Chapter 16 - Muscle Relaxants

Neuromuscular Blocker

paralyzes muscle

Spasmolytics

decreases muscle hyperactivity

What type of receptor is involved in muscle activity?

nicotinic acetylcholine receptors

Structure of Nicotinic ACh receptor

ligand-gated ion channel composed of 5 individual protein subunits arranged symmetrically around a central, water-filled ion pore

What neurotransmitter binds to the nicotinic receptor?

acetylcholine

Neuromuscular junction

point of contact between a motor neuron and a skeletal muscle cell where acetylcholine is releaed and binds to specific ACh receptors on the muscle fiber membrane, leading to action potential along muscle fiber, release of calcium, & contraction

AChE

breaks down ACh, turning off signaling at the neuromuscular junction

Two ways in which neuromuscular blockers can work:

- depolarizing

- nondepolarizing

Depolarizing Mechanism

act as agonists at nicotinic acetylcholine receptors which causes prolonged activation/depolarization which causes desensitization, preventing further nerve transmission & causing muscle paralysis

Nondepolarizing Mechanism

act as competitive antagonists at nicotinic ACh receptor to block receptor & preventing signal

Depolarizing Drug

Succinylcholine

Succinylcholine

leads to prolonged NAChR activation & is not broken down by AChE which allows for prolonged duration of action

Effects of Succinylcholine

- fasciculations within 30 seconds

- flaccid paralysis within 90 seconds (respiratory muscles paralyzed last, & artificial vent. is required)

- recovery usually within 10 min

Main use of Succinylcholine

intubation

Butyrylcholinesterase

enzyme in the liver & plasma that metabolizes succinylcholine

Butyrylcholinesterase Deficiency

body is not able to break down succinylcholine which causes much longer duration of the drug, including prolonged muscle paralysis & inability to breathe which results in requirements of mechanical ventilation

Curare

plant-derived dart and arrow poison used by indigenous South American tribes with a primary toxin d-tubocurarine which was the first nondepolarizing neuromuscular blocker

Use of nondepolarizing blockers

muscle relaxation/paralysis during surgery, along with general anesthesia

Rocuronium

fast-acting nondepolarizing neuromuscular blocker that replaced d-tubocurarine and is used in general anesthesia & critical care; administered IV to temporarily paralyzes skeletal muscles to facilitate trachela intubation

Reversal of Neuromuscular Blockade

- neostigmine

- sugammadex

Neostigmine

acetylcholinesterase inhibitor that prevents breakdown of acetylcholine, increasing neurotransmitter concentration at the neuromuscular junction, displacing muscle relaxant

Sugammadex

reverses rocuronium & vecuronium by binding & encapsulating drug molecule in ring

Spasticity

increased activity of alpha motor neurons that aoriginate in spinal cord, leading to increased reflexes and muscle tone & impairing movement/speech

What causes spasticity?

damge to CNS such as spinal injury, MS, or stroke

GABAa

ligand-gated ion channel which allows negative charged chloride to enter the cell, leading to hyperpolarization of cell which results in decrease in action potential firing

GABAb

G-protein coupled receptor that leads to hyperpolarization and decrease in action potential firing but through secondary mechanisms

a2 receptors

inhibitory receptor that decreases Glu released

Types of Spasmolytics

- benzodiazepines

- botulinum toxin

- baclofen

- tizanidine

Baclofen

- GABAa agonist

- less sedating than benzodiazepines

Tizanidine

- alpha-2 agonist

- less sedating than benzos

- can cause hypotension

Myasthenia Gravis

a chronic autoimmune disease where autoantibodies against NAChR block or lead to destruction of receptor, resulting in muscle weakness (ptosis) that increases with use

Treatment of myasthenia gravis

- pyridostigmine

- thymectomy

- immunosuppressants

Pyridostigmine

anticholinesterase that increases ACh at the junction in order to overcome levels of acetylcholine receptors

What test is used to diagnose myasthenia gravis?

- edrophonium test

- NAChR antibody test