Spasmolytics

Question 1

What is muscle spasticity?

Answer 1

acute injury to muscle or muscle inflammation

Question 2

How do CNS diseases cause muscle spasticity?

Answer 2

1. cause abnormally high reflex activity in neuronal pathways
2. cause painful spasm(rigidity)

Question 3

How does Malignant hyperthermia cause muscle spasticity?

Answer 3

Mutation in RYR1 gene
=Altered Ca release channel
=mutated shannel opens more easily and stays open longer
=increase in intracellular Ca
= sustained muscle contraction (rigidity), stimulated glycogenolysis and aerobic metabolism (excessive heat production)

Question 4

How are spasmolytics administered?

Answer 4

orally

Question 5

Why are spasmolytics preferable to NMBs

Answer 5

They are more selective to NMBs
= they block only increased muscle tone

Question 6

Which are the centrally-acting spasmolytics?

Answer 6

Diazepam
Baclofen
Methacarbamol
Orphenadrine

Question 7

Which are the directly-acting spasmolytics?

Answer 7

Dantrolene

Question 8

What is Baclofen?

Answer 8

Its a GABA derivative

Question 9

MOA of Baclofen

Answer 9

Post-synaptic cleft:
-enhances GABA effects: hyperpolarisation
muscle relaxation
Pre-synaptic cleft:
-decreases glutamate release

Question 10

Indications of Baclofen

Answer 10

Painful muscle spasms of spinal origin
(e.g. MS, Transverse myelitis, traumatic paraplegia and paraparesis)
Pain relief in trigeminal neuroglia

Question 11

Metabolism and Excretion of Baclofen

Answer 11

M: Liver 15%
E: renal (mainly unchanged)

Question 12

SE of Baclofen

Answer 12

Drowsiness
Dizziness
Ataxia (lack of voluntary coordination of muscle movements)

Question 13

What is Diazepam?

Answer 13

is a BDZ

Question 14

MOA of Diazepam

Answer 14

1. enhances GABA effects: hyperpolarisation=muscle relaxation
2. Suppresses postsynaptic and monosynaptic reflexes

Question 15

Indications of Diazepam

Answer 15

Muscle spasticity of any origin including Tetanus and reflief of local origin

Question 16

Administration of Diazepam

Answer 16

IV,
Absorption in IM is unreliable=avoid

Question 17

Metabolism and Excretion of Diazepam

Answer 17

M: liver
E: Renal

Question 18

SE of Diazepam

Answer 18

Sedation

Question 19

Caution in Diazepam

Answer 19

Can kill elderly patients

Question 20

What is Cyclobenzaprine

Answer 20

Is a centrally acting skeletal muscle relaxant with anti depressant activity
Is structurally similar to TCAs

Question 21

MOA of Cyclobenzaprine

Answer 21

Acts primarily within CNS at brain stem level
Reduces tonic somatic motor activity

Question 22

Indications of Cyclobenzaprine

Answer 22

Muscle spasm associated with acute, painful muscloskeletal conditions

Question 23

Is Cyclobenzaprine effective in muscle spasm of CNS origin

Answer 23

YES

Question 24

AE of Cyclobenzaprine

Answer 24

May increase HR

Question 25

What is Methacarbamol

Answer 25

A carbamate derivative of guaifenesin Its a CNS depressant with sedative and musculoskeletal relaxant properties

Question 26

MOA of Methacarbamol

Answer 26

It has no direct action on the muscle, motor end plate or nerve fiber

Question 27

MOA of Methacarbamol as a CNS depressant

Answer 27

it blocks spinal polysynaptic reflexes, decreasing nerve transmission in spinal and supraspinal polysynaptic pathways

Question 28

Indications of Methacarbamol

Answer 28

Adjuvant in painful musculoskeletal conditions

Question 29

Metabolism and Excretion of Methacarbamol

Answer 29

M: Liver E: Renal

Question 30

CI of Methacarbamol

Answer 30

Depression or taking CNS depressants

Question 31

SE of Methacarbamol

Answer 31

sedation Dizziness Lightheadedness Drowsiness Confusion

Question 32

What is Orphenadrine

Answer 32

is an antimuscarinic agent structurally related to diphenhydramine

Question 33

MOA of Orphanedrine

Answer 33

blocks muscarinic ACh receptors. has central anticholinergic activity block glutamate receptor

Question 34

How is Orphenadrine used?

Answer 34

used as a citrate salt (orphenadrine salt) to relieve pain due to muscle spasm. Can be combined with paracetamol

Question 35

Indications of Orphenadrine

Answer 35

pain associated with muscle spasm, tremor/stiffness in parkinsonian

Question 36

Metabolism and Excretion of Orphenadrine

Answer 36

M: liver E: Renal

Question 37

CI of Orphenadrine

Answer 37

Myasthenia gravis

Question 38

SE of Orphenadrine

Answer 38

Sedation Dry mouth Dizziness

Question 39

MOA of Dantrolene

Answer 39

-acts directly on muscle -blocks RYR1 receptor channel -inhibits release of Ca from SR: 1. suppresses excitation-contraction coupling: relieving muscle spasticity 2. reduces Ca: relieving from malignant hyperthermia

Question 40

Indications of Dantrolene

Answer 40

Malignant hyperthermia Muscle spasticity (neuronal origin)

Question 41

PK of Dantrolene Absorption Metabolism Excretion

Answer 41

oral: slow and incomplete absorption (IV is preferred) M: liver E: renal

Question 42

SE of Dantrolene

Answer 42

Drowsiness Dizziness Fatigue