Pharmacology of spinal cord injury: Basic mechanism of action and side effects of commonly used drugs

Journal of Neurologic Physical Therapy, Sep 2003 by Scelza, William, Shatzer, Matthew

ABSTRACT

For individuals with spinal cord injuries (SCI) there are numerous unique medical conditions that exist involving cardiovascular/autonomic systems, pain, depression, spasticity, heterotopic ossification, and bowel/bladder dysfunction. In this article the physiological basis of such conditions and focus on the pharmacological agents used in the management and treatment of these conditions will be reviewed. The basic mechanisms of action and major adverse effects will be discussed.

INTRODUCTION

The incidence of spinal cord injury (SCI) in the United States is approximately 11,000 injuries per year with a prevalence between 180,000-230,000 persons.1 As a consequence of SCI, many functions of the body are disrupted and require intervention to regulate and maintain physiologic function. Clinicians practicing with this population require knowledge of the pharmacological agents used in the treatment of complications due to SCI. In this article an overview of pharmacological agents used in the treatment of pain, depression, spasticity, bowel and bladder abnormalities, and cardiovascular and autonomic dysfunction associated with SCI is presented. The paper is organized by system dysfunction with specific disorders and their management.

CARDIOVASCULAR AND AUTONOMIC DYSFUNCTION

Immediately following SCI, patients may develop neurogenic spinal shock. Spinal shock is a transient depression of cord function below the level of injury characterized by hypotension, bradycardia, and hypothermia. Following its resolution, a variety of cardiovascular and autonomic dysfunctions may ensue.

Autonomic Dysreflexia

Autonomic dysreflexia (AD) is an unopposed sympathetic discharge causing an increase in blood pressure.2 Autonomic dysreflexia is usually seen in patients with injuries at T6 or above with an incidence thought to be from 48% to 85%.3 It is caused by a strong or noxious stimulus (distended bladder, fecal impaction, or pressure ulcer) below the level of the injury. Higher central nervous system centers are unable to modulate the sympathetic response because of the injury to the spinal cord. Patients will present with hypertension, pounding headache, flushing above the level of the lesion, and anxiety. Bradycardia is often seen as a compensatory response since the carotid baroreceptors, sensing the acute hypertension, send inhibitory impulses to the sympathetic system. Occasionally, patients will have silent AD and be completely asymptomatic.4

In those patients with acute AD, prompt action is required to prevent potential end organ damage (cerebral hemorrhage, seizures, myocardial infarction, etc.). The basis of treatment is to remove the underlying noxious stimulus. To manage the situation, first sit the patient upright and attempt to identify the cause. Loosen all clothing and equipment and begin to inspect for urinary distension produced by a blocked catheter. Urinary distension is the most common cause of AD. If no catheter is present, the patient must be catheterized. If symptoms do not resolve, further inspection for a cause must be conducted. An undetected fracture, fecal impaction, pressure ulcers, and tight clothing are other causes of AD. Once the noxious stimulus is found and treated, the symptoms tend to resolve quickly. However, if there is no change in symptoms, pharmacological intervention is necessary to reduce blood pressure.5 Nitroglycerin paste is a rapidly acting vasodilator that can be easily applied and then removed when the symptoms normalize. Nifedipine is another commonly used pharmacological agent that reduces vascular tone by blocking calcium channels in smooth vascular muscle. It should be mentioned that with the administration of antihypertensive medications a rapid swing of blood pressure may occur in the other direction resulting in hypotension.

Orthostatic Hypotension

Orthostatic hypotension is a decrease in blood pressure as a person transitions from a supine to a sitting or standing position. This occurs due to the lack of muscle tone and pumping action that assists venous return to the heart, as well as abnormal autonomic function. Symptoms include dizziness, lightheadedness, and syncope. While it is more likely to occur in those with injuries above T6 and complete injuries, the true incidence is unknown.2 This condition is treated initially with compensatory strategies (ace wraps and abdominal binders) and tends to resolve as muscle tone improves. If orthostatic hypotension continues to be problematic, pharmacological options are available.

Midodrine hydrochloride is a vasoconstrictor that acts by stimulating alpha adrenergic receptors in blood vessels and can be used to help with symptomatic orthostatic hypotension.6 Fludrocortisone, a mineralocorticoid, has also been used to help retain salt and maintain intravascular volume.7 Salt tablets are used fur a similar purpose. Side effects of these medications include the development of hypertension, especially in those who are susceptible to AD, and lower extremity edema.