Skeletal muscle relxants

• Nicotinic (Muscle) receptor blockers –

Skeletal muscle relaxants.
• Nicotinic (Nerve) receptor blockers –
Ganglion blockers
Skeletal muscle relaxants
• Skeletal muscle relaxants block
peripherally at the
neuromuscular junction (Nicotinic
receptor of Ach – Muscle).
• Types of Skeletal muscle relaxants:
 Competitive (Non-depolarizing)
 Non-competitive (Depolarizing)
 Directly acting Muscle relaxants
 Miscellaneous : Aminoglycosides
 Skeletal muscle relaxants
Pharmacokinetics :
• Most peripheral NM blockers are quaternary
compounds – not absorbed orally.
• Administered intravenously.
• Do not cross blood brain barrier or placenta
• SCh is metabolized by Pseudocholinesterase.
• Atracurium is inactivated in plasma by spontaneous
non-enzymatic degradation (Hoffman
elimination).
 Skeletal muscle relaxants
Neuromuscular blockers
• Non - depolarizing ( competitive )
Long acting : Pancuronium,
Pipecuronium,
Intermediate : Vecuronium, Rocuronium,
Atracurium
Short acting : Mivacurium
• Depolarizing blockers : (Non-competitive)
Succinylcholine (Suxamethonium)
 Skeletal muscle relaxants
Neuromuscular blocking agents :
Non-depolarizing agents (Competitive
blockers).
• Mechanism of action : These have an
affinity for the Nicotinic (NM) receptors
at the muscle end plates but have no
intrinsic activity.
• The antagonism is surmountable by
increasing the conc. of Ach.
Skeletal Duration mins
muscle
relaxants
Pancuronium 40-80

Pipecuronium 50-100

Vecuronium 20-40

Atracurium 20-40

Rocuronium 20-40

Succinyl 3-6
choline
 Skeletal muscle relaxants
 Depolarizing block ( Non-competitive ) :
 Succinylcholine have affinity and sub
maximal intrinsic activity at NM receptors.
They open Na channels which
cause initial twitching and fasciculations.
 It do not dissociate rapidly from the
receptors resulting in prolonged
depolarization and inactivation of the Na +
channels
 Skeletal muscle relaxants
Depolarizing block (Non-competitive) :
Succinylcholine
• It causes muscle pain.
• It causes hyperkalemia.
• Malignant Hyperthermia.
 Competitive Non-
Non-depolarizing Competitive
Depolarizing
Paralysis Flaccid Fasciculations---
› Flaccid
Neostigmine Antagonizes Exaggerate /
no effect.
Examples Pancuronium Succinylcholine
 Skeletal muscle relaxants
USES OF NEUROMUSCULAAR
BLOCKERS :
• Adjuvant in general anesthesia
• Intubation and endoscopies
• Brief procedure – reduction of #.
Skeletal muscle relaxants
Directly acting muscle relaxants :
Dantrolene :
Depolarization triggered release of
calcium from the sarcoplasmic
contraction is blocked / reduced.
• Dantrolene is used orally/ i.v to reduces
spasticity in hemiplegia and cerebral
palsy.
• It is the drug of choice – malignant
hyperthermia
 Central skeletal muscle
relaxants
• These produce selective action in the
cerebrospinal axis – acts as skeletal muscle
relaxants
• Theses depress the spinal and supraspinal
polysynaptic reflexes involved in the
regulation of muscle tone.
• Polysynaptic reflex in the RAS – involved in
the wakefulness also depressed – sedative
action.
 Central skeletal muscle
relaxants
Examples of centrally acting skeletal
muscle relaxants :
• Chlorzoxazone, Methocarbamol
• Diazepam
• Baclofen
 Ganglion blockers
• Ganglion blockers are competitive
antagonist at NN receptors in
autonomic ganglia.
• Net effect of the blocker is to reduce
the predominant tone.
• Effects are predictable and depend
on the relative dominance in terms of
PANS and SANS.
 Ganglion blockers
Effector Dominant Effects of ganglionic
organs system blockade
Arterioles/ SANS Vasodilatation, hypotension
veins
Sweat glands SANS Anhydrosis

Genitals PANS/SANS Impotence

Heart PANS Tachycardia

Iris PANS Mydriasis
Ciliary PANS Cycloplegia
Bladder PANS Urinary retention
Salivary PANS Xerostomia
 Ganglion blockers

Ganglionic blocking agents :

• Mecamylamine, Trimethaphan.
• It is used in severe hypertension.
 Ganglion blocking agents
• Ganglion blocking agents block the
autonomic reflexes, including changes in
heart rate elicited by increase / decrease
in blood pressure.
• Hexamethonium will block the reflex
bradycardia that occurs when
phenylephrine causes vasoconstriction, it
will not block a bradycardia that results
from direct activation of muscarinic
receptors in heart.
Glaucoma
 Glaucoma
• Glaucoma is increased intraocular pressure.
• Intraocular pressure is determined by the
balance between fluid input & drainage out of
the globe
----- aqueous humor produced by ciliary
epithelium and drained at the filtration
angle of the anterior chamber.
• Objective of glaucoma therapy : ---
increase outflow & or decrease
production of aqueous humor.
 Glaucoma
• Major route of aqueous humor
drainage is ~ 90% through
trabecular route ~
10% passes through within the ciliary
muscle into episceral vessels
(uveosceral flow)
 Drugs for glaucoma

Beta blockers
Alpha agonist Pilocarpine PG analog
CA inhibitor
 Glaucoma
Muscarinic cholinomimetics :
• Direct-acting : Pilocarpine, Carbachol
• Indirect-acting : Physostigmine
----> contraction of ciliary muscle open
the trabecular spaces so that aqueous
humor drains more easily.
----> iris pulled from angle of anterior
chamber widening the filtration angle and
opening the trabecular network
----> increased outflow of aqueous humor
----> decreased intraocular pressure.
 Glaucoma
Beta adrenoceptor blockers :
Timolol, Betaxolol
• ----> decreased production of
aqueous humor by ciliary epithelium.
• No change in pupil size, No
headache, No fluctuations in IOT are
the advantages of the beta blockers.
 Glaucoma
Carbonic anhydrase inhibitors :
• Dorzolamide
• It blocks the formation of aqueous humor by
blocking the carbonic anhydrase enzyme
required for the synthesis of it.
Alpha Adrenoceptor agonists :
• Apraclonidine
----> alpha 2 agonist acts by reducing the
formation of aqueous humor.
 Glaucoma
Prostaglandins :
• Latanaprost
• It increases the aqueous drainage through
the alternate pathways – uveoscleral route.
• May eventually cause permanent darkening
of the iris to brown (heterochromia),
eyelashes reddening of the eyes.