CNS Depressant & Skeletal Muscle Relaxant Therapy

Central nervous system depressants, also called CNS depressants, are medications that slow brain activity, and are used to promote relaxation, relieve anxiety, and induce sleep. CNS depressants are also used for moderate sedation before and during invasive procedures such as colonoscopies. Commonly prescribed CNS depressants include benzodiazepines like diazepam, lorazepam, and midazolam.

Next, muscle relaxants are medications that reduce muscle spasms and associated pain. They are used to relieve both acute spasms associated with injury or chronic muscle spasticity related to CNS disorders, like multiple sclerosis and stroke. Cyclobenzaprine is the most commonly prescribed muscle relaxant to treat spasms related to musculoskeletal injuries.

Now, midazolam is a benzodiazepine that acts as a central nervous system depressant. It works by enhancing the inhibitory effects of the neurotransmitter gamma-aminobutyric acid, or GABA, which decreases neuronal excitability and promotes sedation.

Okay, so when the CNS is depressed by medications like midazolam, side effects can include headache, slurred speech, weakness, and anterograde amnesia, meaning the patient can’t recall the events that occurred after receiving the medication. Other side effects include nausea and hypotension, as well as pain at the injection site. Importantly, midazolam has a Black Box warning for severe respiratory depression and respiratory arrest. It’s also considered a high-alert medication, meaning it has an increased risk of causing significant patient harm if administered in error.

As far as contraindications go, midazolam should be avoided in patients with acute narrow-angle glaucoma, because it can increase intraocular pressure; and must not be combined with other CNS depressants, such as alcohol, opioids like morphine, or centrally acting muscle relaxants like cyclobenzaprine, because this can result in profound sedation.

Additionally, midazolam shouldn’t be given with grapefruit, since it will increase the serum concentration of midazolam, which will dangerously increase its sedative effects. And since midazolam is a major substrate of the drug metabolizing enzyme CYP3A4, it should not be administered with medications or herbs that induce CYP3A4, such as rifampin or St. John’s wort, since this will decrease the serum level of midazolam. Likewise, it should not be administered with medications that inhibit CYP3A4 like erythromycin, because this will increase the serum level of midazolam.

Okay, let's switch gears and talk about centrally acting muscle relaxants. Although the exact mechanism is unclear, once administered, these medications act on the neurons of the CNS to interfere with muscle reflexes and decrease the skeletal muscle tone.

Now, the main side effects of centrally acting skeletal muscle relaxants like cyclobenzaprine, include drowsiness, dizziness, headaches, and weakness. Other side effects include hypotension, gastrointestinal upset, and ileus.