INTRODUCTION
Botulinum Toxin
Botulinum toxin A decreases facial lines and wrinkles at sites of skin pleating caused by hyperfunctioning mimetic muscles. BOTOX ® (Allergan, Irvine, CA) is FDA approved for treatment of the glabella. Off-label uses have included periorbital lines (crow’s feet), platysmal bands, the forehead, and nasolabial and melolabial lines. BOTOX is also used for hyperhydrosis of the palms and armpits.
Botulinum toxin A (BOTOX®) causes paralysis by inhibiting acetylcholine release at the neuromuscular junction. This is accomplished in three steps. First, the toxin binds the nerve. Second, the toxin is internalized into the nerve. Third, the toxin is cleaved by internal proteolytic enzymes, and the degradation byproducts interfere with the normal process of vesicle fusion to the plasma membrane. This results in the inhibition of the exocytosis of acetylcholine.
The toxin requires 24 to 72 hours to take effect, reflecting the time necessary to disrupt the synaptosomal process. In very rare circumstances, some individuals may require as many as five days for the full effect to be observed. The effects of botulinum toxin last from two to six months.
The dose of the toxin is measured as one standard unit, which is equal to the amount necessary to kill 50% of Swiss-Webster mice injected with that dose. Extrapolating the data from mouse experimentation, Meyer and Eddie estimated that a 104-kilogram adult male would sustain a lethal dose of botulinum toxin type A at amounts exceeding 3500 units, a dose that far surpasses any dosing regimen in the cosmetic treatment of the aging face.
In patients with peripheral motor neuropathic diseases or neuromuscular functional disorders such as Eaton-Lambert syndrome and myasthenia gravis, botulinum toxin is contraindicated. Similarly, botulinum toxin type A is contraindicated in pregnant patients and those who are lactating, although unintentional administration has not resulted in birth defects or pregnancy issues. Finally, caution should be taken when injecting botulinum toxin type A to those taking aminoglycoside antibiotics or other agents that interfere with neuromuscular transmission, since these agents may potentiate the effects of botulinum toxin both locally and regionally.