Antisasmodic And Spasmolytic Agents

Question 1

Spasms vs spasticity

Answer 1

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

Question 2

What causes spasticity?

Answer 2

Deficit in upper motor neuron signaling so lower motor neurons become hyperexcitable.

Usually a cause of neurodegenerative diseases or disorders.

Question 3

Examples of common neurodegenerative diseases

Answer 3

Cerebral palsy, multiple sclerosis or stroke.

Question 4

Targets for spasticity treatment

Answer 4

Lower motor neurons (specifically 1a)

Interneurons in reflex arc
- both excitable or inhibitory

Direct skeletal muscle (dantrolene)

Question 5

Two ways to decrease the alpha motor neuron activity

Answer 5

Reduce stimulation of excitatory interneurons

Enhance stimulation of inhibitory interneurons

Question 6

Excitatory interneurons

Answer 6

Release glutamate which agonizes the AMPA receptors that trigger action potentials.

Activity is reduced via agonism of the inhibitory receptors

Question 7

Inhibitory receptors for excitatory interneurons

Answer 7

(A)2 adrenergic

GABA(b) receptors

G(a)1-coupled GPCRs

Question 8

Inhibitory interneurons

Answer 8

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

Question 9

GABA receptor ligand drugs

Answer 9

Baclofen - (GABAb)

Diazepam - (GABAa)

Tizanidine - (a2-adernergic)

Question 10

Most Common adverse side effect with spasmolytics and centrally active antispasmodic

Answer 10

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

Question 11

Benzodiazepines general characteristics

Answer 11

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.

Question 12

Pharmacokinetics properities of benzodiazepines

Answer 12

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.

Question 13

Most commonly used Benzodiazepine

Answer 13

Diazepam

Question 14

What CYP metabolizes Diazepam?

Answer 14

CYP3A4

Substrates INCREASE apparent dose

Inducers DECREASE apparent dose

Question 15

What drug should not be used with benzodiazepines?

Answer 15

Alcohol, increases absorption and can cause coma and/or respiratory distress

• one of the more common drug-drug overdose reactions*

Question 16

Drug used to treat Benzodiazepine overdoses

Answer 16

Flumazenil: is an antagonist of the benzodiazepine binding sites on GABA receptors.

Question 17

Baclofen definition

Answer 17

Short-acting GABA analog

Agonizes GABAb receptors

First line of treatment for muscle spasticity.

Question 18

Baclofen metabolism and pharmokinetics

Answer 18

Oral or intrathecal administration

Eliminated via renal and liver metabolism

Direct administration into CSF can cause CNS depression

Half life is 3-4 hrs

Question 19

Adverse drug effects of baclofen

Answer 19

High doses = respiratory depression and coma

Triggers seizures in epileptic patients

Birth defects with pregnant women

Intrathecal administration can cause acute withdrawal syndrome

Question 20

Gabapentin

Answer 20

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.

Question 21

Tizanidine definition

Answer 21

(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.

Question 22

Adverse drug effects of Tizanidine

Answer 22

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

Question 23

What CYP works on Tizanidine?

Answer 23

CYP1A2

Induction DECREASES apparent dose: smoking

Inhibition INCREASES apparent dose

Question 24

Botulinum toxin Type A definition

Answer 24

Cleaves SNARE protein which releases neurotransmitters vesicles.

Produced by clostridium botulinum

Causes local paralysis and chemodenervation

Question 25

ADRs of Botox

Answer 25

Contraindications of Botox: overactive bladdder and chronic migraines

ADRs: respiratory tract infections, muscle weakness urinary incontience

Question 26

Treatment of spasms vs spasticity

Answer 26

Antispasmodic for spasms

Spasmolytic for spasticity

Question 27

Off label use for antispasmodic and spasmolytic agents

Answer 27

Chronic lower back pain that cannot be resolved

Question 28

(A) adrenergic proteins

Answer 28

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