Skeletal Muscle Relaxants and Antimigraine Agents Flashcards
Baclofen
Lioresal, Ozobax
Carisoprodol
Soma, Vanadom
C-IV
Cyclobenzaprine
Flexeril
Metaxalone
Skelexin
Methocarbamol
Robaxin
Tizanidine
Zanaflex
Eletriptan
Relpax
Rizatriptan
Maxalt
Sumatriptan
Imitrex
Therapeutic Class - Baclofen
Centrally acting skeletal muscle relaxant
Therapeutic Class - Carisoprodol
Centrally acting skeletal muscle relaxant
Therapeutic Class - Cyclobenzaprine
Centrally acting skeletal muscle relaxant
Therapeutic Class - Metaxalone
Centrally acting skeletal muscle relaxant
Therapeutic Class - Methocarbamol
Centrally acting skeletal muscle relaxant
Therapeutic Class - Tizanidine
Centrally acting skeletal muscle relaxant
Alpha-2 agonist
Therapeutic Class - Eletriptan
Antimigraine serotonin receptor agonist
Therapeutic Class - Rizatriptan
Antimigraine serotonin receptor agonist
Therapeutic Class - Sumatriptan
Antimigraine serotonin receptor agonist
Dosage Forms - Baclofen
Tablet: 5 mg, 10 mg, 20 mg
Dosage Forms - Carisoprodol
Tablet: 250 mg, 350 mg
Dosage Forms - Cyclobenzaprine
Tablet: 5 mg, 7.5 mg, 10 mg
ER Capsule: 15 mg, 30 mg
Dosage Forms - Metaxalone
Tablet: 400 mg, 800 mg
Dosage Forms - Methocarbamol
Tablet: 500 mg, 750 mg
Dosage Forms - Tizanidine
Tablet: 2 mg, 4 mg
Capsule: 2 mg, 4 mg, 6 mg
Dosage Forms - Eletriptan
Tablet: 20 mg, 40 mg
Dosage Forms - Rizatriptan
Tablet: 5 mg, 10 mg
Orally-Disintegrating Tablet: 5 mg, 10 mg
Dosage Forms - Sumatriptan
Tablet: 25 mg, 50 mg, 100 mg Nasal Solution: 5 mg/actuation Nasal Exhaler Powder: 11 mg/nosepiece Solution for Subcutaneous Injection: 3 mg/0.5 mL, 4 mg/0.5 mL, 6 mg/0.5 mL Transdermal (patch): 6.5 mg/4 h
MOA - Baclofen
Inhibits both monosynaptic and polysynaptic reflexes at the spinal level, possibly by hyperpolarization of afferent terminals, although actions at supraspinal sites may also occur and contribute to its clinical effect
Analogue of γ-aminobutyric acid (GABA), but there is no conclusive evidence that actions on GABA systems are involved in the production of its clinical effects.
MOA - Carisoprodol
Block interneuronal activity in the descending reticular formation and spinal cord causing muscle relaxation
MOA - Cyclobenzaprine
Relieves skeletal muscle spasm of local origin without interfering with muscle function.
Ineffective in muscle spasm due to CNS disease
Evidence suggests that the net effect of cyclobenzaprine is a reduction in tonic motor activity, influencing both gamma (𝛾) and alpha (α) motor systems.
MOA - Metaxalone
Not well established likely due to CNS depression. No direct action on the contractile mechanism of striated muscle, the motor end plate, or the nerve fiber.
MOA - Methocarbamol
Not well established likely due to CNS depression. No direct action on the contractile mechanism of striated muscle, the motor end plate, or the nerve fiber.
MOA - Tizanidine
Imidazole derivative, structurally unrelated to other muscle relaxants - centrally acting muscle relaxant. Agonist of alpha-2 adrenergic receptors leads to decreased spasticity by increasing presynaptic inhibition. NO antihypertensive properties
MOA - Eletriptan
Binds with high affinity to serotonin (5-HT) subtypes 1B, 1D, and 1F receptors.
