Drugs that affect skeletal muscle function include which two different therapeutic groups?
used during surgical procedures and in the intensive care unit (ICU) to produce muscle paralysis
those used to reduce spasticity in a variety of painful conditions
____________________ interfere with transmission at the neuromuscular end plate and lack central nervous system (CNS) activity
neuromuscular blocking drugs
How else can neuromuscular blocking drugs be used?
Adjuncts during general anesthesia to optimize surgical conditions and to facilitate endotracheal intubation in order to ensure adequate ventilation
NMB drugs structurally resemble which neurotransmitter?
__________ is a depolarizing agent.
Succinylcholine is a depolarizing agent.
What are you the 2 major families of nondepolarizing agents and the drugs beneath them?
Drug class: Isoquinoline
Drug class: steroid derivatives
Which domains on the nicotinic acetylcholine receptror (nAChR) line the channel pore?
Where do the binding pockets for ACh occur?
α-β and the δ-α subunit interfaces
This drug occupies the receptor AND blocks the channel.
Normal closure of the channel gate is prevented and the blocker may move rapidly in and out of the pore.
This drug may desensitize the end plate by occupying the receptor and causing persistent depolarization.
Which drug is this?
An additional effect of drugs on the end plate channel may occur through changes in the _____________ surrounding the channel.
General anesthetics and alcohols may impair ________________ by this mechanism
An additional effect of drugs on the end plate channel may occur through changes in the lipid environment surrounding the channel.
General anesthetics and alcohols may impair neuromuscular transmission by this mechanism.
What are the names of the idoquinoline derivatives?
What are the names of the steroid derivatives?
Which isoquinoline derivative has spontaneous elimination?
Drugs that are excreted by the _________ typically have longer half-lives, leadring to longer durations of action (>35 minutes).
Drugs that are excreted by the kidney typically have longer half-lives, leadring to longer durations of action (>35 minutes).
Drugs eliminated by the________tend to have shorter half-lives and durations of action.
Drugs eliminated by the liver tend to have shorter half-lives and durations of action.
Rapid initial distribution phase followed by a slower elimination phase.
PK of which drugs?
What is succinylcholine mainly used for?
Used clinically for rapid endotracheal intubation
Opens the ion channels causing depolarization and generation of a muscle action potential which results in brief contractions (fasiculations)
This drug is not hydrolyzed efficiently by junctional AChE
Persists at the nAChR resulting in sustained local muscle endplate depolarization
Causes the voltage-gated Na channel to remain in the inactive state for a prolonged period
Becomes refractory to further presynaptic release of Ach, and flaccid paralysis results
MOA: Agonist at nicotinic acetylcholine (ACh) receptors, especially at neuromuscular junctions depolarizes
May stimulate ganglionic nicotinic ACh and cardiac muscarinic ACh receptors
Initial depolarization causes transient contractions, followed by prolonged flaccid paralysis
Depolarization is then followed by repolarization that is also accompanied by paralysis
Effects of which drug?
What are the 2 clinical applications of succinylcholine?
1. placement of endotracheal tube at start of anesthetic procedure
2. rarely, control of muscle contractions in status epilepticus
PK of Succinylcholine
Rapid metabolism by plasma cholinesterase: normal duration ~5 minutes
What are the 4 toxicities of succinylcholine?
transient increased intra-abdominal, intraocular pressure
postoperative muscle pain
What are the 2 uses of non-depolarizing neuromuscular blockades Tubocuraine & Pancuronium?
maintain skeletal muscle relaxation during surgery
competitively inhibit normal channel activation preventing muscle cell depolarization, causing flaccid paralysis
Small rapidly moving muscles of the face and eyes are affected first followed by fingers, toes, extremities, trunk, intercostals and lastly the diaphragm
MOA of which drug?
Non-depolarizing neuromuscular blockade: Tubocuraine and Pancuronium
How can the action of Tubocuraine and Pancuronium be overcome?
By increasing the amount of ACh in the synaptic cleft: administer cholinesterase inhibitors like neostigmine or pyridostigmine to shorten the duration of neuromuscular blockade
Which class of drugs are usually co-administered with cholinesterase inhibitors?
What are the names of these drugs?
What is the benefit of this coadministration?
Muscarinic receptor antagonists: atropine or glycopyrrolate
Benefit of coadministration: voids the bradydysrhythmias associated with agonism of the cardiac muscarinic receptors