botulinum toxin botulinum toxin by: maica galvez-vergara m.d
TRANSCRIPT
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BOTULINUM TOXINBOTULINUM TOXIN
BY: BY: MAICA GALVEZ-VERGARA M.D.MAICA GALVEZ-VERGARA M.D.
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Botulinum toxin type A Botulinum toxin type A
neurotoxin protein Clostridium botulinumClostridium botulinumGram-positive rod shaped rod shaped anaerobic spore- spore-
former former bacterium
Botulism Latin botulusbotulus = "sausage shape” = "sausage shape”
food poisoningfood poisoning
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Common Indications for Bt-ACommon Indications for Bt-A
Spasmodic Spasmodic TorticollisTorticollis
BlepharospasmBlepharospasm Hemifacial SpasmHemifacial Spasm Post-Stroke Post-Stroke
SpasticitySpasticity Cerebral PalsyCerebral Palsy Dystonia Dystonia Various movement Various movement
disordersdisorders Aesthetics (Wrinkles)Aesthetics (Wrinkles)
Hyperhidrosis Square face and other
remodelling indications Spasmodic dysphonia Myofascial and other
Pain Headache, migraine Drooling Etc., etc., etc.
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Structure of Botulinum ToxinStructure of Botulinum Toxin
Disulfide bond
Light chain:the molecule’s toxic fraction Heavy chain:
responsible for specificityof each serotype
Botulinum Toxin is inactivated by heat
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Mechanism of ActionMechanism of Action
Botulinum Toxins block the exocytosis of acetylcholine at the motor endplate, thereby making neuromuscular transmission impossible
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THE MECHANISM INCLUDES 3 STAGES
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Binding to the Presynaptic Binding to the Presynaptic MembraneMembrane
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Internalization of the ToxinInternalization of the Toxin
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Inhibition of Exocytosis of ACTHInhibition of Exocytosis of ACTH
SNARE (SNAP receptor proteins)• SNAP-25 (SyNaptosomal Associated Protein 25 kDa• syntaxin• Synaptobrevin or VAMP (Vesicular Associated Membrane Protein)
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Recovery by Neuronal PlasticityRecovery by Neuronal Plasticity
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ADVANTAGES:ADVANTAGES:
Safe and rapidly administeredSafe and rapidly administered Effects are profoundEffects are profound 99% successful99% successful Painless Painless No recovery timeNo recovery time Technically straightforward to useTechnically straightforward to use Effects are reversible w/in an acceptable limit of Effects are reversible w/in an acceptable limit of
timetime Complications are rare and self-limiting Complications are rare and self-limiting
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DISADVANTAGES:DISADVANTAGES:
Irreversibility or length of Irreversibility or length of therapeutic effect.therapeutic effect.
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CONTRAINDICATIONSCONTRAINDICATIONS Hypersensitivity to ingredients ( albumin, sodium chloride Hypersensitivity to ingredients ( albumin, sodium chloride
botulinum toxin ) botulinum toxin ) Neuromuscular dx. (myasthenia gravis, motor neuron Neuromuscular dx. (myasthenia gravis, motor neuron
disease)disease) Patients treated with other drugs that may interfere withPatients treated with other drugs that may interfere with neuromuscular transmission; aminoglycosides, neuromuscular transmission; aminoglycosides,
polymixins, penicillamine, quinine, calcium channel polymixins, penicillamine, quinine, calcium channel blockers neuromuscular blocking agents. blockers neuromuscular blocking agents.
Pregnancy and lactationPregnancy and lactation Patients in anti-coagulation therapyPatients in anti-coagulation therapy Inappropriate anatomy ( skin laxity photo damage )Inappropriate anatomy ( skin laxity photo damage ) Poor psychological adjustmentPoor psychological adjustment
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Bt-A Indications in AestheticsBt-A Indications in Aesthetics
DynamicDynamic wrinkles of the wrinkles of the glabellaglabella
DynamicDynamic wrinkles in the wrinkles in the foreheadforehead
DynamicDynamic wrinkles wrinkles around the eyes around the eyes (« crow’s feet »)(« crow’s feet »)
Slight facial asymmetrySlight facial asymmetry Wrinkles in the area Wrinkles in the area
around the platysmal around the platysmal muscle and the neckmuscle and the neck
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Other Indications for Bt-A in Other Indications for Bt-A in Aesthetics.Aesthetics.
Hyperhidrosis
underarms
palms
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Square face and other remodelling indications
Gummy smiles
Calf contouring
Meso Botox
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Different BTXA’sDifferent BTXA’s
Botox - Allergan Irvine, CABotox - Allergan Irvine, CA BTXA - Lanzhou, ChinaBTXA - Lanzhou, China Refinex - ChinaRefinex - China Dysport - Wrexam, Wales UKDysport - Wrexam, Wales UK Korea – Neurotox, Zentox, BotulaxKorea – Neurotox, Zentox, Botulax Xeomin (incobotulinumtoxinA) Merz Xeomin (incobotulinumtoxinA) Merz
Pharmaceuticals, North CarolinaPharmaceuticals, North Carolina
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DoseDose
BTXA – 2-4 units per BTXA – 2-4 units per injection site.injection site.