No significant affinity or pharmacological activity at adrenergic α1, α2, or β; dopaminergic D1or D2; muscarinic; or opioid receptors.
Serotonin receptor agonists are believed to be effective in migraine, either through vasoconstriction (via activation of 5-HT1receptors located on intracranial blood vessels) or through activation of 5-HT1receptors on sensory nerve endings in the trigeminal system, resulting in the inhibition of proinflammatory neuropeptide release.
MOA - Rizatriptan
Binds with high affinity to serotonin (5HT) receptor subtypes 1B and 1D.
Serotonin receptor agonists are believed to be effective in migraine either through vasoconstriction (via activation of 5-HT1receptors located on intracranial blood vessels) or through activation of 5-HT1receptors on sensory nerve endings in the trigeminal system resulting in the inhibition of proinflammatory neuropeptide release.
MOA - Sumatriptan
Binds with high affinity to serotonin (5-HT) subtypes 1B, 1D, and 1F receptors
No significant affinity or pharmacologic activity at adrenergic α1, α2, or β; dopaminergic D1or D2; muscarinic; or opioid receptors.
Serotonin receptor agonists are believed to be effective in migraine either through vasoconstriction (via activation of 5-HT1receptors located on intracranial blood vessels) or through activation of 5-HT1receptors on sensory nerve endings in the trigeminal system resulting in the inhibition of proinflammatory neuropeptide release.
FDA-Approved Indications - Baclofen
- Spasticity: 5 mg TID (can increase by 5 mg/dose every 3 days) (adult MDD = 80 mg)
FDA-Approved Indications - Carisoprodol
- Disorder musculoskeletal system: 250-350 mg TID and QHS
FDA-Approved Indications - Cyclobenzaprine
- Skeletal muscle spasm:
a) IR: 5 mg TID (can titrate up to 10 mg TID) and treat 2-3 weeks
b) ER: 15 mg QD (can titrate up to 30 mg QD)
FDA-Approved Indications - Metaxalone
- Musculoskeletal pain or spasm: 800 mg TID-QID
FDA-Approved Indications - Methocarbamol
- Musculoskeletal pain or spasm: 1500 mg QID for 48-72 hours (can titrate to 750 mg q4h or 1500 mg TID or 1000 mg QID)
FDA-Approved Indications - Tizanidine
- Muscle spasticity: 2 mg up to TID (may titrate to 8 mg q6-8h; MDD = 36 mg)
FDA-Approved Indications - Eletriptan
- Migraine: 20-40 mg at onset of migraine, may repeat in 2 hours PRN (Max single dose: 40 mg; MDD = 80 mg)
FDA-Approved Indications - Rizatriptan
- Migraine (adults): 5-10 mg at onset of migraine, may repeat after 2 h PRN (MDD = 30 mg)
- Migraine (children >6 years old and adolescents <40 kg): 5 mg at onset of migraine, multiple doses in a 24 hour period NOT recommended
FDA-Approved Indications - Sumatriptan
- Migraine
a) Oral: 25-100 mg at onset of migraine, may repeat after 2h PRN (MDD = 200 mg)
b) Nasal: 5-20 mg in 1 nostril, may repeat after 2h (MDD = 40 mg)
c) Subcutaneous: inject 6 mg (MDD = 12 mg)
d) Transdermal: apply 1 patch, may apply a 2nd patch after 2h (MDD = 2 patches) - Cluster headaches: 6 mg SQ once (MDD = 12 mg)
Off-Label Uses - Baclofen
- Intractable hiccoughs: 5-10 mg BID (increase to 15-45 mg/day in 3 divided doses OR 10-20 mg BID-TID)
- Alcohol use disorder: 5 mg TID (may increase to 10 mg TID after 3-5 days; MDD = 60 mg)
- Muscle spasm and/or musculoskeletal pain: 5 mg TID PRN
Off-Label Uses - Cyclobenzaprine
- Temporomandibular Joint Disorder (TMJ):
a) IR: 10 mg QD x 3 weeks - Fibromyalgia: 5-10 mg QHS (may titrate to 10-40 mg in 1 to 3 divided doses)
Off-Label Uses - Tizanidine
- Acute low back pain: 2-4 mg q6-12h (MDD = 24 mg) alone or in combination with NSAIDs
