NEUROMUSCULAR BLOCKING

DRUGS (NMBD)

Dr. Prabowo Wicaksono, SpAn

BAGIAN/SMF ANESTESI FK UNISSULA/ RSISA
2007

PENDAHULUAN
Relaksasi/ lumpuhnya otot merupakan bagian dari TRIAS
ANESTESI (Hipnotik, Analgesia, Relaksasi).
Merupakan komponen yg harus dipenuhi utk capai BALANCED
ANESTESI.
Mulai th 1932 d-Tubocuraruine (ekstrak Curare: racun pd anak
panah di Amerika Selatan) : pada pasien spasme otot e.c.
Tetanus
Th 1942 dipakai utk relaksasi selama GA
Th 1949 succinylcholine
Prinsip kerja NMBD : hambat transmisi impuls saraf di
Neuromuscular Juction (NMJ)

CLINICAL USES
1.To provide skeletal muscle relaxation to facilitate tracheal
intubation
2.To provide skeletal muscle relaxation to improve surgical
working condition during GA.

KLASIFIKASI NMBD
Berdasarkan mekanisme aksi:
Depolarizing NMBD menyerupai kerja asetilkolin
Contoh: Succinylcholine (SCh)
Non depolarizing NMBD ganggu kerja asetilkolin: dibagi lagi
berdasar durasi:
- Short acting NDMR (non depolarizing muscle relaxant):
Mivacurium
- Intermediate NDMR: Atracurium, Vecuronium, Rocuronium
- Long acting: Pancuronium, Doxacurium.

NEUROMUSCULAR JUNCTION
The NMJ consists of a prejunctional motor nerve ending separated
from a highly folded postjucntional membrane of the skeletal muscle
fiber by a synaptic cleft that is 20-30 nm wide and filled with
extracellular fluid.
The nonmyelinated nerve ending contains mitochondria, endoplasmic
reticulum and synaptic vesicles necessary to synthesize acetlycholine.
The resting transmembrane potensial (-90 mV) across nerve and
skeletal muscle membranes is maintaned by distribution of K and Na
ions across the membrane.
The NMJ contains three types of nicotinic cholinergic receptor; two are
postsynaptic on the skeletal muscle surface (junctional and

NEUROMUSCULAR TRANSMISSION
As a nerves action potensial depolarizes its terminal, an influx of Ca ions into the
nerve cytoplasm allows storage vesicles to fuse with the terminal membrane and
release their contents of ACh, which diffuse across the synaptic cleft to bind with
nicotinic cholinergic receptors on the motor endplate.
Each ACh receptor consists of five protein subunits, two of which are identical
and capable of binding ACh molecules. If both binding sites are occupied by ACh,
a conformational change in the core receptor occur.
Cation flow thrugh the open channel (sodium and calcium in, potassium out),
generating and end plate potential. The content of single vesicle, a quantum of
ACh, produce miniature endplate potential. If enough receptors are occupied by
ACh, the endplate potential will be sufficiently strong to depolarize the
perijuctional membrane.Sodium channels within this portion of the muscle
membrane open when voltage is developed across them, as opposed to end
plate receptors that open when ACh is applied. The resulting action potential
propagates along the muscle membrane and T tubule system, opening sodium
channels and releasing Ca from sarcoplasmic reticulum. This intracellular Ca
allow the contractile protein actin and myosin to interact bringing about muscle
contraction.

ACh is rapidly hydrolyzed into acetate and cholin by enzyme

acetylcholinesterase. This enzyme is embedded into the motor end plate
membrane immediately adjacent to the ACh receptors. Eventually, the receptors
ion channels close, causing the endplate to repolarize. When action potential
generation ceases, the sodium channels in the muscle membrane also close. Ca
is resequestered in the sarcoplasmic reticulum, and the muscle cell relaxes.

ACETYLCHOLINE
The neurotransmitter at the NMJ is acetylcholine. The acetylcholine in
motor nerve endings is synthesized by the acetylation of choline under
the controle of enzyme cholin acetylase. The acetylcoline is stored in
synaptic vesicles in motor nerve endings and release into synaptic cleft
as a packets (quanta), each of which contains 1000 molecules of
acetylcholine.
Arrival of nerve impulse causes the release of hundreds of quanta of
acetylcholine that bind to nicotinic colinergic receptors on postsynaptic
membranes, cause a change in membrane permeability to ions, cause a
decrease in the transmembrane potential from approximately -90 mv to
-45 mv (treshold potential). At this point, a propagated action
potential spreads over the surfaces of skeletal muscle fibers leading to
their contraction.
Calcium ions mut be present for the release of acetylcholine from
synaptic vesicles into the synaptic cleft.
Situated in close proximity to cholinergic receptors is the enzyme
acetylcholinesterase; responsible for the rapid hydrolysis (< 15 ms)
of acetylcholine to acetic acid and choline.
Choline can reenter motor nereve endings to agin participate in the
synthesis of new acetylcholine. The rapid hydrolysis of acetylcholine
prevents sustained depolarization of the NMJ.

DEPOLARIZING
DRUGS

NEUROMUSCULAR

BLOCKING

The only depolarizing NMBD in clinical use is succinylcoline

(SCh).
SCh 0.5- 1 mg/kg IV has a rapid onset (30-60 seconds) and short
duration (3 5 minutes). This characteristics make SCh a useful
drug for providing skeletal muscle relaxations to facilitate
intubation.

