1.6 Neuromuscular and Ganglionic Blockers

Jackson be fr rn

cholinergic agents/ agonists

parasympathomimetics

cholinergic blocking/antagonists

parasympatholytic

adrenergic agent/agonists

sympathomimetic

adrenergic blockers/antagonists

sympatholytic

clinical relevance of neuromuscular and ganglionic blocking agents

muscle relaxation in surgery, facilitation of intubation and ventilation, tx of malignant hyperthermia, nad HTN emergencies

muscle relaxants can either be ____ or _____ acting

peripherally or centrally

explain the presynaptic events in the Neuromuscular junction

Na, K, and Ca currents flow and lead to Ca influx, which leads to vesicle exocytosis and release of Ach into the celf

explain the cleft events in the Neuromuscular junction

ACh diffuses and is either hydrolyzed by AChE or binds to receptors

what does AChE do to ACh

it inactivates our girl via hydrolysis

explain the postsynaptic events in the Neuromuscular junction

ACh binds to Nicotinic M receptors causing Na and K channels to open, leading to depolarization, which leads to an AP, which finally leads to muscle contraction

peripherally acting muscle relaxant subcategories

depolarizing, nondepolarizing, and direct acting

example of a depolarizing peripherally acting muscle relaxant

succinylcholine

classification of succinylcholine

depolarizing peripherally acting muscle relaxant

examples of nondepolarizing peripherally acting muscle relaxant

tubocurarine, pancuronium, vercuronium, rocuronium

classification of tubocurarine, pancuronium, vercuronium, rocuronium

nondepolarizing peripherally acting muscle relaxant

examples of direct acting peripherally acting muscle relaxants

dantrolene and quinine

classification of dantrolene

direct, peripheral acting muscle relaxant

classification of qunine

direct, peripheral acting muscle relaxant

examples of centrally acting muscle relaxants

Chlorzoxazone, Diazepam, Baclofen, Tizanidine, Metaxalone

classification of Chlorzoxazone

centrally acting muscle relaxant

classification of Diazepam

centrally acting muscle relaxant

classification of Baclofen

centrally acting muscle relaxant

classification of Tizanidine

centrally acting muscle relaxant

classification of Metaxalone

centrally acting muscle relaxant

non depolarizing muscle relxants can be further categorized as…

short acting, intermediate acting, and long acting

indications of non-depolarizing neuromuscular blockers (peripherally acting)

adjuvants to surgical anesthesia

intubation

precurarization

indications of depolarizing neuromuscular blockers (peripherally acting)

rapid intubation

electroshock therapy

effect on competitive neuromuscular blockers when extra ACh is added

reverses the effects of the blocker by increases the odds of ACh binding to receptors instead of the blockers

effect on non-competitive neuromuscular blockers when extra ACh is added

instead of reversing the effects, it actually further desensitizes the receptor so there is an increased blocking effect

when is tubocurarine used? (indication)

surgery adjunct to relax muscle and increase safety anesthetics

tubocurarine _____ cross the BBB

does not

what is the prototype to new non-depolarizing competitive muscle relaxants

tubocurarine

MOA of tubocurarine in small doses

act predominantly at nicotinic receptor sites (blocks post synaptic receptors)

MOA of tubocurarine in high doses

blocks prejunctional Na channels (decreases ACh release)

tubocurarine’s effects can be reversed by..

increasing ACh or giving an AChE inhibitor

tubocurarine can ______ the sympathetic nervous system

suppress

tubocurarine can cause ____ in histamine concentration due to ____

increases; mast cell degranulation

when succinylcholine is contraindicated, which drug can be used instead?

