Botulinum Toxin Flashcards
Which product has the greatest diffusion?
Azzalure (Dysport) - good for hyperhidrosis
Botulinum Toxin Types
Type A - Cosmetic
Type B - Rimabotulinumtoxin B - Cervical Dystonia
Type C - Rarely used, causes slow degeneration of motor neurones
Dysport (Azzalure) : Botox Ratio
2.5:1
Bocoture : Botox ratio
1:1
Botox storage - reconstituted
2-8C, use within 14 days
Botox reconstitution
2.5ml saline per 100 units, 4IU per 0.1ml, 2IU per 0.05ml
Bocouture reconstitution
2.5ml saline per 100 units, 4IU per 0.1ml, 2IU per 0.05ml
Azzalure reconstitution
0.63ml saline per 125SU, 10SU per 0.05ml
Toxin equipment - needles
21G for reconstitution, 30G and higher for adminiistration
Absolute contraindications
Botulinum allergy
Body dysmorphhia
Infection over site
Neuromuscular disorders
Dysphadi or aspiration history
Pregnancy & Breast feeding
Relative contraindications
Under 18
Anticoagulant & Antiplatelets
Aminoglycoside - enhance effect
Calcium antagonist - antagonise effect
Non-cosmetic uses
Spastic skeletal muscles
Antiparasympathetic - sweat and salivary glands
Prevention of wound dehiscence
Factors affecting dose
Sex
Extent of wrinkles
Previous response to toxins
Ethnicity
Dynamics of facial express
Size of muscles mass
BNT mode of action
Blocks acetylcholine excretion - selectively and irreversibly bind to the presynaptic terminal
Hyperkinetic patients
No concordance between muscular contraction and emotion expressed.
Stronger muscles. May contract involuntarily during speech.
Results may last 4-6 months.
Hypertonic patients
Lack of control of facial muscles
Wrinkles remain present after treatment.
Shorter results 1-2 months
Medications affecting botox
Calcium Antagonist - decrease effects
Aminoglycosides - increase effects
Immunosuprressants - increase risk of infection
When did BTX become FDA approved for hyperhidrosis treatment
2004
Mechanism of action for botox
inhibits the release of
acetylcholine at the neuromuscular junction
resulting in partial paralysis of the muscles.
Botox toxin type
onabotulinum toxin type A (Botox)
Dysport toxin type
abobotulinum toxin type A
Azzalure toxin type
onabotulinum toxin type A (Botox)
Bocouture toxin type
Incobotulinumtoxin type A
What differs the different toxin A types
presence or absence of complexing proteins
How was botox discovered
1895
Emile va Ermengem
Identified clostridium botulinum as a source of botulism
Purification of botox
1940s
Edward Schantz
purified during military experiments for biological wapons
First treatment/experimentation with botox
1977
Alan Scott
Strabismus in monkeys - extraocular muscles
First aesthetics use/publication of botox
1992
Jean and Alistair Carruthers
Blepharospasm patients treated in perioribtal region
Reduced glabellar lines
Botox moecule structure
Neurotoxin
150kDA
Heavy and light chain
Heavy chain
100kDA
Binds synaptic membrane
allows light chain to enter cell and cleave proteins of the NSF receptor complex
Light chain
50kDa
active part of the toxin
Zinc dependent endopeptidase
How many serotypes of botulinum toxin
Eight
How is botox toxin activated
cleavage between 448 & 449 AA
Producing Heavy and light chain connected via disulphide bond
bond reduced after cell internalisation
Normal neuromusclar junction activity
Action potention causes calcium entry into presynaptic membrane
Triggers acetylcholine vesicle release into synaptic cleft
Binding of ACTH at posynaptic membrane gated channels allowin sodium entry
Sodium entry causes depolarisation at post synaptic membrane allowing calcium entry and muscle contraction
Botox affect on NMJ
Heavy chain binds GT1b - a glycosphingolipid in the membrane of presynaptic vesicle
causing endocytosis of toxin and acidification of the endosome and translocation of the light chain into the axon terminal cytoplasm.
SNAP-25 is cleaved by the light chain and can no longer mediate fusion of vesicles to pre-synaptic membrane
How does Botox wear off
SNARE protein are slowly regenerated.
formation of new NMJs to restore activity
Which SNARE proteins are cleaved
Snap 25 by toxin A, C, E
Snaptobrevin by toxin B, D, E, F, G
Synactin by toxin C
Snare protein targets of toxin
SNAP 35
Snaptobrebin
Syntacin
Peak of botox action
14-30 days
Immunogenicity
Antibody formation against Toxin
Rarely reported in litrature
Can be detected after repeated treatment for years
Primary vs secondary immunity
Failed response after first treament
loses reponsiveness to product over time with repeated treatment
Why is Bocouture marketed as “pure”
No accessory proteins only 150kDA neurotoxin
unlikely to cause immunogenic response
Antibodies that dont intefered with toxin activity
Antibodies against the NAPs
non toxic accessory proteins
Azzalure units
Speywood units
Licensed applications of botox
cervical dystonia
severe primary axillary hyperhidrosis
blepharospasm,
neurogenic detrusor overactivity
chronic migraine,
upper limb spasticity
glabellar lines (moderate to severe)
How allergan units are measured
cellular assay
How speywood units are measured
amount of toxin that kills 50% of genetically homogenous mice population
Company that produces dysport and azzalure
Medicis Pharmaceutical Corp
Storage
2-8 degrees
discard after 24 hours
Bocouture does not require refrigeration
Product spread
Azzalure has greater spread than botox and bocouture
Product onset of action
Azzulure faster
Factors affecting product selection(5)
Patient preference
Pricing
Spread
Onset of action
Storage
When does muscle activity return
7-8 weeks
When was botox FDA approved
2002, glabella lines
