All about Botulinum Toxin – Botox and Xeomin
Background of Botulinum
- Botulinum Toxin is one of the most poisonous biological substances known to mankind. It is a neurotoxin produced by Clostridium botulinum. It has been called “miracle poison” because of its various uses despite being one of the most poisonous substances known and a potential bioterror weapon.
- Botulinum toxin is being increasingly used in clinical practice over the past 2 decades across all fields of medicine. It was initially approved by the US FDA in 1989 as a possible therapeutic modality in the management of strabismus and blepharospasm. It has been used ever since for both functional and cosmetic indications in ophthalmology and oculofacial plastic surgery cases. There has been a steady rise in the use of botulinum toxin for various cosmetic and neurological disorders over the past couple of decades such that it is now the most often performed nonsurgical cosmetic procedure.
- Following are some of the applications of this wonder drug over the past two decades:
- 1989 – For the management of strabismus and blepharospasm
- 1992 - It has been used for management of Facial rhytids with significant clinical improvement
- 2002 – FDA approval for the aesthetic management of glabellar furrows
- Presently, it is an efficient and reliable option in minimally invasive facial rejuvenation, facial and cervical dystonias, achalasia cardia, bruxism, hemifacial spasm, headaches, hypersalivation, hyperhidrosis, correction of lines, creases, and wrinkles over the face, chin, neck and chest.
- Botulinum toxin is available as various preparations, each with its distinct chemical and therapeutic characteristics. The most commonly available preparations are Botox and Xeomin and have been extensively studied for various cosmetic and neurological uses.
Source of Botulinum Toxin
- Botulinum Toxin is a product of the gram-positive anaerobic, spore-forming rod, Clostridium botulinum and is commonly found on plants, soil, water and gastrointestinal tract of animals. It is a potent neurotoxin which inhibits the release of acetylcholine at the neuromuscular junction of the peripheral nervous system blocking neural transmission after acting on the presynaptic terminal. When injected into any muscle, it leads to muscle paralysis thereby causing its therapeutic effect.
- Botulinum toxin has 7 different serotypes, serotypes A through G, each derived from a different strain of the bacteria. However, only types A and B are found to be clinically useful and approved by the FDA for intramuscular injections. The most potent of them, Type A botulinum toxin is approved for both aesthetic and functional use while Type B botulinum toxin is approved only for the management of cervical dystonia.
Mechanism of Action of Botulinum
- Toxin Botulinum Toxin acts by blocking neural transmission at four different sites in the body - the neuromuscular junction, autonomic ganglia, postganglionic parasympathetic nerve endings and postganglionic sympathetic nerve endings that release acetylcholine. It irreversibly blocks the release of acetylcholine, the principal neurotransmitter at the neuromuscular junction, without causing degeneration of the nerve terminals.
- The botulinum-induced irreversible paralytic effect starts in 24 to 72 hours and is complete in four to seven days after injection. There is recovery of muscle function only with the formation of new nerve terminals and new synaptic contacts which takes about two to three months.
- Hence, repeat injections should be given every three or four months based on individual response to therapy. It should be kept in mind that tolerance to the drug develops with repeated injections due to antibody formation. Therefore, it is advised that the lowest effective dose be given as infrequently as possible.
Available Preparations of Botulinum Toxin
- Botulinum toxin serotype A was the only commercially available form of botulinum toxin for clinical use for quite some time but recently, Myobloc, a botulinum toxin type B preparation has been used with some success in cervical dystonia.
- Following is a list of available preparations of Botulinum toxin with their clinical uses:
- OnabotulinumtoxinA (Botox, Botox Cosmetic): First commercially available preparation of Botulinum toxin. It is highly potent and has a well-established safety profile. Botox is stored in a freezer at or below -5°C and has to be used within 4 hours of reconstitution with 0.9% saline. Treats excessive, abnormal contractions in blepharospasm by binding to receptor sites on motor nerve terminals and inhibiting release of ACh, which, in turn, inhibits transmission of impulses in neuromuscular tissue.
