology

Overdose
• Prolonged apnea, massive histamine release, and
cardiovascular collapse

Preparations, dosage, and administration

No longer used in the United States
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Competitive Neuromuscular
Blockers II: Others
Long-acting
agents
Intermediateacting agents
Short-acting
agents
• Doxacurium
• Metocurine
• Pipecuronium
• Cisatracurium
• Pancuronium
• Rocuronium
• Vecuronium
• Mivacurium
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Fig. 16-3. Structural formulas of representative neuromuscular blocking agents.
Note that all of these agents contain quaternary nitrogen atoms and therefore cross membranes
poorly. Consequently, they must be administered parenterally and have little effect on the central
nervous system or a developing fetus.
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Fig. 16-4. Mechanism of competitive neuromuscular blockade.
Tubocurarine competes with acetylcholine (ACh) for binding to nicotinicM receptors on the motor end-plate. Binding of
tubocurarine does not depolarize the end-plate and therefore does not cause contraction. At the same time, the
presence of tubocurarine prevents ACh from binding to the receptor, hence contraction is prevented.
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Depolarizing Neuromuscular
Blockers: Succinylcholine


Mechanism of action
Pharmacologic effects




Pharmacokinetics


Ultrashort-acting
• (peak 1 min, fades 4–10 min)
Muscle relaxation
Central nervous system
Eliminated by plasma cholinesterases
Therapeutic uses

Muscle relaxation during intubation
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Depolarizing Neuromuscular
Blockers: Succinylcholine

Adverse effects




Prolonged apnea in patients with low
pseudocholinesterase activity
Malignant hyperthermia
Postoperative muscle pain
Hyperkalemia
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Depolarizing Neuromuscular
Blockers: Succinylcholine

Drug interactions




Cholinesterase inhibitors
Antibiotics
Toxicology
Preparations, dosage, and administration
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Therapeutic Uses of
Neuromuscular Blockers
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
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Muscle relaxation during surgery
Facilitation of mechanical ventilation
Adjunct to electroconvulsive therapy
Endotracheal intubation
Diagnosis of myasthenia gravis
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Ganglionic Blocking Agents




Mechanism of action
Pharmacologic effects
Pharmacokinetics
Therapeutic use


Adverse effects
• Antimuscarinic effects
• Orthostatic hypotension
• CNS effects
Preparations, dosage, and administration
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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