MSKS Pharmacology Lecture 2_Antispasmodic and Spasmolytic Agents Flashcards
What are antispasmodic agents used to treat?
Acute local spasm due to injury or muscle strain
What are spasmolytic agents used to treat?
Neurodegenerative disorders (Multiple Sclerosis, ALS), cerebral palsy, spinal injury
What causes Spasticity?
deficit in upper motor neuron signaling leaves lower motor neurons hyperexcitable (because they upregulate their receptors)
What are the three targets of Pharmacological treatments of spasticity
• Lower motor neurons • Interneurons in the reflex arc • Skeletal muscle directly
How do CNS-active spasmolytics decrease alpha motor neuron activity
• (1) reducing activity of the excitatory interneurons • (2) enhancing activity of the inhibitory interneurons
What two inhibitory receptors are on the inter motor neuron?
alpha 2 and GABAb (both of which are Gi coupled receptors)
What inhibitory receptors are on the lower motor neuron?
alpha 2 and GABAb (both of which are Gi coupled receptors) and GABAa (which is a Cl- ion channel)
What receptor does Baclofen act on?
GABAb
What receptor does Diazepam act on?
GABAa
What receptor does Tizanidine
𝛼2-adrenergic receptor agonists
Baclofen, Diazepam, and Tizanidine are all examples of what?
Centrally acting spasmolytic agents
What are Benzodiazepines (BZDs) used to treat and what is their mechanisium of action?
They are used as CNS-active sedatives and anxiolytics. Their mechanisium of action is Positive allosteric modulation (this means that they are not direct agonists but they will alter the structure of the GABAa receptor such that when GABA does bind, the Cl channel is open longer) of GABAa receptors.
How are BZDs metabolized?
Hepatically by CYP3A4
What are the Adverse drug responses to Diazepam
• Daytime drowsiness and sedation (especially for long-acting) • Rebound insomnia/anxiety • Anterograde amnesia • Coma and respiratory depression when used with other CNS depressants (esp. alcohol) • Alcohol improves rate of absorption and acts at GABAA receptor
What is Flumazenil used for? What is a key consideration with its use?
Flumazenil is used to treat BZD overdoses. Flumazenil has a very short half life (less than 1.5 hours) which means it can be matabolized from the system while there are still overdose levels of the BZD
How does Baclofen work?
It is a direct agonist of the GABAb receptors. Agonizing GABAb receptors opens K+ channels, leading to hyper polarization of a cell.
What is the mechanisium of action of Gabapentin?
It reduces the exitation of lower motor neurons by inhibiting the releasae of glutamate from the interneuron. It does this by preventing the opening of the presynaptic Ca channels. It is typically well tolorated with few adverse side effects
What is the ADR of Tizanidine?
Because it acts on Alpha 2 receptors, it will also agonize these receptors in the ANS. This can lead to hypotention. It also causes hepatotoxicity and is metabolized by CYP1A2 (smoking is an inducer of this enzyme)
What is the mechanisium of action of Botulinum Toxin Type A?
It cleaves the SNARE proteins that Meadiate the release of ACh from the neuron.
Three facts about Antispasmodics
• Centrally active agents that treat peripheral muscle spasms by targeting the brain stem • Largely unknown MOA • Major interactions with other CNS-depressant drugs
Cyclobenzaprine has what side effects?
Strong antimuscarinic side effects, significant sedation, confusion and transient visual hallucinations, seizures, tachycardia, hypotension • Rare, but life threatening: Neuroleptic malignant syndrome (can be reversed with dantrolene)
Why is carisoprodol at risk of abuse?
Carisoprodol is metabolized to meprobamate (CYP2C19), a Schedule IV drug with sedative action and abuse liability
Cyclobenzaprine and carisoprodol are examples of what?
Antispasmodics
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