Spasmolytics

Question 1

Spasmolytics

Answer 1

tending or having the power to relieve spasms or convulsions.

Question 2

Spasmolytics relation with Ach?

Answer 2

The spasmolytic drugs do not resemble
ACh in structure or effect

Question 3

Spasmolytics site of action?

Answer 3

They act in CNS and in one case, in the
skeletal muscle cell, rather than at the
NMJ

Question 4

Where are polysynaptic reflexes act?

Answer 4

Polysynaptic reflexes involved in
maintenance of muscle tone are
inhibited at both spinal & supraspinal
level

Question 5

What is the goal of spasmolytic therapy?

Answer 5

The goal of spasmolytic therapy in
both chronic and acute conditions is
reduction of excessive skeletal
muscle tone without reduction of
strength. Reduced spasm results in
reduction of pain and improved
mobility

Question 6

What causes spasms?

Answer 6

acute injury
or inflammation of muscle leads to
spasm and pain

Question 7

Malignant hyperthermia causes?

Answer 7

Due to inhaled anaesthetics caused by a genetic disposition

1. Mutation in the RYR1 gene
2. Altered Ca2+ release channel (RyR1)
   3 .Mutated channel opens more easily and stays open longer
3. Increase in intracellular Ca2+
4. Sustained muscle contraction (rigidity), stimulated glycogenolysis,
   glycolysis and aerobic metabolism (excessive heat production)

Question 8

Centrally acting spasmolytics?

Answer 8

SPA Picture mnemonic

Orphenadrine
Diazepam
Methocarbamol
Baclofen
Cyclobenzaprine

Question 9

Orphenadrine MOA?

Answer 9

*Antimuscarinic agent structurally related to diphenhydramine

blocks muscarinic acetylcholine receptors
inhibits central cholinergic receptor
inhibits the excitatory neurotransmitter (glutamate) receptor

Question 10

Orphenadrine used as what?

Answer 10

Used as a citrate salt (orphenadrine citrate) to relieve pain due to muscle spasm

Question 11

Which drug can orphenadrine be combined with to relive pain?

Answer 11

Can be combined with paracetamol

Question 12

Orphenadrine I?

Answer 12

I: pain assoc. with muscle spasm, tremor assoc. with parkinsonism

S/E: sedation, dry mouth, dizziness

Question 13

Orphenadrine P/K?

Answer 13

PK: M = liver, E: renal

Question 14

Orphenadrine CI?

Answer 14

CI: myasthenia gravis

Question 15

Orphenadrine S/E?

Answer 15

S/E: sedation, dry mouth, dizziness

Question 16

Diazepam MOA?

Answer 16

binds on GABA-A receptors

enhances GABA effects hyperpolarization

muscle relaxation

reduces muscle tone by depressing polysynaptic and monosynaptic reflexes

At higher doses, a spinally mediated muscle relaxant effect is obtained effective in tetanus and paraplegia

Question 17

Diazepam I?

Answer 17

I: muscle spasticity of any origin including tetanus and reflex spasm of local origin
Muscle relaxant of choice in the tx of spasticity of cerebral origin (i.e. cerebral palsy)

Question 18

Diazepam adminstration?

Answer 18

Admin: IV. Absorp. unreliable in IM Avoid

Question 19

Diazepam P/K?

Answer 19

M = liver, E: renal

Question 20

Diazepam S/E?

Answer 20

S/E: sedation

Question 21

Methocarbamol MOA?

Answer 21

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

MOA:
thought to be via general CNS depression
blocking spinal polysynaptic reflexes, decreasing nerve transmission in spinal and supraspinal polysynaptic pathways
No direct action on the muscle, the motor end plate or the nerve fiber.

Question 22

Methocarbamol I?

Answer 22

I: adjuvant in painful musculoskeletal conditions

S/E: sedation, dizziness or lightheadedness, drowsiness, confusion

Question 23

Methocarbamol P/K?

Answer 23

PK: M = liver, E: renal

Question 24

Methocarbamol CI?

Answer 24

CI: Depression or taking CNS depressants

Question 25

Methocarbamol S/E?

Answer 25

S/E: sedation, dizziness or lightheadedness, drowsiness, confusion

Question 26

Baclofen MOA?

Answer 26

*GABA agonist (as a source of GABA that readily crosses BBB)
binds on both presynaptic and postsynaptic GABA-B receptors
Postsynaptic: enhances GABA (inhibitory neurotransmitter) effects:
hyperpolarization
muscle relaxation
Presynaptic: decreases release of excitatory neurotransmitter, glutamate

Question 27

Baclofen I?

Answer 27

I: spasticity of spinal origin (i.e. multiple sclerosis, transverse myelitis, traumatic paraplegia and paraparesis), pain relief in trigeminal neuralgia
Less effective in spasticity of cerebral origin.

“At the back so there back origin”

Question 28

Baclofen P/K?

Answer 28

PK: M = liver (15%), E: renal mainly unchanged

Question 29

Baclofen S/E?

Answer 29

S/E: drowsiness, dizziness, ataxia (lack of voluntary coordination of muscle movements)

Question 30

Cyclobenzaprine MOA?

Answer 30

structurally similar to tricyclic antidepressants

*centrally acting skeletal muscle relaxant with antidepressant activity

Acts primarily within the central nervous system at brain stem level

Reduces tonic somatic motor activity

Question 31

Cyclobenzaprine I?

Answer 31

I: muscle spasm assoc. with acute, painful musculoskeletal conditions.

Effective in muscle spasm of local origin rather than CNS origin

Question 32

Cyclobenzaprine S/E?

Answer 32

A/E: may increase HR

Question 33

What is a direct muscle relaxtant?

Answer 33

Dantrolene

Question 34

Dantrolene MOA?

Answer 34

acts directly on the muscle

differs from classical NMBDs in that it inhibits the release of Ca2+ from sarcoplasmic reticulum (skeletal muscle Ca2+ store) by blocking ryanodine receptor channel (RyR1)
suppresses excitation-contraction coupling, relieving from muscle spasticity
reduces the Ca2+ levels associated with malignant hyperthermia crises

Question 35

Dantrolene I?

Answer 35

I: malignant hyperthermia, muscle spasticity caused by spinal cord injury, stroke, cerebral palsy, or multiple sclerosis

Question 36

Dantrolene P/K?

Answer 36

PK: Absorption from oral slow and incomplete (IV preferred), M = liver, E= renal

Question 37

Dantrolene S/E?

Answer 37

S/E: drowsiness, dizziness, fatigue

Question 38

Dantrolene treats?

Answer 38

Treat:
muscular pain or spasms from peripheral musculoskeletal conditions
muscular spasticity from upper motor neuron syndromes

Question 39

Dantrolene adminstratins?

Answer 39

*usually administered by the oral route

Question 40

Spasticity?

Answer 40

Spasticity: a condition in which muscles are continuously contracted causing stiffness or tightness which may interfere with movement and speech

*Often occurs as a symptom of neurologic disorders such as cerebral palsy, multiple sclerosis and stroke
*Muscle relaxants are preferable to NMBDs for treating spasticity because they are more selectiv