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Botulinum Toxin
Botulinum toxins (Serotypes A-G) are
secreted by Clostridium Botulinum
bacteria.
Clostridium Botulinum, a gram positive,
anaerobic, spore forming bacillus
7 serotypes A to G
Type A is the most potent toxin
Botulinum Neurotoxin Serotypes
Seven serotypes (A-G)
Intracellular target varies
Molecular weight 150kD
Only intact molecule works
Does not penetrate the skin
No topical application
Botulinum neurotoxin development
1944-toxin isolated from Clostridium botulinum
1950s-discovery of NMJ blockade
1980s first use of BTX-A in humans
1989-FDA approval for non-cosmetic purposes
1970s –monkey experiments
2006 –MHRA approval for glabellarlines
Neurotoxin Physical characteristics
Complex size 900 kDa, vaccumedried
1 vial contain 5ng (100 units)
webstermice after interaperitonealinjection (LD50)
LD50 in humans approximately 40U/kg
Typical cosmetic doses ranges from 10-60 units
1 unit = median amount necessary to kill 50% of female swiss-
Basic Concepts
Botulinum toxins are high molecular weight protein complexes that
are secreted by clostridialbacteria.
It exert its effects by binding to and cleaving specific proteins in the
presynaptic nerve terminal, thus preventing release of acetylcholine
and locally preventing nerve terminal
Injection-related complications can largely be avoided with good
technique and a detailed understanding of the regional anatomy
Mechanism of action
Chemical denervation
This protease exotoxin exert its effects by preventing exocytosis of
acetylcholine from nerve terminal-chemical denervation.
Neurotoxin heavy chain bind specific receptor on the presynaptic
nerve terminal
It lead to toxin-receptor endocytosis
Light chain release through vesicle lysis
Light chains cleave specific protein isoforms necessary for docking,
fusion and release of acetylcholine from this nerve terminus.
Binding site for each toxin are different
Toxins A,C and E cleave SNAP-25
Toxin B, D, F and G cleave VAMP
Botulinum toxin acts at 4 different sites
Neuromuscular junction
Post ganglionic parasympathetic nerve endings
Post ganglionic sympathetic nerve endings that release acetyl choline
Autonomic ganglia
It smoothesdynamic rhytidesby inhibiting the activity at the
neuromuscular junction
Synaptic regeneration collateral spouting reverses the paralytic
effect with in 3-6 months
Muscle paralysis occurs in 3-7 days approx
General Pretreatment tips
Take Consent
Pretreatment Photographs
Explain Procedure
Explain efficacy (3-4 months)
Potential side effects
Document Scars and asymmetry
It smooth dynamic wrinkles by inhibiting the activity at the
neuromuscular junction
Synaptic regeneration reverses the paralytic effect with in 3-6
months
Muscle paralysis occurs in 3-7 days
Neurotoxin Physical characteristics
1 vial contain 5ng (100 units)
Median lethal dose in humans is approx40U/kg (2500-3000 U in 70kg
man)
Typical cosmetic doses ranges from 10-70 units/session
0.1 ml usually diffuses 1 cm dia, however if injected in loose areolar
connective tissue space it can go upto4.5cm, can travel in linear
plane along muscles
Botox Dilution Chart
Factors Which May Affect Potency
Storage time and temperature of diluted
toxin Agitation of the bottle or syringe
Un-reconstituted: store in fridge at 2 –8 C or in freezer at -5 C or
below
Reconstituted: store in fridge at 2-8 C
Bubbles
Client assessment
Note for any asymmetry
Ask about their
concerns Observe the
client
Take photographs in relaxed and active contraction of facial
muscles
Large muscle mass and males reqlarger doses
In conversation during the consultation
In relaxed and forced contraction of facial muscles
Note Wrinkles –static/dynamic; associated atrophy
Contraindications
Pregnancy and lactation
Hypersensitivity to ingredients (Albumin, BoNT)
Neuromuscular disease ( Myestheniagravis..)
Drugs interfere with neuromuscular transmission(aminoglycosides,
polymixins, penicillamines, calcium channel blockers, neuromuscular
blocking agents)
Patient on anticoagulant therapy
Poor psychological adjustment
CONTRAINDICATIONS
Absolute contraindications:
psychological unstabe.
Reaction to toxin or albumin
Pregnancy and lactating females
Infection at the injection site.
History of mystehniagravis, Eaton-Lambortsyndrome, neuropathies,
Relative contraindications:
Following medicines should be avoided in patients treated with
botulinum toxin.
Penicillamine, quinine, and HCQ may reduce effect.
Calcium channel blocker and blood thinning agents eg. Warfarin or
aspirin may result in bruising.
aminoglycosides …may increase effect of botox.
