Spasmolytics Flashcards
Spasmolytics
tending or having the power to relieve spasms or convulsions.
Spasmolytics relation with Ach?
The spasmolytic drugs do not resemble
ACh in structure or effect
Spasmolytics site of action?
They act in CNS and in one case, in the
skeletal muscle cell, rather than at the
NMJ
Where are polysynaptic reflexes act?
Polysynaptic reflexes involved in
maintenance of muscle tone are
inhibited at both spinal & supraspinal
level
What is the goal of spasmolytic therapy?
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
What causes spasms?
acute injury
or inflammation of muscle leads to
spasm and pain
Malignant hyperthermia causes?
Due to inhaled anaesthetics caused by a genetic disposition
- Mutation in the RYR1 gene
- Altered Ca2+ release channel (RyR1)
3 .Mutated channel opens more easily and stays open longer - Increase in intracellular Ca2+
- Sustained muscle contraction (rigidity), stimulated glycogenolysis,
glycolysis and aerobic metabolism (excessive heat production)
Centrally acting spasmolytics?
SPA Picture mnemonic
Orphenadrine
Diazepam
Methocarbamol
Baclofen
Cyclobenzaprine
Orphenadrine MOA?
*Antimuscarinic agent structurally related to diphenhydramine
blocks muscarinic acetylcholine receptors
inhibits central cholinergic receptor
inhibits the excitatory neurotransmitter (glutamate) receptor
Orphenadrine used as what?
Used as a citrate salt (orphenadrine citrate) to relieve pain due to muscle spasm
Which drug can orphenadrine be combined with to relive pain?
Can be combined with paracetamol
Orphenadrine I?
I: pain assoc. with muscle spasm, tremor assoc. with parkinsonism
S/E: sedation, dry mouth, dizziness
Orphenadrine P/K?
PK: M = liver, E: renal
Orphenadrine CI?
CI: myasthenia gravis
Orphenadrine S/E?
S/E: sedation, dry mouth, dizziness
Diazepam MOA?
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
Diazepam I?
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)
Diazepam adminstration?
Admin: IV. Absorp. unreliable in IM Avoid
Diazepam P/K?
M = liver, E: renal
Diazepam S/E?
S/E: sedation
Methocarbamol MOA?
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.
Methocarbamol I?
I: adjuvant in painful musculoskeletal conditions
S/E: sedation, dizziness or lightheadedness, drowsiness, confusion
Methocarbamol P/K?
PK: M = liver, E: renal
Methocarbamol CI?
CI: Depression or taking CNS depressants
Methocarbamol S/E?
S/E: sedation, dizziness or lightheadedness, drowsiness, confusion
Baclofen MOA?
*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
Baclofen I?
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”
Baclofen P/K?
PK: M = liver (15%), E: renal mainly unchanged
Baclofen S/E?
S/E: drowsiness, dizziness, ataxia (lack of voluntary coordination of muscle movements)
Cyclobenzaprine MOA?
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
Cyclobenzaprine I?
I: muscle spasm assoc. with acute, painful musculoskeletal conditions.
Effective in muscle spasm of local origin rather than CNS origin
Cyclobenzaprine S/E?
A/E: may increase HR
What is a direct muscle relaxtant?
Dantrolene
Dantrolene MOA?
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
Dantrolene I?
I: malignant hyperthermia, muscle spasticity caused by spinal cord injury, stroke, cerebral palsy, or multiple sclerosis
Dantrolene P/K?
PK: Absorption from oral slow and incomplete (IV preferred), M = liver, E= renal
Dantrolene S/E?
S/E: drowsiness, dizziness, fatigue
Dantrolene treats?
Treat:
muscular pain or spasms from peripheral musculoskeletal conditions
muscular spasticity from upper motor neuron syndromes
Dantrolene adminstratins?
*usually administered by the oral route
Spasticity?
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
