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BOTULINUM

TOXIN

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BOTULISM
“Black Sausage” poisoning – causes muscle paralysis

Toxin was first used to treat hypermotility disease such


as St. Vitus’ Dance

1970- Scott, an ophthalmologic surgeon used


botulinum toxin to selectively inactivate ocular muscle
spasticity in strabismus

Cosmetic use – serendipitous discovery of Alistair &


Jean Carruthers treating blepharospasm patients

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BACTERIOLOGY &
PHARMACOLOGY
Neurotoxin product from cultures of Clostridium
botulinum

Harvested by centrifugation & acidification

Toxin A – used for cosmetic & therapeutic indications

Toxin B – for cervical dystonia

Di- chain polypeptide molecule with a 50 kDa light


chain & a 100 kDa heavy chain linked by a disulfide
bonding

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MECHANISM OF
ACTION

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COMMON COSMETIC
INDICATIONS
Elimination of wrinkles & rhytides on the upper face
(glabellar frown lines & worry lines on the forehead and
crow’s feet), mid and lower face (suborbital lines,
perioral lines, chin irregularities and depressed mouth
corners)

Neck : correction of vertical platysmal bands and


horizontal “necklace” lines

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Chemical brow lift: for aging related decent of
eyebrow; injection of BTX-A into the depressor
supercilii muscles & into the lateral fibers of the
orbicularis oculi  weakens it

Masseteric hypertrophy treatment: an asymptomatic


enlargement of one or both masseter muscles
associated with abnormal habits such as bruxism &
habitual clenching

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CONTRAINDICATIONS

Absolute

• Neuromuscular disorders ( Myasthenia gravis Lambert-


Eaton syndrome, muscle weakness, absence of tendon
reflexes, autonomic dysfunction
• Known hypersensitivity to any ingredient

• Local infection at the site of injection


• Pregnancy & lactation

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• Treatment with aminoglycoside antibiotics or spectinomycin in
last 3 days (interfere with neuromuscular impulse
transmission  accentuate the effects of botulinum toxin 
complete muscle paralysis instead of weakening
Relative

• Coagulation defects, anticoagulant use & patients with


unrealistic expectations.
• Medications including aminoglycosides (may increase effect
of botulinum toxin), penicillamine, quinine, chloroquine and
hydroxychloroquine (may reduce effect), calcium channel
blockers, and blood thining agents eg. warfarin or aspirin
(may result in bruising).

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DOSAGE & DILUTION FOR
AESTHETIC MEDICINE

Available as 100 u of freeze-dried powder in a glass


vial under vacuum

Before dilution - to be stored in freezer at -5°C

After reconstitution – stored at 2-8°C ; can be stored


upto 6 weeks without losing the potency

Diluents used – normal saline with or without


preservatives (0.9% benzyl alcohol)

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Diluent added (0.9% Resulting dose in units
NaCl injection) (mL) (U) per 0.1 mL botulinum
toxin
1 10
2 5
2.5 4

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2.5 mL of diluent per 100 unit vial for upper face & 1-2
mL per vial for smaller muscles in the lower face to
avoid larger volumes of fluid diffusing into nontargeted
muscles

As dilution increases, the volume injected increases


and so the diffusion

Each patient to be assessed for dose requirement


depending upon the age, sex and the bulk of the target
muscle

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Lethal dose in humans – not precisely known; but in a
70 kg human – about 2800 dose as LD50

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PROCEDURE

Written informed consent & a pretreatment photograph

Area to be treated is cleaned with povidone iodine solution &


allowed to dry

Patient is asked to contract the targeted muscle & injected


sites – belly of the muscles – marked

Ice pack applied before & after the procedure to avoid pain &
bruising

Toxin drawn in a 1 mL syringe & injected using a 30G needle

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GLABELLAR FROWN
LINES
Muscles – depressors of the glabella

• Corrugator supercillii that draws the eyebrow medially


and downward
• Orbicularis oculi that pulls it medially
• Procerus & depressor supercilii that draws the eyebrows
downwards

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Dose –

• 6U in procerus midway just below the line joining the


medial ends of both eyebrows
• 4U in each corrugator on a point 1cm above the vertical
line joining the inner canthus & superior orbital rim
• 2U into the lateral tail of the corrugator more
superficially but medial to the mid pupillary point

