1. Shumez

2. History Justinus Kerner described botulinum toxin as a "sausage poison" because the bacterium that produces the toxin grew in improperly handled or prepared meat products. In the early 1970s, Alan Scott, an opthalmologist used botulinum toxin injections to treat strabismus and blepharospasm. 3. Alistair and Jean Carruthers were the first to use botulinum toxin for the treatment of glabellar lines in 1992. On April 12 2002, the FDA approved the use of botulinum toxin type A (Botox Cosmetic) to temporarily improve the appearance of glabellar lines. Since then, botulinum toxin has been approved for a number of cosmetic indications in over 20 countries. 4. Introduction Botulinum toxin is a neuroexotoxin which specifically targets the release of acetylcholine. It is produced by the anaerobic bacterium Clostridium botulinum. There are harvested by centrifugation and acidification. 5. 7 antigenically distinct serotypes (A - G) They are immunologically distinct. Incapable of cross neutralization. Vary in potency and duration of effect. Type A is used for cosmetic purposes. 6. Manufacturing process Botulinum toxin type A is produced by fermentation of Hall strain of Clostridium botulinum. It is grown in a medium containing casein hydrolysate, glucose, and yeast extract. It is purified from the culture solution by dialysis and a series of acid precipitations to a complex consisting of the neurotoxin, and several accessory proteins. 7. Structure Botulinum neurotoxins are polypeptides. Botulinum toxin comprises a protein molecule (150kd) which can be cleaved into a heavy (100kd) and a light (50kd) chain. These chains are normally held together by a disulphide bond, which is heat labile. Disruption of this bond inactivates the neurotoxin. 8. Mechanism of action Normally, Motor nerve fibre is stimulated. Release of Ach from pre-junctional membrane. Reaches the junctional membrane. Attaches to end plate receptors. Local current initiates muscle contraction. 9. BTX A attaches to the cholinergic receptor sites on the cell membrane of a presynaptic motor nerve end plate. Plasma membrane of nerve cell invaginates around the toxin receptor complex forming a toxin containing vesicle. Translocation of the neurotoxin into the cytoplasm. Blocks fusion of Ach vesicles onto nerve terminal plasma membrane. 10. This inhibition occurs as the neurotoxin cleaves SNAP-25, a protein integral to the successful docking and release of acetylcholine from vesicles situated within nerve endings. Thus, impeding exocytosis of Ach and its release into the synaptic cleft. There is no neuromuscular transmission and theres paralysis of the affected muscle. Therapeutic effect of the BTX-A is seen within 24 72 hrs and lasts for 3-6 months. 11. Botulinum toxin is not detected in the peripheral blood following intramuscular injection at the recommended doses. Pregnancy Category C Not recommended in children, patients >65 yrs, pregnant and lactating mothers. 12. Commercial forms 2 commercially available botulinum toxins: Botulinum toxin A : Botox (USA) Dysport ( UK) Botulinum toxin B : Myobloc (USA) Neurobloc (Europe) 13. Botulinum toxin A 14. BOTOX MYOBLOC Vaccum dried lyophilized form Type A serotype pH - 7 Diluted with 1.0 or 2.5 ml NS providing conc. of 40 units/ml or 100 units/ml Comes with sterile saline with preservative (benzyl alcohol)- lessens the sting Aqueous solution Type B serotype pH - 5.6 5000 units /ml aqueous solution 15. Cosmetic indications Chemical brow lifting Suborbital hypertrophic orbicularis Infraorbital crows feet Nasal scrunch (Bunny line) Nasal flare Nasolabial folds Perioral lip line 16. Marionette lines Mental crease Popply chin Hypertrophic mandibular angles Facial asymmetry 17. Other indications Cervical dystonia Blepharospasm Primary hyperhidrosis Strabismus Achalasia Chronic focal neuropathies Chronic migraine Bruxism 18. Neurogenic detrusor overactivity Incontinence due to neurogenic bladder Anal fissure Vaginismus Diabetic neuropathy Vocal cord dysfunction Excessive salivation Painful bladder syndrome 