Complications
Local
Systemic
Pain, swelling, erythema, bruising, tenderness, headache
Nausea, fatigue, severe generalized weakness, malaise, flu like
Asymmetry, loss of facial expression, incomplete muscle paralysis
Regional
symptoms, allergy(albumin)
General Pre-treatment tips
Take Consent
Pre-treatment photographs
Explain procedure
Explain efficacy (3-4 months)
Potential side effects
Document scars and asymmetry
General Post-treatment advice
Remain upright for 4hrs
Refrain from strenuous exercise for 24hrs
Do not rub/massage injection sites for
24hrs Avoid saunas/hot tubs/sun beds for
24hrs
Do exercise of treated muscles frequently for 1-2hrs
TRANSIENT AND BENIGN EVENTS
Transient and benign side effects
Injection site adverse effects:
localized pain
Infection–rare,
Ecchymosis or bruising-11 to 25%
creams
History-vitamin E, aspirin, warfarin and non-steroidal anti-inflammatory drugs
The injection site should be cleaned with an antiseptic solution, an aseptic
technique, remove makeup and it should not be reapplied for at least 6
hrs to allow the open injection sites to close.
(NSAIDs); herbal remedies, such as ginseng, ginkgo, and high doses of
garlic Use Ice packs before procedure and apply Pressure when dought
Needle bevel up and injecting slowly,correct needle size, topical anesthetic
Others
Dry skin and subsequent flakiness-decreased sweat gland activity
Headache-muscle spasm (toxin initially causes muscle spasm then
complete paralysis), needle hitting the periosteumor deep muscle
hematomas.
Paresthesia or dysesthesia-rare, and may be caused by nerve
trauma
urticariato anaphylactic shock
Allergic reactions-wide spectrum-ranging from edema, erythema,
MISPLACEMENT OF BOTULINUM
TOXIN
Cause by temporary denervation of adjacent muscles outside of
the intended treatment area leading to both aesthetic and
functional problems
Most are self limiting with time-usually 2-4 weeks
Eyelid ptosis-levatorpalpebraesuperiorisparesis
Eyebrow ptosis-lower part of frontalis muscle paresis
Diplopia-mostly associated with inferior oblique paresis or rarely with
lateral rectus paresis
asymmetric smile/ lip ptosis-zygomaticus major paresis. The
injection should not be close to the inferior margin of the zygomato
avoid this.
Other periorbitalcomplications are pseudoherniationof infraorbital
fat pads, lagophthalmosand dry eye.
Over-activity of remaining/ surrounding muscles-compensatory
action of the lateral portion of frontalis, when there is complete
paralysis of central region, bunny lines become more prominent and
Mask-like face-expressionless. Repeated/ excessive use of toxin.
Eyebrow ptosis
Common 1/100, 1%
Unable to lift eyebrows
Pt Look tired and she complains
that forehead feels heavy and
eyelids have drooped.
Treatment
Wait –often improves after 1
month, exercise remaining muscle
help further. Treat remaining brow
depressors ( orbicularis oculi,
procerus, depressor supercilli,
corrugator)
Eyelid ptosis
1% chance, with good technique it reduces to
1/10,000
Droopy eyelid-effecting vision by obstructing
pupil
Related to the depth of the injection
Check for congenital ptosis before botox
Treatment –apraclonidineor oxymetazolineHCL
(Lodopine1 drop TDS)–mimic the sympathetic
response on smooth muscle-muller’smuscle and
temporarily lift the eye for 4-6hrs
Eyelid ptosis-Mechanism
When Injection is given deep at lateral
site for corrugator, toxin makes it way
into the orbit and affect levator
palpebraemuscle.
POTENTIALLY SERIOUS EVENTS
Botulism-like features-systemic spread of toxin leading to botulism
like features. Dysphagia and muscle weakness are common
symptoms of botulism, the spectrum range from muscle weakness to
paralysis, dysarthria, dysphonia, dysphagia and respiratory arrest.
Treatment-neurotrophicdrugs, systemic support and symptomatic
treatment, and the injection of botulinum antitoxin serum.
Neck muscles are prone to diffusion of botulinum toxin, and paralysis
of the wrong muscles leads to dysphonia, dysphagia or dystonia.
Dysphagia usually occurs after a week and lasts on average 3.5
weeks.
anaphylactic shock-
Using standard emergency protocols and medications such as
rather than diphenhydramine, because of its anticholinergic
effects.
epinephrine and methylprednisolone is advised when indicated,
Serious adverse events included dysphagia, respiratory compromise,
generalized muscle weakness, marked bilateral ptosis,
pseudoaneurysmof the frontal branch of the temporal artery,
necrotizing fasciitis, sarcoidalgranuloma, Fournier gangrene, and
cervical kyphosis. Death was attributed to botulism or anaphylactic
shock.
Prevention
Start with lower
doses Avoid Danger
areas
Inject at proper depths
Follow site according to the patient requirement