Muscle Relaxants

dr. Boby Suryawan

 Triad of Anaesthesia

Analgesia
Pain control w/ opioid and non-opioid analgesics
Hypnosis
Drug induced sleep
Muscle Relaxation
To minimize patient movement and/or facilitate
ventilation
 Muscle Relaxation

Relaksasi Otot dapat dicapai dengan:

Mendalamkan anestesia umum
inhalasi
Melakukan blokade saraf regional
Pemberian pelumpuh otot
 What is a Muscle Relaxer?

A muscle relaxer, also known as

a muscle relaxant, is a drug
which affects skeletal
muscle function and decreases
the muscle tone. It may be used
to alleviate symptoms such as
muscle spasms, pain.
History of Muscle Relaxers

The earliest known use of muscle

relaxant drugs dates back to the
16th century, when European
explorers encountered natives of
the Amazon were using poison-
tipped arrows that produced death
by skeletal muscle paralysis. By
1943, neuromuscular blocking
drugs became established as muscle
relaxants in the practice
of anesthesia and surgery.
Muscle Relaxers and the Nervous System

Muscle relaxers refer

to two major
therapeutic groups:
neuromuscular
blockers
and spasmolytics
 Two Therapeutic Muscle Relaxers
Neuromuscular Blockers Spasmolytics

Neuromuscular blockers act Spasmolytics, also known as

by interfering with
transmission at the
neuromuscular end plate
and have no central nervous
system activity. They are
often used during surgical
procedures and in intensive
care and emergency
medicine to cause
temporary paralysis.
"centrally acting" muscle
relaxants, are used to alleviate
musculoskeletal pain and
spasms and to reduce spasticity
in a variety of neurological
conditions.
 Neuromuscular Blockers
Most neuromuscular blockers function by blocking transmission at the end
plate of the neuromuscular junction.
Normal end plate function can be blocked by two mechanisms. Non
depolarizing agents, such as tubocurarine, block the agonist, acetylcholine,
from binding to nicotinic receptors and activating them, thereby preventing
depolarization.
Alternatively, depolarizing agents, such as succinylcholine, are nicotinic
receptor agonists which mimic Ach, block muscle contraction by depolarizing
to such an extent that it desensitizes the receptor and it can no longer initiate
an action potential and cause muscle contraction.
Both of these classes of neuromuscular blocking drugs are structurally similar
to acetylcholine, the endogenous ligand, in many cases containing two
acetylcholine molecules linked end-to-end by a rigid carbon ring system, as
in pancuronium (a nondepolarizing agent).
 Depolarizing Muscle Relaxants

Depolarizing Muscle Relaxants bekerja seperti acetylcholine, tetapi tidak

dapat dirusak oleh cholinesterase di celah saraf.

Depolarizing Muscle Relaxants menyebabkan depolarisasi yang

ditandai oleh fasikulasi yang disusul oleh relaksasi otot lurik.

Termasuk golongan pelumpuh otot depolarisasi adalah succinylcholine dan

decamethonium.

Durasi kerja succinylcholine sangat pendek

Succinylcholine dimetabolisme oleh enzim plasma cholinesterase
(pseudocholinesterase) di pembuluh darah.
 Depolarizing Muscle Relaxants
Efek samping succinylcholine adalah:
Nyeri otot, terjadi pada 90% kasus, dapat dikurangi dengan memberikan
pelumpuh otot non-depolarisasi dosis kecil sebelumnya.
Peningkatan tekanan intraokular
Peningkatan tekanan intrakranial
Peningkatan tekanan intragastrik
Peningkatan kadar kalium plasma (hiperkalemia)
Aritmia jantung
Salivasi
Alergi, anafilaksis
Malignant hyperthermia
 Non-depolarizing Muscle Relaxants

Non-depolarizing muscle relaxants berikatan dengan

muscarinic cholinergic receptors, sebagai inhibitor
acetylcholine, sehingga acetylcholine tidak dapat bekerja
dan tidak terjadi depolarisasi.
 Berdasarkan susunan molekul, non-depolarizing
muscle relaxants digolongkan menjadi:

Benzylisoquinol : tubocurarine, metocurine, atracurium,

inium doxacurium, mivacurium
Steroid : pancuronium, vecuronium, pipecuronium,
rapacuronium, rocuronium

Phenol ethers : Gallamine

Nortoxiferine : Alcuronium
 Dosis awal Dosis rumatan Durasi
Efek Samping
(mg/kg) (mg/kg) (menit)

Nondepol long-acting
1. Tubocurarine (tubarin) 0.40-0.60 0.10 30-60 Histamin +, hipotensi
2. Pancuronium 0.08-0.12 0.015-0.020 30-60 Vagolitik, takikardi, tensi
3. Metocurine 0.20-0.40 0.05 40-60 Histamin -, hipotensi
4. Pipecuronium 0.05-0.12 0.01-0.015 40-60 Kardiovaskular stabil
5. Doxacurium 0.02-0.08 0.005-0.010 45-60 Kardiovaskular stabil
6. Alcuronium (alloferin) 0.15-0.30 0.05 40-60 Vagolitik, takikardia
Nondepol intermediate acting
1. Gallamine (flaxedil) 4-6 0.5 30-60 Histamin , hipotensi
2. Atracurium (tracrium) 0.5-0.6 0.1 20-45 Aman untuk hepar, ginjal
3. Vecuronium (norcuron) 0.1-0.2 0.015-0.02 25-45
4. Rocuronium (esmeron) 0.6-1.0 0.10-0.15 30-60
5. Cistacuronium 0.15-0.20 0.02 30-45 Isomer atrakurium

Nondepol short acting

1. Mivacurium (mivacron) 0.20-0.25 0.05 10-15 Histamin +, hipotensi
2. Ropacuronium 1.5-2.0 0.3-0.5 15-30

Depol short acting

1. Succinylcholine (scolin) 1.0 3-10
2. Decamethonium
 Muscle Relaxants
Pilihan muscle relaxants
1. Gangguan faal ginjal : Atracurium, vecuronium
2. Gangguan faal hati : Atracurium
3. Miastenia gravis : Jika dibutuhkan, dosis 1/10 atracurium
4. Bedah singkat : Atracurium, rocuronium, mivacuronium
5. Kasus obstetri : Semua dapat digunakan kecuali gallamine

Tanda-tanda kekurangan pelumpuh otot

Cegukan (hiccup)
Dinding perut kaku
Ada tahanan pada inflasi paru
 Antidotum Neuromuscular Blocker

Penawar pelumpuh otot atau acetylcholinesterase inhibitor (anti-cholinesterase)

bekerja pada neuro-muscular junction untuk mencegah acetylcholinesterase.

Anti-cholinesterase yang paling sering digunakan adalah neostigmine

(prostigmin), piridostigmin, dan edrophonium.

Penawar pelumpuh otot bersifat muscarinic sehingga menyebabkan hipersalivasi,

keringatan, bradikardia, kejang bronkus, hipermotilitas usus, dan pandangan kabur.

Pemberian obat penawar pelumpuh otot harus disertai oleh obat

vagolytic
 Antidotum Neuromuscular Blocker

Dosis obat-obatan penawar muscle relaxants

neostigmine adalah 0,04-0,08 mg/kg;

pyridostigmine 0,1-0,4 mg/kg;

edrophonium 0,5-1,0 mg/kg;

dan physostigmine 0,01-0,03 mg/kg.

Dosis obat-obatan vagolytic

atropine dosis 0,01-0,02 mg/kg atau

glycopyrrolate dosis 0,005-0,01 mg/kg sampai 0,2-0,3 mg pada dewasa.

