Pharm: muscle relaxants Flashcards
Baclofen
- centrally acting spasmolytic
MOA: agonist at GABAb receptors –> hyperpolarization: d/t closure of Ca2+ and increased K+ conductance
Comparison: as effective as diazepam in reducing spasticity and causes less sedation; does not reduce overall muscle strength as much as dantrolene.
ADR’s: drowsiness
- increased seizure risk in epileptics
- confusion, dizziness, hypotonia, mm. weakness
USE: reversible spasticity associated with multiple sclerosis or spinal cord lesions; intrathecal administration is used for treatment of intractable spasticity caused by spinal cord injury, multiple sclerosis, and other spinal disease (e.g., spinal ischemia or tumor, transverse myelitis, cervical spondylosis, degenerative myelopathy).
Tizanidine
- centrally acting spasmolytic
MOA: alpha2 agonist (similar to clonidine) - reinforces pre and postsynaptic inhibition of the cord
- inhibits nociceptive transmission in the dorsal horn
Comparison: comparable in efficacy in relieving muscle spasm to diazepam, baclofen, and dantrolene
ADRs: less muscle weakness but produces drowsiness (take dose at night), hypotension, dizziness, dry mouth, asthenia, and hepatotoxicity.
Therapeutic use: muscle spasticity.
Diazepam
“valium” - centrally acting spasmolytic
MOA: benzodiazepine; promotes binding of γ-aminobutyric acid (GABA) to the GABAA receptor, enhances GABA-induced ion currents; leads to increased inhibitory transmission and a reduction in spasticity.
Therapeutic use:
- sedation, hypnotic effects, muscle relaxation, anxiolytic, and anticonvulsant effects.
- management of anxiety disorders, ethanol withdrawal symptoms
- skeletal muscle relaxation, treatment of convulsive disorders, preoperative or pre-procedural sedation, and amnesia.
ADRs:
- generalized CNS depression
- produces sedation at the doses required to reduce muscle tone. - risk of dependence (Schedule IV category of controlled substances)
- depression of CNS functions, amnestic effects, and additional CNS depression when combined with other drugs that depress the CNS (e.g., ethanol).
Carisoprodol
- local mm. spasmolytic
MOA: unclear; acts as CNS depressant.
PK: metabolized by CYP2C19; use with caution when co-administered with CYP450 inhibitors
Therapeutic use: short-term treatment (2-3 weeks, lack of evidence of effectiveness with prolonged use) of musculoskeletal pain.
ADRs: drowsiness & dizziness. Schedule IV category of controlled substances (addictive properties).
Cyclobenzaprine
- local mm. spasmolytic
MOA: unclear; reduces tonic somatic motor activity by influencing both alpha and gamma motor neurons.
PK: metabolized by CYP450s; use with caution when co-administered with CYP450 inhibitors.
use: treatment of muscle spasm associated with acute, painful musculoskeletal conditions (do not use longer than 2-3 weeks); ineffective in treating muscle spasm due to cerebral palsy or spinal cord injury.
ADRs:
- structurally related to tricyclic antidepressants and produces antimuscarinic side effects (may cause significant sedation, confusion, and transient visual hallucinations).
- Additional effects: dizziness, and xerostomia.
Dantrolene
-non-central acting spasmolytic
** In contrast to the centrally acting drugs, dantrolene reduces skeletal muscle strength by interfering with excitation-contraction coupling in the muscle fibers.
MOA: causes inhibition of the ryanodine receptor (RyR) calcium channel; blocks the release of calcium through the sarcoplasmic reticulum and muscle contraction is impaired.
- Cardiac and smooth muscle are unaffected due to a different RyR channel subtype.
use: treatment of spasticity associated with upper motor neuron disorders (e.g., spinal cord injury, stroke, cerebral palsy, or multiple sclerosis) and management of malignant hyperthermia.
ADRs: generalized muscle weakness, sedation, and occasionally hepatitis (contraindicated in patients with hepatitis).
Botulinum toxin
-non-central acting spasmolytic
MOA: zinc endopeptidase cleaves specific proteins involved in vesicle fusion. Disruption of fusion proteins prevents the release of acetylcholine.
use:
- treatment of cervical dystonia; blepharospasm;
- temporary improvement in the appearance of lines/wrinkles of the face;
- treatment of severe primary axillary hyperhidrosis;
- treatment of generalized spasticity;
- prophylaxis of chronic migraine headache; and treatment of incontinence due to overactive bladder.
ADRs: focal muscle weakness in the area of injection, which may last up to several months.
Interferons
drugs for MS- (beta1a and beta1b)
MOA: enhances suppressor T cell activity, reduces proinflammatory cytokines, down-regulates antigen presentation, reduces trafficking of lymphocytes into the CNS.
** Improves MRI lesions, decreases relapse rate, and disease severity in patients with secondary progressive MS.
ADRs: injection site reactions, flu-like symptoms, high prevalence of asymptomatic liver dysfunction. Other reactions include: leukopenia, anemia, and suicide.
glatiramer acetate
drugs for MS - Biological agent used for management of relapsing-remitting type MS.
MOA: mixture of random polymers of four amino acids (L-alanine, L-glutamic acid, L-lysine, and L-tyrosine) that is antigenically similar to myelin basic protein, which is an important component of the myelin sheath of nerves.
- Thought to induce and activate T-lymphocyte suppressor cells specific for a myelin antigen; also proposed to interfere with the antigen-presenting function of certain immune cells opposing pathogenic T-cell function.
ADRs: local injection site reactions and transient systemic postinjection reactions (chest pain, flushing, dyspnea, palpitations, anxiety).
mitoxantrone
drugs for MS - Antineoplastic agent used to treat multiple sclerosis, acute myeloid leukemia, and advanced, hormone-refractory prostate cancer.
MOA: intercalates into DNA resulting in cross-links and strand breaks (related to anthracyclines).
** Reserved for rapidly advancing disease who have failed other therapies (cardiac toxicity and limited evidence of benefit).
Glucocorticoids
drugs for MS
Monthly bolus IV glucocorticoids (typically 1000 mg of methylprednisolone) are used for treatment of primary or secondary progressive MS alone or in combination with other immunomodulatory or immunosuppressive medications.
malignant hyperthermia
A rare heritable disorder that can be triggered by a variety of stimuli, including general anesthetics (e.g., volatile anesthetics) and neuromuscular blocking drugs (e.g., succinylcholine).
Patients at risk for this condition have a hereditary alteration in Ca2+ release via the RyR channel or impairment in the ability of the sarcoplasmic reticulum to sequester Ca2+.
* After administration of a triggering agent, there is a sudden and prolonged release of calcium with massive muscle contraction, lactic acid production, and increased body temperature.*
- Reduction of calcium is accomplished with administration of dantrolene.
