13.

Skeletal muscle relaxants

Skeletal muscle relaxants Nm blockers patient is CONSCIOUS, but paralyzed
– direct acting Nondepolarizing – curare derivatives e.g., roCURonium (Zemuron)
competitive inhibition means reversed with AChE inhibitors (e.g., neostigmine, pyridostigmine) also suggamedex
may be used to reverse rocuronium by binding to it – as the free fraction goes down, rocuronium will leave Nm
receptor
when we reverse curare with AChE inhibitors, we get salivation, lacrimation, defecation, bradycardia, and
sometimes increased BP.

we reverse most of these symptoms with antimuscarinic e.g., SCOPolamine

adverse effects – paralysis; itching/bronchospasm, etc. from (rare) histamine release
Depolarizing = succinylcholine (Quelicin)
“succinylcholine is acetylcholine x 2” – initially activates Nm, but then won’t let go → paralysis from
desensitization
Metabolized by plasma esterases (aka butyrylesterase aka pseudocholinesterase) – patients who have
inherited low plasma esterase activity may have very prolonged effect
“Dual” mechanism (FYI)
in phase I – acts as depolarizing blocker
in phase II – due to alterations in Nm receptor acts more like a nondepolarizing agent (with long-term
exposure)

adverse effects:
muscle fasciculations, muscle pain
transient hyperkalemia (bad in burns, crush injury, may be worse in those with long-standing neurologic injury)
risk of malignant hyperthermia
may cause histamine release (less so than some of the curare deriv)
NOT generally reversed by acetylcholinesterase inhibitors!!!! (it noncompetitively inhibits the Nm by causing
prolonged activation)

dantrolene (Dantrium)- blocks ryanodine receptor, decreasing Ca++ release from SR

uses:
1. neuroleptic malignant syndrome antidote?
2. malignant hyperthermia antidote!!
3. skeletal muscle relaxant/spasmolytic
side effects:
1. idiosyncratic hepatitis
2. drowsiness, fatigue
3. risk of falls

Botulinum toxins – block release of acetylcholine from cholinergic neurons

FYI uses – many!
1. achalasia
2. cosmetic
3. dystonia
4. essential tremor
5. overactive bladder
6. spasticity
adverse effects – risk of spreading paralysis – may be life threatening!

Centrally acting GABAb agonist – baclofen )Lioresal®)

use - spasmolytic; less sedation that benzos, some analgesia
adverse effects
a. potential withdrawal seizures
b. sedation (titrate up)

Benzodiazepines – GABAa agonists – generally need a higher dose, sedation limits daily usefulness e.g., diazepam
(Valium) – increase frequency of GABAa open in the presence of GABA

GABAa agonist: carisoprodol (Soma®) is C-IV

benefit - NONE
adverse effects: death (respiratory depression) – binds to a different site than benzos
b. hypotension and tachycardia
c. sedation
13. Skeletal muscle relaxants
d. tolerance, dependance, withdrawal (anxiety, seizures); addiction potential
Misc agents, mechs not well described, “general CNS depression”
a. global adverse effects with all the central agents
1. sedation (less with methocarbamol Robaxin®))
2. CNS depression, incoordination, fall/driving risk
3. euphoria in some cases
b. drug to know: cyclobenzaprine (Flexeril®) (chemically related to TCA)
1. Sedating
2. antimuscarinic
3. Na+ channel block
c. FYI other drugs individual side effects
1. hepatotoxicity: chlorzoxazone (Parafon), metaxolone (Skelaxin)
2. anticholinergic (antimuscarinic): orphenadrine, cyclobenzaprine (Flexeril)
3. urine discoloration: chlorzoxazone

Alpha 2 agonist : tizadindine (Zanaflex®) (FYI also intrathecal clonidine)

benefit: short action so it doesn’t cause prolonged effect (but downside have to take multiple doses)
adverse drug effects
1. sedation
2. dry mouth
3. hypotension, bradycardia
4. hallucinations
5. hepatotoxicity