Musculoskeletal Pharmacology Part I

Question 1

Skeletal Muscle Relaxants

Answer 1

• treat conditions with hyperexcitable skeletal muscle (i.e. spasticity and muscle spasms)
• goal is to normalize muscle excitability without profound decrease in muscle function

Question 1

UMN Lesions

Answer 1

• Site: Cerebral hemispheres, cerebellum, brainstem, spinal cord
• Muscle weakness: quadriplegia, hemiplegia, diplegia, paraplegia
• Muscle tone: spasticity, rigidity
• Sensory loss: cortical sensations

Question 2

LMN Lesions

Answer 2

• Site: AHC, Nerve roots, peripheral nerves, NMJ, muscles
• Muscle weakness: proximal (myopathy), distal (neuropathy)
• Muscle tone: hypotonia
• Sensory loss: peripheral sensations

Question 3

Spasticity

Answer 3

• velocity dependent increase in muscle tone caused by increased excitability of muscle stretch reflex
• central disorder (UMN)
• symptoms include stiffness, hypertonicity, hyperreflexia

Question 4

Spasms

Answer 4

• involuntary, sudden muscle contractions
• peripheral disorders (LMN), muscle sprain or injury, nerve compression, inflammation, electrolyte imbalances
• symptoms include jerks, twitches, cramps

Question 5

Spasticity common neurologic disorders

Answer 5

1. multiple sclerosis
2. stroke
3. CP
4. SCI, brain injuries
5. Neurodegernative disorders affected UMN, pyramidal and extrapyramidal pathways

Question 6

Common symptoms of severe spasticity

Answer 6

• muscle stiffness (flexing or extending)- adducted shoulder with IR, flexed elbow, pronated forearm, flexed wrist and fingers, thumb in palm, clenched fist
• muscle spasms
• Clonus- rapid muscle contractions
• Contractures- fixed joints
• Exxagerated muscle jerks
• pain or tightness around joints

Question 7

Primary goal of skeletal muscle relaxants

Answer 7

1. selective decrease in skeletal muscle excitability
2. decrease pain
3. without causing profound decrease in muscle function
4. either antispasticity or antispasmodic (spasmolytic) agents

Question 8

Baclofen

Answer 8

• common antispasticity drug
• Acts on GABA-B receptors in spinal cord to inhibit reflexes and decrease spasticity
• can be taken orally or adminstered into spinal fluid

Question 9

Dantrolene

Answer 9

• common anti-spasticity drug
• acts directly on skeletal muscle, inhibits calcium release and thus muscle contraction

Question 10

Tizanidine

Answer 10

• common anti-spasticity drug
• Alpha-2 adrenergic agonist that reduced spasticity by increase presynaptic inhibition

Question 11

Botulinum toxin

Answer 11

• common anti spasticity drug
• injected directly into spastic muscles, inhibits ACh release, reducing muscle contractoin

Question 12

Carisoprodol (Soma)

Answer 12

• common spasmolytic
• exact mechanism unknown, alters interneuronal activity in spinal cord and descending reticular formation in brain

Question 13

Cyclobenzaprine (Flexeril)

Answer 13

• common spasmolytic
• works centrally, decreases activity in brainstem to relieve muscle spasms

Question 14

Methocarbamol (Robaxin)

Answer 14

• common spasmolytic
• mechanism not fully understoof, central muscle relaxant properties

Question 15

Orphenadrine (Norflex)

Answer 15

• common spasmolytic
• Anti cholinergic properties are believed for be responsible for muscle relaxant effect

Question 16

Key differences between spasmolytics and anti-spasticity drugs

Answer 16

1. target: anti spasticity mainly target conditions with increased muscle tone due to CNS disorders, spasmolytics target PNS conditions involving acute, painful muscle contractions
2. Mechanicsm: anti spasticity drugs have more specific targets (NMJ), spasmolytics less clear and can be diverse
3. Usage: anti spasticity drugs more chronic in nature (treating MS, CP, etc.), spasmolytics used for acute conditions (muscle strain, injury)

Question 17

Polysynaptic Inhibitors (Antispasm drugs)

Answer 17

• diverse group of drugs including carisoprodol (SOMA), cyclobenzaprine (Flexeril), Methocarbamol (Robaxin), Orphenadrine citrate (Norflex)
• adjuncts to rest and PT for relief of spasms
• may be incorporated into alagesics (acetaminophen or aspirin): norgesic
• MOA: theorized to act on polysynaptic reflex arc in spinal cord, could decrease alpha motor neuron excitability causing relaxation of skeletal muscle
• AE: drowsiness, dizziness, nausea, lightheadedness, vertigo, ataxia, headache, tolerance, and physical dependence

Question 18

Diazepam (Valium)

Answer 18

• Benzodiazepine agent, developed originally as antianxiety drug
• MOA: Increases inhibitory effects at CNS synapses that use GABA

Question 19

GABA

Answer 19

primary neurotransmitter that causes inhibition at pre/post synaptic neurons in brain and spinal cord (alpha receptors)