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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


  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


  • 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 


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



  • 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


  • 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


  • 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.


  • 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



  • 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


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


  • 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 


    • 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