 Spasmolytics
Spasmolytic agents generally work by either enhancing the level
of inhibition, or reducing the level of excitation.
Inhibition is enhanced by mimicking or enhancing the actions of
endogenous inhibitory substances, such as gamma-
Aminobutyric acid (GABA).
GABA is the chief inhibitory neurotransmitter in
the mammalian central nervous system. It plays a role in
regulating neuronal excitability throughout the nervous system.
In humans, GABA is also directly responsible for the regulation
of muscle tone.
Spasmolytics are referred to as centrally acting muscle
relaxants because they can be used to target specific regions of
the body such as low back and neck.
Spasmolytics
 Spasmolytic drugs

Definition of muscle spasm (spasticity):

1. Increased muscle tone
2. together with muscle weakness
It is often associated with cerebral palsy, multiple
sclerosis, and stroke.
 Centrally acting spasmolytic drugs

Drug Mechanism
1- Diazepam GABA receptor
2- Baclofen GABA receptors causing hyperpolarization
by increasing potassium conductance
Adverse effects: drowsiness and increased
seizure activity
3- Tizanidine 2 adrenoreceptor agonist
4- Gabapentin
 DIAZEPAM
Benzodiazepines facilitate the action of -
aminobutyric acid (GABA) in the central nervous
system.
Diazepam acts at GABAA synapses, and its action
in reducing spasticity is at least partly mediated in
the spinal cord
Although diazepam can be used in patients with
muscle spasm of almost any origin (including
local muscle trauma), it produces sedation at the
doses required to reduce muscle tone.
 BACLOFEN
Baclofen (p-chlorophenyl-GABA) was designed to be an
orally active GABA-mimetic agent, its spasmolytic
activity at GABAB receptors, this result in:
hyperpolarization, probably by increased K+
conductance.
inhibition of reducing calcium influx
This will reduce excitation of spinal cords and
reduce pain in patients with spasticity, perhaps by
inhibiting the release of substance P (neurokinin-1)
in the spinal cord.
Baclofen is at least as effective as diazepam in reducing
spasticity while producing less sedation. In addition,
baclofen does not reduce overall muscle strength as
much as dantrolene.
 Adverse effects:
Drowsiness, tolerant to the sedative effect with chronic
administration.
Increased seizure activity has been reported in
epileptic patients.
Therefore, withdrawal from baclofen must be
done very slowly.
 TIZANIDINE

Adverse effects, including drowsiness,

hypotension, dry mouth, and asthenia.
 OTHER CENTRALLY ACTING
SPASMOLYTIC DRUGS
Gabapentin
It is an antiepileptic drug that has shown considerable promise
as a spasmolytic agent in several studies involving patients with
multiple sclerosis.
Pregabalin
is a new analog of gabapentin that may also prove useful.
Progabide and glycine have also been found in preliminary
studies to reduce spasticity. Progabide is a GABAA and GABAB
agonist and has active metabolites, including GABA itself.
Glycine is another inhibitory amino acid neurotransmitter. It
appears to possess pharmacologic activity when given orally
and readily passes the blood-brain barrier.
Idrocilamide and riluzole
They are newer drugs for the treatment of amyotrophic lateral
sclerosis that appear to have spasm-reducing effects, possibly
through inhibition of glutamatergic transmission in the central
nervous system.
 Peripheraly acting spasmolytic drugs
Dantrolene:
Mechanism of action:
Dantrolene reduces skeletal muscle strength by interfering with
excitation-contraction coupling in the muscle fibers
Normal contraction involves release of calcium from its stores
in the sarcoplasmic reticulum through a calcium channel
Dantrolene interferes with the release of calcium through
this sarcoplasmic reticulum calcium channel.
Cardiac muscle and smooth muscle are depressed only
slightly, perhaps because the release of calcium from their
sarcoplasmic reticulum involves a different process.
 Dantrolene:
Indications:
1- Muscle spasticity
2- Malignant hyperthermia:
o Patients at risk for this condition have a hereditary impairment in the ability
of the sarcoplasmic reticulum to sequester calcium.
o Following administration of one of the triggering agents (general anesthetics
or succinylcholine) there is a sudden and prolonged release of calcium, with
massive muscle contraction, lactic acid production, and increased body
temperature.
Treatment of malignant hyperthermia:
1. control acidosis and body temperature
2. Reduce calcium release with intravenous dantrolene
Major adverse effects
are generalized muscle weakness, sedation, and occasionally hepatitis.
THANKS