โดย : พญ.สุณิสา สินธุวงค์ จักษุแพทย์ โรงพยาบาลเมตตาประชารักษ์(วัดไร่ขิง)

1. Clinical Pharmacology
of Botulinum Toxin A
Sunisa Sintuwong, M.D.
Mettapracharak (Wat Raikhing) Hospital
Sunday, August 26, 2012 1

2. • introduction
• synthesis and structure of Botulinum
neurotoxins
• mechanism of action
• clinical pharmacology
Sunday, August 26, 2012 2

3. introduction
• first used for treatment of strabismus and
blepharospasm (muscular overactivity)
• then use in facial aesthetics
• most popular non-surgical aesthetic
procedure in USA
• only BOTOX is currently approved for
cosmetic use in USA
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4. Synthesis and Structure
of Botulinum neurotoxins
• “proteins” produced by different clostridial
bacterial species
• related to tetanus toxin
• progenitor toxin and associated proteins
• different bacterial strains -> different
botulinum neurotoxin serotype (type
A,B,C1,D,E,F,G)
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5. • various serotypes form different complex
sizes
• only type A forming largest complex (900
kd)
• active neurotoxin 150 kd
• and cleaved in an active dichain: 100 kd
heavy chain and 50 kd light chain
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6. Mechanism of Action
• inhibition of acetylcholine release
• inhibit exocytosis of Ach at NMJ
• begins when BTX bind cholinergic receptor
on cholinergic nerve terminals
• BTX molecules internalized into the cell
• heavy and light chain separated
• light chains act as an enzyme: cleaving bond
of proteins needed for exocytosis of Ach
(SNARE)
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7. • SNARE (Soluble N-ethyl-maleimide-
sensitive factor attachment protein
receptor)
• inhibit Ach release then reduce muscular
contraction
• results in nerve sprout at NMJ and release
Ach (temporary)
• temporary and reversible
• needs repeated injection and dose and
injection site adjustment
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8. • multistep process: time lag btw exposure to
toxin and onset of muscle weakness
• also inhibit release of Ach of autonomic
terminals: Rx sialorrhea and primary
axillary hyperhidrosis
• Kozaki et al and Dong et al: identified
synaptotagmin protein with gangliosides
(GT1b) receptor for BTX type B and G
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9. Clinical Pharmacology
• Unit Doses
• units of biologic activity (U)
• doses not standardized among different
BTX products
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10. Time Course of Clinical
Effects
• BTX type A injected IM
• onset 3-7 days
• duration 3-5 months
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11. Clinical Adverse Events
• most focal muscle weakness
• systemic side effects: rare (BOTOX
information)
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