Pharmacology - Skeletal Muscle Relaxants Flashcards
Give an example of a depolarizing neuromuscular depolarizing drugs?
- Succinylcholine
Give an example of a long duration and a short duration non-depolarizing neuromuscular blocking drugs?
- Long duration: tubocurarine
- Short duration: mivacurium
Give 3 types of drugs that work on the CNS of chronic spasmolytic conditions?
- baclogen, diazepam, tizanidine
Give 3 type of drug that work on the muscle for chronic conditions of chonic spasmolytic conditions?
- dantrolene
Give one drug that treats acute conditions of spasmolytic conditions?
- Cyclobenzaprine
What are neuromuscular blocking drugs?
- They are used to produce muscle paralysis in order to facilitate surgery or artificial ventilation.
What are spasmolytic drugs?
- A drug that reduces abnormally elevated muscle tone (Spasticity) without paralysis.
What are Spasms?
Spasms are sudden, violent, painful, involuntary contractions of a muscle or group of muscles.
What type of neurons are involved in spasms?
- There is involvement of Motor neurons, which maintain a balance between musculoskeletal movement and body posture.
How does a contraction occur in a spasm?
- Acetylcholine is released from the nerve terminal and stimulates nicotinic receptors on the muscle producing a contraction.
What is the difference between a spams and spasticity?
- Spasticity is an increase in the passive stretch resistance of a muscle or muscle group that cause stiff awkward movements.
- Spasm: a sudden, violent, painful involuntary contractions of a muscle or group of muscles
Is spasticity considered acute or permeant? What can assist in its management?
- Permeant
- Therapy
What are the common causes of spasticity?
- Head injuries
- Cerebral palsy
- MS
- Stroke
- Others: Hemiplegia, Paraplegia, Quadriplegia, Poliomylelitis, Spinal Cord trauma, Cerebrovascular accident
Are spasm or spasticity mediators Lower motor neurons (LMN)
-Are Spasm or Spasticity mediators Upper motor neurons (UMNs)
- LMN : Spasm
- UMN : Spasticity
What are some etiologies for Spasm?
- Bursitis
- Fracture
- Herniated disc
- Hypocalcemia
- Other: Dislocation, Epilepsy, Myositis, Neuritis, Strains, Whiplash injuries
What are skeletal muscle relaxants members of?
- Where do they interfere with transmission?
- What are they definitely not?
- What are some examples of them?
- Members of neuromuscular blockers
- Interfers with transmission at the neuromuscular end plate.
- The are definitely not central acting drugs!!
- Atracurium, pancuronium, and gallamine
Where do a majority of spasmolytics act?
What are some examples of spasmolytics?
Dantrolene (a spasmolytic) acts where?
- Centrally acting
- Baclogen, diaszepam, tizanidine
- Peripherally acting ( the only apparent exception)
What are the two main treatments for spasmolytic drugs?
- Muscle strains and back pain
What is the stretch reflex arc pathway?
Upon muscle stretch of a muscle, Ia afferents send a signal to the dorsal root, this signal is carried by an interneuron that then sends an inhibitory signal ( via Gaba) out through the ventral root via extrafusal efferents that effect muscle relaxation.
When is the stretch reflex arc active?
It is tonically active at all times
Name 4 centrally-acting skeletal muscle relaxants that treat spasticity?
- Baclofen
- Botulinum toxin type A
- Diazepam
- Tizanidine
What is the one peripherally-acting drug for spasticity?
- Dantrolene
Where does Baclofen work and what does it do?
What is it an analog of?
Acts within the spinal cord to sprpress hyperactive reflexes involved in regulation of muscle movement.
- It is a structural analog of GABA (which may act by mimicking GABAs actions)
What type of GABA is Baclofen more selective for?
- GABA B > GABA A allowing it to stick around for longer
What is the postulated sites of spasmolytic action of diazepm and baclofen in the spinal cord?
