Botulinum toxin is produced by Clostridium botulinum bacteria. It works by blocking the release of acetylcholine at neuromuscular junctions, preventing muscle contraction. It has been used since the 1980s to treat medical conditions involving muscle overactivity like strabismus and dystonia. In the 1990s, its use was explored for cosmetic purposes to reduce facial wrinkles. The FDA approved its use for frown lines in 2002 and excessive underarm sweating in 2004. It is injected into specific facial muscles to weaken them and smooth wrinkles. Common sites include the glabella, forehead, crow's feet, bunny lines, marionette lines and platysmal bands. Potential complications include

1. Botulinum Toxin in
Aesthesis
Dr. S.Satish Kumar

2. HISTORICAL ASPECT
• A German poet, doctor and scientist , Dr. Justinus Kerner of
Wurttemberg, first explained the disease called botulism (1817 to
1822) caused by ‘sausage poison’.
• Dr Emile Pierre van Ermengem (belgium) in 1895 successfully
isolated this bacterium, named it Bacillus botulinus.
• Botulinum toxin was first used to treat human disease(1980) by Drs
Alan Scott (opthalmologist) and Edward Schantz, in treating
strabismus.
• In 1987, ophthalmologist Jean Carruthers observed that frown lines
disappeared after the use of botulinum toxin A for blepharospasm.
• In 1996, they published the first paper on the use of Botox for
cosmetic purposes.

3. HISTORICAL ASPECT
• In 2002, the FDA announced the approval of BOTOX® Cosmetic to
temporarily improve the appearance of moderate-to-severe frown lines
between the eyebrows (glabellar lines).
• In July 2004, the FDA approved BOTOX® to treat severe underarm
sweating, known as primary axillary hyperhidrosis, that cannot be
managed by topical agents.

4. BOTULINUM TOXIN (BTX OR BoNT)
• Produced by Clostridium botulinum, a gram-positive anaerobic, spore
forming bacillus.
• BoNT is broken into 7 neurotoxins (labeled as types A, B, C [C1, C2],
D, E, F, and G), which are antigenically and serologically distinct but
structurally similar.
• Type A is the most potent toxin, followed by types B and F toxin.
• Human botulism is caused mainly by types A, B, E, and (rarely) F.
Types C and D cause toxicity only in animals.

5. MICROBIOLOGY
The BoNT molecule is
synthesized as a single
chain (150 kD) and then
cleaved to form the
di-chain molecule with a
di-sulfide bridge.

6. MICROBIOLOGY
• The light chain (~50 kD) acts as
a zinc endopeptidase with
proteolytic activity located at the
N-terminal end.
• The heavy chain (~100 kD)
provides cholinergic specificity
and is responsible for binding
the toxin to presynaptic
receptors.

7. MECHANISM OF ACTION
Botulinum toxins act at four different sites in the body:
• The neuromuscular junction
• Autonomic ganglia
• Postganglionic parasympathetic nerve endings
• Postganglionic sympathetic nerve endings that release acetylcholine.

8. MECHANISM OF ACTION
• Release of acetylcholine at the
neuromuscular junction is mediated by
the assembly of a synaptic fusion
complex.
• Allows the membrane of the synaptic
vesicle containing acetylcholine to
fuse with the neuronal cell membrane.
• The synaptic fusion complex is a set
of SNARE proteins (Synaptobrevin,
SNAP-25 and Syntaxin)
• After membrane fusion, acetylcholine
is released into the synaptic cleft and
then bound by receptors on the muscle
cell.

9. MECHANISM OF ACTION
• Botulinum toxin binds to the neuronal cell
membrane at the nerve terminus and enters the
neuron by endocytosis.
• The light chain of botulinum toxin cleaves
specific sites on the SNARE proteins,
preventing complete assembly of the synaptic
fusion complex thereby blocking acetylcholine
release.
• Botulinum toxins
- types B, D, F, and G cleave synaptobrevin
-types A, C, and E cleave SNAP-25
-type C cleaves syntaxin.
• Without acetylcholine release, the muscle is
unable to contract.

10. MECHANISM OF ACTION
• Induces weakness of striated muscles by inhibiting alpha motor
neurones at the neuromuscular junction.
• Used in conditions with muscular overactivity, such as dystonia.
• Transmission is also inhibited at gamma neurones in muscle spindles,
which may alter reflex overactivity.
• Also inhibits release of acetylcholine in all parasympathetic and
cholinergic postganglionic sympathetic neurons.
• Used as a treatment for overactive smooth muscles (for eg, achalasia)
or abnormal activity of glands (for eg, hyperhidrosis).

11. MECHANISM OF ACTION
• The toxin requires 24-72 hours to take effect
(the time necessary to disrupt the synaptosomal process.)
• In very rare circumstances, some individuals may require as many as
five days for the full effect to be observed.
• Peaking at about 10 days, the effect of toxin lasts nearly 8-12 weeks.

