Neuromuscular Blocking Drugs

These flashcards cover key terms and concepts related to neuromuscular blocking drugs and their pharmacological effects, mechanisms of action, types, adverse effects, and clinical uses.

Types of Skeletal Muscle Relaxants

peripherally acting muscle relaxants (NM blockers)

centrally acting muscle relaxants

directly acting muscle relaxants

Action of Peripherally Acting Muscle Relaxants (NM Blockers)

interfere with transmission at NM junction

no CNS activity

Uses for Peripherally Acting Muscle Relaxants (NM Blockers)

adjunct to general anesthesia during surgery to optimize conditions

ET intubation in ICUs

Subtypes of Peripherally Acting Muscle Relaxants (NM Blockers)

Competitive/Non-Depolarizing

Non-Competitive/Depolarizing

Examples of Competitive/Non-Depolarizing Blockers (Peripheral)

d-tubocurarine

anything with cur in the name (-curonium or -curium)

M/A of Competitive/Non-Depolarizing Blockers (Peripheral)

tubocurarine binds to and blocks NM receptors

competitive blockage of ACh action, causes skeletal muscle relaxation

Skeletal Muscle Effects: Competitive/Non-Depolarizing Blockers (Peripheral)

IV injection causes motor weakness and flaccidity

fast small muscles first impacted, then larger muscles

diaphragm impacted last

recovery is diaphragm, then larger muscles, then fast small muscles

no soreness on recovery

Cardio Effects: Competitive/Non-Depolarizing Blockers (Peripheral)

hypotension from ganglion blockade, histamine release, decreased venous return from limb muscle paralysis

Histamine Release Effects: Competitive/Non-Depolarizing Blockers (Peripheral)

d-tubocurarine produces weak ganglion blockade

pancuronium causes moderate M2 blockade (vagolytic causes tachycardia)

Respiratory Effects: Competitive/Non-Depolarizing Blockers (Peripheral)

bronchospasm from histamine release

GI Effects: Competitive/Non-Depolarizing Blockers (Peripheral)

decreased tone and motility causing constipation

Features of Competitive/Non-Depolarizing Blockers (Peripheral)

QACs

does not cross blood brain OR placental barriers (safe for C section)

no CNS side effects

no pharmacogenetic variation

Features of Atracurium & Cisatracurium (Peripheral)

spontaneous Hoffman’s elimination

metabolite laudanosine crosses blood brain barrier and causes seizure

Adverse Effects of Competitive/Non-Depolarizing Blockers (Peripheral)

hypoxia and respiratory paralysis

hypotension and bronchospasm from histamine

constipation

Example of Non-Competitive/Depolarizing Blocker (Peripheral)

Succinylcholine

Succinylcholine Mechanism of Action

affinity and submaximal intrinsic activity

produces biphasic block on prolonged exposure and high doses

Sch Phase 1 (Depolarizing) Block

depolarize end plate by opening Na channels

does not dissociate rapidly from receptor (resistant to acetylcholinesterase)

induces longer depolarization with brief period of repetitive excitation causing transient muscle contraction (twitching and fasciculations)

followed by inactivation of Na channels to prevent EP repolarization

Ach released cannot generate ATP, leads to flaccid paralysis

Sch Phase 2 (Non-Depolarizing) Block

higher doses over time convert Phase 1 to Phase 2

no depolarization, can be reversed by acetylcholinesterase

Skeletal Muscle Effects: Succinylcholine

fasciculations over the chest and abdomen 30 seconds after 1 dose IV

complete relaxation in 1-2 minutes

muscle soreness on recovery

Serum K Effects: Succinylcholine

hyperkalemia

Eye Effects: Succinylcholine

rapid rise in intraocular pressure

GI Effects: Succinylcholine

increased intragastric pressure

Features of Succinylcholine

QAC

genetic variation in metabolism

5-10 minutes duration of action

Sch apnea

abnormal enzyme activity detected by dibucaine number

Why is the duration for Succinylcholine ultrashort?

rapid hydrolysis by pseudocholinesterase in plasma and butyrylcholinesterase in liver

Sch Apnea

NM blockade by Sch prolonged by atypical pseudocholinesterase found in some people causing prolonged apnea

Adverse Effects of Succinylcholine

hyperkalemia

Sch apnea

increased intragastric pressure

increased intraocular pressure

muscle soreness

malignant hyperthermia

Malignant Hyperthermia from Succinylcholine

ryanodine receptor mutation

treat with dantrolene and rapid cooling

QAC

polar and ionized

not absorbed orally, given IV

does not cross placenta or blood brain barriers

Clinical Use of All Peripheral Muscle Relaxants

adjuvant to general anesthesia (skeletal muscle relaxation during surgery and ET intubation)

atracurium and ciastracurium used as adjuvant in patients with renal or hepatic insufficiency

prevent trauma during ECT

treat convulsions and spastic conditions

control mechanical ventilation

Reversal of NM Blockade for Competitive/Non-Depolarizing Blockers

neostigmine or pyridostigmine inhibits acetylcholinesterase (increases ACh availability)

causes reversal of block

used with long and intermediate acting agents

Reversal of NM Blockade for Succinylcholine

neostigmine potentiates phase 1 block

can potentially reverse only phase 2 block

Succinylcholine DDIs

halothane and isoflurane aggravate malignant hyperthermia

calcium channel blockers and antiarrhythmics can potentiate NM blockade

Competitive/Non-Depolarizing Blocker DDIs

aminoglycosides

calcium channel blockers

antiarrhythmics

diuretics (hypokalemia)

Subtypes of Centrally Acting Muscle Relaxants

spasmolytics

antispasmodic

Centrally Acting Muscle Relaxants

cause partial muscle relaxation by acting on the motor endplate

Types of Spasmolytics

GABA-B agonist

Central a2 agonist

GABA-A Chloride ion channel complex facilitator

glutaminergic transmission inhibitor

Example of GABA-B Agonist

baclofen

Example of Central a2 Agonist

tizanidine

Example of GABA-A Chloride Ion Channel Complex Facilitator

diazepam

Example of Glutaminergic Transmission Inhibitor

riluzole

Directly Acting Muscle Relaxants

dantrolene

BoTox

Dantrolene Uses

malignant hyperthermia due to halothane and succinylcholine

neuroleptic malignant syndrome due to antipsychotic agents

Dantrolene Mechanism of Action

binds and blocks ryanodine receptors, inhibiting calcium release from SR

inhibits muscle contraction, leads to skeletal muscle relaxation

Botulinum Mechanism of Action

directly injected into muscle

prduces local paralysis by inhibiting presynaptic ACh release at NMJ

FDA Approved Botulinum Uses

strabismus, blepharospasm

cervical or focal dystonias

tic disorders

facial wrinkles

migraine

stroke or TBI spasticity

Off Label Botulinum Uses

low back pain

neuropathic pain

palmar/axillary hyperhidrosis

TMJ disorders

sialorrhea