MECHANISM OF ACTION
SCh attached to nicotinic cholinergic receptor and mimics the
action of acetylcholine thus depolarizing the postjuctional
membrane. Compared with acetylcholine, the hydrolysis of SCh
is slow, resulting in sustained depolarization (opening) of the
receptor ion channels.
Neuromuscular blockade develops because
a depolarized
postjuctional membrane cannot respond to subsequent release
of acetylcholine (depolarizing neuromuscular blockade)

Depolarizing MR physically resemble ACh and therefore bind to ACh receptors,

generating a muscle action potential. However, unlike ACh, these drugs are not
metabolized by acetylcholinesterase. Thus, their concentration in the synaptic cleft
does not fall as rapidly, resulting in a prolonged depolarization of the muscle end
plate.
Continuous endplate depolarization causes muscle relaxation in the following way.
As has been explained, and endplate potential of sufficient strength will result in
generation of action potential in the neighboring perijunctional membrane.
However, the subsequent opening of the perijunctional sodium channels is time
limited. After initital excitation and opening, these ion channels close. Furthermore,
these sodium channels cannot reopen until the endplate repolarizes, which is not
possible as long as a depolarizer continues to bind to ACh receptors. Once the
perijuctional channels close, the action potential disappears and the membrane
downstream returns to its resting state, resulting in muscle relaxation. This is phase
I block.

SUCCINYLCHOLINE

NONDEPOLARIZING
BLOCKING DRUGS

NEUROMUSCULAR

Mechanism of Action
Act by combining with postjuctional nicotinic cholinergic
receptors , act competively with acethycholine, weaken
neuromuscular transmission.
In addition, these drugs, especially at high doses, may act by
blocking the prejunctional ion receptor channels (Na), interrupt
acetylcholine mobilization at nerve ending.

ATRACURIUM BESYLATE (NDMR)

FARMAKOLOGI KLINIK
Pemberian obat-obat nondepolarisasi bereaksi dari otot-otot yang
berfungsi dalam gerakan cepat seperti rahang dan mata, selanjutnya
otot-otot besar anggota tubuh. Terakhir diafragma lumpuh dan
respirasi berhenti. Penyembuhan terjadi dalam urutan terbalik,
dengan diafragma berfungsi pertama kali.
Obat-obat depolarisasi berawal dibagian dada dan perut, untuk
selanjutnya berjalan ke otot-otot lengan, leher dan kaki. Penghambatan
terjadi dalam 1 menit. Karena hidrolisis yang cepat oleh kolinesterase
plasma dan hati, lamanya berlangsung dalam 5-10 menit

EFEK KARDIOVASKULAR
Vekuronium, pipekuronium, doksakurium, dan rokuronium, mempunyai
efek yang kecil terhadap KV.
Metokurin, mivakurium, atrakrium menyebabkan hipotensi walaupun
dalam jumlah yang kecil karena pembebasan histamin.
Pankuronium menyebabkan peningkatan detak jantung dan penurunan
curah jantung, dengan sedikit perubahan pada SVR.
Suksinilkolin meyebabkan berbagai jenis aritmia jantung. Pemberian
berulang sering menyebabkan bradikardi, dapat dicegah dengan
pemberian sulfas atropin.

EFEK LAIN DARI OBAT-OBAT DEPOLARISASI:

1.
Hiperkalemia
Sustained opening of receptor ion channels and resulting
depolarization of postjuctional membrane produced by SCh is
associated with leakage of potassium from interior of cells sufficient
to produce an average 0.5 mEq/L increase inserum potassium
concentration.
2.
Peningkatan tekanan intra okuler.
3.
Peningkatan tekanan intra gastrik.
4.
Nyeri otot.

INTERAKSI DENGAN OBAT LAIN

1.
2.
3.

4.

Anestetik: obat-obat inhalasi meningkatkan penghambatan

neuromuskular obat nondepolarisasi. Secara berurutan: isofluran,
desfluran, enfluran, halotan, N2O.
Antibiotik: terjadi peningkatan penghambatan neuromuskular,
terutama golongan aminoglikosida.
Anestetik lokal dan antiaritmia: Obat-obat anestesi lokal
meningkatkan penghambatan neuromuskular oleh obat depol dan
nondepol. Hal yang sama terjadi dengan antiaritmia seperti
kuinidin
Obat-obat penghambat neuromuskular lain
Pelemas otot depolarisasi diantagonis oleh penghambat
nondepolariasai.Suatu dosis kecil tubokurarin diberikan sebelum
suksinilkolin, biasanya mengurangi fasikulasi dan nyeri pasca
operasi.

EFEK PENYAKIT DAN RESPON PADA LANJUT USIA

-Miastenia gravis meningkatkan hambatan neuromuskular
-Umur tua memperpanjang lama kerja nondepolarisasi
-Luka bakar hebat dan penyakit motor neuron resisten dengan obat
nondepol

PEMULIHAN PENGHAMBATAN NEUROMUSKULAR NON

DEPOLARISASI
Neostigmin dan piridostigmin meningkatkan keberadaan asetilkolin pada
motor endplate, terutama dengan penghambatan asetilkolin esterase.

Penggunaan lain pelumpuh otot

1.
Pengatur ventilasi
Pada pasien gagal nafas, sering menginginkan pengaturan ventilasi agar
mendapatkan volume yang cukup untuk pengembangan paru-paru
2.
Pengobatan kejang
Digunakan untuk manifestasi perifer kejang akibat epilepsi atau toksisitas
anestesi lokal, tapi tidak ada efek sentrak karena tidak melewati sawar
darah otak.

Thank you.............