Skeletal muscle relaxants Dr. Pond

Question 1

What is Spasticity?

Answer 1

Condition in which certain muscles are continuously
contracted
-> too much skeletal muscle activation through somatic neuron activity

Question 2

What is the cause of Spasticity?

Answer 2

damage to the portion of the brain or spinal cord that controls voluntary movement

Question 3

What are the major pathways that control somatic neurons?

Answer 3

Corticospinal and brainstem pathway neurons
->they activate somatic motor neurons in the
ventral horn of the spinal cord

Question 4

Which NT is involved in activating somatic neurons?

Answer 4

Glutamate
-> EPSP (excitatory)

Question 5

What is the approach to reduce Spasticity?

Answer 5

reduce the activity of excitatory somatic neurons
OR
enhancing inhibiton neurons -> that release GABA to bind to GABA(A) receptors on motor neuron

Question 6

How does Benzodiazepine work for skeletal muscle relaxation?

Answer 6

it is in GABA(A) modulator -> enhance the IPSPs that are created by inhibitor neuron -> decreases action potential frequency in the somatic neuron

-> also cause sedation since we have GABA(A) receptors in the brain

Question 7

Which receptors are targeted by Baclofen?

Answer 7

Baclofen is a GABA(B) agonist
-> GABA(B) receptors

-> presynaptic: closes voltage-gated Ca2+channels and prevents release of Glutamate - inhibits excitatroy neuron

-> postsynaptic: opens K+channel -> IPSP and the action potential is less likely to fire

Question 8

What is the BBW for Baclofen?

Answer 8

BBW: worse with intrathecal formulation
-rebound spasticity, and muscle rigidity
-high fever
-altered mental status

ADE:
-drowsiness (tolerance can develop to this), dizziness, fatigue
-constipation
-increased seizure activity in epileptic patients

Question 9

Which receptor is targeted by Tizanidine?

Answer 9

alpha-2-receptor agonist (similar to clonidine but less cardiovascular effect, less decrease in HR, hypotension)

-> found presynaptically (autoreceptor) -> cause closing of voltage-gated Ca2+channels
-> decrease release of Glutamine

-> also found postsynaptically opening K+channels

Question 10

Which drug targets the Ca2+ influx into skeletal muscle cells?

Answer 10

Dantrolene by blocking ryanodine receptors
-> cardiac and smooth muscle cells are minimally affected

Question 11

Which receptors can be found presynaptically and postsynaptically?

Answer 11

GABA (B)

also alpha-2-receptor -> targeted by Tizanidine

Question 12

Which skeletal muscle relaxant targets GABA (B)?

Answer 12

Baclofen

Question 13

Adverse effects of Dantrolene

Answer 13

-muscle weakness!!!
-sedation
-occasionally hepatitis

Question 14

How does Carisoprodol work?

Answer 14

-not fully understood
-CENTRALLY ACTING, C-IV
-thought to work on GABA(A) receptors rather in the brain than on the spinal cord

-> actually has mild effects on spasticity, but helps with pain secondary to muscle spasm

-should only be used in acute muscle spasms (due to dependency and abuse)

ADE:
-Drug abuse, drug dependence-withdrawal
-drowsiness, dizziness, headache
-CAUTION: additive with other CNS depressants

Question 15

What is the metabolite of Carisoprodol?

Answer 15

it is metabolized to meprobamate
-> sedative hypnotic
-> causes dizziness, drowsiness (in top of Carisoprodol itself)

Question 16

Which antispasm drug has a structural similartiy with amitriptyline?

Answer 16

Cyclobenzaprine (Flexeril) for acute spasm
CENTRALLY ACTING

ADE:
-signifacant sedation, confusion
-heart palpitations
-anti-cholinergic (dry mouth, constipation, like with TCAs)

Question 17

Where are Cyclobenzaprine (Flexeril) and Metaxalone (Skelaxin) thought work in the brain?

Answer 17

in the brain stem
-> MOA for both is not understood

Question 18

What factor affects the absorption of Metaxalone (Skelaxin)?

Answer 18

higher absorption with food
->patients should take it always the same way to have predictable kinetics

Question 19

MOA of Methocarbamol

Answer 19

MOA unknown
CENTRALLY ACTING
-potential carbonic anhydrase inhibitor

ADE:
dizziness, headache, lightheadness, somnolence (but not as severe as with the muscle relaxants)