Phase I block augmented by cholinesterase inhibitors

Phase I: Agonist at nicotinic ACh receptor (causing transient contractions). Membranes remain depolarized and unresponsive (prolonged flaccid paralysis).
↑ by AChE inhibitors.

Phase II: membrane repolarized but cannot easily be depolarized again because of desensitization (paralysis similar to non-d. block)

↓ by AChE inhibitors.

Arrhythmias, hyperkalemia, transient increased intrabdominal and intraocular pressure, postoperative muscle pain

Placement of tracheal tube at start of anesthetic procedure

Rarely, control of peripheral muscle contractions in status epilecticus (but does not enter CNS)

Reversal of blockade by cholinesterase inhibitors

Competitive antagonist at nicotinic ACh receptors, preventing depolarization and causing flaccid paralysis

Can also block prejunctional Na⁺ channels, interferes with ACh mobilization at nerve endings

Histamine release with hypotension

Prolonged apnea

Prolonged relaxation with surgical procedures

relaxation of respiratory muscles to facilitate mechanical ventilation in IC

GABA_B agonist

hyperpolarization by ↑ K⁺ conductance => ↓Ca⁺² influx & ↓ excitatory transmitter release;

↓ Substance P release

Sedation, weakness

Excessive somnolence, respiratory depression, even coma

Severe spasticity due to cerebral palsy, multiple sclerosis, stroke

Bind to GABA_A receptor subunits at CNS neuronal synapses facilitating GABA mediated Cl^- channel opening; ↑ internueuron inhibition of primary motor afferents in spinal cord; central sedation

Extensions of CNS depressant effects, dependence liability

Diplopia, nystagmus

Chronic spasm due to cerebral palsy, stroke, spinal cord injury

acute spasm due to muscle injury

α₂-adrenoceptor agonist in the spinal cord; pre- and postsynaptic inhibition of reflex motor output

congener of clonidine (See CH 11)

Drowsiness, hypotension, dry mouth, asthenia

Spasm due to multiple sclerosis, stroke, amyotrophic lateral sclerosis

Blocks ryanodine receptor RyR1 Ca⁺² release channels in the sarcoplasmic reticulum of skeletal muscle
Reduces actin-myosin interaction, weakens skeletal muscle contraction

Muscle weakness

Hepatic toxicity

IV: Malignant hyperthermia (triggered by volatile anesthetics CH 16; or NMJ blocking drugs, e.g. succinylcholine)

Oral: Spasm due to cerebral palsy, spinal cord injury, multiple sclerosis

Prevents fusion of presynaptic vesicles with the presynaptic membrane, thereby inhibiting release of ACh into the synaptic cleft => Flaccid paralysis

Botulinum – paralytic illness

Ophthalmic purposes, local muscle spasm (See CH 6)

Generalized spastic disorders (e.g. cerebral palsy)