Spasmolytics Flashcards
What is muscle spasticity?
acute injury to muscle or muscle inflammation
How do CNS diseases cause muscle spasticity?
- cause abnormally high reflex activity in neuronal pathways
- cause painful spasm(rigidity)
How does Malignant hyperthermia cause muscle spasticity?
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)
How are spasmolytics administered?
orally
Why are spasmolytics preferable to NMBs
They are more selective to NMBs
= they block only increased muscle tone
Which are the centrally-acting spasmolytics?
Diazepam
Baclofen
Methacarbamol
Orphenadrine
Which are the directly-acting spasmolytics?
Dantrolene
What is Baclofen?
Its a GABA derivative
MOA of Baclofen
Post-synaptic cleft:
-enhances GABA effects: hyperpolarisation
muscle relaxation
Pre-synaptic cleft:
-decreases glutamate release
Indications of Baclofen
Painful muscle spasms of spinal origin
(e.g. MS, Transverse myelitis, traumatic paraplegia and paraparesis)
Pain relief in trigeminal neuroglia
Metabolism and Excretion of Baclofen
M: Liver 15%
E: renal (mainly unchanged)
SE of Baclofen
Drowsiness
Dizziness
Ataxia (lack of voluntary coordination of muscle movements)
What is Diazepam?
is a BDZ
MOA of Diazepam
- enhances GABA effects: hyperpolarisation=muscle relaxation
- Suppresses postsynaptic and monosynaptic reflexes
Indications of Diazepam
Muscle spasticity of any origin including Tetanus and reflief of local origin
Administration of Diazepam
IV,
Absorption in IM is unreliable=avoid
Metabolism and Excretion of Diazepam
M: liver
E: Renal
SE of Diazepam
Sedation
Caution in Diazepam
Can kill elderly patients
What is Cyclobenzaprine
Is a centrally acting skeletal muscle relaxant with anti depressant activity
Is structurally similar to TCAs
MOA of Cyclobenzaprine
Acts primarily within CNS at brain stem level
Reduces tonic somatic motor activity
Indications of Cyclobenzaprine
Muscle spasm associated with acute, painful muscloskeletal conditions
Is Cyclobenzaprine effective in muscle spasm of CNS origin
YES
AE of Cyclobenzaprine
May increase HR
What is Methacarbamol
A carbamate derivative of guaifenesin
Its a CNS depressant with sedative and musculoskeletal relaxant properties
MOA of Methacarbamol
It has no direct action on the muscle, motor end plate or nerve fiber
MOA of Methacarbamol as a CNS depressant
it blocks spinal polysynaptic reflexes, decreasing nerve transmission in spinal and supraspinal polysynaptic pathways
Indications of Methacarbamol
Adjuvant in painful musculoskeletal conditions
Metabolism and Excretion of Methacarbamol
M: Liver
E: Renal
CI of Methacarbamol
Depression or taking CNS depressants
SE of Methacarbamol
sedation
Dizziness
Lightheadedness
Drowsiness
Confusion
What is Orphenadrine
is an antimuscarinic agent structurally related to diphenhydramine
MOA of Orphanedrine
blocks muscarinic ACh receptors.
has central anticholinergic activity
block glutamate receptor
How is Orphenadrine used?
used as a citrate salt (orphenadrine salt) to relieve pain due to muscle spasm.
Can be combined with paracetamol
Indications of Orphenadrine
pain associated with muscle spasm,
tremor/stiffness in parkinsonian
Metabolism and Excretion of Orphenadrine
M: liver
E: Renal
CI of Orphenadrine
Myasthenia gravis
SE of Orphenadrine
Sedation
Dry mouth
Dizziness
MOA of Dantrolene
-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
Indications of Dantrolene
Malignant hyperthermia
Muscle spasticity (neuronal origin)
PK of Dantrolene
Absorption
Metabolism
Excretion
oral: slow and incomplete absorption
(IV is preferred)
M: liver
E: renal
SE of Dantrolene
Drowsiness
Dizziness
Fatigue
