Pharm III - Skeletal muscle relaxants

Antispasmodic agents

metaxalone, carisoprodol, methocarbamol, cyclobenzaprine, orphenadrine, tizanidine, and diazepam

Antispasticity agents

baclofen, dantrolene, tizanidine

What kind of agent should you use for upper motor neuron lesions (cerebral palsy, multiple sclerosis)

Antispasticity agents

What kind of agent should you use for peripheral musculoskeletal conditions (backache)

Antispasmodic agents

SE for Antispastic/antispasmodic agents

Anticholinergic (sedation, somnolence, dry mouth, constipation, urinary retention)

T/F: There is evidence supporting long-term use in both Antispasticity and antispasmodic agents

False, no evidence for long-term use for antispasmodics

Which drugs provide both antispasticity and antispasmodic properties

Diazepam

Tizanidine

Baclofen MOA

spasticity - similar to GABA -> decreases synaptic transmission on spinal cord

Baclofen elimination

Extensive renal elimination, requires adjustment

Black box warning for baclofen

Avoid abrupt discontinuation

Baclofen ADE

Weakness, vertigo, insomnia

Dantrolene MOA

spasticity - structurally related to phenytoin, interferes w Ca release

Black box warning for dantrolene

hepatotoxicity

Ideal agent for malignant hyperthermia

Dantrolene

Tizanidine MOA

centrally acting alpha 2 agonist on spinal neurons

Antispasticity and antispasmodic

Tizanidine DDI

Ciprofloxacin, fluvoxamine contraindicated - increases tizanidine 7-10 fold

ADE of tizanidine

Hypotension, hepatotoxicity

Mixed category muscle relaxant that has abuse potential

Diazepam

Diazepam MOA

Antispasticity and antispasmodic - benzodiazepine

Enhances GABA inhibition at spinal and supra-spinal

Methocarbamol MOA

Unclear, CNS depression

- derivative of guaifenesin

Methocarbamol ADE

Lightheadedness

Discolored urine

Can exacerbate Myasthenia Gravis

Less sedation

Carisoprodol class

Controlled substance (C4)

Carisoprodol MOA

CNS suppression and reduction of pain perception

How is carisoprodol metabolized?

Active metabolite meprobamate (prodrug)

- anxiolytic in 1950s

- half life increase with chronic use

Carisoprodol abuse combination warning

Abuse potential w hydrocodone and alprazolam

Cyclobenzaprine structure

Similar to tricyclic antidepressant

ADE for cyclobenzaprine

Arrhythmias, prolonged QTC

Metaxalone MOA

Unclear, attributed to sedation

- no abuse, mild withdrawal

Metaxalone bioavailability

High fat meals increase bioavailability

When is metaxalone contraindicated?

Severe renal/liver dysfunction

Which patients should you avoid using metaxalone for

Pts with history of anemia

Orphenadrine structure

Similar to diphenhydramine

Atropine like effects - related to CNS anticholinergic activity and NMDA antagonism

Orphenadrine ADE

Highly anticholinergic related, GI disturbances, cardiovascular (palpitations, tachycardia)

Which patients should you avoid using Orphenadrine in?

Elderly - due to anticholinergic effects

Pts with CV disease, GI obstruction, or myasthenia gravis

T/F: prescribe baclofen or dantrolene for MSK pain

False - sparse evidence to support antispasticity agents for MSK conditions. Use antispasmodics

1st line for MSK conditions

NSAIDs

1st line for spasticity

Baclofen

Which muscle relaxants require tapering

Baclofen, tizanidine, orphenadrine

Baclofen reaction to abrupt withdrawal

Hallucinations and seizures

Tizanidine reaction to abrupt withdrawal

HTN, tachycardia, hypertonia, tremor, anxiety

Orphenadrine reaction to abrupt withdrawal

Malaise and flu-like symptoms

Which muscle relaxants have the highest potential for abuse

Carisoprodol followed by cyclobenzaprine