Antisasmodic And Spasmolytic Agents Flashcards
Spasms vs spasticity
Spasms: painful involuntary muscle contractions
- caused by dehydration, injuries, infection, neurodegenerative issues
Spasticity: involuntary contraction of skeletal muscle that causes stiffness and in there’s with mobility and speech. Not usually painful
- only caused by neurodegenerative issues or spinal injuries
What causes spasticity?
Deficit in upper motor neuron signaling so lower motor neurons become hyperexcitable.
Usually a cause of neurodegenerative diseases or disorders.
Examples of common neurodegenerative diseases
Cerebral palsy, multiple sclerosis or stroke.
Targets for spasticity treatment
Lower motor neurons (specifically 1a)
Interneurons in reflex arc
- both excitable or inhibitory
Direct skeletal muscle (dantrolene)
Two ways to decrease the alpha motor neuron activity
Reduce stimulation of excitatory interneurons
Enhance stimulation of inhibitory interneurons
Excitatory interneurons
Release glutamate which agonizes the AMPA receptors that trigger action potentials.
Activity is reduced via agonism of the inhibitory receptors
Inhibitory receptors for excitatory interneurons
(A)2 adrenergic
GABA(b) receptors
G(a)1-coupled GPCRs
Inhibitory interneurons
Release GABA
Activates GABA receptors (both a and b).
In order to decrease motor neuron activity, drugs either enhance GABA signaling channels or enhance the GABA receptors
GABA receptor ligand drugs
Baclofen - (GABAb)
Diazepam - (GABAa)
Tizanidine - (a2-adernergic)
Most Common adverse side effect with spasmolytics and centrally active antispasmodic
Sedation and fatigue.
- caused by the drug having to cross the BBB and bind to the neurons in the brain in order to get to the target
Benzodiazepines general characteristics
Positive allosteric modulator of GABAa receptors
* DOES NOT directly agonize the GABAa receptors*
Allows for GABAa receptors to open more frequently and enhance permeability of CL- in interneurons.
Hyperpolarizes the neuron and prevents spasms and spasticity.
Pharmacokinetics properities of benzodiazepines
Orally administered and carried via blood albumin.
Can be
- short acting: anxiety disorders
- long acting: spasmolytic
Long acting tends to be promoted more since it has less of a chance of developing withdrawal symptoms.
Most commonly used Benzodiazepine
Diazepam
What CYP metabolizes Diazepam?
CYP3A4
Substrates INCREASE apparent dose
Inducers DECREASE apparent dose
What drug should not be used with benzodiazepines?
Alcohol, increases absorption and can cause coma and/or respiratory distress
- one of the more common drug-drug overdose reactions*
Drug used to treat Benzodiazepine overdoses
Flumazenil: is an antagonist of the benzodiazepine binding sites on GABA receptors.
Baclofen definition
Short-acting GABA analog
Agonizes GABAb receptors
First line of treatment for muscle spasticity.
Baclofen metabolism and pharmokinetics
Oral or intrathecal administration
Eliminated via renal and liver metabolism
Direct administration into CSF can cause CNS depression
Half life is 3-4 hrs
Adverse drug effects of baclofen
High doses = respiratory depression and coma
Triggers seizures in epileptic patients
Birth defects with pregnant women
Intrathecal administration can cause acute withdrawal syndrome
Gabapentin
Targets presynaptic calcium channels and inhibits these.
Cause decreased glutamine release and excitatory muscles
DOES NOT ACT ON GABA RECEPTORS
can also be used to treat shingles
Is not metabolized at all.
Tizanidine definition
(A2)- adrenergic agonist
Reduces firing at the presynaptic neurons and inhibits G-protein coupled receptors.
More effective than baclofen, dantrolene and diazepam but has a more stringent population it can work on.
Adverse drug effects of Tizanidine
Contraindicated in patients with orthostatic hypotension (cant regulate blood pressure with changes of altitude and pressure)
Hypotension and dry mouth
Drowsiness, fatigue
Hepatotoxicity in patients with impaired renal or liver impairments
What CYP works on Tizanidine?
CYP1A2
Induction DECREASES apparent dose: smoking
Inhibition INCREASES apparent dose
Botulinum toxin Type A definition
Cleaves SNARE protein which releases neurotransmitters vesicles.
Produced by clostridium botulinum
Causes local paralysis and chemodenervation
ADRs of Botox
Contraindications of Botox: overactive bladdder and chronic migraines
ADRs: respiratory tract infections, muscle weakness urinary incontience
Treatment of spasms vs spasticity
Antispasmodic for spasms
Spasmolytic for spasticity
Off label use for antispasmodic and spasmolytic agents
Chronic lower back pain that cannot be resolved
(A) adrenergic proteins
Found on alpha motor neurons and excitatory interneurons
Target for tizanidine which inhibits intracellular activity and release of glutamate in the excitatory neurons
- also inhibits activity in the Motor neurons