Kinetics - Baclofen
Absorption: F = 100%
Distribution: Vd = 59.1 L; 30% protein bound
Metabolism: Limited
Elimination: Renal 60-80%; T1/2 = 3-7 hours
Hepatic Dose Adjustment: None
Renal Dose Adjustment: Monitor
Kinetics - Carisoprodol
Absorption: unknown Distribution: unknown Metabolism: hepatic; major CYP2C19 substrate Elimination: renal; T1/2 = 8 hours Hepatic Dose Adjustment: low and slow Renal Dose Adjustment: none
Kinetics - Cyclobenzaprine
Absorption: F = 33-55% Distribution: 93% protein bound Metabolism: extensive hepatic; CYP1A2 substrate Elimination: renal 50%; T1/2 = 18 hours Hepatic Dose Adjustment: a) Mild: 5 mg QD (IR; avoid ER) b) Severe: avoid Renal Dose Adjustment: none
Kinetics - Metaxalone
Absorption: ?? food enhances Distribution: Vd = 800 L Metabolism: hepatic; multiple CYP substrate Elimination: renal; T1/2 = 8-9 hours Hepatic Dose Adjustment: low and slow Renal Dose Adjustment: low and slow
Kinetics - Methocarbamol
Absorption: ??
Distribution: protein-binding 45-50%
Metabolism: hepatic via dealkylation and hydroxylation
Elimination: renal (as metabolites); T1/2 = 1-2 hours
Hepatic Dose Adjustment: low and slow
Renal Dose Adjustment: none
Kinetics - Tizanidine
Absorption: F = 40%, food increases tablet absorption and decreases capsule absorption; hepatic 1st pass
Distribution: Vd = 2.4 L/kg; 30% protein bound
Metabolism: extensive hepatic; CYP1A2 substrate
Elimination: renal 60%; T1/2 = 2 hours
Hepatic Dose Adjustment: not recommended
Renal Dose Adjustment: CrCl <25 mL/min = reduce dose
Kinetics - Eletriptan
Absorption: F = 50%; high fat food increases 20-30%
Distribution: Vd = 138 L
Metabolism: hepatic; CYP3A4
Elimination: nonrenal 90%; T1/2 = 4 hours
Hepatic Dose Adjustment: severe = AVOID
Renal Dose Adjustment: none
Kinetics - Rizatriptan
Absorption: F = 45% Distribution: Vd = 110-140 L Metabolism: hepatic via MAO Elimination: renal 82%, feces; T1/2 = 2-3 hours Hepatic Dose Adjustment: none Renal Dose Adjustment: none
Kinetics - Sumatriptan
Absorption: F = 15%, high fat food increases
Distribution: Vd = 2.4 L/kg; 14-21% protein bound
Metabolism: hepatic via MAO
Elimination: renal 60%; T1/2 = 2.5 hours
Hepatic Dose Adjustment: max single dose = 50 mg
Renal Dose Adjustment: none
Drug Interactions - Cyclobenzaprine
- CYP1A2 inducers/inhibitors = monitor
- CNS depressants (opioids, benzodiazepines, alcohol) = AVOID
- Anticholinergic agents = AVOID
Drug Interactions - Carisoprodol
- CYP2C19 inducers/inhibitors = monitor
2. CNS depressants (opioids, benzodiazepines, alcohol) = AVOID
Drug Interactions - Metaxalone
- CNS depressants = AVOID
Drug Interactions - Methocarbamol
- CNS depressants = AVOID
Drug Interactions - Tizanidine
- CYP1A2 inducers/inhibitors = do not co-administer with inhibitors
- CNS depressants = AVOID
- Phenytoin/Fosphenytoin = monitor
Drug Interactions - Eletriptan
- CYP3A4/5 = monitor
- SSRIs = AVOID
- Other 5-HT agonists = contraindicated if administered within 24 hours
Drug Interactions - Rizatriptan
- SSRIs = AVOID
- Other 5-HT agonists = contraindicated if administered within 24 hours
- Ergot alkaloids = contraindicated
- MAOI = contraindicated
Drug Interactions - Sumatriptan
- SSRIs = AVOID
- Other 5-HT agonists = contraindicated if administered within 24 hours
- Ergot alkaloids = contraindicated
- MAOI = contraindicated
Baclofen in Pregnancy/Lactation
Pregnancy: risk
Lactation: probably compatible
Carisoprodol in Pregnancy/Lactation
Pregnancy: no data
Lactation: probably compatible
Cyclobenzaprine in Pregnancy/Lactation
Pregnancy: low risk?
