Skeletal muscle relaxants

Definition and Scope
Skeletal muscle relaxants (SMRs) are a diverse group of pharmacological agents that are used to reduce skeletal muscle tone, relieve muscle spasms, treat spasticity, and manage musculoskeletal pain. They do not act at the neuromuscular junction but rather target central nervous system (CNS) pathways or muscle contractile mechanisms to alleviate involuntary muscle activity.

They are broadly divided into two major categories:

1. Spasmolytics (used for muscle spasms due to musculoskeletal conditions)

2. Antispasticity agents (used for chronic neurological conditions with spasticity)

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Classification

Type	Description	Common Drugs
Centrally Acting SMRs	Act on brainstem/spinal cord to reduce motor output	Baclofen, Cyclobenzaprine, Tizanidine
Direct-Acting SMRs	Act at the muscle fiber itself	Dantrolene
Neuromuscular Blockers	Act peripherally at the neuromuscular junction (not typically classified as SMRs in standard therapeutic use)	Succinylcholine, Rocuronium (excluded from SMR scope)

Mechanism of Action

1. Centrally Acting SMRs

   • Inhibit polysynaptic reflex arcs and/or alpha motor neurons in the spinal cord.

   • Reduce tonic somatic motor activity.

   • Main targets: GABA-B receptors, alpha-2 adrenergic receptors, histamine receptors, and voltage-gated ion channels.

2. Direct-Acting SMRs

   • Dantrolene interferes with calcium ion release from the sarcoplasmic reticulum in skeletal muscle.

   • Reduces excitation-contraction coupling.

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Therapeutic Indications

Indication	SMRs Used
Acute musculoskeletal conditions	Cyclobenzaprine, Methocarbamol, Carisoprodol
Chronic spasticity (e.g., MS, SCI)	Baclofen, Tizanidine, Dantrolene
Fibromyalgia	Cyclobenzaprine (off-label)
Cerebral palsy	Baclofen, Dantrolene
Malignant hyperthermia	Dantrolene (emergency use)
Trigeminal neuralgia	Tizanidine (off-label)

Common Skeletal Muscle Relaxants

Generic Name	Brand Name(s)	Type
Baclofen	Lioresal	Centrally acting, antispastic
Tizanidine	Zanaflex	Centrally acting, alpha-2 agonist
Cyclobenzaprine	Flexeril, Amrix	Centrally acting, TCA derivative
Methocarbamol	Robaxin	Centrally acting, general CNS depressant
Carisoprodol	Soma	Centrally acting (prodrug of meprobamate)
Metaxalone	Skelaxin	Centrally acting
Orphenadrine	Norflex	Anticholinergic, analgesic properties
Chlorzoxazone	Parafon Forte	Centrally acting
Dantrolene	Dantrium	Direct-acting muscle relaxant

Dosing Overview

Drug	Typical Adult Dose
Baclofen	5 mg TID → titrate to 40–80 mg/day
Tizanidine	2–4 mg every 6–8 h; max 36 mg/day
Cyclobenzaprine	5–10 mg TID; max 30 mg/day
Methocarbamol	1500 mg QID (initial); taper
Carisoprodol	250–350 mg TID and HS; max 1400 mg/day
Dantrolene	25 mg/day → titrate to 100 mg QID

Note: Many SMRs are intended for short-term use (2–3 weeks), especially in acute musculoskeletal conditions.

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Adverse Effects

Class/Agent	Common Side Effects	Serious Effects
Centrally acting	Sedation, dizziness, dry mouth, fatigue	CNS depression, hepatotoxicity (Tizanidine)
Cyclobenzaprine	Anticholinergic effects (dry mouth, urinary retention)	QT prolongation (rare)
Carisoprodol	Drowsiness, abuse potential	Dependence, withdrawal symptoms
Baclofen	Weakness, confusion, urinary retention	Seizures on abrupt withdrawal
Dantrolene	Muscle weakness, diarrhea	Hepatotoxicity, especially with long-term use

Contraindications

Agent	Contraindications
Baclofen	History of seizures, psychiatric disorders
Tizanidine	Liver disease, use with CYP1A2 inhibitors
Cyclobenzaprine	Hyperthyroidism, recent MI, arrhythmias
Methocarbamol	Hypersensitivity, renal dysfunction (caution)
Carisoprodol	History of drug abuse, porphyria
Dantrolene	Active liver disease

Drug Interactions

Agent	Interacting Drugs	Effect/Concern
Tizanidine	Ciprofloxacin, fluvoxamine (CYP1A2 inhibitors)	Severe hypotension
Cyclobenzaprine	MAOIs, SSRIs, alcohol	Serotonin syndrome, CNS depression
Carisoprodol	CNS depressants	Additive sedation
Baclofen	CNS depressants, alcohol	Increased sedation, confusion
Dantrolene	Verapamil	Hyperkalemia, cardiac suppression

Monitoring Parameters

Agent	Monitoring Required
Baclofen	Mental status, muscle tone, renal function
Tizanidine	Liver function tests (LFTs) periodically
Dantrolene	LFTs regularly due to hepatotoxicity
All SMRs	Sedation level, signs of misuse

Use in Special Populations

Population	Consideration
Elderly	Start low, go slow; fall risk, sedation
Pregnancy	Limited data; avoid unless benefit outweighs risk
Hepatic impairment	Avoid tizanidine, dantrolene
Renal impairment	Adjust baclofen dose

Clinical Considerations and Practice Guidelines

• SMRs are not first-line for chronic low back pain unless short-term adjunctive therapy is needed.

• Avoid long-term use of carisoprodol due to dependence and abuse risk.

• For spasticity from neurologic diseases, baclofen and tizanidine are generally preferred.

• Dantrolene is the only SMR used in malignant hyperthermia, a medical emergency.

• Intrathecal baclofen pumps may be implanted for patients with severe, refractory spasticity.

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Comparison Summary

Agent	Best For	Notes
Baclofen	Spasticity (MS, SCI)	Avoid abrupt withdrawal
Tizanidine	Spasticity, off-label for headaches	Hepatotoxic; short half-life
Cyclobenzaprine	Acute back pain, fibromyalgia	Structurally similar to TCAs
Carisoprodol	Acute musculoskeletal pain	High abuse potential
Dantrolene	Chronic spasticity, malignant hyperthermia	Direct-acting, hepatotoxic risk
Methocarbamol	Short-term use in strains/sprains	Fewer CNS side effects compared to others