Diazepam facilitates GABA-mediated presynaptic inhibition and Baclogen interferes with release of excitatory transmitters
What receptors do Benzodiazepine act on and what NT does it reinforce?
- Acts on the ryanodine receptor and reinforces GABA
What is the big picture point of Baclofen action to remember?
- Acts at the level of spinal cord to restore inhibiting tone
What can therapeutic use of baclofen reduce and what disorders can it be used for?
- Reduce spasticity and associated with MS, spinal cord injury, and cerebral palsy. (Not effective in a stroke)
What does Baclofen actually do?
- Decreases flexor and extensor spasms and suppresses resistance to passive movement, hopefully reducing the discomfort of spasticity and allowing increased performance.
During what conditions is Baclofen preferred to dantrolene?
- Does Baclogen relieve the spasticity of Parkinson’s?
- in patients whose spasticity is associated with significant muscle weakness.
- DOES NOT relieve Parkinson’s disease
Baclofen: what is the time to peak conc? what is the half-life? Where is it metabolized? What is it excreted by?
- Peak conc.: 2-3 hours
- Half-life: 2.5-4 hours
- Metabolized in liver
- Excreted in the kidneys
Where do Baclofen’s most common side-effects occur?
What are the CNS effects?
- in the CNS and GI tract (sites of action and the site of metabolization/excretion)
- CNS depressant, Frequently causes drowsiness, dizziness, weakness, and fatigue.
What are the contraindication for Baclofen?
What can occur if ignored? What could potentiate the problem?
- Alcohol intake, antihistamines, MAO inhibitors, and CNS depressants (since baclogen potentiates the depressant action of these drugs)
- CNS depression Increased risk of hepatotoxicity with combination of chlorzoxazone and alcohol
What family is diazepam a member of?
What is its MOA?
- A member of the benzodiazepine family ( the only benzodiazepine labeled for treating spasticity)
- It acts within the CNS by facilitating GABA- mediated presynaptic inhibition in the spinal cord and brain
What types of muscles spasm can diazepam be used for?
- Can be used in patients with muscle spasm of almost any origin, including local muscle trauma.
What does Diazepam produce in most patients at the doses required to significantly reduce muscle tone?
- It produces sedation **
This drug is preferred over dantrolene in what patients?
- In patients whose strength is marginal
What types of drugs might interact with Chlorphenesin?
What types of interactions could occur?
- Tricyclic antidepressants
- Increased CNS depression; increased risk of hepatotoxicity with combination of chlorzoxazone and alcohol
Where does dantrolene act?
What is its MOA?
- It acts directly on skeletal muscle to relieve spasticity (unlike baclofen and diazepam)
- Primary action is the suppression of calcium release from the sarcoplasmic reticulum (ryanodene receptors) which decreases the ability of the skeletal muscles to contract.
How many calcium pools are there is skeletal muscle?
1) IP3
2) Ryanodene receptor
What are the extent of effect of Dantrolene on the smooth muscle and the cardiac muscle?
- What are the therapeutic uses?
- Minimal effects
- Spasticity, Malignant hyperthermia
How can dantrolene treat spasticity?
- Can relieve spasticity associated with MS, cerebral palsy, and spinal cord injury
- Treatment may be associated with a significant decrease in strength
What is a major therapeutic effect of Dantrolene?
- Does not work on smooth muscle therefore it won’t increase bp
What is malignant hyperthermia (that dantrolene is used to treat)?
- A life-threatening syndrome that can be triggered by any general anesthetic and by succinylcholine, a neuromuscular blocking agent.
What are the symptoms of malignant hyperthermia?
How is the heat generated?
- Muscle rigidity and profound elevation of temperature (no shit)
- The heat of malignant hyperthermia is generated by muscle contraction occuring to massive release of calcium from the SR.
How does Dantrolene relieve symptoms?
- By acting on Sarcoplamic reticulum to block calcium release by blocking the ryanodene receptors.
What is the most serious adverse effects of Dantrolene?
