PHARMACOLOGIC MANAGEMENT

SYMPTOMATIC THERAPY Includes therapies for constipation, spinal instability, pain, and psychological and social distress Constipation arises in these patients from autonomic dysfunction, inactivity, and opioids It must be treated aggressively because the pain of cord compression increases with a Valsalva maneuver, such as straining at stool Osmotic agents, such as polyethylene glycol 3350 (MiraLax), are often needed in addition to stool softeners and stimulants to promote regular, soft stools

Control of the pain caused by spinal cord compression usually requires a combination of opioids and adjuvants for nerve and bone pain Corticosteroids are effective adjuvants in the relief of both neuropathic and bone pain, and NSAIDs may be helpful for patients with bone pain who are unable to take corticosteroids

CORTICOSTEROIDS Used most commonly in patients that develop spinal cord compression with neurologic deficits Glucocorticoids with antioxidant or antioxidant- like activity (such as methylprednisolone) – reduce the release of total free fatty acids (including arachidonic acid) and prostanoids and prevent lipid hydrolysis and peroxidation, thereby reducing injury from traumatic spinal cord injury Dexamethasone I – nhibits PGE2 and VEGF production and activity and, as a consequence, decreases ischemic edema, which is partially mediated by increased levels of PGE2 and VEGF

Studies in animal models indicate a dose-dependent response of vasogenic edema to corticosteroids, even without radiation therapy High doses of corticosteroids – better than low doses in reversing edema and improving neurologic function Loading dose of 10 to 100 mg is administered, followed by a 16- to 96-mg/day maintenance dose High doses have been recommended (100 mg loading dose followed by 24 mg every 6 hours × 3 days) to quickly restore ambulation, although may increase the incidence of serious adverse effects Adverse effects of steroids – insomnia, increased appetite, edema, hyperglycemia, leukocytosis, increased risk of infection, and gastrointestinal bleeding

21-AMINOSTEROIDS e.g. U-74006F 21-aminosteroids that lack glucocorticoid or mineralocorticoid activity These potent inhibitors of lipid peroxidation for the acute treatment of central nervous system trauma and ischemia Inhibit the release of free arachidonic acid from injured cells

ANALGESICS Opioid and non-opioid Mild pain – nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are – Acetaminophen-preferred in patients with thrombocytopenia, renal dysfunction, those receiving nephrotoxic agents, or at risk for gastrointestinal bleeds – In patients with liver dysfunction, NSAIDs are preferred for mild pain

ANALGESICS Moderate to severe pain – Opioid analgesics – begin with low doses of immediate release agents (typically 5-15 mg per os morphine or 2-4 mg intravenous morphine) – Reassess patient every 1 to 2 hours for effect – After 24 hours of pain control on a short-acting regimen, patients should be converted to a long- acting agent (morphine, oxycodone, fentanyl, or methadone).

“ Radiation therapy is also the standard of care. Radiotherapy is delivered to the site of disease and to one or two levels above and below. It is typically given as 3,000 cGy in Gy fractions. With this regimen, 50% of patients are able to walk again, Dr. Wen noted” management of spinal cord compression, journal of supportive oncology, volume 6, 2008