Lactation: probably compatible
Metaxalone in Pregnancy/Lactation
Pregnancy: no data
Lactation: potential toxicity
Methocarbamol in Pregnancy/Lactation
Pregnancy: low risk
Lactation: probably compatible
Tizanidine in Pregnancy/Lactation
Pregnancy: risk
Lactation: potential toxicity
Eletriptan in Pregnancy/Lactation
Pregnancy: moderate risk
Lactation: compatible
Rizatriptan in Pregnancy/Lactation
Pregnancy: moderate risk
Lactation: probably compatible
Sumatriptan in Pregnancy/Lactation
Pregnancy: moderate risk
Lactation: probably compatible
Black Box Warning - Baclofen
Avoid abrupt discontinuation of oral or intrathecal product
Drugs with Beers Criteria
- Carisoprodol
- Cyclobenzaprine
- Metaxalone
- Methocarbamol
Contraindications - Carisoprodol
- Hypersensitivity to meprobamate
2. Acute intermittent porphyria
Contraindications - Cyclobenzaprine
- Concomitant MAOI use
- Heart failure
- Acute coronary phase of AMI
- Heart block
- Hyperthyroidism
Contraindications - Metaxalone
- Significantly impaired renal or hepatic function
Contraindications - Tizanidine
- Concurrent use with CYP1A2 inhibitors
Contraindications - Eletriptan
Cerebrovascular syndromes, hemiplegic or basial migraine, ischemic bowel disease, ischemic heart disease, peripheral vascular disease, severe hepatic impairment, uncontrolled HTN
Contraindications - Rizatriptan and Sumatriptan
Cerebrovascular syndromes, hemiplegic or basial migraine, ischemic bowel disease, ischemic heart disease, peripheral vascular disease, severe hepatic impairment, uncontrolled HTN, MAOIs, ergot alkaloids
Adverse Effects - Baclofen
Common: Nausea, asthenia, dizziness, somnolence, confusion
Less common: Constipation, fatigue, hypotension, shivering, urinary symptoms, peripheral edema, difficulty in micturition
Rare but serious: Slowed or difficult breathing when used in combination with opioids, pneumonia, GI hemorrhage, seizure
Adverse Effects - Carisoprodol
Common: drowsiness, dizziness
Less common: headache
Rare but serious:Slowed or difficult breathing when used in combination with opioids, seizure, drug dependence, withdrawal symptoms upon discontinuation after chronic use
Adverse Effects - Cyclobenzaprine
Common: Xerostomia, headache, dizziness, drowsiness
Less common: onstipation, indigestion, nausea, pharyngeal dryness, asthenia, confusion, blurred vision
Rare but serious: Cardiac dysrhythmia, cholestasis, hepatitis, jaundice, anaphylaxis, immune hypersensitivity reaction, slowed or difficult breathing when used in combination with opioids
Adverse Effects - Metaxalone
Common: dizziness
Less common: N/V, headache, somnolence
Rare but serious: Hemolytic anemia, leukopenia, jaundice, immune hypersensitivity reaction, maculopapular rash, slowed or difficult breathing when used in combination with opioids
Adverse Effects - Methocarbamol
Common: somnolence
Less common: Flushing, pruritus, rash, urticaria, nausea, vomiting, dizziness, headache, nystagmus, vertigo, blurred vision, conjunctivitis
Rare but serious: Bradyarrhythmia, hypotension, syncope, leukopenia, anaphylactoid reaction, slowed or difficult breathing when used in combination with opioids
Adverse Effects - Tizanidine
Common: Hypotension, xerostomia, asthenia, dizziness, somnolence, muscle weakness
