EXPERIMENT 12

NEUROMUSCULAR BLOCKING DRUGS

Asst. Prof. Carol Geraldine Pablo, MSc.

Mr. Jay P. Jazul, MSc.
UST Faculty of Pharmacy

DRUGS THAT AFFECT SKELETAL MUSCLE

FUNCTION AS TWO VERY DIFFERENT
THERAPEUTIC GROUPS:
1.

Neuromuscular blockers - drugs that

completely paralyze skeletal muscles (from normal
tone to zero) by interfering with acetylcholine at
neuromuscular junction.

2.

Spasmolytics - drugs that used to relieve skeletal

muscle spasm & bring them from hypertonic state to
normal muscle tone.

Neuromuscular

blocking drugs - interfere with

transmission at the neuromuscular end plate and
lack central nervous system activity.

 Chemistry

All of the available neuromuscular blocking drugs

bear a structural resemblance to acetylcholine.

Phamacokinetics

All of the neuromuscular blocking drugs are highly

polar and inactive orally and must be
administered parenterally.

ROLE OF NMBS IN SURGERY:

1.

NMBs are co-administrated with anesthetics in

the induction phase to induce muscle paralysis.
2. Facilitate the surgery, especially intra-abdominal
and intra-thoracic surgeries
3. Facilitate endotracheal intubation.
Nb.

Because NMB may paralyze muscles required

for breathing, mechanical ventilation should be
available to maintain adequate respiration.

CLASSIFICATION OF MUSCLE RELAXANTS

ACCORDING TO MECHANISM OF ACTION
1.

Depolarizing - non competitive, agonist. Ex.

Succinylcholine (suxamethonium/ Anectine )
2. Non depolarizing - competitive, antagonist.
Ex. Tubocurarine
Ultra-Short

Short

Intermediate

Long

Succinylcholine

Mivacurium

Vecuronium

Pancuronium

Atracurium
Rocuronium
Cis-atracurium

1. Depolarizing
Resembles two acetylcholine molecules linked
end to end, it has two quaternary ammonium
cations which interact with the anionic sites on the
muscle end plate receptors.

Member

drugs:
1.1 Succinylcholine (Anectine) - used to
produce complete muscle relaxation for various
surgical procedures.
1.2 Decamethonium bromide (Syncurine) used as a muscle relaxant for relatively short
surgical procedures.

DEPOLARIZING CONT....
MOA-

Act like an excess of acetylcholine to

depolarize the muscle receptor site and prevent its
repolarization. Thus, there is an initial depolarization
at the neuromuscular junction producing muscle
contraction; but since the muscle receptor site cannot
depolarize, complete skeletal muscle relaxation
follows.

Figure above shows a depolarizing blocker both occupying the receptor and blocking the channel. Normal closure of
the channel gate is prevented and the blocker may move rapidly in and out of the pore. Depolarizing blockers may
desensitize the end plate by occupying the receptor and causing persistent depolarization.

SUCCINYLCHOLINE :
MAJOR SIDE EFFECT CATEGORIES
increased
hyperkalemia arrhythmia myalgia intraocular
pressure
increased ICP

skeletal

(intracranial

muscle

pressure)

contractions

myoglobin
uria

increased
intragastric
pressure

Nb. Many succinylcholine side effects may be reduced by prior

administration of non-paralyzing doses of nondepolarizing
neuromuscular-blocking agents.

2. Nondepolarizing - agents also contain a "doubleacetylcholine" form; however this form is hidden by
ring systems-- e.g. pancuronium (Pavulon).
- Contains 1-2 quaternary nitrogens which resultin
limited lipid-solubility

Pancuronium

may be viewed as two acetylcholinelike fragments (outlined in color) oriented on a

steroid nucleus.

MAJOR CLASSES OF NONDEPOLARIZING

BLOCKING DRUGS:
Isoquinoline

derivatives
Tubocurarine
Atracurium (Tracrium)
Doxacurium (Nuromax)
Mivacurium (Mivacron)
Steroid derivatives
Pancuronium (Pavulon)
Vecuronium (Norcuron)
Pipecuronium (Arduan)
Rocuronium (Zemuron)

 MOA

- These drugs combine with nicotinic receptors

and prevent binding of acetylcholine so prevent
depolarization of the muscle cell membrane so
inhibiting muscle contraction.
- these drugs competitively block the receptors this
means that you can overcome their action by increase
Ach concentration by giving Ach esterase inhibitors
such as pyridostigmine or neostigmine.

Figure above: A nondepolarizing blocker eg, rocuronium, is shown as preventing the opening of the
channel when it binds to the receptor.

CONSIDERATION FOR CHOOSING A MUSCLE

RELAXANT INCLUDE:
Duration

of action required
Route of excretion
Tendency to release histamine
Cardiopulmonary side effects
The ability to reverse the blockage
Contraindication to any specific muscle relaxant.
Cost