Along with new therapeutic interventions that have emerged in the growing field of physical medicine and rehabilitation, pharmacologic agents continue to play an important role in management of the patient’s rehabilitation course. This chapter reviews an array of medications that are often used for conditions frequently managed in physiatric practice. Detailed discussion of each of these conditions—spasticity, traumatic brain injury, pain, and venous thromboembolism (deep vein thrombosis)—is found elsewhere in this book, and readers are referred to those chapters for additional information.
In spasticity, a motor neuron disorder (most often involving the upper motor neuron) leads to an abnormal increase in muscle tone secondary to hyperexcitability of the stretch reflex. (See Chapter 6 for additional information.) Current pharmacologic treatment utilizes oral antispasmodic medications and invasive chemodenervation agents. The choice of agents involves consideration of benefits versus complications of spasticity and expectations of the antispasmodic, such as functional benefit or pain relief.
Oral Antispasticity Agents
A variety of oral antispasmodic agents is available; however, only four medications are approved by the U.S. Food and Drug Administration (FDA) for spasticity management: baclofen, diazepam, tizanidine, and dantrolene. These oral agents have a systemic effect, reducing generalized muscle tone; however, all are associated with significant systemic side effects. Because all four medications involve a degree of hepatic metabolism, caution is advised in patients with liver disease. Table 10–1 contrasts key features of these medications.
Table 10–1Antispasticity agents. |Favorite Table|Download (.pdf) Table 10–1 Antispasticity agents.
|Medication ||Mechanism of Action ||Side Effects |
|Baclofen ||Acts on GABAB receptors ||Sedation, weakness, lower seizure threshold |
|Diazepam ||Acts on GABAA receptors ||Sedation, memory impairment, weakness, decreased rapid eye movement sleep |
|Tizanidine ||Centrally acting α2-adrenergic agonist ||Sedation, hypotension, dry mouth, bradycardia, dizziness, weakness |
|Dantrolene ||Inhibits calcium release at sarcoplasmic reticulum ||Sedation, weakness, diarrhea, hepatotoxicity, nausea |
Baclofen is a centrally acting antispasmodic agent that binds to the presynaptic and postsynaptic γ-aminobutyric acid B (GABAB) receptors as a GABA agonist. Activation of the GABAB receptors suppresses excitatory neurotransmitters and reduces γ motor neuron excitability and muscle spindle sensitivity. Side effects include sedation and weakness; therefore, baclofen is started at a low dose and titrated to a tolerable dose. Other potential side effects include lowering of the seizure threshold. The greatest risk with this medication is sudden withdrawal, which can lead to seizures, hallucinations, rebound spasticity, and fever. In addition, patients with renal disease may require a dosage adjustment since baclofen is renally excreted. Overdose of baclofen can be treated with physostigmine.
Diazepam is a centrally acting antispasmodic agent that binds to the GABAA receptors and causes membrane hyperpolarization by opening membrane chloride channels. The most common side effect is sedation. Other side ...