Less common: Constipation, vomiting, dyskinesia, amblyopia, feeling nervous, syncope, depression
Rare but serious: AMI, thrombocytopenia, hepatitis, PE, hypersensitivity, death, slowed or difficult breathing when used in combination with opioids
Adverse Effects - Eletriptan
Common: weakness
Less common: Nausea, asthenia, dizziness, somnolence
Rare but serious: Angina, cardiac dysrhythmia, coronary arteriosclerosis, heart block, HTN, acute myocardial infarction, aphasia, cerebral ischemia, stroke, dystonia, hemiplegia, neuropathy, transient ischemic attack, oculogyric crisis
Adverse Effects - Rizatriptan and Sumatriptan
Common: none
Less common: Nausea, asthenia, dizziness, somnolence
Rare but serious: Angina, cardiac dysrhythmia, coronary arteriosclerosis, heart block, HTN, acute myocardial infarction, aphasia, cerebral ischemia, stroke, dystonia, hemiplegia, neuropathy, transient ischemic attack, oculogyric crisis
Drug Monitoring - Baclofen
Efficacy: Reduction in muscle spasm, passive limb movement and pain relief
Toxicity: Severe dizziness, confusion, sedation, or rebound spasticity occurs.
Drug Monitoring - Carisoprodol
Efficacy: Reduction in pain and muscle spasms
Toxicity: Idiosyncratic symptoms such as extreme weakness, transient quadriplegia, dizziness, confusion occur within minutes or hours after first dose
Drug Monitoring - Cyclobenzaprine
Efficacy: Reduction in pain and muscle spasms
Toxicity: Sx of Hepatic failure
Drug Monitoring - Metaxalone
Efficacy: Reduction in pain and muscle spasms
Toxicity: Monitor LFTs and CBC
Drug Monitoring - Methocarbamol
Efficacy: Reduction in pain and muscle spasms
Toxicity: Idiosyncratic symptoms such as extreme weakness, transient quadriplegia, dizziness, and confusion occur within minutes or hours after 1st dose; Vital signs
Drug Monitoring - Tizanidine
Efficacy: Reduction in pain and muscle spasms & in passive limb movement
Toxicity: Monitor BP, LFTs, SCr, and CBC
Drug Monitoring - Eletriptan, Rizatriptan, and Sumatriptan
Efficacy: Resolution of signs of migraine headache
Toxicity: Ischemic bowel disease (eg, sudden severe abdominal pain, bloody diarrhea) or peripheral vascular disease (eg, Raynaud syndrome), serotonin syndrome (eg, agitation, hallucinations, tachycardia, hyperreflexia, incoordination, diarrhea, nausea), ischemic cardiac syndrome, or hypertensive crisis
Counseling and Pearls - Baclofen
Counseling: Caution when operating motor vehicles or dangerous machinery due to sedation. CNS effects may be additive when used with alcohol or other CNS depressants.
Pearls: Implantable pumps that administer baclofen intrathecally are also available for patients with spasticity. Constipation occurs in 100% of patients undergoing intrathecal administration, and abrupt discontinuation of intrathecal therapy (intentional or inadvertent) can result in seizures, coma, and death. Avoid concomitant use with opioids.
Counseling and Pearls - Carisoprodol
Counseling: Avoid consuming alcohol. Avoid activities requiring mental alertness or coordination until drug effects are known, as drug may cause dizziness or sedative effects. Patients withdrawing from prolonged therapy should be monitored carefully for withdrawal symptoms, including seizures.