12. AESTHETIC USES
• Indicated for all facial wrinkles
produced due
to persistent muscular contractions.
• These include-
Horizontal forehead lines
Glabellar lines and vertical frown lines
Platysmal
bands

13. Crow’s feet and Marionette
lines
Bunny lines
Dimpling of chin

14. THERAPEUTIC USES
Sweating, salivary, and allergy
disorders
• Axillary and palmar hyperhidrosis
• Frey syndrome
• Drooling in cerebral palsy and other
neurological disorders
• Nasal allergy
Strabismus and nystagmus
Smooth muscle hyperactive disorders
• Neurogenic bladder – Detrusor
hyperreflexia, BPH
• Achalasia cardia
• Hemorrhoids, Chronic anal fissures
Focal dystonias
• Cervical dystonia (spasmodic
torticollis)
• Blepharospasm (eyelid closure)
• Laryngeal, Limb,
Oromandibular,
Orolingual, Truncal dystonia
Spasticity
Nondystonic disorders of
involuntary
muscle activity
• Hemifacial spasm, trismus
• Tremors, tics, myoclonus

15. THERAPEUTIC USES
Chronic pain and disorders of localized muscle spasms
• Chronic low back pain
• Tension headache
• Chronic migraine headache
• Medication overuse headache
• Lateral epicondylitis
• Knee, Shoulder neuropathic pain

16. CONTRAINDICATIONS
• Patients afflicted with a preexisting motor neuron disease, myasthenia
gravis, Eaton-Lambert syndrome, neuropathies, psychological instability.
• History of reaction to toxin or albumin.
• Pregnancy and lactating females.
• Infection at the injection site.
DRUG INTERACTIONS
• Aminoglycosides (may increase effect of botulinum toxin)
• Penicillamine, Quinine, Chloroquine and Hydroxychloroquine (may reduce
effect)

17. PREPARATION
• Serotype A is the only commercially available form of botulinum toxin
for clinical use.
• The potency of BoNT-A is measured in mouse units (MU).
• One MU of BoNT-A is equivalent to the amount of toxin that kills
50% of a group of 20 g Swiss-Webster mice within 3 days of
intraperitoneal injection.
• According to one report, 1 nanogram of toxin contains approximately
20 U of BOTOX® (ie, 1 U of BOTOX® is equal to approximately
0.05 nanogram of the toxin).

18. RECONSTITUTION AND HANDLING

19. RECONSTITUTION AND HANDLING
• Follow all usual precautions of sterility and skin preparation before
injection.
• Seat the patient with chin down and head slightly lower than the
physician's.
• Plastic single use insulin syringes with 30-32 gauge needles are
recommended, and toxin is injected into affected muscles
• Topical anesthetics are generally reserved for the very sensitive. Ice
could be used as a numbing agent.
• Injections can also be administered under the guidance of
electromyograph (EMG) monitoring for better accuracy.

20. GLABELLAR AND VERTICAL FROWN LINES
• Corrugator supercili
• Procerus
• Depressor supercili.
• Site - Injections given into the
corrugator (red and blue
circles) and procerus (green
circle)
• Dosage – 10-25 U

22. HORIZONTAL FOREHEAD LINES
• Muscle : frontalis
• Treatment goal is to achieve a
balance between brow elevation
with forehead smoothing.
• Site - Injection given at blue
circles and optional red Xs.
• Dosage – 10-30 U

24. CROW'S FEET
• orbicularis oculi muscle.
• The treatment goal is reducing
dynamic rhytides and softening
static rhytides.
• Site - Injection given in each of
the 3 blue circles (photo) on each
side and the red X’s.
• Dosage – 5-15 U/side

26. BUNNY LINES
• the transverse portion of the nasalis.
• Treatment goal is to soften the
bunny lines on smiling.
• Site - Injections given into the two
blue circles.
• Dosage – 5-10 U

28. DIMPLED CHIN
• Contraction of the mentalis :
causes a "cobblestone"
appearance of the skin and
possible deepening of the
mentolabial crease.
• Site -1 central or 2 lateral
injections, about one half to 1 cm
above the chin (blue ovals)
• Injections should be kept at least
1 cm from the lower lip.
• Dosage – 2-6 U

30. PLATYSMAL BANDS
• Occur due to diastasis of the midline
platysma and loss of submental fat,
give the appearance of turkey neck.
• Site - Series of superficial/intradermal
injections directly into the contracted
muscular band. The number of
injection points depends on length of
each band.
• Dosage – 25-50U

32. MARIONETTE LINES
• Contraction of the depressor anguli oris
• Deep marionette lines give the
impression of an unhappy frowning
face.
• Site - 1 injection point into the posterior
aspect of each DAO.
• Injections should be at least 1 cm lateral
to the mouth corner to avoid adverse
outcomes.
• Dosage – 3-6 U/side

34. COMPLICATIONS
Local site
• Pain
• Edema
• Erythema
• Ecchymosis
• Short-term hyperesthesia.
Generalised reactions
• Nausea
• Malaise
• Flu-like symptoms
• Cutaneous eruptions
Diffusion of neurotoxin
into the systemic
circulation

35. SPECIFIC COMPL.
• Glabellar region - ptosis of the upper eyelid
• Forehead – Brow ptosis
• Crow’s feet – bruising
diplopia
ectropion
asymmetric smile -caused by injection of the
zygomaticus major.
• Lower face - asymmetric smile and lip ptosis
• Neck - weakness of the neck flexors and dysphagia

36. TOPICAL BTX
• BoNTA cream based on commercially viable ionic nanoparticle
technology.
Advantages over conventional injections
• Eliminates the need for multiple traumatic injections for better comfort
• Self administration
• Cause only a mild weakening. Potentially safer for use in the areas
where muscles are highly sensitive to smaller doses of the toxin.

38. THANK YOU