Use of Botulinum Toxin in Central Nervous System Disorders

Botulinum toxin is a neurotoxin that is produced by Clostridium botulinum. At one time, this toxin was only seen as a lethal substance, but now scientists have found many medical uses for it. There are eight distinctive toxins (A-H), but only A and B currently have clinical uses. Botulinum toxin A has three different versions that are U.S. Food and Drug Administration (FDA) approved: onabotulinumtoxinA (Botox®), abobotulinumtoxinA (Dysport®), incobotulinumtoxinA (Xeomin®). Botulinum toxin B is also FDA approved as rimabotulinumtoxinB (Myobloc®). The toxins work by inducing reversible, local, dose-dependent chemodenervation by inhibiting acetylcholine release from presynaptic terminals. These drugs are approved to treat many different types of disorders but have found significant use for the treatment of migraines, dystonias and cerebral palsy. Botulinum toxin has proven to be efficacious in prophylactically treating those patients with migraines who have failed other pharmacologic and nonpharmacologic treatments. Botulinum toxin is also FDA approved for the treatment of dystonias; more specifically, all three types of botulinum toxin A and the rimabotulinumtoxin B have FDA approval for the treatment of cervical dystonia. Perhaps the most important use for botulinum toxin is in patients with cerebral palsy. Botulinum toxin is efficacious in patients with upper limb spasticity who are not good surgical candidates. It also proves useful as an adjunct to physiotherapy in these patients. This can help reduce or slow progression in patients with cerebral palsy. Exercise has been shown to be an efficacious treatment in patients with migraines, dystonias and cerebral palsy. Further research is necessary to determine the potential benefits the combination of exercise and botulinum toxin can have in these patients. While the high cost of botulinum toxin might deter some patients, it is a good option for those that have exhausted other options or are not good candidates for surgery

Prevention and Treatment of Glucocorticoid-Induced Osteoporosis

Osteoporosis is a disease state resulting in decreased bone mineral density (BMD) and increased risk of fracture, specifically of the vertebrae, spine and hip. Risk factors and high risk populations for developing osteoporosis include low BMD, long-term glucocorticoid therapy, genetics, diet, postmenopausal women and patients with inflammatory or chronic disease states. A variety of signaling pathways involving hormones, cytokines and other signaling molecules are involved in bone formation and are affected by long-term glucocorticoid therapy, leading to the development of glucocorticoid-induced osteoporosis (GIO). There are a variety of drugs that work efficaciously to prevent and treat GIO. Alendronate is a potent bisphosphonate that has shown efficacy in increasing BMD and decreasing bone turnover. Risedronate, another potent bisphosphonate, has demonstrated similar effects in patients suffering from GIO and has been observed to decrease fractures. Zoledronic acid is another bisphosphonate option that has proven efficacy and noninferiority to oral bisphosphonates in GIO, but it is unique in that it is given intravenously once a year. Additionally, teriparatide is a recombinant human parathyroid hormone (PTH) which is a newer therapy for the treatment of GIO and is beginning to replace older therapies such as testosterone and estrogen. The once daily administration of teriparatide induces bone formation, which allows for increase in bone mass thus reducing the risk of vertebral and nonvertebral fractures. Furthermore, calcium and vitamin D are usually seen as prophylaxis and adjunctive therapy. At the initiation of therapy, pharmacists should recommend bone density tests to evaluate if medication is appropriate for the patient. Subsequent action includes patient education and monitoring of initiated therapy and disease progression