NEUROMUSCULAR BLOCKING AGENTS

PGI GUZMAN, RUBY JOAN

 POSTSYNAPTIC MOTOR
NEURON

NICOTINIC ACETYLCHOLINE RECEPTORS

(nAChRs)

q Located in the folds of the

postsynaptic muscle
membrane in very high
concentrations
q Found preferentially at the end
plate, on the crest of the
membrane invaginations
(folds) a2Bo
q “Fetal” or “Immature”
q “Mature” or “adult:”
q Alpha-recognition site
RECEPTOR UP- AND DOWNREGULATION
RECEPTOR UPREGULATION
Ø Number of immature (fetal) nAChRs increases
Ø Immature nAChRs have increased
sensitivity to agonists, and decreased
sensitivity to nondepolorizing NMBAs
Ø May allow systemic release of lethal doses of
intracellular K in response to administration of
SCh
RECEPTOR DOWNREGULATION
Ø Mature AChRs downregulate during periods of
sustaines agonist stimulation or organophosphate
poisoning
Ø Increased resistance to AGONIST (SCh), but
extreme sensitivity to nondepolorizing
NMBAs
Ø May allow systemic release of lethal doses of
intracellular K in response to administration of SCh
PHARMACOLOGIC CHARACTERISTICS

Determined by the dose required to produce a certain effect

POTENCY and is calculated from dose-response sigmoidal curve
> Effect (response) : DEPRESSION OF NORMAL
MUSCLE CONTRACTION

ONSET OF The time from drug administration until maximal neuromuscular

block.
ACTION > Can be affected by: rate of delivery to the site of action,
receptor affinity, drug potency, mechanism of action and plasma
clearance

DURATION Time from IV drug administration until spontaneous recovery of

of ACTION ST to 25% of baseline (normal) strength

(DUR 25%) TOTAL DURATION OF

ACTION RECOVERY INDEX
- Time from drug administration - Time of spontaneous recovery of
until spontaneous recovery of TOF ST from 25% to 75% of control
ration to 0.90 (DUR 0.90)
NEUROMUSCULAR
BLOCKERS
DEPOLARIZING NMBA

SUCCINYLCHOLINE: “Ideal” NMBA

üSCh is the only depolarizing NMBA available clinically.
üindicated for rapid attainment of optimal intubating conditions
and prevention of regurgitation and pulmonary aspiration of
gastric contents in patients at risk in the "rapid sequence
induction and intubation" (RSI) scenario.
DEPOLARIZING NMBA

SUCCINYLCHOLINE: “Ideal” NMBA

ü Fastest onset, (1 minute at 1.5 mg/kg)
ü Shortest duration, (5 to 10 minutes at 1 mg/kg dose),
ü and Greatest reliability (i.e., narrowest onset variability
around the mean) of any NMBA.
DEPOLARIZING NMBA

SUCCINYLCHOLINE
DEPOLARIZING NMBA

SUCCINYLCHOLINE: SIDE EFFECTS

o Significant bradycardia and asystole

o Premature ventricular escape beats
o Fasciculations (80-90%)
o Myalgia

• Small dose of non-depolarizing NMBA (10% ED95)

• 5 to 10 mg of SCh : “”Self taming”
• NSAID (aspirin or diclofenac)
DEPOLARIZING NMBA

SUCCINYLCHOLINE: SIDE EFFECTS

o Significant bradycardia and asystole
o Premature ventricular escape beats
o Fasciculations (80-90%)
o Myalgia
o Increased IOP
o Increased ICP
o Malignant Hyperthermia
o Masseter muscle spasm
o Allergic reactions (Anaphylaxis)
DEPOLARIZING NMBA

SUCCINYLCHOLINE

BLACK BOX Warning on the use of SCh in

PEDIATRIC population.
SCh should only be used for emergency
tracheal intubation.
DEPOLARIZING NMBA

SUCCINYLCHOLINE: CONTRAINDICATIONS
o History of MH
o States of receptor upregulation
• Potential for lethal hyperkalemia
• Critical care patients or immobilized for prolonged periods
• Psuedocholinesterase deficiency
 NON-DEPOLARIZING NMBA

NONDEPOLARIZING

AMINOSTEROID BENZYLISOQUINOLINIUM

INTERMEDIATE- INTERMEDIATE-
ULTRALONG LONG-ACTING ULTRALONG SHORT-ACTING
ACTING ACTING
NON-DEPOLARIZING NMBA

PANCURONIUM
AMINOSTEROID • LONG-ACTING with high predilection for
significant accumulation
• Vagolytic effects and direct sympathomimetic
effects
INTERMEDIATE-
• Blocks norepinephrine presynaptic uptake
ULTRALONG LONG-ACTING ACTING • Obsolete because of significant risk of
postop residual neuromuscular weakness

PIPERUCONIUM
PIPECURONIUM PANCURONIUM VECURONIUM ROCURONIUM • Structurally similar to Pancuronium and
Veruconium
NON-DEPOLARIZING NMBA

VECURONIUM
AMINOSTEROID • Devoid of cardiovascular effects
• 3-OH (3-desacetyl) metabolite: likely
responsible for persistent paralysis in
critically ill patient
INTERMEDIATE-
• Precipitates in IV tubig if administered
ULTRALONG LONG-ACTING ACTING immediately after thiopental, but not after
propofol

