Botulinum toxin part 1

• Botulinum Toxin


  One of the minimally invasive procedures listed in the scope of aesthetic medical practice

  
• Botulinum toxin


  A toxin produced by Clostridium botulinum bacterium
• It's now FDA approved for medical usage in Blepharospasm, Strabismus, Cervical Dystonia as well as Aesthetic application in glabella wrinkles
• Botox


  Top most performed minimally invasive cosmetic procedures, rated as best treatment for dynamic facial wrinkles
• Growing demand in Botulinum toxin injections


  • Overwhelming patient satisfaction
  • Very safe procedure
  • Simple and fast treatment
  • Virtually no downtime
  • Affordable treatments
  • Convenient. just need to have 2-3 sessions treatment per year
  • Low adverse effect profile. manageable even it happens
• Botulinum toxin was discovered through food poisoning in Germany


  1817
• Botulinum


  Word derived from the Latin word meaning sausage, used during a sausage related food-borne botulism in Germany
• The disease was associated with a bacteria, Clostridium botulinum


  1895
• Crystalline form of BTA was isolated


  1946
• Discovered the inhibitory effect of acetylcholine release at neuromuscular junction in experimental animal


  1960
• First human medical indication of BTA was on blepharospasm, by an Ophthalmologist


  1970
• FDA approved BTA for Strabismus and Blepharospasm


  1989
• Improvement of glabella rhytides seen for blepharospasm treatment

  1997
• BTA was approved by FDA for cervical dystonia treatment

  2000
• BTX was approved by FDA for temporary improvement of moderate to severe glabella lines in adult less than 65 yo

  2002
• BOTOX, was approved by FDA to treat axillary hyperhydorsis

  2004
• Abobotulinumtoxin A ( Dysport ) , was approved by FDA for cervical dystonia treatment


  2009
• Approved for treatment of spasticity and chronic migraine

  2010
• Botulinum Toxin


  Contains a unique zinc-dependent endopeptidase with a Neurotoxin and complexing proteins components together weighing about 900kD
• Neurotoxin


  A single polypeptide chain with a molecular mass of 150kDa
• Heavy chain


  100kDa, binds selectively to cell membrane receptor and initiate the endocytosis of the entire neurotoxin complex
• Light Chain


  50kDa, cleaving a specific part of SNARE complex
• Physiology of neuromuscular junction


  1. Aggregation of Acethylcholine vesicles, await for further nerve stimuli

  2. SNARE proteins (SNAP-25 + Syntaxin) at presynaptic plasma membrane, binds with synaptobrevin on transport vesicles to mediate the release of ACH ( initiated by depolarization of nerve terminal )

  3. ACH is then released into synaptic cleft, and activate the post-synaptic nicotinic cholinergic receptors of muscle fibers --> causing muscle contractions
• Mechanism of action of BTX

  1. Internalization

  2. Cleavage of specific site on SNARE protein

  3. Prevent release of ACH into synaptic cleft
• Commercially available BTX brands


  • Botox cosmetic
  • Dysport
  • Xeomin
  • Neuronox
  • Neurobloc
  • Myobloc
• All are BTX A, except neurobloc and myobloc are BTX B
• Onset of BTA action will take several days, the delay is related to time needed for the endocytosis, disruption of SNAP-25 protein
• With time, nerve sprouting occurs and new neuromuscular junctions are formed, leading to reactivation of intoxicated neurons
• Clinical action of BTX are temporary and fully reversible over time
• Onabotulinum A (Botox) and Abobotulinum A (Dysport) units


  Not equivalent, ranging from 1 : 2.5 to 1 : 4
• Dysport will have more diffusion due to its smaller molecular size (500-900), while Botox is 900
• Reconstitution of Botox


  Reconstitute with 2.5ml Normal saline, thus each 0.05ml = 2 units, 0.1ml = 4 units
• Reconstitution of Dysport


  1. Reconstitute with 2.5ml Normal saline, 0.05ml = 10units, 0.1ml= 20units

  2. Reconstitute with 3ml NS, 0.05ml = 8units, 0.1ml = 16 units

  3. Reconstitute with 5ml NS, 0.05 = 5 units, 0.1ml = 10 units
• How to reconstitute GENTLY


  1. Release vacuum with another needle, then infuse the NS into the vial gently/slowly without utilizing the vacuum in vial to draw in saline

  2. Swing the vial gently side-side, up-down, rolling
• Storage


  • +2 to 8 celcius (up to 36mths if unopened)
  • Manufacturer recommends to use product within 4 hours once reconstituted
  • Can actually retain its potency up to 6 weeks at 2-8 celcius
• Dosage of Botox (100u)


  • Forehead lines: 6-20 u
  • Glabella lines: 12-40 u
  • Crows feet: 12-24 u
  • Neck platysma bands: 30-40 u
  • Axillary hyperhydrosis: 40-50 u per side
• Indications


  • All wrinkles produced by muscle contraction: Forehead wrinkles, glabellar lines, crow's feet, bunny lines, perioral wrinkles
  • Cosmetic enhancement: Popply chin, Gummy smile, Chemical brow lift, Facial asymmetry, Masseter hypertrophy, Meso BTA over face, Calf muscle contouring
  • Miscellaneous indication: Hyperhydrosis, Migraine, Spasm: blepharospam, strabismus facial spasm, cervical dystonia, bladder spasm, Keloid
• Contraindications - Absolute


  • Neuromuscular disorder (Myastenia gravis, Eaton-Lambert syndrome, Neuropathies, muscle weakness etc)
  • Allergy to BTA components (toxins, human albumin, saline, lactose, sodium succinate)
  • Infection at injection site
  • Pregnancy, Lactation (pregnancy category C)
• Contraindications - Relative


  • Coagulation defects
  • On aspirin or warfarin and oral antibiotics
  • Patient consuming green tea and vitamin E for more than 2-3 weeks
  • On medication like aminoglycoside, penicillamine, quinine, calcium channel blocker (potentiate BTA effects)
  • On muscle relaxant (Tubocurarine, Dantrolene) as it causes enhanced muscle relaxation or dysphagia
  • Patient dependent on intact facial movement and expressions for their livelihood (actor, singer, musician, media personalities)
  • Patient who are psychologically unstable, unrealistic expectations
• Counselling: Pre-operatively


  1. Proper assessment: History taking, Examination, Mirror examination

  2. Patient Selection

  3. Detail explanation about the treatment, desired effects, longevity of the result, importance of preventative treatments, adverse effects

  4. Provide brochure for patient, allow patient to seek more informations

  5. Clear away unrealistic expectations

  6. Explained that result can be seen within a week, and the effect will wane of within 3-6 months, and repeated treatment required

  7. Offer multimodalities treatment if indicated (Filler, meso-HA, EBD, peels etc)

  8. Consent form

  9. Pre-operative Medical Photography

  10. Procedure preparation: Consider numbcream, Insulin syringe 1ml, Needles 30-33G (4mm - 12mm), Ice/cold pad, or vibrating device, Alcohol swab, Gauze, 0.9% Sodium Chloride (DO NOT USE WATER to DILUTE)