Nursing Pharmacology Chapter 20:  Neuromuscular Blockers

• Diazepam (Valium)

  •  Enhances CNS GABA inhibitory activity; active at most (all) GABA_A synapses.

  •  Anti-spasmolytic effect in part due to action in the spinal cord {effective in patients with cord transection}

  •  Tends to be sedating

• Baclofen (Lioresal)

  • Mechanism: GABA agonist at GABA_B 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

  • Pharmacokinetics:

    • Orally active;well absorbed

    • Half-life: 3-4 hours

  •   Adverse Effects

    • drowsiness; 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)

  • Overview

    • Tizanidine (Zanaflex) is related to clonidine (Catapres)

    • Enhances both pre-and postsynaptic inhibition in the spinal cord

      • Also inhibits nociceptive transmission (dorsal horn)

  • Clinical Use

    • 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

  • Adverse Effects:

    • drowsiness, dry mouth, asthenia, hypotension

• Dantrolene (Dantrium)

  • Overview

    •  Unique mechanism given the drug 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}

  • Pharmacokinetics

    • Bioavailability: about 33% of oral dose absorbed

  •   Adverse Effects

    • Muscle weakness

    • Sedation

    • Hepatitis (occasional)

  • Other Clinical Use

    •  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:

      •  General anesthesia

      •  Neuromuscular blocking drugs

    • 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.