Medical Pharmacology Chapter 20: Neuromuscular Blocking Agents and Muscle Relaxants
Enhances CNS GABA inhibitory activity; active at most (all) GABAA synapses.
Anti-spasmolytic effect in part due to action in the spinal cord (effective in patients with cord transection)
Tends to be sedating
Mechanism: GABA agonist at GABAB receptors
Receptor activation causes increased K+ conductance (hyperpolarization) in the brain and spinal cord
Spinal cord effects probably occur following increased presynaptic inhibition which reduces transmitter released by reducing calcium influx.
Similar anti-spasticity compared to diazepam (Valium) but with less sedation
Orally active;well absorbed
half-life: 3-4 hours
Increased seizure activity in patients with epilepsy
Intrathecal Baclofen (Lioresal) use:
Management of severe spasticity/pain when nonresponsive to medication by other routes of administration.
Few peripheral symptoms; higher concentrations may be used
Partial tolerance may develop
Major disadvantage: maintaining the integrity of the delivery catheter.
Advantage: significant improvement of quality of life in some patients
Tizanidine (Zanaflex) is related to clonidine (Catapres)
Enhances both pre-and postsynaptic inhibition in the spinal cord
Also inhibits nociceptive transmission (dorsal horn)
Probably a significant benefit for patients with spasticity (several types)
Comparable efficacy compared to: diazepam (Valium), baclofen (Lioresal), and dantrolene (Dantrium)
Dosage must be carefully titrated for each patient
Drowsiness, dry mouth, asthenia, hypotension
Unique mechanism: acts outside the CNS
Interferes with muscle fiber excitation-contraction coupling
Mechanism of action
Blockade of sarcoplasmic reticulum calcium channel (ryanodine channel)
Reduced calcium concentration diminishes actin-myosin interaction
Motor units contracting more rapidly are more sensitive to dantrolene (Dantrium)
Cardiac muscle and smooth muscle are only slightly affected (different calcium release mechanism)
Bioavailability: about 33% of oral dose absorbed
Malignant hyperthermia, is associated with hereditary abnormality in sarcoplasmic reticulum calcium sequestration affecting probably, in some cases affecting the ryanodine receptor (calcium channel in the SR) is triggered by:
Neuromuscular blocking drugs
Malignant Hyperthermia Clinical Presentations:
Significant muscle contractions
Sudden and prolonged calcium release
Increased lactic acid production
Increased body temperature
Dantrolene (Dantrium) reduces calcium release
Other interventions are required to reduce body temperature and manage acidosis.