Pearls: Carisoprodol should be used for only short periods (up to 2 or 3 wk). It was approved in 1959, so limited pharmacologic and kinetic data available. May require tapering at discontinuation after chronic use. Avoid concomitant use with opioids.
Counseling and Pearls - Cyclobenzaprine
Counseling: Avoid activities requiring mental alertness or coordination until drug effects are known, as drug may cause dizziness or sedative effects. Take extended-release capsule same time each day.
Pearls: Cyclobenzaprine should be used for only short periods (up to 2-3 wk). Avoid concomitant use with opioids. Use with caution in patients with glaucoma, increased IOP, urinary retention, etc, as cyclobenzaprine has anticholinergic-like effects. Avoid use in elderly; may be more sensitive to effects.
Counseling and Pearls - Metaxalone
Counseling: Avoid activities requiring mental alertness or coordination until drug effects are known, as drug may cause dizziness or sedative effects.
Pearls: Metaxalone should be used for only short periods (up to 2 or 3 wk). Not for use in children <12 y of age. Use with caution in elderly who may be more susceptible to adverse effects. Should avoid concomitant use with opioids.
Counseling and Pearls - Methocarbamol
Counseling: Avoid activities requiring mental alertness or coordination until drug effects are known, as drug may cause dizziness or sedative effects.
Pearls: Methocarbamol should be used for only short periods (up to 2 or 3 wk). Drug may color urine brown, black, or green. Injectable form available, used for spasticity associated with tetanus. Should avoid concomitant use with opioids.
Counseling and Pearls - Tizanidine
Counseling: Be cautious of risk of dizziness and somnolence when initiating therapy; do not drive until effects of drug are known. Rise slowly from a lying/sitting position, as this drug may cause hypotension. May cause xerostomia (dry mouth) and asthenia (weakness).
Pearls: While this drug may be taken with or without food, patients should take the drug in the same way (fasting or fed) every time to avoid inconsistent absorption patterns and resulting changes in efficacy and adverse effects. Effect of food on extent of absorption differs for tablets and capsules. Abrupt discontinuation can cause rebound HTN and tachycardia. Taper dose by 2-4 mg/d if used at high dose (20-28 mg daily) or for an extended period of time. Should avoid concurrent use with opioids. Capsules and tablets are not interchangeable.
Counseling and Pearls - Eletriptan
Counseling: Avoid activities requiring mental alertness or coordination until drug effects are realized, as this drug may cause dizziness or somnolence
Pearls: These agents are not for prophylaxis—these are used for the treatment of acute migraine headache. Several serotonin agonists (“triptans”) exist for migraine, administered via a variety of routes (oral, inhaled, injected). Each differs in onset and duration of action. If an agent is ineffective atmaxdose, recommend changing agents or route. Instruct patient to take a 2nd dose ≥2 h after the 1st if needed, but no >80 mg/d. Overuse of acute migraine medications can lead to medication overuse headache that may present similarly to migraine; may require detoxification including management of withdrawal symptoms.
Counseling and Pearls - Rizatriptan
Counseling: Avoid alcohol, CNS depressants. Caution with driving and other tasks requiring alertness. Allow disintegrating tablet to dissolve on tongue and then swallow, do not chew.
Pearls: Serotonin agonists are not for prophylaxis; only for the treatment of acute migraine headache. Several serotonin agonists (“triptans”) are available for migraine, administered via a variety of routes (oral, inhaled, and injected). Each differs in onset and duration of action. If one agent is ineffective atmaxdose, recommend changing agents or route.
Counseling and Pearls - Sumatriptan
Counseling: Avoid activities requiring mental alertness or coordination until drug effects are realized, as this drug may cause dizziness or somnolence.
Pearls: Sumatriptan is also available in formulations for injectable administration, and as an oral dosage form in combination with naproxen. These agents are not for prophylaxis; only for the treatment of acute migraine headache. Several serotonin agonists (“triptans”) exist for migraine, administered via a variety of routes (oral, inhaled, and injected). Each differs in onset and duration of action. If 1 agent is ineffective atmaxdose, recommend changing agents or route.
