Kruse DSA: Skeletal Muscle Relaxants Flashcards
What are the centrally acting spasmolytics?
- Baclofen
- Cariprodol
- Cyclobenzaprine
- Diazepam
- Tizanidine
What are the non-centrally acting spasmolytics?
- Danrtrolene
- Botulinum toxin
What are the immunologic drugs for Multiple sclerosis?
- Glucocorticoids
- Glatiramer acetate
- Interferons 1a and 1b
- Mitoxantrone
Baclofen MOA
- agonist at GABA(B) receptors
- results in hyperpolarization and inhibition of excitatory neurotransmitter release in the brain and spinal cord
- increased K+ conductance
Adverse effects of Baclofen
- drowsiness, which patients become tolerant to with chronic administration
- increased seizure activity in epileptic pts (withdrawl must be done slowly)
What is Baclofen used to treat?
- reversible spasticity associated with multiple sclerosis or spinal cord lesions
- intrathecal administration is used for tx of intractable spasticity caused by spinal cord injury, ms, and other spinal disease
What does Carisprodol act as?
- a CNS depressant
- short term tx (2-3 weeks) of msk pain
Adverse effects of Carisprodol?
-dizziness and drowsiness
What is Carisprodol metabolized by?
- CYP2C19
- use with caution when coadministered with CYP450 inhibitors
What is carisprodol metabolized to?
- meprobamate
- has anxiolytic and sedative effects
MOA or Chlorzoxazone?
- acts on spinal cord and subcortical levels by depressing polysynaptic reflexes
- used for symptomatic tx of muscle spasm and pain associated with acute msk conditions
What does cyclobenzaprine do?
-reduces tonic somatic motor activity by influencing both alpha and gamma motor neurons
What is cyclobenzaprine used to treat?
- muscle spasm associated with acute, painful msk conditions
- ineffective in treating muscle spasm due to cerebral palsy or spinal cord injury
What is cyclobenzaprine metabolized by?
- CYP450
- use with caution when coadministered with CYP450 inhibitors
Adverse effects of cyclobenzaprine?
-drowsiness, dizziness, and xerostomia
Diazepam MOA
-promote the binding of the major inhibitory neurotransmitter in the CNS GABA(a) receptor, enhancing GABA-induced ion currents; leads to increased inhibitory transmission and a reduction in spasticity
common used of diazepam?
-management of anxiety disorders, ethanol withdrawal symptoms, skeletal muscle relaxation, tx of convulsive disorders, preoperative or preprocedural sedation, and amnesia
Common adverse effects of diazepam?
-generalized CNS depression
Disadvantages to using benzo’s
- risk of dependence
- depression of CNS functions
- amnestic effects
- additional CNS depression when combined with other drugs that depress the CNS
Tizanidine MOA
- alpha2 adrenergic agonist that decreases excitatory input to alpha motor neurons
- used for tx of muscle spasticity
adverse effects of Tizanidine?
-drowsiness, hypotension, dry mouth, and asthenia/muscle weakness
What does Dantrolene do?
-in contrast to the centrally acting drugs, reduces skeletal muscle strength by interfering with excitation-contraction coupling in the muscle fibers
MOA of Dantrolene
-causes inhibition of the RyR calcium channel; blocks the release of calcium through the sarcoplasmic reticulum and muscle contraction is impaired
Why arent Cardiac and smooth muscle affected by Dantrolene?
-different RyR channel subtypes
Side effects of Dantrolene
-generalized muscle weakness, sedation, and occasionally hepatitis (contraindicated in hepatitis patients)
What do we use Dantrolene for?
-tx of spasticity associated with upper motor neuron disorders and management of malignant hyperthermia
What is malignant hyperthermia?
- rare heritable disorder that canbe triggered by a variety of stimuli, including the combination of general anesthetics and succinylcholine
- patients at risk for this condition have a hereditary impairment in the ability of the sarcoplasmic reticulum to sequester calcium
- after administration of a triggering agent, a sudden and prolonged release of calcium causes massive muscle contraction, lactic acid production, and increased body temperature
- reduction of calcium is accomplished with administration of dantrolene
MOA for botulinum toxin
-cleaves components of the core CNARE complex involved in exocytosis, preventing the release of ACh
adverse effects of Botulinum toxin
-focal muscle weakness in the area of injection, which may last up to several months
glucocorticoids
-monthly bolus IV glucocorticoids are used for tx of primary or secondary progressive MS alone or in combo with other immunomodulatory or immunosuppressive medications
MOA of glatiramer acetate?
-a mixture of random polymers of four amino acids that is antigenically similar to myelin basic protein, which is an important component of the myelin sheath of nerves
Interferons MOA
- Acts on BBB by interferin with T-cell adhesion to the endothelium by binding VLA-4 on T cells or by inhibiting the T-cell expression of MMP
- results in a reduction of relapses by one-third, a reduction of new MRI T2 lesions and the volume of enlarging T2 lesions, a reduction in the number and volume of Fd-enhancing lesions, and a slowing of brain atrophy
What is Mitoxantrone?
-Antineoplastic agent used to tx MS, AML, and advanced hormonere-refractory prostate cancer
MOA of Mitoxantrone?
-intercalates into DNA resulting in cross-links and strand breaks
