Direct-acting skeletal muscle relaxants

Direct-acting skeletal muscle relaxants

Dantrolene is the most common direct-acting skeletal muscle re-laxant. Although dantrolene has a similar therapeutic effect to the centrally acting drugs, it works through a different mechanism of action. Because its major effect is on the muscles, dantrolene has a lower incidence of adverse CNS effects; high therapeutic doses, however, are toxic to the liver.

Common adverse effects of dantrolene include drowsiness, dizziness, malaise, fatigue, and weakness. More serious adverse effects include seizures and hepatitis. (See Dantrolene.)

In the head

Dantrolene seems most effective for spasticity of cerebral origin. Because it produces muscle weakness, dantrolene is of question-able benefit in patients with borderline strength.

Pharmacokinetics

Although the peak drug concentration of dantrolene usually oc-curs within about 5 hours after it’s ingested, the patient may not notice the therapeutic benefit for a week or more.

Absorption

Dantrolene is absorbed poorly from the GI tract and is highly plas-ma protein–bound. This means that only a small portion of the drug is available to produce a therapeutic effect.

Metabolism and excretion

Dantrolene is metabolized by the liver and excreted in urine. Its elimination half-life in healthy adults is about 9 hours. Because dantrolene is metabolized in the liver, its half-life may be pro-longed in patients with impaired liver function.

Pharmacodynamics

Dantrolene is chemically and pharmacologically unrelated to the other skeletal muscle relaxants.

Dantrolene works by acting on the muscle itself. It interferes with calcium ion release from the sarcoplasmic reticulum and weakens the force of contractions. At therapeutic concentrations, dantrolene has little effect on cardiac or intestinal smooth muscle.

Pharmacotherapeutics

Dantrolene helps manage all types of spasticity but is most effec-tive in patients with:

·                 cerebral palsy

·                 MS

·                 spinal cord injury

·                 stroke.

Dantrolene is also used to treat and prevent malignant hyper-thermia. This rare but potentially fatal complication of anesthesia is characterized by skeletal muscle rigidity and high fever. (See How dantrolene reduces muscle rigidity.)

Drug interactions

·                 CNS depressants can increase the depressive effects of dantro-lene, resulting in sedation, lack of coordination, and respiratory depression.

·                 Estrogens, when given with dantrolene, can increase the risk of liver toxicity.

·                I.V. verapamil, when given with dantrolene, may result in cardio-vascular collapse; these drugs shouldn’t be administered concur-rently.

·                 Alcohol may increase CNS depression when given with dantro-lene.

·                 Sun exposure may cause photosensitivity.