ROCURONIUM
PIPECURONIUM PANCURONIUM VECURONIUM ROCURONIUM • Low potency
• Minimal risk of accumulation
• Does not cause significant hemodynamic
perturbations and releases no histamine
• Anaphylaxis Tx: Sugammadex
NON-DEPOLARIZING NMBA
DOXACURIUM
• Very potent, least rapid in onset (3 to 10
BENZYLISOQUI minutes), and also the longest acting (77
NOLINIUM
to 164 minutes) nondepolarizing NMBA
• releases no histamine in doses up to 2.7
times its ED95, so is very stable from
cardiovascular standpoint
INTERMEDIATE- • Used preferentially during long surgical
ULTRALONG SHORT-ACTING
ACTING
procedures, particularly in cardiac surgery,
and in the ICU

DOXACURIUM ATRACURIUM CISTRACURIUM MIVACURIUM ATRACURIUM

• shares, with most of the isoquinolinium
compounds, a unique, dual metabolic
pathway
• Onset can be shortened by increasing the
dose, but above 0.5 mg/kg, atracurium
induces histamine release, resulting in skin
flushing, tachycardia, and hypotension
NON-DEPOLARIZING NMBA
CISATRACURIUM
• Developed in an attempt to reduce
BENZYLISOQUI
NOLINIUM Atracurium's propensity for
histamine release
• It is a potent cis-cis isomer of
atracurium, and its onset time is longer
than that of atracurium
INTERMEDIATE-
ULTRALONG SHORT-ACTING
ACTING

DOXACURIUM ATRACURIUM CISTRACURIUM MIVACURIUM

NON-DEPOLARIZING NMBA
MIVACURIUM
• developed initially as the "ideal
BENZYLISOQUI nondepolarizing neuromuscular blocking
NOLINIUM
agent”
• rapid onset with a duration of action
significantly shorter than that of
intermediate-duration agents.
INTERMEDIATE-
ULTRALONG
ACTING
SHORT-ACTING • High potency, large doses (3 to 4 × EDgs)
are needed for good intubating conditions
and rapid onset, but at these doses,
histamine release is observed

DOXACURIUM ATRACURIUM CISTRACURIUM MIVACURIUM ü Factors for achieving excellent

conditions:
ü increasing mivacurium dose;
ü opioid coadministration;
ü delaying time to intubation (from 1
minute to 2 minutes); and
ü patient age (>70 years).

REVERSAL: Anticholinesterase
DRUG INTERACTIONS
ADDITIVE POTENCY
ATRACURIUM CISATRACURIUM with no effect on total
duration

CISATRACURIUM ROCURONIUM SYNERGISTIC EFFECT

VECURONIUM RECOVERY will

MIVACURIUM
FOLLOW the LOADING
DOSE DRUG
(LOADING DOSE DRUG) (MAINTENANCE DRUG)
DRUG INTERACTIONS

• Depolorizing and Non-depolorizing NMBAs: Mutual antagonism

• Inhalational anesthetic agents: potentiate neuromuscular block
• Local anesthetics: potentiates NMBAs
• Acute administration of anticonvulsants
• Antibiotics
• Corticosteroids
REVERSAL OF NEUROMUSCULAR BLOCKADE
ANTICHOLINESTERASE AGENTS
DRUG ONSET OF ACTION USE
ENDROPHORIUM Fastest (1 to 2 mins) **Co-administered with atropine (Enlon-
Plus)
NEOSTIGMINE Intermediate MOST FREQUENTLY USED
(7 to 11 minutes) anticholinesterase today

**Co-administered with Glycopyrrolate

(preferred) or Atropine
PYRIDOSTIGMINE Longest Used most often as an oral
(12 to 16 minutes) cholinesterase inhibitor for treatment of
myasthenia gravis
SELECTIVE RELAXANT BINDING AGENTS
SUGAMMADEX 2 to 4 minutes Indicated for reversal of steroidal
NMBAs, particularly Rocuronium and
Vecuronium
Sugammadex Versus Neostigmine For Routine
Reversal of Rocuronium Block In Adult Patients:
A Cost Analysis

JOURNAL

William E Hurford 1, Jeffrey A Welge 2, Mark H Eckman 3

J Clin Anesth. 2020 Dec;67:110027.

doi: 10.1016/j.jclinane.2020.110027.Epub 2020 Sep 25.
Study objective: This report analyzes the comparative costs, efficacy and side effects of a newer, more
expensive reversal drug, sugammadex, with its generic counterpart, neostigmine combined with
glycopyrrolate, or no reversal agent when used routinely to reverse rocuronium-induced neuromuscular
blockade in adult patients.

Results: Cost analysis suggested that reversal with sugammadex is preferable to neostigmine or no reversal
drug when operating room (OR) time was valued at ≥$8.60/min (base case $32.49/min). Net costs of
sugammadex were less than no treatment or neostigmine reversal when the probability of UPMV exceeded
0.019 and 0.036, respectively. Neither sugammadex nor neostigmine reversal was preferable to no treatment
in a base-case analysis that considered the effect of the reversal agent on only drug and PONV costs,
disregarding costs of OR time or UPMV.

Conclusions: Routine reversal with sugammadex is preferable to choosing neostigmine or no reversal drug
when accounting for potential savings in OR time. Sugammadex might also be a reasonable choice for
patients at high risk of UPMV. If the cost of OR time is not considered, the analysis does not support the
routine use of sugammadex in patients with perceived increased risk or solely to reduce PONV.