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HORIZONTAL
FOREHEAD LINES
Muscle – Anterior belly of Occipitofrontalis muscle

Dose – 1-2U at a distance of 1.5 cm into the frontalis


staying 2 finger widths above the supraorbital rim
lateral to the midpupillary line to avoid ptosis

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CROW’S FEET
Muscle – Lateral aspect of the orbicularis oculi
encircling the eye

Dose –

• Palpate the orbital rim & inject 4U, 1.5cm from the
lateral canthus
• Then inject 4U, 1cm above & below this site

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NECK BANDS
To treat vertical platysmal bands

Muscle – large but thin muscle, Platysma

Dose –

• For one platysmal band – 15 units; 5U in the


proximal portion of the muscle, 5U 2cm below this
site & 5U 1.5-2 cm further down but a finger
breadth above the pharynx

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HORIZONTAL
NECKLACE LINES
This requires intramuscular injections either in a
staggered distribution along the lines as used to treat
the transverse forehead lines; OR

1-2U every 2cm along the line as intradermal bleb

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ADVANCED
INDICATIONS
Suborbital hypertrophic orbicularis – during smiling, the size
of the palpebral fissure tends to dimish partly due to
contraction of the pretarsal orbicularis. Hypertrophy of this
 “jelly roll” appearance of the lower lid

Infraorbital crows’ feet – medial crow’s feet due to


contraction of the orbicularis oculi medially

Nasal scrunch (Bunny lines) – naso-glabellar lines that occur


in the upper third of the nose due to contraction of the upper

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nasal fibers
Nasal flare – in some who repeatedly dilate their
nostrils, exposed side of septum is cosmetically
displeasing

Perioral lip line

Marionette lines – melolabial folds created by downward


angled corners of mouth

Mental crease

Popply Chin – loss of dermal collagen & subcutaneous


fat at the mentum results in “orange peel” appearance
of the chin.

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POST PROCEDURE
INSTRUCTIONS
Patient to remain erect for 4 hours (to avoid unwanted
diffusion)

Not to manipulate the treated area for 4 hours

Exercise the treated muscles during first 2 hours –


squint or smile to exercise the muscles that causes
crow’s feet, frown for glabellar lines or raise the
eyebrows for horizontal forehead lines

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FOLLOW-UP
EXAMINATION

Follow up after 2 weeks to assess the outcome of


treatment & the observation to be documented &
photographed for patient’s record

Adverse events or unusual occurrences to be


noted

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COMPLICATIONS
Adverse effects –

• Mild pain, bruising at the injection site, local edema,


erythema, transient numbness, mild nausea, transient
headache & flu-like symptoms

Complications –
• Levator (lid) ptosis – if toxin diffuses below the orbital septum
where it affects the upper eyelid levator muscle; managed by
alpha-adrenergic antagonists, apraclonidine eye drops, 1-3
drops daily for as long as symptoms persist. This stimulates
the Mullers muscle & elevates the upper eyelid.

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• Brow ptosis – due to injections being placed too low on
the forehead or due to a poor patient selection
• Elevation of the lateral end of the eyebrow – due to
uneven muscle paralysis  Quizzical brow or Dr Spock
brow
• Deep injections into platysmal bands – difficulty in
swallowing, forming high notes & flexing the head from
the supine position

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THERAPEUTIC FAILURE

Patients with rhytids that are not dynamic in origin (eg,


photodamage, age-related changes) do not respond.

Improper injection technique or the denatured toxin may also


result into therapeutic failure.

Some patients may have neutralizing antibodies from prior


subclinical exposure, or individual variations in docking
proteins may exist. Secondary nonresponders respond
initially but lose the response on subsequent injections. Most
of these patients may have developed neutralizing antibodies.

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CLINICAL
RESISTANCE
Theoretically , BTX are immunogenic proteins & can
develop circulating neutralizing antibodies, depending
on the dose injected & the frequency of treatment

Immune resistance minimized by using the minimum


effective dose of BTX-A & by increasing the time
interval between the subsequent injections to atleast 3
months

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THANK
YOU!

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