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PHARMACOLOGY

Botulinum toxin is a protein produced by the bacterium Clostridium botulinum. Seven serotypes exist, designated as A, B, C1, D, E, F, and G. Each one of them is a protease with a light chain linked to a heavy chain by a disulfide bond.

Each is antigenically distinct. However, botulinum toxin A (BTX-A), B (BTX-B), and F are the only serotypes currently available for clinical use (Table 4.1).

TABLE 4.1Botulinum Toxin Preparations

MECHANISM OF ACTION

Inhibition of acetylcholine release at the neuromuscular junction resulting in muscular flaccid paralysis. Receptor site binding is mediated by the heavy chain portion of the toxin, is specific for the toxin serotype, and is irreversible. Once bound, the receptor–neurotoxin complex is internalized into the nerve terminal and the toxin light chain acts as a protease to cleave specific synaptic protein peptide bonds required for acetylcholine formation. The target of BTX-A is the synaptasome-associated protein of 25 kDa, SNAP-25. BTX-B and BTX-E cleave the vesicle-associated membrane protein, synaptobrevin.

DILUTION

BTX-A is stored in lyophilized vials. It can be reconstituted in preserved saline or preservative-free saline. Dilutions vary according to physician preference and experience with BTX. A dilution ranges from 1 mL (10 U/0.1 cc) to 4 mL (2.5 U/0.1 cc). Dysport diluted to 2.5 mL will attain a concentration of 20 U/0.1 cc. The injected volume must be sufficiently small to provide accurate toxin delivery without an excessive volume effect or delivery of toxin to surrounding muscles other than the targeted muscles. The volume must be sufficiently large to permit accurate injection into the targeted muscles.

CONTRAINDICATIONS

Absolute

  • Underlying neuromuscular condition such as myasthenia gravis or amyotrophic lateral sclerosis

  • Pregnancy/breast-feeding—pregnancy category C

  • Active infection in treatment area

  • Unrealistic patient expectations

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