Kruse DSA: Skeletal Muscle Relaxants

Question 1

What are the centrally acting spasmolytics?

Answer 1

• Baclofen
• Cariprodol
• Cyclobenzaprine
• Diazepam
• Tizanidine

Question 2

What are the non-centrally acting spasmolytics?

Answer 2

• Danrtrolene

- Botulinum toxin

Question 3

What are the immunologic drugs for Multiple sclerosis?

Answer 3

• Glucocorticoids
• Glatiramer acetate
• Interferons 1a and 1b
• Mitoxantrone

Question 4

Baclofen MOA

Answer 4

• agonist at GABA(B) receptors
• results in hyperpolarization and inhibition of excitatory neurotransmitter release in the brain and spinal cord
• increased K+ conductance

Question 5

Adverse effects of Baclofen

Answer 5

• drowsiness, which patients become tolerant to with chronic administration
• increased seizure activity in epileptic pts (withdrawl must be done slowly)

Question 6

What is Baclofen used to treat?

Answer 6

• 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

Question 7

What does Carisprodol act as?

Answer 7

• a CNS depressant

- short term tx (2-3 weeks) of msk pain

Question 8

Adverse effects of Carisprodol?

Answer 8

-dizziness and drowsiness

Question 9

What is Carisprodol metabolized by?

Answer 9

• CYP2C19

- use with caution when coadministered with CYP450 inhibitors

Question 10

What is carisprodol metabolized to?

Answer 10

• meprobamate

- has anxiolytic and sedative effects

Question 11

MOA or Chlorzoxazone?

Answer 11

• 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

Question 12

What does cyclobenzaprine do?

Answer 12

-reduces tonic somatic motor activity by influencing both alpha and gamma motor neurons

Question 13

What is cyclobenzaprine used to treat?

Answer 13

• muscle spasm associated with acute, painful msk conditions

- ineffective in treating muscle spasm due to cerebral palsy or spinal cord injury

Question 14

What is cyclobenzaprine metabolized by?

Answer 14

• CYP450

- use with caution when coadministered with CYP450 inhibitors

Question 15

Adverse effects of cyclobenzaprine?

Answer 15

-drowsiness, dizziness, and xerostomia

Question 16

Diazepam MOA

Answer 16

-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

Question 17

common used of diazepam?

Answer 17

-management of anxiety disorders, ethanol withdrawal symptoms, skeletal muscle relaxation, tx of convulsive disorders, preoperative or preprocedural sedation, and amnesia

Question 18

Common adverse effects of diazepam?

Answer 18

-generalized CNS depression

Question 19

Disadvantages to using benzo’s

Answer 19

• risk of dependence
• depression of CNS functions
• amnestic effects
• additional CNS depression when combined with other drugs that depress the CNS

Question 20

Tizanidine MOA

Answer 20

• alpha2 adrenergic agonist that decreases excitatory input to alpha motor neurons
• used for tx of muscle spasticity

Question 21

adverse effects of Tizanidine?

Answer 21

-drowsiness, hypotension, dry mouth, and asthenia/muscle weakness

Question 22

What does Dantrolene do?

Answer 22

-in contrast to the centrally acting drugs, reduces skeletal muscle strength by interfering with excitation-contraction coupling in the muscle fibers

Question 23

MOA of Dantrolene

Answer 23

-causes inhibition of the RyR calcium channel; blocks the release of calcium through the sarcoplasmic reticulum and muscle contraction is impaired

Question 24

Why arent Cardiac and smooth muscle affected by Dantrolene?

Answer 24

-different RyR channel subtypes

Question 25

Side effects of Dantrolene

Answer 25

-generalized muscle weakness, sedation, and occasionally hepatitis (contraindicated in hepatitis patients)

Question 26

What do we use Dantrolene for?

Answer 26

-tx of spasticity associated with upper motor neuron disorders and management of malignant hyperthermia

Question 27

What is malignant hyperthermia?

Answer 27

- 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

Question 28

MOA for botulinum toxin

Answer 28

-cleaves components of the core CNARE complex involved in exocytosis, preventing the release of ACh

Question 29

adverse effects of Botulinum toxin

Answer 29

-focal muscle weakness in the area of injection, which may last up to several months

Question 30

glucocorticoids

Answer 30

-monthly bolus IV glucocorticoids are used for tx of primary or secondary progressive MS alone or in combo with other immunomodulatory or immunosuppressive medications

Question 31

MOA of glatiramer acetate?

Answer 31

-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

Question 32

Interferons MOA

Answer 32

- 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

Question 33

What is Mitoxantrone?

Answer 33

-Antineoplastic agent used to tx MS, AML, and advanced hormonere-refractory prostate cancer

Question 34

MOA of Mitoxantrone?

Answer 34

-intercalates into DNA resulting in cross-links and strand breaks