Transcript Chapter_016
Chapter 16
Drugs That Block Nicotinic Cholinergic
Transmission: Neuromuscular Blocking
Agents and Ganglionic Blocking Agents
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Neuromuscular Blockers
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
Basic concepts (see Fig. 16-1)
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
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Fig. 16-1. The depolarization-repolarization cycle of the motor end-plate and muscle membrane.
(ACh = acetylcholine.)
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Fig. 16-2. Steps in excitation-contraction coupling.
(ACh = acetylcholine.)
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Competitive Neuromuscular
Blockers I: Tubocurarine
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
Mechanism of action
Quaternary nitrogen atom
Competes with ACh for nicotinicM receptors
Pharmacologic effects
Muscle relaxation: flaccid paralysis
Hypotension
Central nervous system
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Competitive Neuromuscular Blockers
Pharmacokinetics
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
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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.
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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.
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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
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
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