Botulinum toxin a

Author: Prof. Dr. med. Peter Altmeyer

Co-Autor: Hadrian Tran

All authors of this article

Last updated on: 08.04.2021

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Definition
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Heat-labile 150 kDa exotoxin of Clostridium botulinum (anaerobic, gram-positive bacterium). First used medicinally in 1979 for the treatment of strabismus. Approved as a drug since 1993. The light chain of botulinum toxin is a zinc endopeptidase. This enyzm is taken up into nerve cells by endoyztosis. There it leads to an enzymatic destruction of the exocytosis proetin SNAP-25 anchored to the axolem, thus blocking the endocytotic release of acetylcholine.

Pharmacodynamics (Effect)
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The neurotoxin blocks the fusion of the acetylcholine vesicles with the plasma membrane in the synapses of the motor end plate. This blocks the exocytotic release of acetylcholine into the synaptic cleft and thus the transmission of the impulse arriving in the peripheral nerve to the muscle and inhibits its activity. The nerve endings of the neurons degenerate after exposure to the toxin and have to be replaced by new formations (Graefe et al 2016)

Indication
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Hyperhidrosis; wrinkling. The effect usually lasts about 3 months; repeat treatments are usually necessary.

Only the preparation Botox is approved for the treatment of severe hyperhidrosis axillaris. Other products containing botulinum toxin A (e.g. Dysport) are not approved for the treatment of hyperhidrosis axillaris. With the same active ingredient, an off-label use is nevertheless present here.

Products containing botulinum toxin A are not approved for the indication palmar and plantar hyperhidrosis.

Benign prostatic hyperplasia: Botulinum toxin A is injected into the prostate gland where it causes shrinkage of the gland (Graefe KH 2016).

Anal fissure

Limited indication
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Simultaneous therapy with aminoglycoside antibiotics (streptomycin, neomycin, gentamicin, kanamycin), spectinomycin or other drugs with an effect on the neuromuscular excitation conduction (e.g. local anaesthetics).

Pregnancy/nursing period
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Clostridium botulinum toxin must not be used during pregnancy and lactation. If treatment is required during the breastfeeding period, the baby must be weaned.

Dosage and method of use
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Remember! Dose is given in units, the dose of the commercial preparations is different!

Undesirable effects
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In rare cases, skin irritation or infection at the injection site; local signs of paralysis, e.g. ptosis.

In cosmetic use, swallowing disorders (dysphagia) and in individual cases, among others, sarcoidosis at the injection site as well as haematoma due to arterial damage (pseudoaneurysm) have been reported most frequently.

About 5% of patients complain of increased sweating outside the injection sites. Skin reactions, including erythema exsudativum multiforme, anaphylactic reactions and sometimes fatal cardiovascular complications such as cardiac arrhythmias and sudden deaths have been reported as rare adverse effects.

Generalised muscle weakness (botulism-like syndrome), autonomic disturbances such as accommodation disorders and dryness of the mouth and throat with swallowing difficulties as well as severe, therapy-resistant headaches are rare.

Interactions
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In the case of botulinum toxin-A, interactions are to be expected if active substances that impair neuromuscular transmission or reduce muscle tone are administered simultaneously. As long as the effect of botulinum toxin-A persists, polymyxin, tetracyclines and lincomycin should be used with special caution.

Contraindication
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Absolute contraindications: Generalized disorders of muscle activity (myasthenia gravis, Lambert-Eaton-Rooke syndrome).

Proven hypersensitivity to one of the components, local infection of the injection sites, pregnancy and lactation.

Relative contraindications:

  • Coagulopathy and therapeutic anticoagulation, poor patient cooperation, unstable patient mental constellation, unrealistic patient expectations, unrealistic fear of systemic botulism.
  • Use in children/adolescents < 18 yrs (insufficient data).

Preparations
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Botulinum toxin type A: Botox, manufacturer Allergan Botox Ltd, Ireland. Distributed by Pharm-Allergan GmbH, Ettlingen. 100 units per bottle.

Botulinum toxin type A: Dysport, manufacturer Speywood Biopharm Ltd, England. Distributed by Ipsen Pharma GmbH, Ettlingen. 500 units per bottle.

Note(s)
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Caution. Poisoning by oral ingestion of spoiled food leads to botulism.

Remark. If treatment is necessary in women of childbearing age, pregnancy must be ruled out before starting treatment!

Literature
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  1. Carruthers JA et al (2002) A multicenter, double-blind, randomized, placebo-controlled study of the efficacy and safety of botulinum toxin type A in the treatment of glabellar lines. J Am Acad Dermatol 46: 840-849
  2. Glogau RG (2002) Review of the use of botulinum toxin for hyperhidrosis and cosmetic purposes. Clin J Pain 18(6 Suppl): S191-197
  3. Graefe KH et al. Parasympathetic nervous system. In: Graefe KH et al (Eds) Pharmacology and Toxicology. Georg Thieme Publisher Stuttgart S.121
  4. Jost WH, Kohl A (2001) Botulinum toxin: evidence-based medicine criteria in rare indications. J Neurol 248 Suppl 1: 39-44
  5. Jost WH, Kohl A (2001) Botulinum toxin: evidence-based medicine criteria in blepharospasm and hemifacial spasm. J Neurol 248 Suppl 1: 21-24
  6. Kreyden OP et al (2000) Botulinum toxin: from poison to drug. A historical review. dermatologist 51: 733-737
  7. Lowe NJ et al (2007) Botulinum toxin type A in the treatment of primary axillary hyperhidrosis: a 52-week multicenter double-blind, randomized, placebo-controlled study of efficacy and safety. J Am Acad Dermatol 56: 604-611

Authors

Last updated on: 08.04.2021