Allergan China and Allergan China and NeurotoxNeurotox
Dysport – 5-10 units per Dysport – 5-10 units per injection site.injection site.
100 units/vial100 units/vial Dilute to 2.5cc of NSS to Dilute to 2.5cc of NSS to
make 2units of .05ml make 2units of .05ml tuberculin syringe.tuberculin syringe.
500 units/vial500 units/vial Dilute to 2.5cc of NSS to Dilute to 2.5cc of NSS to
make 5units of .05ml make 5units of .05ml tuberculin syringe.tuberculin syringe.
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PharmacokineticsPharmacokinetics
Time to action: 24 to 72 hoursTime to action: 24 to 72 hours
Time to peak: 8-15 days afterTime to peak: 8-15 days after
Duration of action: 3 - 6 months (longer in Duration of action: 3 - 6 months (longer in certain indicationscertain indications
After about the 7After about the 7thth injection, this period is injection, this period is significantly prolongedsignificantly prolonged
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TOXICITYTOXICITY
2500 TO 3000 units in a 70kg human 2500 TO 3000 units in a 70kg human based on the median lethal dose of 40 based on the median lethal dose of 40 units / kg.units / kg.
Single dose of 500 units may produce Single dose of 500 units may produce acute symptoms and signs of botulism.acute symptoms and signs of botulism.
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Facial MusclesFacial Muscles
Frontalis> elevates Frontalis> elevates brows. brows. Forehead linesForehead lines
Corrugators> pull Corrugators> pull eyebrows medially eyebrows medially Procerus, Depressor Procerus, Depressor supercilli> pulls eyebrow supercilli> pulls eyebrow down medially. down medially. Frown Frown lineslines
Orbicularis oculi> Orbicularis oculi> depresses brows esp. depresses brows esp. laterally. laterally. Crows feetCrows feet
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Dynamic wrinkles of the foreheadDynamic wrinkles of the forehead
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Korean RecommendationsKorean Recommendations
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Axillary hyperhydrosisAxillary hyperhydrosis Positive starch-iodine Positive starch-iodine
test.test.
50 units to 100 units/ 50 units to 100 units/ axilla.axilla.
Palmar hyperhydrosisPalmar hyperhydrosis
50 units to 100 units/50 units to 100 units/
hand. hand.
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COMPLICATIONSCOMPLICATIONS
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Areas To AvoidAreas To Avoid Around the orbit (less than 1 Around the orbit (less than 1
cm)cm)
Lateral area of the brow less Lateral area of the brow less than 1 finger breaththan 1 finger breath
Lower eyelid – Neg. Snap testLower eyelid – Neg. Snap test
Lower face (nasolabial)Lower face (nasolabial)
Around the mouthAround the mouth
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Rare Secondary EffectsRare Secondary Effects
Pain, burning sensationPain, burning sensation Hematoma, edemaHematoma, edema Ptosis, drooping of eyelid- naphcon A or apraclonidine 0.5% Ptosis, drooping of eyelid- naphcon A or apraclonidine 0.5%
eye drops.eye drops.
Always REVERSIBLE and related to dose and individual sensitivity of each patient
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MEPHISTO LOOK…. SPOCKMEPHISTO LOOK…. SPOCK
Usually resolves in weeksUsually resolves in weeks May consider injection at the arch, lateral side to bring May consider injection at the arch, lateral side to bring
down the brow.down the brow.
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FROZEN EXPESSIONSFROZEN EXPESSIONS
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LOCALLOCAL PAINPAIN SWELLINGSWELLING EDEMAEDEMA ERYTHEMAERYTHEMA HEMATOMAHEMATOMA RASHRASH BRUISINGBRUISING ECCHYMOSISECCHYMOSIS TENDERNESSTENDERNESS HEADACHEHEADACHE SHORT TERM PARESTHESIASHORT TERM PARESTHESIA
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REGIONALREGIONAL
ASSYMETRYASSYMETRY
LOSS OF FACIAL EXPRESSIONLOSS OF FACIAL EXPRESSION
INCOMPLETE MUSCLE PARALYSISINCOMPLETE MUSCLE PARALYSIS
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SYSTEMICSYSTEMIC
NAUSEANAUSEA FATIGUEFATIGUE SEVERE GENERALIZED WEAKNESSSEVERE GENERALIZED WEAKNESS MALAISEMALAISE FLULIKE SYMPTOMSFLULIKE SYMPTOMS ALLERGY 2NDARY TO ALBUMINALLERGY 2NDARY TO ALBUMIN
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POINTS TO PONDERPOINTS TO PONDER
KNOW YOUR ANATOMY WELL.KNOW YOUR ANATOMY WELL. KNOW YOUR PRODUCTS WELL.KNOW YOUR PRODUCTS WELL. KNOW YOUR PATIENTS WELL IF KNOW YOUR PATIENTS WELL IF
POSSIBLE.POSSIBLE. USE MINIMUM DOSAGING.USE MINIMUM DOSAGING. FOLLOW UP IN 2 WEEKS.FOLLOW UP IN 2 WEEKS. ALWAYS TAKE BEFORE AND AFTER ALWAYS TAKE BEFORE AND AFTER
PICTURES.PICTURES.
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THANK YOUTHANK YOUVERY MUCH !!!VERY MUCH !!!