Botulinum Toxin for Laryngeal Dystonia Medication

Updated: Dec 20, 2016
  • Author: Jayita Poduval, MS, MBBS, DNB(ENT), DORL; Chief Editor: Arlen D Meyers, MD, MBA  more...
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Medication

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Mechanism of action of botulinum toxin. Mechanism of action of botulinum toxin.
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Neuromuscular Blockers, Botulinum Toxins

Class Summary

Botulinum toxin exists in up to 8 different forms: A, B, C1, C2, D, E, F, and G; A and B types are the most commonly used. [1]

Botulinum toxin A is available in the United States as BOTOX® (Allergan) and in Europe as Dysport (Speywood), while botulinum toxin B is known as Myobloc in the United States and Neurobloc in Europe. Only type A is used extensively in laryngology, [4] and all dosages and parameters of use mentioned herein are with regard to the brand BOTOX®.

Botulinum toxin affects the neuromuscular junction by binding presynaptically and blocking the release of the neurotransmitter acetylcholine, thereby preventing muscle contraction in the innervated area. It causes a temporary paresis or paralysis that may be reversed by the production of new axon terminals and the production of new cellular proteins (see image below). [1]

Botulinum toxin exists in nature as a clostridial neurotoxin that is extracted from fermented culture media, precipitated, purified, and crystallized with ammonium sulfate. [1, 4] It is commercially prepared as a single-chain polypeptide that is inert and must be converted into a double chain to achieve potency. [1] The double chain has a heavy chain that is required for intracellular binding and transportation and a light chain that has zinc endopeptidases that disrupt the proteins involved in the release of acetylcholine into the postsynaptic cleft. [1]

To be effective, BOTOX® is diluted in preservative-free saline and used within 4 hours of reconstitution. [1] It is stored at a temperature below 20°C, and with a pH maintained between 4.2 and 6.8. It must not be stirred, shaken, or frozen and should not be mixed with preservatives. [1] BOTOX® is dispensed in 100-U vials and is usually used in a concentration of 2.5-10 U/0.1 mL (ie, one vial may be diluted in 1-4 mL of saline). [1]

Approximately 0.1-0.2 mL may be injected into one vocal cord. Effects of BOTOX® start in 24-72 hours, maximizing at about 2 weeks. The action may last from 3-6 months. [1]

Onabotulinumtoxin A (BOTOX®)

This is one of several toxins produced by Clostridium botulinum. It blocks neuromuscular transmission through a 3-step process, described below.

Step 1

BOTOX® binds to the motor nerve terminal. The binding domain of the type A molecule appears to be the heavy chain, which is selective for cholinergic nerve terminals.

Step 2

BOTOX® is internalized via receptor-mediated endocytosis, a process in which the plasma membrane of the nerve cell invaginates around the toxin-receptor complex, forming a toxin-containing vesicle inside the nerve terminal. After internalization, the light chain of the toxin molecule, which has been demonstrated to contain the transmission-blocking domain, is released into the cytoplasm of the nerve terminal.

Step 3

BOTOX® blocks acetylcholine release by cleaving SNAP-25, a cytoplasmic protein that is located on the cell membrane and that is required for the release of this transmitter. The affected terminals are inhibited from stimulating muscle contraction. The toxin does not affect the synthesis or storage of acetylcholine or the conduction of electrical signals along the nerve fiber.

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