- Hepatic dose related liver damage (most serious; 1 in 1000; death can occur; liver function tests should be done prior to treatment and throughout)
What are some other CNS adverse and Urinary adverse effects?
- CNS: Drowsiness
- ->Dizziness
- ->Malaise
- ->Lightheadness
- ->Insomnia
- ->Fatigue
- ->Confusion - Urinary: Increased urinary frequency
What are the possible drug interactions with Dantrolene?
- Estrogen (hepatotoxicity)
- CNS depressants (SEDATION)
- Clindamycin (increased neuromuscular blockade)
- Verapamil (HYPERKALEMIA AND CARDIAC DEPRESSION)
- Warfarin
- Clofibrate
- Tolbutamine
What are the centrally acting muscle relaxants used for acute muscle spasms in the LMN?
- Carisoprodol
- Chlorphenesin
- Chlorzoxazone
- Cyclobenzaprine
- Diazepam
- Metaxalone
- Methocarbamol
- Vigabatrin
What is Carisoprodol?
Is a muscle relaxant that was a modification of meprobamate, intended to be a better muscle relaxant and less potential for abuse or overdose. Not successful because it can be combined with rohypnol to enhance date rape drug effects.
What is Chlorphenesin?
not available for use in US. secondary usage as anti-fungal and anti-biotic
What is cyclobenzaprine used for?
Injury-related spasms
What is Diazepam used for?
Muscle relaxant effecting both the UMN and LMN
What is Metaxalone used for and what should it be taken with?
- Strains and sprains
- Should be taken with food to limit the possibility of headaches and dizziness
What are the negative usage of Methocarbamol?
High risk in elderly, can slow down heart rate, cause skin rashes, and can depress the CNS
What is functionally significant about Vigabatrin?
- A GABA transaminase inhibitor that allows GABA to be present longer.
What are the drugs used for acute local muscle spasm?
- Chlorphenesin (contraindicated during pregnancy)
- Chlorzoxazone
- Metaxalone
- Methocarbamol
- Orphenadrine (anticholinergic properties)
- Carisoprodol
- Cyclobenzaprine
Cyclobenzaprine is believed to act where?
Due to some muscarinic effects what effect does it have on the bladder?
What two muscle spasm disorders does it not effect?
- level of the brainstem
- contraction of the detrusor muscle by the bladder
- Cerebral palsy or spinal cord injury
What skeletal muscle relaxants have the greatest half-lives and protein binding?
- Cyclobenzprine (1-3 days and 93% protein binding)
- Carisoprodol - (8 hours and 30% protein binding)
- Orphenadril - (14 hours)
- Dantrolene - (6-9 hours and >90% protein binding)
Why is Orphenadril considered very complex?
- Centrally acting but it inhibits H1 receptors and is an anticholinergic, and inhibits NMDA receptors in the CNS, as well as NE uptake. SOOO it can me used to treat muscle pain AND fibromyalgia
What are the contraindication of
1) Baclofen
2) Carisoprodol
3) Cyclobenzaprine
4) Dantrolen
1) Baclofen: Skeletal muscle spasms caused by Rheumatoid Arthritis
2) Carisoprodol: Patients with known hypersensitivity to meprobamate
3) Cyclobenzaprine: MI, cardiac conduction disorders, hyperthyroidism
4) Dantrolene: Active hepatic disease, muscle spasms caused by Rheumatoid Arthritis
What is Tixanidine and what does it treat?
- Tixanidine is an alpha2 agonist
- Treats hypotension, drowsiness, and dry mouth
- *Like clonadine but without the withdrawl effects.
What is botulinum toxin used for?
- Spasticity from cerebral palsy
- Cosmetic surgery
What is malignant hyperthermia (that dantrolene is used to treat)?
- A life-threatening syndrome that can be triggered by any general anesthetic and by succinylcholine, a neuromuscular blocking agent.
What are the symptoms of malignant hyperthermia?
How is the heat generated?
