Pharmacology Of NMJ + NMJ CIS Flashcards
_________ is a drug/primary neurotransmitter at cholinergic nerve endings (preganglionic ANS, postganglionic parasympathetic, postganglionic sympathetic to thermoregulatory sweat glands, and somatic neuromuscular end plates
Acetylcholine
__________ = sympathomimetic drug that facilitates the release of catecholamines from adrenergic nerve endings
Amphetamine
_______ _______ is a bacterial toxin that enzymatically disables release of acetylcholine from cholinergic nerve endings
Botulinum toxin
What early neuromuscular blocking agent was one of the first used for muscular relaxation in general anesthesia and later led to the development of compounds like gallamine and pancuronium?
Curare
What are some of the ways that neuromuscular blockers are classified?
Mechanism of action Duration of action Speed of onset and offset of action Selectivity of action and safety margin Adverse effects
What type of NMJ blocking agent is curare?
Competitive (non-depolarizing)
Competitive (non-depolarizing) agents like curare operate by competing with ACh for binding to the receptor.
What type of paralysis do they cause?
Flaccid, relaxed paralysis
Competitive (non-depolarizing) agents like curare operate by competing with ACh for binding to the receptor.
What are some non-NMJ effects caused by these agents?
Ganglia, muscarinic blocking, histamine release
Competitive (non-depolarizing) agents like curare operate by competing with ACh for binding to the receptor.
How is this type of NMJ block reversed?
Acetylcholinesterase inhibitors
What type of NMJ blocking agent is succinylcholine?
Non-competitive (depolarizing)
What are the 2 phases associated with the MOA of non-competitive (depolarizing) NMJ blocking agents like succinylcholine?
Phase 1 block: membrane depolarization; transient fasciculations followed by paralysis
Phase 2 block: desensitization; membrane repolarizes, hyposensitive to ACh
T/F: Both competitive and non-competitive NMJ blocking agents can be reversed by administering acetylcholinesterase inhibitors
False; competitive inhibitors CAN be reversed by AChE inhibitors, but non-competitive CANNOT
What is the progression of paralysis due to blocking the NMJ? In what order do these muscles recover?
Small rapidly moving muscles (eyes, fingers), then limbs, the last is respiratory muscles
These are recovered in reverse order
General poisoning due to ________ occurs after ingestion of various species of puffer fish. It is lethal even in small doses
Tetradotoxin
What is the MOA of tetradotoxin?
Tetradotoxin blocks diffusion of sodium through sodium channels, thus preventing depolarization and propagation of action potentials in nerve cells
All of the observed toxicity of tetradotoxin is secondary to blockade of the _______ _________. It acts on the central and peripheral nervous systmes.
In recent studies using tetradotoxin therapeutically in conjunction with __________, local anesthetic effect can be prolonged.
However, clinical use of tetradotoxin may increase the incidence of toxicity
Action potential
Bupivacaine
What agent affecting the action nerve potential produces COMPLETE sensory block, and its effect on motor function differs with varying concentrations?
Bupivacaine
Which of the following would you use to provide motor blockade for caudal, epidural, or nerve block, but muscle relaxation may be inadequate for operations in which complete muscle relaxation is ESSENTIAL?
A. 0.25% Bupivacaine B. 0.5% Bupivacaine C. 0.75% Bupivacaine D. 0.5% Tetradotoxin E. 0.75% Tetradotoxin
B. 0.5% Bupivacaine
Which of the following agents would you use for caudal, epidural, or peripheral nerve block to produce incomplete motor block in which muscule relaxation is not important?
A. 0.25% Bupivacaine B. 0.5% Bupivacaine C. 0.75% Bupivacaine D. 0.5% Tetradotoxin E. 0.75% Tetradotoxin
A. 0.25% Bupivacaine
Which of the following would you use to produce complete motor block, especially when performing epidural block in abdominal operations requiring complete muscle relaxation?
A. 0.25% Bupivacaine B. 0.5% Bupivacaine C. 0.75% Bupivacaine D. 0.5% Tetradotoxin E. 0.75% Tetradotoxin
C. 0.75% Bupivacaine
[note that you would NOT use this for epidural anesthesia for obstetrical procedures]
A major cause of adverse reactions to ________ include excessive plasma levels, overdose, unintentional intravascular injection, or slow metabolic degradation
Bupivacaine
What are some drug interactions associated with bupivacaine?
Patients taking MAOIs or TCAs may produce severe, prolonged hypertension
Concurrent use of these agents should generally be avoided and careful patient monitoring is essential
What are the 2 agents discussed in class that affect vesicular acetylcholine release?
Botulinum toxin
Tetanus toxin
What produces botulinum toxin?
Clostridium botulinum, a gram-positive anaerobic bacteria
