THERAPEUTICS

Brands

• Onabotulinumtoxin A (Botox, Botox cosmetic), Abobotulinumtoxin A (Dysport), Incobotulinumtoxin A (Xeomin), Vistabel, Neuronox

Generic?

• No

Class

• Neurotoxin

Commonly Prescribed for

(FDA approved in bold)

• Prophylaxis of chronic migraine

• Upper limb spasticity in adult patients

• Cervical dystonia (CD) in adult patients

• Overactive bladder (OAB) with an inadequate response to or if patients are intolerant of an anticholinergic medication

• Severe axillary hyperhidrosis

• Blepharospasm associated with dystonia in patients ≥ 12 years of age

• Strabismus in patients ≥ 12 years of age

• Glabellar lines

• Focal dystonia

• Essential tremor

• Palmar hyperhidrosis

• Cosmetic use

• Hemifacial spasm

• Spasmodic torticollis

• Spasmodic dysphonia (laryngeal dystonia)

• Writer's cramp and other task-specific dystonias

• Spasticity associated with stroke

• Dynamic muscle contracture in cerebral palsy

• Acquired nystagmus

• Oscillopsia

• Sialorrhea (drooling)

• Temporomandicular joint dysfunction

• Diabetic neuropathic pain

• Myofascial pain

• Tics

• Achalasia (esophageal motility disorder)

How the Drug Works

• It blocks acceptor nerve terminals, entering the nerve terminals, and inhibiting the release of acetylcholine and other neurotrasmitters (e.g., glutamates, substance P, calcitonin gene-related peptide), and subsequently their downstream activation. The heavy chain (HC) binds to presynaptic gangliosides on the cell surface and promotes translocation of light chain (LC) into cytosolic endosomes. Once released into cytosol, LC (a zinc endopeptidase) cleaves SNAP-25 (synaptosomal-associated protein 25), a protein integral to the successful docking and release of neurotransmitters from vesicles situated within nerve endings. It may also affect membrane trafficking of other receptors and channel proteins

• It acts locally (due to limited diffusion from its large size), as well as distally possibly via axonal transports to central terminals, transcytosis to second-order neurons and glia, and even possible hematogenous spread

• It produces partial chemical denervation of the muscle and sweat gland, detrusor efferent activity, and facilitates pain. However, it has no role in acute antinociception peripherally