- Botox: cervical dystonia, severe primary axillary hyperhidrosis, strabismus, blepharospasm
- Botox Cosmetic: moderate-to-severe glabellar lines
- AbobotulinumtoxinA (Dysport): Botox is four times more potent than Dysport
- Uses include cervical dystonia, moderate-to-severe glabellar lines
- IncobotulinumtoxinA (Xeomin): It is a highly purified Botulinum Type A formulation containing pure 150 kD neurotoxin, free from complexing proteins of the natural toxin, hence it does not induce antibody formation. Its potency is equal to that of Botox. It is an acetylcholine release inhibitor and neuromuscular blocking agent.
- Used in cervical dystonia and blepharospasm previously treated with Botox
- Rimabotulinumtoxin B (Myobloc or Neurobloc): It has a shelf life of more than a year after reconstitution but is less potent than Botox.`
- Used in cervical dystonia
Technique of Administration
- Botulinum toxin is administered by injecting an appropriate dose into the affected muscle or gland using a 30-gauge 1-inch needle. Lower doses are preferred in females and those with pre-existing weakness.
- The injections are administered through hollow Teflon coated needles directly into affected or overactive muscles and are occasionally guided by electromyography.
Precautions after Botulinum toxin injection
- A patient should go home immediately and take rest after receiving Botulinum toxin injection.
- To prevent toxins from affecting neighbouring muscles, the patient should avoid any strenuous physical activity for one to two days, and refrain from laser/IPL treatments, facials and facial massage for one to two weeks after injections.
- Patient selection and the proper choice of dose and administration site are the most important determinants for a favourable response to botulinum toxin injections.
Indications for Botulinum Toxin
- Botulinum toxins have found veritable applications in the management of various medical, neurological, dermatological, ophthalmic and cosmetic conditions with good response to treatment.
- Clinical Applications include:
- Focal dystonias
- Hemifacial spasms
- pastic movement disorders
- Alternative to surgery in chronic anal fissures
- Achalasia cardia
- Gustatory sweating after parotid gland surgery
- Dermato-Cosmetological Applications include:
- Glabellar lines
- Correction of lines, creases and wrinkles all over the face, chin, neck, and chest
- Depressor anguli oris, nasolabial folds, mentalis, medial and lateral brow lifts
- Lessen shadows on one's face
- Maintain a smooth outline of the jaw and cheeks from all directions
- Localized axillary or palmar hyperhidrosis nonresponsive to conventional therapy
Adverse Effects of Botulinum Toxin
Botulinum toxin injections are generally well-tolerated and cause relatively few side-effects which are divided into two groups: paralysis of the wrong muscle group and allergic reaction.
- Unwanted weakness or paralysis of the wrong muscle group: It is the most feared adverse effect but it is temporary and lasts from a few weeks to several months.
- Upper lid or brow ptosis
- Double vision
- Uneven smile
- Weakness of the lower eyelid or lateral rectus resulting in exposure keratitis
- Dysphagia due to toxin reaching the oropharynx
- Neck weakness due to weakening of the sternocleidomastoid muscles
- Rare cases of generalized weakness
- Allergic Reaction
- Rare but can occur due to hypersensitivity towards any of the components of the injections such as egg albumin.
- Systemic Side Effects
- Flu-like syndromes
- Immune-mediated plexopathy
- Blurred vision
- Dry mouth
- Swelling and redness at injection site
Contraindications to Botulinum Toxin Injection
- Preexisting motor neuron disease
- Myasthenia gravis
- Eaton-Lambert syndrome
- Psychological unstability
- History of allergy to toxin or albumin
- Pregnancy and lactating mothersnfection at the injection site
- Aminoglycosides accentuate the effect of botulinum toxin
- Penicillamine, quinine, chloroquine, and hydroxychloroquine reduce the effect of botulinum toxin
- Calcium channel blockers and blood thinning agents such as warfarin and aspirin might cause bruising
Why does Botulinum Toxin Injection fail often?
- Photodamage and age-related changes which are not dynamic in origin
- Improper injection technique
- Denatured toxin used for injection
- Neutralizing antibodies due to repeated exposure or individual variation
Future of Botulinum Toxin
- The future of botulinum toxin is bright as it has revolutionized the treatment of various ophthalmic spastic disorders, facial dystonias and periocular wrinkles. As we gain more insight into the uses of various toxins for chemodenervation, there is hope for better uses of botulinum toxin.