Week 9: Neuromuscular Blocking Agents

Spasmolytics:

Centrally acting muscle relaxants that reduce muscle hyperactivity

Neuromuscular blockers:

Peripherally acting muscle relaxants that induce muscle paralysis

Are neuromuscular blockers used routinely in the dental office?

No, they are only administered by clinicians with access to resp/cardio resuscitation

What are neuromuscular blockers used for?

Intubation for general anesthesia

Primary neurotransmitter at the neuromuscular junction:

Acetylcholine

What receptor is targeted at the neuromuscular junction?

Nicotinic cholinergic receptor

What happens when the postsynaptic membrane is activated at the NMJ?

Depolarization occurs and the signal propagates along the muscle fiber

What happens when the NMJ is blocked?

Signal propagation along the muscle fiber is prevented

Non-depolarizing neuromuscular blockers:

Large molecules with variable onset and medium to long duration that inhibit ACh receptors

Examples of non-depolarizing neuromuscular blockers:

d-tubocurarine, atracurium, mivacurium, pancuronium, vecuronium, rocuronium

Depolarizing neuromuscular blocker:

Succinylcholine(Suxamethonium)

Rapid onset and short duration

d-Tubocurarine:

Prototype non-depolarizing NM blocker, not commonly used due to side effects

What are side effects of d-tubocurarine?

Hypotension from autonomic ganglia blockade and mast cell histamine release

Pancuronium:

Non-depolarizing NM blocker that moderately increases heart rate, has no histamine release, and no ganglion blockade

How is pancuronium eliminated from the body?

excreted by kidney with minimal hepatic metabolism

Vecuronium:

Non-depolarizing NM blocker with very little vagolytic, histaminic, or ganglionic activity

Atracurium:

Non-depolarizing NM blocker removed by Hoffman elimination, so it is unaffected by renal or hepatic impairment

Causes histamine release

Cisatracurium:

Isomer of atracurium that is more potent and does not cause histamine release

Mivacurium:

Fast onset, non-depolarizing NM blocker with histamine release, no cardiac effects, and elimination by plasma cholinesterases

Rocuronium:

non-depolarizing NM blocker with very rapid onset, hepatic excretion, and no histamine release

Why does rocuronium have rapid onset?

less potent NM blockers have faster onset

What consideration is important with rocuronium and pts with hepatic impairment?

use caution in patients with hepatic impairment (because of hepatic excretion)

What are the cardiovascular ADRs of NM blockers?

Hypotension from histamine release and tachycardia

What are the respiratory ADRs of NM blockers?

Prolonged apnea and bronchospasm from histamine release

What is a major ADR of neuromuscular blockers overall?

Excessive histamine release

What drug interactions can potentiate NM blockers?

some inhalation anesthetics and drugs that inhibit presynaptic ACh release

Sugammadex:

Reversal agent for aminosteroidal "-curonium" drugs

Reverses block without systemic cholinesterase inhibition

Neostigmine:

Acetylcholinesterase inhibitor used to reverse effects of neuromuscular blockers

Succinylcholine:

Depolarizing NM blocker also called suxamethonium chloride

What are brand names for succinylcholine?

Anectine, Quelicin, Sucostrin

How does succinylcholine work?

Persistent stimulation and depolarization of muscle while maintaining the ion channel open

Is succinylcholine antagonized by acetylcholinesterase inhibitors?

No

Phase I succinylcholine action:

Initial depolarization causes muscle contractions/fasciculations for 30-60 seconds, followed by flaccid paralysis for 5-10 minutes

Phase II succinylcholine action:

Continued long term exposure allows slow repolarization but no further depolarization while drug is present

*Long exposure not common clinically

What are adverse effects of succinylcholine?

Bradycardia, hyperkalemia, respiratory failure, postoperative muscle pain, histamine release

Malignant hyperthermia:

Dangerous overheating from excessive muscle contraction/metabolism associated with succinylcholine

Dantrolene:

treats malignant hyperthermia by inhibiting calcium release in muscle

What is succinylcholine contraindicated in?

Eye injury

Botulinum toxin/Botox:

Blocks acetylcholine release and causes long-lasting local blockade for weeks to months

What is botox used for in ophthalmology?

Correcting ocular deviations

What are dental concerns with Botox?

Xerostomia, facial pain, local paralysis

What is the Botox mechanism?

Botulinum neurotoxin cleaves SNARE proteins and prevents acetylcholine release