pharmacology of skeletal muscle Flashcards
Classification of drugs acting on the
skeletal muscles
- Drugs causing contractions
Tetanus toxin – strong spastic contraction.
Activators of the mutated ryanodine receptors – halothan, succynylcholine, probably antipsychotics (see neurolpetic malignant syndrome)
Sympathomimetics – increase muscle strength
Centrally acting – any convulsive agent
2. Relaxants A. Centrally acting – „spasmolytics”- B. Peripherally acting Blockers of the neuromuscular junction Botulinum toxin Tetracyclines, aminoglycosides
spasmolytic goal
therapy goal in both chronic (cerebral palsy, multiple sclerosis, strokes) and acute forms is to reduce the excessive skeletal muscle tone without reduction of strength-> reduction of pain.
neuromuscular junctions blockers
usually have no CNS activity and have an important role in induction of muscle paralysis as part of a preoperative general anesthesia.
spasmylytic agent
usually work by either enhancing the level of inhibition or reduction of level of excitation of descending motor neurons
drugs- general
Drugs for spasticity only:
baclofen – GABAB agonist, highly sedative
Drugs for acute muscle spasm (unknown
mechanism)
mephenesine, guaiphenesin
chlorzoxazone
Centrally acting skeletal muscle
relaxants
Drugs for both acutely and for spasticity
diazepam – benzodiazepine
tizanidine – 2 agonist, structural relative of
clonidine (imidazoline)
tolperisone – unknown mechanism
carisoprodol (its metabolite is meprobamate) –
it has abuse potential, meprobamate is
hepatotoxic
Diazepam (a benzodiazepine)
Mechanism: interacts with GABA-A (ionotropic channel) and agonist of it-> less muscle spams (postsynpase).
Indication:
1/cervical and lumbar syndromes (transection?).
2/ multiple sclerosis, myelopathys etc..
Kinetics
Oral and IV
adverse effects:
marked sedation.
hypotonia.
rebound effects at withdrawl.
tizanidine
Mechanism:
presynaptic inhibition via alpha 2 agonist.
Indication
Muscle spasm.
Cervical and lumbar syndrome.
Kinetics
Taken orally.
Adverse asthenia. Drowsiness. Dry mouth Hypotension.
baclofen
Mechanism:
GABA B agonist
1) Presynaptic: GABA B exicted-> Less glutamate (excitatory) released.
2) Postsynpatic (gaba B)- K influx-> less excitation (hyperpolarization)
Indications:
MS, Spacicity, Alcoholics.
kinetics:
admin: Oral and intrathecal)
Adverse:
1. Sedative (less than diazapam).
2. enhancement of sedative and respiratory depressive 3/ effects of opiates and alcohol.
4/ Hallucinogenic.
Rilozole
orally taken
inhibition of glutamatergic tramission.
indication: ALS.
adverse: hepatotoxicity, neutropenia, GI.
other centrally acting spasmolytics
tolperisone – unknown mechanism
carisoprodol (its metabolite is meprobamate) –
it has abuse potential, meprobamate is
hepatotoxic.
mephenesin and guaiphenesin (parentally)- unknown mechanism.
dantrolene
Mechanism: Acts on the skeletal muscle cells to reduce the release of Ca from the SR by interacting with the RyR1 receptor channel (Ca channel in skeletal muscle)-> less actin myosin interaction.
Cardiac and SMC use RyR2.
Pharmacokinetics: orally about 1/3 of dose is absorbed and elimination half life is about 8 hours.
Indication:
- Malignant hyperthermia.
- spinal injury and
- after stroke.
adverse:
1. hepatotoxic (1-2% chance occuring, lethal if does).
2. generalized muscle weakness.
3. Sedation.
botulinum toxin
exotoxin of clostridium botulinum.
Theraputic use:
opthalmic-
1. plepharospasm (uncontrolled movements of eye lid)
2. strabismus (eyes are not pointing in the same direction)
3. generalized spastic disorders (cerebral palsy)
4. dystonia
5. cosmetics.
Mechanism: inhibits release of ACh by binding to synaptobrevin.