Skeletal Muscle Relaxants, Spasmolytics, Local Anesthetics

Neuromuscular blockers - completely paralyze skeletal muscle during surgical and orthopedic procedures. peripherally acting. (hospital)

spasmolytics - elicit a more modulatory effect on muscle contraction; does not completely block activity. Reduce muscle spasms. either central or peripherally acting. (ambulatory patients)

Natural occurring alkaloids found in various South American plants. The most important alkaloid is d-tubocurarine.

- chemically most are bisquaternary ammonium compounds

- either nondepolarizing (competitive) or depolarizing blocking drugs

Positively charged:
poorly absorbed from gut and generally rapidly excreted
will not cross BBB
will not cross placenta
administered IV

Aka "competitive" "-ium"
- block NMJ nicotinic receptors competitively. They compete for the receptor with ACh.
- long acting (>35 mins) : pancuronium - moderate blockade of cardiac muscarinic receptors
- intermediate acting (20-35 min) : vecuronium, atracurium (slight effect on histamine release), rocuronium, cisatracuium
- short acting (5-15 min) : succinylcholine (stimulation of autonomic ganglia, slight effect on histamine release, stimulation of cardiac muscarinic receptors)

- increase [ ] of endogenous ACh at the NMJ.
- use ChE inhibitors such as neostigmine, physostigmine, edrophonium together with atropine (to protect muscarinic receptors against excessive stimulation by increased levels of ACh)

Phase 1 block: initial depolarization of the end-plate region; transient muscle fasciculation followed by relaxation.

Phase 2 block: desensitization of the receptor to ACh. End-plate repolarization possibly due to conformational change of the receptor molecule.

* cholinesterase inhibitors: during phase 1 block they will intensify response to succinylcholine. during late phase 2 block they may reinitiate muscle contraction.

Takes place in the plasma whereas ACh metabolism takes place at the NMJ

ChE for succinylcholine is different than AChE. Plasma ChE is synthesized in the liver thus patients with liver dysfunction/decreased hepatic blood flow/genetic abnormalities show prolonged responses to succinylcholine.

1:3000 pts have genetic related decrease of plasma ChE
==> tx is mechanical respiration

1. small rapidly contracting muscles (extrinsic muscles of the eye)
2. muscles for speech and deglutition
3. trunk and limbs
4. respiratory muscles

- do not enter the brain --> CNS fully functional, pain is not dulled

Depolarizing Drug (Succinylcholine)
- fasciculation can result in: post operative muscle stiffness and pain, increase of intraocular pressure - contraction of the extraocular muscles, increased intragastric pressure - occasionally leading to emesis, hyperkalemia

Nondepolarizing Drug (Atracurium, occasionally succinylch.)
- release of endogenous histamine into circulation - bronchospasm, increased excretions, vasodilation resulting in decreased blood pressure ==> tx: antihistamines
- pharmacological response potentiated by: some general anesthetics and local anesthetics, antibiotics, fluid & electrolyte imbalance.

Dantroline - interfers from SR Ca++ release
indications: chronic disorders characterized by muscle spasms (hepatotoxicity!); malignant hyperthermia - genetic disorder, autosomal dominant, triggered by halogenated anesthetic and/or succinylcholine, sudden rise of Ca++ in muscle fiber with increase of body temperature, rigidity

Baclofen - GABAb receptor agonist (prevents release of excitatory neurotransmitters -glutamate- onto motor neurons)
diazepam - enhances action of GABA in the spinal cord
indications: chronic disorders characterized by muscle spasticity
side effects: sedation and drowsiness

tizanidine - mechanism of action unclear. Derivative of clonidine - has significant alpha-2 adrenoceptive agonist activity. Appears to reinforce pre- and postsynaptic inhibition in the cord. Inhibits nociceptive transmission in the cord.
indications: chronic disorders characterized by muscle spasticity
side effects: sedation, drowsiness, hypOtension, dry mouth, asthenia

* sedative drugs used for acute local muscle spasm *

side effects: most are sedative hypnotics and some have antimuscarinic activity

* drug used for acute local muscle spasm *

inhibits release of ACh from cholinergic nerve terminals. Benefits may persist for weeks after injection.

potential toxicity: may spread beyond injection point and lead to difficulty swallowing and breathing

BOTOX: strabismus, uncontrollable blinking, cervical dystonia, moderate-severe frown lines between eyebrows, appears to be effective for headache

Reversibly block nerve conduction along axons and other excitable membranes that utilize sodium channels; this action is used clinically to reduce pain sensation or sympathetic vasoconstrictor impulses to specific areas of the body