MCMP 407

SpasmolyticsSpasmolytics

• Chronic neurologic diseases•Cerebral Palsy, Multiple Sclerosis

• Acute Injury•Spinal cord damage, muscle inflamation

Goal of therapy: Reduce spasticity and pain, while retaining function

MCMP 407

SpasmolyticsSpasmolytics

Benzodiazepines (Diazepam, etc.)

GABAA Receptors CNS and Spinal Cord Side Effects: Sedation

N

N

H3CO

Cl

Diazepam

(Valium)

MCMP 407

SpasmolyticsSpasmolytics

Baclofen

(Lioresal

Cl

CO2HH2N

GABAB receptor agonist Activation of K+ channels CNS and Spinal cord (-)-Baclofen is the active isomer Less sedation than BZDs Intrathecal pumps now used in chronic

conditions Warning for severe withdrawal syndrome from

intrathecal use Altered mental status, hyperpyrexia, exaggerated

spasticity, muscle rigidity, and rhabdomyolysis

MCMP 407

SpasmolyticsSpasmolytics

2 adrenergic receptor agonist Congener of clonidine Presynaptic inhibition of motor

neurons 1/10-1/50th potency as clonidine

in lowering blood pressure Side Effects: Drowsiness,

hypotension, dry mouth

Tizanidine

(Zanaflex)

NS

N

Cl

N

NH

HN

MCMP 407

SpasmolyticsSpasmolytics

Tricyclic structure May act at level of brain stem Strong antimuscarinic effects

(sedation) Ineffective in the treatment of

chronic neurological disorders Use: Relief of acute muscle

spasm due to injury or strain

Cyclobenzaprine

(Flexeril)

CHCH2CH2N(CH3)2

MCMP 407

Atropine vs. CyclobenzaprineAtropine vs. Cyclobenzaprine

MCMP 407

SpasmolyticsSpasmolytics

Other drugs similar to Cyclobenzaprine (Flexeril)

Chlorzoxazone (Paraflex, Parafon) Orphenadrine (Norflex) Carisprodol (Soma)

MCMP 407

SpasmolyticsSpasmolytics

Interferes with excitation-contraction coupling

Reduces release of Ca++ from the sarcoplasmic reticulum

Blocks contraction

Dantrolene Sodium

(Dantrium)

OO2N

HC N N

N-O

O

Na+

Side Effects: Muscle weakness, sedation, rare hepatitis

Uses: Cerebral palsy, multiple sclerosis

Also Malignant Hyperthermia

MCMP 407

Action PotentialC

a2+

Motor neuron

Na +

ACH

ACHACH

ACH

ACHACH

ACH

ACHACH

ACH

ACH

ACH

ACH

Na+

SkeletalMuscle

ACHEsterase

Neuromuscular Blockers

MCMP 407

Properties of neuromuscular blockersProperties of neuromuscular blockers

Drug Elimination via Duration of action (minutes)

Short-acting

Mivacurium Plasma AChE 10-20

Intermediate-actingAtracurium Spontaneous 20-35Vecuronium Hepatic and renal 20-35Rocuronium Hepatic and renal 20-35

Long-actingPancuronium Renal 60

Succinylcholine Plasma AChE 5-10

MCMP 407

Clinical use of neuromuscular blockersClinical use of neuromuscular blockers

Muscle relaxation during surgical procedures Endotracheal intubation Maintain controlled ventillation

MCMP 407

Clinical problems associated with Clinical problems associated with neuromuscular blockersneuromuscular blockers

Potentiated by inhaled anesthetics (Isoflurane) Potentiated by aminoglycosides and calcium

channel blockers Can block autonomic ganglia at higher doses Respiratory paralysis