skeletal muscle relaxant
TRANSCRIPT
SKELETAL MUSCLE RELAXANT
S. Parasuraman, M.Pharm., Ph.D.,Senior Lecturer, Faculty of Pharmacy,
AIMST University
Skeletal muscle relaxant
• Skeletal muscle relaxants are drugs that act
peripherally at neuromuscular junction/ muscle fibre
itself or centrally in the cerebrospinal axis to reduce
muscle tone and/or cause paralysis.
• A muscle relaxants is a drug that affects skeletal
muscle function and decreases the muscle tone. It
may be used to improve symptoms such as muscle
spasms, pain, and hyperreflexia.
Peripherally acting muscle relaxants
Neuromuscular blocking agents
• Nondepolarizing (Competitive) blockers
– Long acting: d-Tubocurarine, Pancuronium, Doxacurium, Pipecuronium
– Intermediate acting: Vecuronium, Atracurium, Cisatracurium, Rocuronium, Rapacuronium
– Short acting: Mivacurium
• Depolarizing blockers: Succinylcholine (Sch), Decamethonium
Nondepolarizing (Competitive) blockers
• MOA: The site of action of both competitive anddepolarizing blockers is the end plate of skeletalmuscle fibres.
• Pharmacological actions:– Skeletal muscles: Intravenous injection of nondepolarizing
blockers rapidly produces muscle weakness followed byflaccid paralysis.
– Autonomic ganglia: produce some degree of ganglionicblockade
– Histamine release: d-TC releases histamine from mast cells.Histamine release contributes to the hypotension producedby d-TC. Flushing, bronchospasm and increased respiratorysecretions are other effects.
Nondepolarizing (Competitive) blockers
• Pharmacological actions (Cont.,):
– Cardiovascular system: d-Tubocurarine producessignificant fall in BP. This is due to
• ganglionic blockade
• histamine release and
• reduced venous return
– Gastrointestinal tract: The ganglion blocking activity ofcompetitive blockers may enhance postoperative paralyticileus after abdominal operations.
– Central nervous system: All neuromuscular blockers arequaternary compounds—do not cross blood-brain barrier.
Nondepolarizing blockers - Individual compounds
• d-Tubocurarine:
– Not clinical used do to its histaminic effects.
• Succinylcholine:
– SCh is the most commonly used muscle relaxant for passingtracheal tube. It induces rapid, complete and predictableparalysis with spontaneous recovery in ~5 min.
– Occasionally SCh is used by continuous i.v. infusion forproducing controlled muscle relaxation of longer duration.
– It should be avoided in younger children unless absolutelynecessary, because risk of hyperkalaemia and cardiacarrhythmia is higher.
• Pancuronium:
– It is a synthetic steroidal compound, ~5 times more potentand longer acting than d-TC.
– Because of longer duration of action, needing reversal, itsuse is now restricted to prolonged operations, especiallyneurosurgery.
• Pipecuronium:
– Muscle relaxant with a slow onset and long duration ofaction; steroidal in nature; recommended for prolongedsurgeries.
Nondepolarizing blockers - Individual compounds
• Vecuronium:
– It is a most commonly used muscle relaxant for routinesurgery and in intensive care units..
• Atracurium:
– Four times less potent than pancuronium and shorteracting.
• Rocuronium:
– Muscle relaxant with a rapid onset and intermediateduration of action which can be used as alternative to SChfor tracheal intubation without the disadvantages ofdepolarizing block and cardiovascular changes.
Nondepolarizing blockers - Individual compounds
Nondepolarizing blockers - Individual compoundsUses
• Adjuvants to general anaesthesia: The mostimportant use of neuromuscular blockers is asadjuvants to general anaesthesia. Choice of theneuromuscular blocker depends on the nature andduration of the procedure, pharmacokinetics of theblocker and cardiovascular stability that it provides.Vecuronium and rocuronium are the most frequentlyselected nondepolarizing blockers.
• Assisted ventilation: Critically ill patients in intensivecare units often need ventilatory support.
• Convulsions and trauma from electroconvulsivetherapy can be avoided by the use of musclerelaxants without decreasing the therapeutic benefit.
• Assisted ventilation: Critically ill patients in intensivecare units often need ventilatory support.
Nondepolarizing blockers - Individual compoundsUses
Directly acting muscle relaxants
• Dantrolene: Dantrolene acts on the RyR1 (Ryanodine
receptor) calcium channels in the sarcoplasmic
reticulum of skeletal muscles and prevents Ca2+
induced Ca2+ release through sarcoplasmic reticulum.
• Dantrolene is slowly but adequately absorbed from
the g.i.t. It penetrates brain and produces some
sedation, but has no selective effect on polysynaptic
reflexes responsible for spasticity.
Centrally acting muscle relaxants
Centrally acting Peripherally acting
Decrease muscle tone without reducing voluntary power
Cause muscle paralysis, voluntary movements lost
Selectively inhibit polysynaptic reflexes in CNS
Block neuromuscular transmission
Cause some CNS depression No effect on CNS
Given orally, sometimes parenterally
Practically always given i.v.
Used in chronic spastic conditions, acute muscle spasms, tetanus
Used for short-term purposes (surgical operations)
Comparative features of centrally and peripherally acting muscle relaxants
Centrally acting muscle relaxants
• Classification
Class Example
Mephenesin congeners MephenesinCarisoprodolChlorzoxazoneChlormezanoneMethocarbamol
Benzodiazepines Diazepam and others
GABA mimetic BaclofenThiocolchicoside
Central α2 agonist Tizanidine
Centrally acting muscle relaxants
Baclofen:
• This analogue of the inhibitory transmitter GABA actsas a selective GABAB receptor agonist.
• The primary site of action of baclofen is considered tobe in the spinal cord where it depresses bothpolysynaptic and monosynaptic reflexes.
• As such, it does produce muscle weakness, but is lesssedative than diazepam.
• Baclofen is well absorbed orally and is primarilyexcreted unchanged in urine with a t½ of 3–4 hours.
Centrally acting muscle relaxants
Baclofen:
• Side effects are drowsiness, mental confusion,weakness and ataxia; serum transaminases may rise.Sudden withdrawal after chronic use may causehallucinations, tachycardia and seizures.
Centrally acting muscle relaxants
Tizanidine:
• This clonidine congener is a central α2 adrenergic
agonist—inhibits release of excitatory amino acids in
the spinal interneurones. It may facilitate the
inhibitory transmitter glycine as well.
Centrally acting muscle relaxants
Tizanidine:
• Side effects are dry mouth, drowsiness, night-time
insomnia and hallucinations.
• Dose-dependent elevation of liver enzymes occurs.
Though no consistent effect on BP has been
observed, it should be avoided in patients receiving
antihypertensives, especially clonidine.
Uses of centrally acting muscle relaxants
• Acute muscle spasms
• Torticollis, lumbago, backache, neuralgias
• Anxiety and tension
• Spastic neurological diseases
• Tetanus
• Electroconvulsive therapy
• Orthopedic manipulations
References
• Tripathi KD. Essentials of Medical Pharmacology,7th Ed, New Delhi: Jaypee Brothers MedicalPublisher (P) Ltd, 2013.