Cyclobenzaprine

1. Drug Overview

• Generic name: Cyclobenzaprine
• Brand names: Flexeril, Amrix, Fexmid
• Drug class: Centrally acting skeletal muscle relaxant
• Therapeutic category: Muscle relaxant for relief of skeletal muscle spasm
• Chemical class: Tricyclic amine derivative (structurally related to tricyclic antidepressants like amitriptyline)

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2. Mechanism of Action (MOA)

• Site of action: Brainstem (not directly on skeletal muscle or neuromuscular junction).
• Cyclobenzaprine acts on alpha and gamma motor neurons in the central nervous system to reduce tonic somatic motor activity.
• It inhibits the facilitation of motor neurons at the level of the brainstem, leading to muscle relaxation.
• Does not interfere with neuromuscular transmission or act directly on skeletal muscle fibers.
• Pharmacological effect: Reduces hyperactive muscle reflexes → relieves local muscle spasm without loss of muscle strength.

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3. Pharmacological Actions

System	Action
Skeletal muscle	Relaxes skeletal muscles in acute musculoskeletal conditions
CNS	Sedation due to central action
Cardiovascular	Mild anticholinergic and antiadrenergic effects (due to TCA-like structure)

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4. Pharmacokinetics (ADME)

Parameter	Description
Absorption	Well absorbed orally; bioavailability ≈ 33–55%
Distribution	Highly protein bound (~93%)
Metabolism	Extensively metabolized in the liver (mainly via CYP1A2)
Elimination half-life	8–37 hours (longer in elderly or hepatic impairment)
Excretion	Primarily in urine as metabolites

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5. Therapeutic Uses (Indications)

• Acute muscle spasm due to musculoskeletal conditions (e.g., strain, sprain, injury).
• Adjunct to physical therapy and rest in acute painful musculoskeletal disorders.
• Occasionally used off-label in fibromyalgia (limited benefit).
• Not effective in spasticity of CNS origin (e.g., cerebral palsy, spinal cord injury).

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6. Dosage

Form	Adult Dose
Tablet (5–10 mg)	5 mg orally three times daily; may increase to 10 mg TID if needed
Extended-release (15–30 mg)	Once daily, typically at bedtime
Duration of therapy	Short-term use only (≤ 2–3 weeks) — effectiveness beyond this not established

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7. Adverse Effects

Most adverse effects are CNS-related due to its tricyclic structure.

Common:

• Drowsiness
• Dizziness
• Dry mouth
• Fatigue
• Blurred vision
• Constipation

Less Common:

• Confusion, especially in elderly
• Urinary retention
• Tachycardia
• Headache
• Nausea

Serious / Rare:

• Cardiac arrhythmias (especially with overdose)
• Serotonin syndrome (if combined with serotonergic agents)
• CNS depression (in combination with alcohol or other sedatives)

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8. Contraindications

• Recent MAOI use (within 14 days) → risk of hyperpyretic crisis, seizures, or death
• Hyperthyroidism (increased risk of arrhythmia)
• Cardiac conditions: Arrhythmias, heart block, recent myocardial infarction, congestive heart failure
• Hypersensitivity to cyclobenzaprine

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9. Drug Interactions

Interacting Agent	Result
MAOIs	Hypertensive crisis, seizures
CNS depressants (alcohol, opioids, benzodiazepines)	Additive sedation, respiratory depression
Anticholinergic drugs (antihistamines, TCAs)	Enhanced dry mouth, constipation, urinary retention
Serotonergic drugs (SSRIs, SNRIs, tramadol)	Risk of serotonin syndrome
CYP1A2 inhibitors (ciprofloxacin, fluvoxamine)	↑ Cyclobenzaprine levels

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10. Precautions

• Use with caution in elderly (increased sensitivity, risk of confusion).
• Avoid prolonged use; not effective for chronic conditions.
• Avoid driving or operating machinery due to sedation.
• Avoid in hepatic impairment (metabolism reduced).

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11. Toxicity and Overdose

• Symptoms: CNS depression, agitation, hallucinations, cardiac conduction disturbances, anticholinergic toxicity (mydriasis, dry mucosa, hyperthermia).
• Management: Supportive care; gastric lavage or activated charcoal if early; physostigmine for severe anticholinergic symptoms; cardiac monitoring essential.

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12. Mechanistic Comparison (Summary Table)http://Drugs.com

Drug	Mechanism	Use	Distinctive Feature
Cyclobenzaprine	Central (brainstem) inhibition of motor neurons	Acute muscle spasm	Structurally related to TCAs
Baclofen	GABA_B receptor agonist	Spasticity (CNS origin)	Used in multiple sclerosis
Tizanidine	α₂-adrenergic agonist	Spasticity	Causes hypotension, sedation
Methocarbamol	CNS depressant	Muscle spasm	Less anticholinergic
Carisoprodol	CNS depressant (GABAergic metabolite)	Short-term spasm	Risk of abuse/dependence

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13. Clinical Pearls

• Only effective in acute musculoskeletal conditions, not spasticity.
• Sedation is the most prominent effect — often taken at bedtime.
• Structurally similar to amitriptyline, explaining anticholinergic and cardiac effects.
• Should be used short-term, combined with physiotherapy and rest.

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14. Summary

Parameter	Detail
Drug Class	Centrally acting skeletal muscle relaxant
Mechanism	Reduces tonic somatic motor activity via brainstem
Indication	Acute muscle spasm
Dose	5–10 mg TID (short term)
Half-life	8–37 h
Major AE	Drowsiness, dry mouth, dizziness
Metabolism	Hepatic (CYP1A2)
Contraindications	MAOI use, cardiac disorders, hyperthyroidism
Key Caution	Avoid in elderly and hepatic impairment
Distinctive Feature	Tricyclic structure; central muscle relaxant, not antispastic