rocuronium

tubocurarine is used for precurarization to prevent ____ due to succinylcholine

postoperative myalgias

tubocurarine is used for precurarization to prevent postopertative myalgias due to _____

succinylcholine

tubocurarine admin

IV due to poor oral bioavailability

ADE of tubocurarine

release of histamine from mast cells which decreases BP and causes bronchospasms

drug interactions of nondepolarizing neuromuscular blockers

aminoglycosides, AChEi, CCBs, halogenated carbon anesthetics

why are aminoglycosides contraindicated with non-depolarizing neuromuscular blockers

they decrease ACh release by competing with Ca

why are CCBS contraindicated with non-depolarizing neuromuscular blockers

increase the actions of non-depolarizing drugs by decreasing ACh release

why are halogenated carbon anesthetics contraindicated with non-depolarizing neuromuscular blockers

they decrease excitability further and decrease BP

noncompetitive neuromuscular depolarizing agents

ACh and succinylcholine

what is desensitization block

when the receptor channels become unresponsive to an agonist which prevents the opening of the channel even when the agonist is bound

indications of succinylcholine

endotracheal intubations

electro shock therapy

adjuvant to anesthesia

ADE of succinylcholine

apnea, fasciculations (twitching), myocyte rupture, myalgia, potassium extravasation, sinus bradycardia, malignant hyperthermia (if have inherited trait)

what is the prototype for depolarizing agents

succinylcholine

succinylcholine is the prototype of…

depolarizing neuromuscular blockers

MOA of succinylcholine (phase I)

cholinergic channels open —> depolarization of membrane —> muscle fasciculation(twitching)

MOA of succinylcholine phase II

end plate eventually repolarizes, succinylcholine continues to occupy the cholinergic receptor to desensitize the end plate

the blocking effects of succinylcholine is augmented by…

AChE inhibitors

therapeutic uses for depolarizing neuromuscular blockers

adjuvant drugs in surgical anesthesia

depolarizing neuromuscular blocking agents duration of action

short bc it is rapidly broken down by plasma cholinesterases

if depolarizing neuromuscular blocking agents are given with _____ it could lead to malignant hyperthermia if they have the inherited trait

halothane

if depolarizing neuromuscular blocking agents are given with halothane it could lead to_____

malignant hyperthermia (inheirted disease)

malignant hyperthermia is only going to occur if…

succinylcholine and halothane are co-admin ANDDDDDD if the person has the inherited autosomal dominant condition

tx for the inherited malignant hyperthermia due to succinylcholine and halothane co-admin

rapid cooling of the body and admin of dantrolene

how does dantrolene work

interferes with EC coupling by decreasing Ca efflux from the SR

depolarizing muscle relaxants depolarize the…

end plate nicotinic receptor

succinylcholine has a ____ duration due to plasma cholinesterases

short

most common side effect of succinylcholine

muscle pain

contraindications of succinylcholine

neuromusclar disease

denervation

immobilization

burns

malignant hyperthermia susceptibility

sepsis

infection

allergy to succinylcholine

succinylcholine drug interactions

inhaled anesthetics, AMGs, CCBs, opioids, lidocaine, pheytoin

succinylcholine interaction with inhaled anesthetics

produce synergistic neuromuscular blockade with these agents.

succinylcholine interaction with AMGs

decreases ACh release from cholinergic nerves to produce additive neuromuscular blockade

succinylcholine interaction with CCBs

may decrease availability of Ca ion for contraction and enhance the effects of neuromuscular blockers

what is the ONLY ganglionic blocker

mecamylamine

mecamylamine class

competitive nicotinic ganglionic blocker

mecamylamine is_____ acting (long or short)

short

mecamylamine must be given ____ bc it is short acting

IV

indication of mecamylamine

lower BP in emergencies

preggo hoes might have less plasma cholinesterases so action of neuromuscular blockers might be _____ (increased or decreased)

increased

preggo hoes might have ______ (more or less) plasma cholinesterases so action of neuromuscular blockers might be increased

less

pts with hepatic or renal issues may have altered elimination of which type of neuromuscular blocker

non-depolarizing

pts with burns are resistant to which type of neuromuscular blocker

non-depolarizing

pts with burns are sensitive to which type of neuromuscular blocker and why

succinylcholine bc it can lead to hyperkalemia