Skeletal Muscle Relaxtants

List the classes and the clinical uses of skeletal muscle relaxants

CLASSES & CLINICAL USES

• NMJ blockers → procedural paralysis

• Spasmolytics → acute painful spasm

• Antispasticity drugs → chronic UMN spasticity

• Rocuronium / succinylcholine / vecuronium → paralysis

• Cyclobenzaprine / methocarbamol / carisoprodol → CNS spasm relief

• Baclofen / tizanidine → chronic spasticity

Differentiate between the mechanism of Nondepolarizers and depolarizers

Nondepolarizers (competitive antagonists)

• Occupy Nm → ACh can’t bind → no end- plate depolarization → flaccid paralysis

Succinylcholine (depolarizer)

• Nm agonist → opens channel → stays depolarized (“can’t reset”) → paralysis

Describe the absorption of Quaternary amines

• Permanently charged nitrogen atom (R₄N⁺)

• Poor absorption from GI tract

• Poor membrane penetration

• Do not cross theBBB

Describe the ORDER OF BLOCKADE & RECOVERY of muscle relaxtants

Describe the TRAIN-OF-FOUR

• What is it?

• TOF of NOrmal?

• Nondepolarizers

• succinylcholine?

TRAIN-OF-FOUR

• What is it?

  • TOF = 4 nerve stimuli → 4 twitches

• Normal (no drug)

  • All 4 twitches same height (no fade)

• Nondepolarizers

  • Fade (T4 < T1) with repetitive stimulation

• Succinylcholine

  • Phase I: no fade (uniformly decreased twitches)

  • Phase II (prolonged): fade can appear

    • (behaves “like nondepolarizer”)

NOTE: Fade = competitive block (or Phase II SCh)

Describe Succinylcholine (SCh)

• What type is it?

• onset

• Duration

• MOA

• Adverse Effects

Succinylcholine (SCh)

• What type is it?

  • Depolarizing NM blocker

• Onset

  • Very fast → ideal for rapid sequence intubation

• Duration

  • Short (rapid hydrolysis by plasma pseudocholinesterase)

• MOA

  • Nm agonist → channel opens → sustained depolarization → paralysis

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ADVERSE EFFECTS

• Hyperkalemia risk

  • Avoid burns, crush/trauma, denervation/spinal cord injury, neuromuscular disease/immobility (↑ extrajunctional AChRs)

• Malignant hyperthermia trigger

  • w/ volatile anesthetics

• Bradycardia (esp. pediatrics or repeat dosing)

• ↑ IOP / ↑ intragastric pressure + myalgias (post- op muscle pain)

• Prolonged paralysis

  • Atypical pseudocholinesterase or inhibitors → slow breakdown → slow recovery

NOTE: Brief fasciculations → flaccid paralysis

Describe NONDEPOLARIZERS

• MOA

• Two Classes/Drugs in the class

• Potency vs onset

• Elimination

• MOA:

  • Nm antagonists → blocks Ach from binding -> flaccid paralysis 

• Two Classes/Drugs in the class

  • Aminosteroids

    • Ro-curonium, 

    • ve-curonium, 

    • pan-curonium

  • Benzylisoquinoliniums

    • Cis-atra-curium, 

    • atra-curium, 

    • miva-curium

• Potency vs onset

  • Less potent → faster onset

• Elimination

  • Cisatracurium/atracurium

    • Hofmann elimination ± ester hydrolysis → organ-independent (useful in liver/kidney dysfunction)

Describe MIVACURIUM

• What is it?

• Clinical Use

• Meta.

• Adverse Effects

• What is it?

  • Short-acting nondepolarizing blocker

• Clinical Use:

  • For Brief paralysis / intubation

• Metabolism

  • Rapid plasma cholinesterase metabolism

• Adverse Effects:

  • Prolonged in pseudocholinesterase deficiency

  • Histamine release → 

    • flushing, hypotension, bronchospasm

Describe PSEUDOCHOLINESTERASE DEFICIENCY

• What is it?

