Baclofen is a gamma-aminobutyric acid (GABA) agonist used as a skeletal muscle relaxant. It is known to be particularly useful in treating muscle spasticity associated with spinal cord injury. This drug has recently been studied for the management of alcohol withdrawal, however, a conclusion has not been reached regarding baclofen efficacy in this condition.
Baclofen is administered for the relief of signs and symptoms of spasticity resulting from multiple sclerosis, particularly for the relief of flexor spasms and associated pain and clonus, in addition to muscular rigidity.
Patients receiving this drug should have reversible spasticity for baclofen to promote the restoration of residual function. This drug is not indicated in the treatment of skeletal muscle spasm caused by rheumatic disorders.
The efficacy of baclofen in stroke, cerebral palsy, and Parkinson's disease has not been determined and, therefore, baclofen is not recommended for these conditions.
In neurological diseases associated with spasm of the skeletal muscles, the clinical effects of baclofen occur due to baclofen action on reflex muscle contractions and of significant relief from painful spasm, automatism, as well as clonus.
Baclofen, when used as indicated, improves mobility, increasing levels of independence, and facilitates both passive and active physiotherapy. Baclofen also stimulates gastric acid secretion.
GABA-B receptor activation by baclofen may produce protective neurological effects. Baclofen also possesses anti-inflammatory properties that may be of interest in the study of addiction treatment.
Preclinical studies have shown that GABA-B receptors have roles in memory storage and retrieval, reward, motivation, mood, as well as anxiety. Neuroimaging studies in humans indicate that baclofen produces region-specific alterations in brain activity.
The exact mechanism of action of baclofen is not fully understood at this time. Many studies indicate that baclofen is a GABA-B receptor agonist. Despite this, there is no conclusive evidence that effects of baclofen on GABA systems are involved in the production of its clinical effects.
Baclofen is an effective and widely used antispastic agent with a spinal site of action. Its mechanism of action and pharmacological properties are different from the effects of other antispastic agents. In addition, baclofen has central sites of action, shown by its adverse event profile and general CNS depressant properties. GABA-B receptors interact with signal transduction pathways and neurotransmitter systems. Baclofen exerts an antinociceptive effect. The clinical significance of this warrants further research data for clarification.
Baclofen depresses monosynaptic and polysynaptic reflex transmission, by various actions, and possibly including the stimulation of GABAβ-receptors. This stimulation results in the inhibition of excitatory neurotransmitter (glutamate and aspartate) release, which may normally contribute to pain and spasticity. Although baclofen is an analog of the inhibitory neurotransmitter gamma-amino-butyric acid (GABA), there are no conclusive data indicating GABA systems are involved in its clinical effects.
Metabolism: Approximately 15% of the dose is metabolized in the liver, mainly by deamination. In a clinical study with radiolabeled baclofen, approximately 85% of the dose was excreted unchanged in the urine and feces. The γ-hydroxy metabolite, 3-(p-chlorophenyl)-4-hydroxybutyric acid, is produced after the deamination of baclofen. Because baclofen is partially metabolized in the liver, patients with impaired liver function should be regularly monitored with liver function tests.
Absorption: Rapidly and almost completely absorbed from the gastrointestinal tract. Absorption may be dose-dependent, being reduced with increased doses. Baclofen, when introduced directly into the intrathecal space, allows for effective CSF concentrations to be achieved with resulting plasma concentrations 100 times less than concentrations occurring with oral administration.
Route of elimination: Baclofen is rapidly and extensively eliminated from the body. There is significant intersubject variation in elimination rates. Baclofen is excreted mainly by the kidney as unchanged drug. Seventy to eighty (70 - 80%) of a dose is measured in the urine as unchanged drug. The remainder of the dose is excreted as unchanged drug in the feces or as metabolites in the urine and feces. Excretion is complete within 72 hours after administration.
Half life: Elimination half-life: Approximately 5.5 hours.
All medicines may cause side effects, but many people have no, or minor, side effects.Some medical conditions may interact with Baclofen.
Tell your doctor or pharmacist if you have any medical conditions.
Overdosage: Vomiting, muscular hypotonia, drowsiness, accommodation disorders, coma, respiratory depression, and seizures may occur with overdosage.
Pregnancy: This drug is a pregnancy category C drug. There are no adequate and well-controlled studies that have been performed with pregnant women. Baclofen should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Excretion in breastmilk: It is unknown whether this drug is excreted in human breast milk. Because many drugs are excreted in human milk, caution is warranted when baclofen is administered to a nursing woman.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider.