- Muscle rigidity and profound elevation of temperature (no shit)
- The heat of malignant hyperthermia is generated by muscle contraction occuring to massive release of calcium from the SR.
How does Dantrolene relieve symptoms?
- By acting on Sarcoplamic reticulum to block calcium release by blocking the ryanodene receptors.
What is the most serious adverse effects of Dantrolene?
- Hepatic dose related liver damage (most serious; 1 in 1000; death can occur; liver function tests should be done prior to treatment and throughout)
What are some other CNS adverse and Urinary adverse effects?
- CNS: Drowsiness
- ->Dizziness
- ->Malaise
- ->Lightheadness
- ->Insomnia
- ->Fatigue
- ->Confusion - Urinary: Increased urinary frequency
What are the possible drug interactions with Dantrolene?
- Estrogen (hepatotoxicity)
- CNS depressants (SEDATION)
- Clindamycin (increased neuromuscular blockade)
- Verapamil (HYPERKALEMIA AND CARDIAC DEPRESSION)
- Warfarin
- Clofibrate
- Tolbutamine
What are the centrally acting muscle relaxants used for acute muscle spasms in the LMN?
- Carisoprodol
- Chlorphenesin
- Chlorzoxazone
- Cyclobenzaprine
- Diazepam
- Metaxalone
- Methocarbamol
- Vigabatrin
What is Carisoprodol?
Is a muscle relaxant that was a modification of meprobamate, intended to be a better muscle relaxant and less potential for abuse or overdose. Not successful because it can be combined with rohypnol to enhance date rape drug effects.
What is Chlorphenesin?
not available for use in US. secondary usage as anti-fungal and anti-biotic
What is cyclobenzaprine used for?
Injury-related spasms
What is Diazepam used for?
Muscle relaxant effecting both the UMN and LMN
What is Metaxalone used for and what should it be taken with?
- Strains and sprains
- Should be taken with food to limit the possibility of headaches and dizziness
What are the negative usage of Methocarbamol?
High risk in elderly, can slow down heart rate, cause skin rashes, and can depress the CNS
What is functionally significant about Vigabatrin?
- A GABA transaminase inhibitor that allows GABA to be present longer.
What are the drugs used for acute local muscle spasm?
- Chlorphenesin (contraindicated during pregnancy)
- Chlorzoxazone
- Metaxalone
- Methocarbamol
- Orphenadrine (anticholinergic properties)
- Carisoprodol
- Cyclobenzaprine
Cyclobenzaprine is believed to act where?
Due to some muscarinic effects what effect does it have on the bladder?
What two muscle spasm disorders does it not effect?
- level of the brainstem
- contraction of the detrusor muscle by the bladder
- Cerebral palsy or spinal cord injury
What skeletal muscle relaxants have the greatest half-lives and protein binding?
- Cyclobenzprine (1-3 days and 93% protein binding)
- Carisoprodol - (8 hours and 30% protein binding)
- Orphenadril - (14 hours)
- Dantrolene - (6-9 hours and >90% protein binding)
Why is Orphenadril considered very complex?
- Centrally acting but it inhibits H1 receptors and is an anticholinergic, and inhibits NMDA receptors in the CNS, as well as NE uptake. SOOO it can me used to treat muscle pain AND fibromyalgia
What are the contraindication of
1) Baclofen
2) Carisoprodol
3) Cyclobenzaprine
4) Dantrolen
1) Baclofen: Skeletal muscle spasms caused by Rheumatoid Arthritis
2) Carisoprodol: Patients with known hypersensitivity to meprobamate
3) Cyclobenzaprine: MI, cardiac conduction disorders, hyperthyroidism
4) Dantrolene: Active hepatic disease, muscle spasms caused by Rheumatoid Arthritis
What is Tixanidine and what does it treat?
- Tixanidine is an alpha2 agonist
- Treats hypotension, drowsiness, and dry mouth
- *Like clonadine but without the withdrawl effects.
What is botulinum toxin used for?
- Spasticity from cerebral palsy
- Cosmetic surgery