19. Contraindications Myasthenia gravis Lambert Eaton syndrome Muscle weakness Absence of tendon reflexes Autonomic dysfunction Local infection Hypersensitivity to any ingredient Pregnancy and lactation Treatment with aminoglycoside in the past 3 months 20. Drug Interactions Effect of the toxin may be potentiated with other agents interfering with neuromuscular transmission like : Aminoglycosides Lincosamides Polymyxins Quinidine Magnesium sulfate Anticholinesterases Succinylcholine chloride 21. Dosage and Dilution BTX-A is available as 100 units of freeze dried powder in a glass vial under vacuum. Stored in a freezer at -5 C. After reconstitution , stored at 2-8 C. Diluents used are normal saline with or without preservatives (0.9% benzyl alcohol) and equal parts of saline and lidocaine. 22. Diluent added Dose in UNITS per 0.1 ml 1.0 ml 2.0 ml 2.5 ml 10.0 U 5.0 U 4.0 U 2.5 ml per vial for the upper face. 1 - 2 ml for smaller muscles in the lower face. 23. Pre - procedure care Pre treatment consultation. Counsel the patients regarding limitations of the treatment. Pre procedure photographs. Upright position. Support head with head rest. Avoid alcohol and anticoagulants few days before the treatment. Oral antibiotics can be given 2 days prior & 3 days after the procedure. 24. Glabellar frown lines Corrugator supercilii draws the eyebrow medially and downwards. Orbicularis oculi pulls it medially. Procerus and depressor supercilii draw the eyebrow downwards. 25. 6 U injected into the procerus midway just below a line joining the medial end of both eyebrows. 4 U into each corrugator on a point above the vertical line joining the inner canthus and superior margin of bony orbit. 2-4 U injected 1 cm superior to the above point. 26. Response Rates Day Investigators assessment 7 74 % 30 80 % 60 70 % 90 48 % 120 25 % 27. Horizontal forehead lines Occipitofrontalis raises eyebrows and is resposible for horizontal forehead lines. 2 U is injected at a distance of 1.5cm into the frontalis, staying 2 finger widths above the supraorbital rim to avoid ptosis. 28. Crows feet Orbicularis oculi has 3 parts. Orbital part: protrusion of the eyebrows and voluntary eyelid closure. Palpebral part: closes lids during blinking. Lacrimal part: draws lids and lacrimal papillae medially, compresses the lacrimal sac. 29. Palpate the orbital rim 1 - 1.5 cm from the lateral canthus. Inject 4 U at this site and 1 cm above and below this site. 30. Neck bands Platysma shows vertical bands. Anterior fibers : assist mandibular depression Intermediate fibers : depress the lower lip Posterior fibers : depress the buccal angle 31. Dose for 1 platysmal band is 15 U. 5 U in the top of the muscle band. 5 U injected 2 cm below this site. 5 U injected 2 cm further down. For horizontal necklace lines, 1-2 U injected every 2 cm along the line as an intradermal bleb. 32. Post procedure instructions To sit upright for 4 hours. To exercise the treated muscle during the first 2 hours. Not to manipulate the treated area for 4 hours. Patients is followed up after 2-4 weeks. Photographs should be taken to assess the results. 33. Complications Ecchymosis Pain / edema / erythema at injection site Lid ptosis Brow ptosis Lip ptosis Impaired blink reflex Mephisto sign Asymmetry of face 34. Botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. These may include asthenia, generalized muscle weakness, diplopia, blurred vision, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence and breathing difficulties. These symptoms have been reported hours to weeks after injection. Swallowing and breathing difficulties can be life threatening and there have been reports of death. 35. Hyperhidrosis Intradermal injections of BTX - A are effective in the treatment of palmar hyperhidrosis. 50 100 U are injected into each palm. Inject in a grid-type pattern with 2 cm distance between sites. After injection, keep palms down as much as possible for 1 2 hours to minimize penetration to intrinsic muscles of hand. Complications - Sensory deficits in injected area and intrinsic hand muscle weakness.