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Botulinum Toxin

  • Botulinum toxin is an injectable neuromodulator 
  • Produced in nature by the Clostridium botulinum bacterium
  • Inhibits neurotransmission between peripheral nerve endings and muscle fibers
  • Causes temporary weakness or paralysis of skeletal muscle

Contents

  1. Basic Science 
  2. Mechanism of Action 
  3. Indications
  4. Formulations
    1. Botox
      1. Reconstitution & Dosing
    2. Dysport
      1. Reconstitution & Dosing
    3. Xeomin
  5. Complications
    1. Ptosis
    2. Peri-Orbital Edema
    3. Hypersensitivity Reaction

Basic Science

Clostridium botulinum produces botulinum toxin

  • Gram positive, spore-forming, obligate anaerobic bacteria
  • Produces seven distinct toxins (A -G)
    • Most potent = A type
    • Types A and B used medicinally

Biochemistry

  • Botulinum toxin is produced as a single chain protein (protoxin) composed of two chains (heavy and light) linked by disulfide bonds
  •  

Mechanism of Action

Irreversible inhibitor of acetylcholine release as the neural synapse (i.e. once injected, it cannot be reversed)

  1. Binding
    • The heavy chain binds to the axonal foot-plate 
  2. Uptake 
    • The peptide is endocytosed into the nerve terminal
  3. Translocation 
    • The heavy and light chains dissociate
    • The light chain translocates across the vesicle and cleaves the SNARE proteins
  4. Inhibition of transmitter exocytosis
    • Disables binding and exocytosis of the ACh from the terminal endplate (in peripheral cholinergic nerves) into the synaptic cleft 

Indications

Aesthetic Indications

  • Glabellar lines
    • Associated with corrugator and procerus muscle activity
  • Lateral canthal lines (“crows feet”) 
    • Associated with orbicularis oculi muscle activity
  • Forehead lines 
    • Associated with frontalis muscle activity

Medical (Non-Aesthetic) Indications

  • Upper motor neuron syndrome
    • Cerebral palsy
  • Focal hyperhidrosis
  • Blepharospasm
  • Strabismus
  • Chronic migraines
  • Bruxims (teeth grinding at night)
  • Cervical dystonia

Formulations

Botox

  • Produced by Allergan
  • Initially FDA approved in 1989
  • Duration of Effect = ~3 months
    • May be longer if routinely administered
  • Max dose = 400 units in 3 month interval

Calculating Dilution

  • 50 units diluted in 1.25ml of sterile saline
  • Divide 50 units by (12.5 x 0.1ml) = 4 units per 0.1ml

Dosing

  • Glabellar lines
    • 16 – 20 units 
      • 4 units in procerus
      • 4 units in most prominent muscle belly of bilateral corrugator muscles
      • 2 – 4 units in tail of bilateral corrugator muscles
  • Forehead lines
    • 20 units over 5 injection sites along the most active areas of frontalis activity
  • Lateral canthal lines
      • 6 – 12 units in bilateral crow’s feet spread over 2 – 3 injection sites

Storage

  • Unopened vials of BOTOX Cosmetic should be stored in a refrigerator 2° to 8°C (36º to 46ºF) 
  • Reconstituted BOTOX Cosmetic should be stored in a refrigerator 2° to 8°C (36º to 46ºF) and administered within 24 hours.

Dysport

  • Produced by Galderma

Calculating Dilution

  • 300 units diluted in 1.5ml 
  • Divide 300 units by (15 x 0.1ml) = 20 units per 0.1ml
    • 10 units per 0.05ml

Xeomin

Storage

  • Unopened vials of XEOMIN can be stored at:
    •  Room temperature 20° to 25°C (68° to 77° F)
    • In a refrigerator at 2° to 8°C (36° to 46°F)
    • In a freezer at -20° to -10°C (-4° to 14°F) for up to 36 months. 
  • Reconstituted XEOMIN should be stored:
    • In a refrigerator at 2° to 8°C (36° to 46°F) and administered within 24 hours

Complications

Eyelid Ptosis

  • Occurs in 3%
  • Paralysis of levator muscle
    • Origin: Lesser wing of sphenoid bone
    • Insertion: Orbicularis oculi, upper eyelid dermis and tarsus
    • Innervation: Superior division of Oculomotor nerve (CN III)
    • Action: Provides 10-12mm of eyelid elevation
    • Embryology: Develops in the 3rd month of gestation from the superior rectus muscle
  • Most frequently reported following glabellar injections

Prevention

  • Avoid injection near the levator palpebrae superioris, particularly in patients with larger brow depressor complexes
  • Lateral corrugator injections should be placed at least 1 cm above the bony supraorbital ridge
  • Ensure the injected volume/dose is accurate and where feasible kept to a minimum
  • Do not inject toxin closer than 1 cm above the central eyebrow 

Treatment

    • Apraclonidine hydrochloride (Iopidine)
      • Selective α2- adrenergic agonist
      • Causes Muller’s muscle contraction resulting in 1-3mm of lid elevation
        • Innervated by the sympathetic system and unaffected by the loss of cholinergic nerve terminals
      • Also reduces intra-ocular pressure (for glaucoma) and increases muscle tone in Horner’s Syndrome 

Periorbital Edema

  • Occurs in 1%
  • Most frequently reported following lateral canthal injections