• Side Effects

• Management

• Diagnosis

PSEUDOCHOLINESTERASE DEFICIENCY

• What is it?

  • Inherited/Acquired Low/abnormal plasma cholinesterase

• Side Effects

  • Succinylcholine + mivacurium affected

    • Markedly prolonged paralysis/apnea

• Management: 

  • ventilatory support until recovery

• Diagnosis:

  • Prolonged Blockade

  • Dibucaine # test

Describe AChE INHIBITORS

• MOA

• Drug Family/Members

• Synergy?

AChE INHIBITORS

• MOA:

  • ↑ ACh to outcompete nondepolarizer at Nm

• Drug Family/Members:

  • Quaternary ammonium

    • Neostigmine 

      • (intermediate acting)

    • Pyridostigmine 

      • (long acting, MG maintenance)

  •  Tertiary amine

    • Physostigmine

      •  (crosses CNS, not for NMJ reversal)

• Synergy?

  • Pair w/ antimuscarinic ->  prevents bradycardia + secretions

    • Glycopyrrolate (or atropine)

Describe SUGAMMADEX

• What is it?

• MOA

• Synergy?

• Adverse Effects?

SUGAMMADEX

• What is it?

  • Selective relaxant binding agent 

  • (“molecular trap”)

• MOA:

  • Encapsulates rocuronium + vecuronium → pulls drug out of circulation → rapid reversal (even deep block)

• Synergy?

  • No antimuscarinic needed 

    • (not an AChE inhibitor)

• Adverse Effects?

  • can bind steroidal molecules & may lower exposure to estrogen/progestin contraceptives

List and describe the potential Muscle Relaxants Interactions

• Potentiation (↑ paralysis)

  • Volatiles, aminoglycosides, Mg²⁺, lithium → lower dose + monitor TOF

• Myasthenia gravis

  • Fewer functional Nm receptors → very sensitive to nondepolarizers 

    • (small doses, prolonged effect)

• Burns/denervation

  • Avoid succinylcholine → massive K⁺ efflux → hyperK arrest risk

    • (after ~24–48 h, for weeks–month

Describe MALIGNANT HYPERTERMIA

• Causes

• Earliest red flag

• Symptoms

• Treatment

MALIGNANT HYPERTERMIA

• Causes:

  • Volatile anesthetics + succinylcholine

• Earliest red flag

  • Rapid ↑ETCO₂ despite adequate ventilation

• Symptoms:

  • Classic clinical signs

    • Muscle rigidity, 

    • tachycardia, 

    • Acidosis

  • Later/complications

    • Hyperthermia (late),

    • rhabdomyolysis → hyperK, 

    • arrhythmias 

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TREATMENT

1. Stop triggers -> switch to 100% O₂ / hyperventilate

2. Antidote: Dantrolene 

   1. RyR1 inhibitor → ↓ Ca²⁺ release → ↓ rigidity + heat

3. Active cooling (ice packs/cold fluids) + treat acidosis + hyperK (arrhythmia risk)

Differentiate between SPASM vs. SPASTICITY

• Spasm

  • Acute, painful muscle tightening

  • Often follows peripheral muscle injury

• Spasticity

  • Chronic ↑ tone + hyperreflexia

  • Classically from upper motor neuron (UMN) lesions

    • MS, SCI, CP, stroke

Describe SPASMOLYTICS drugs

• What are they?

• Clinical Usage

• Adverse Effects

• Members

SPASMOLYTICS

• What are they?

  • Outpatient “muscle relaxants”

    • Acute spasm meds (not NMJ blockers)

• Clinical Usage

  • For Acute low back/neck spasm after strain

  • Short-term adjunct to NSAIDs/acetaminophen + early mobility

• Adverse Effects:

  • Sedation/dizziness

    • Caution with driving, alcohol, CNS depressants

• Members

  • Cyclobenzaprine → anticholinergic

  • Methocarbamol / metaxalone 

    • sedation

  • Carisoprodol

    • misuse/dependence risk

  • Chlorzoxazone

    • hepatotoxicity

Describe CYCLOBENZAPRINE

• Clinical Usage

• MOA

• Adverse Efffects

• Synergy?

CYCLOBENZAPRINE

• Clinical Usage:

  • Central muscle relaxant for acute spasm (short course)

• MOA:

  • Acts centrally in brainstem to reduce tonic somatic motor activity 

    • (likely via 5-HT/NE modulation)

• Adverse Effects

  • Sedation + anticholinergic 

    • (dry mouth, urinary retention, blurred vision, constipation) 

  • confusion/falls

• Synergy?

  • Avoid w/  MAOIs 

    • (risk of serious toxicity/serotonergic effects)

1. Why muscle relaxants -> Sedation/Fall?

2. Deadly Synergies w/ Muscle Relax.?

3. Safety rule?

• Why muscle relaxants -> Sedation/Fall

  • Many “muscle relaxants”  = CNS depressants

    • Drowsiness, 

    • slowed reaction time, 

    • impaired driving

• Deadly Synergies w/ Muscle Relax.

  • Alcohol, benzodiazepines, opioids → excess sedation/resp depression.

• Safety rule:

  • start at night, short course, & avoid other sedatives when possible

Describe ANTISPASTICITY DRUGS

• Clinical Usage

• Members/MOA

• Key limitations

ANTISPASTICITY DRUGS

• Clinical Usage:

  • Chronic UMN spasticity

• Members/MOA:

  • Baclofen → GABAB agonist

  • Tizanidine → α2 agonist

  • Diazepam → enhances GABAA

  • Dantrolene → direct skeletal muscle action

  • Botulinum toxin → blocks ACh release

• Key Limitations:

  • sedation, 

  • weakness, 

  • dizziness, 

  • falls

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NOTE:

• Baclofen or tizanidine often first

• Add/consider dantrolene or selected benzodiazepines

• Use botulinum toxin for focal spasticity

Describe TIZANIDINE

• MOA

• Adverse Effects

• How to stop?

TIZANIDINE

• MOA

  • Central α2-agonist → ↓ excitatory outflow to motor neurons → ↓ spasticity/spasm

• Adverse Effects:

  • Sedation + dizziness

  •  ↓ BP / bradycardia

    • (additive with other CNS depressants/antihypertensives)

  • Rare hepatotoxicity

    • Check LFTs

• How to stop?

  • Taper it

    • abrupt stop = rebound HTN/tachycardia (esp high dose/long use)

Describe BACLOFEN

• MOA

• Adverse Effects

• Abrupt Withdrawl?

BACLOFEN

• MOA

  • Spinal GABA(B) agonist -> 

    • ↓ excitatory transmitter release

    • Relieves muscle spasticity

• Adverse Effects:

  • sedation, weakness, dizziness

• Abrupt Withdrawal?

  • Dangerous

    • Withdrawal risk ↑ with intrathecal use

Describe BENZODIAZEPINES

• MOA

• Adverse Effects

BENZODIAZEPINES

• MOA:

  • enhances GABAA -> inhibitory CNS signaling

    • Reduce spasticity

• Adverse Effects 

  • Sedation

  • Dependence

  • Respiratory depression risk 

    • w/ other depressants

Describe DANTROLENE

• What is it?

• MOA?

• clinical Usage

• Adverse Effects

DANTROLENE

• What is it?

  • Peripheral muscle relaxant

• MOA:

  • Blocks RyR1 in skeletal muscle -> ↓ SR Ca²⁺ release

• Clinical Usage:

  • malignant hyperthermia (MH)

  • selected spasticity

• Adverse effects 

  • Weakness

  • hepatotoxicity

Describe BOTULINUM TOXIN

• What is it

• MOa

• Uses

• Adverse Effects

BOTULINUM TOXIN

• What is it?

  • presynaptic blocker

• MOA:

  • Blocks ACh release at NMJ via SNARE cleavage → focal weakness

• Uses:

  •  focal spasticity

  • dystonia

• Adverse effects

  • local weakness, 

  • rare spread effects