BTX-A/Botox (BoNTs) are the etiological agents responsible for botulism, a disease characterized by the peripheral neuromuscular blockade and a characteristic flaccid paralysis of humans? BoNTs are the most lethal known poisons affecting humans and has been recognized as a potential bioterrorist threat. Current treatments for botulinum poisoning are predominately prophylactic in nature relying on passive immunization with antitoxins. Inhibition of the BoNT light chain metalloprotease (LC) has emerged as a new therapeutic strategy for the treatment of botulism that may provide an effective post-exposure remedy.
Neurotoxin produced by fermentation of Clostridium botulinum type B. The protein exists in noncovalent association with hemagglutinin and nonhemagglutinin proteins as a neurotoxin complex. The neurotoxin complex is recovered from the fermentation process and purified through a series of precipitation and chromatography steps.
Another Name
- AbobotulinumtoxinA
- Botulinum A neurotoxin
- Botulinum toxin A
- Botulinum toxin type A
- BTX-A
- Evabotulinumtoxina
- IncobotulinumtoxinA
- OnabotulinumtoxinA
- Prabotulinumtoxin A
- Toxins botulínica A
-
Toxine botulinum A
Botulinum toxin is sold commercially under the names
- Botox, Vistabel, Botox cosmetic (OnabotulinumtoxinA or botulinum toxin type A)
- Dysport (AbobotulinumtoxinA or botulinum toxin type A)
- Bocouture, Xeomin (IncobotulinumtoxinA or botulinum toxin type A)
- Myobloc (RimabotulinumtoxinB or botulinum toxin type B).
Mechanism of Action BTX-A
Botulinum toxin acts by inhibiting neurotransmitter release. It binds to peripheral neuronal synapses, is internalized and moves by retrograde transport up the axon into the spinal cord where it can move between postsynaptic and presynaptic neurons. It inhibits neurotransmitter release by acting as a zinc endopeptidase that cleaves syntaxin.
Botulinum Toxin Type B binds to and cleaves the synaptic Vesicle Associated Membrane Protein (VAMP, also known as synaptobrevin) which is a component of the protein complex responsible for docking and fusion of the synaptic vesicle to the presynaptic membrane, a necessary step to neurotransmitter release.
Botulinum Toxin Type B inhibits acetylcholine release at the neuromuscular junction via a three-stage process: 1) Heavy Chain mediated neuro specific binding of the toxin, 2) internalization of the toxin by receptor-mediated endocytosis, and 3) ATP and pH-dependent translocation of the Light Chain to the neuronal cytosol where it acts as a zinc-dependent endoprotease cleaving polypeptides essential for neurotransmitter release.
or
Botulinum Toxin Type A blocks neuromuscular transmission by binding to acceptor sites on the motor or sympathetic nerve terminals, entering the nerve terminals, and inhibiting the release of acetylcholine. 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.
A 150 kDa neurotoxic protein produced from the fermentation of Hall strain Clostridium botulinum type A 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. Botulinum Toxin Type A is not expected to be present in the peripheral blood at measurable levels following IM or intradermal injection at the recommended doses. The recommended quantities of neurotoxin administered at each treatment session are not expected to result in systemic, overt distant clinical effects, i.e. muscle weakness, in patients without other neuromuscular dysfunction. However, sub-clinical systemic effects have been shown by single-fiber electromyography after IM doses of botulinum toxins appropriate to produce clinically observable local muscle weakness.
Indications of BTX-A
For the treatment of cervical dystonia in adults to decrease the severity of abnormal head position and neck pain associated with cervical dystonia. Also for the treatment of severe primary axillary hyperhidrosis that is inadequately managed with topical agents and for the treatment of strabismus and blepharospasm associated with dystonia, including benign essential blepharospasm or VII nerve disorders in patients 12 years of age and above. Also used cosmetically to temporarily improve the appearance of moderate-to-severe frown lines between the eyebrows (glabellar lines) as well as for the treatment of excessive underarm sweating.
- For the treatment of patients with cervical dystonia to reduce the severity of abnormal head position and neck pain associated with cervical dystonia.
- A temporary improvement in the appearance of moderate to severe lateral canthal lines associated with orbicularis oculi activity
- A temporary improvement in the appearance of moderate to severe glabellar lines associated with procerus and corrugator muscle activity
- Blepharospasm
- Cervical Dystonia
- Chronic Migraine
- Chronic Spasticity
- Dystonia
- Facial Wrinkles
- Hyperhidrosis
- Lower Limb Spasticity
- Migraine
- Migraine Prevention
- Overactive Bladder
- Strabismus
- Upper Limb Spasticity
- Urinary Frequency
- Urinary Incontinence
- Equinus deformity of the foot, acquired
- Lower Limb Spasticity
- Sialorrhea
- Strabismus
- Urinary Bladder, Overactive
- Urinary Incontinence (UI)
- Detrusor overactivity, neurologic conditions
- Hypertonicity disorders of the 7th nerve
- Severe axillary hyperhidrosis
Others Indication of BTX-A
- The use of a topical botulinum toxin composition is disclosed for the treatment of a disorder amenable to treatment by botulinum toxin. The disorder may comprise the symptoms associated with hyperhidrosis. The topical botulinum toxin composition comprises phospholipid micelles, one or more primary stabilizers, and one or more skin penetration enhancers.
- Botulinum toxin is used to treat a number of disorders characterized by overactive muscle movement, including post-stroke spasticity, post-spinal cord injury spasticity, spasms of the head and neck,[rx] eyelid,[rx] vagina,[rx] limbs, jaw, and vocal cords.[rx] Similarly, botulinum toxin is used to relax the clenching of muscles, including those of the esophagus, jaw, lower urinary tract, and bladder,[14] or clenching of the anus which can exacerbate anal fissure.
- Other muscle disorders – Strabismus is caused by imbalances in the actions of muscles that rotate the eyes, and can sometimes be relieved by weakening a muscle that pulls too strongly or pulls against one that has been weakened by disease or trauma. Muscles weakened by toxin injection recover from paralysis after several months, so it might seem that injection would then need to be repeated. However, muscles adapt to the lengths at which they are chronically held,[rx]
- In January 2014, botulinum toxin was approved by UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) for the treatment of restricted ankle motion due to lower limb spasticity associated with stroke in adults.[rx]
- In cosmetic applications, botulinum toxin is considered safe and effective for the reduction of facial wrinkles, especially in the uppermost third of the face.[rx] Commercial forms are marketed under the brand names Botox Cosmetic/Vistabel from Allergan, Dysport/Azzalure from Galderma and Ipsen, Xeomin/Bocouture from Merz, and in the US only, Jeuveau from Evolus, manufactured by Daewoong.[rx]
Contra-Indications of BTX-A
- Lou Gehrig’s Disease
- A disorder of the peripheral nerves that enable movement called peripheral motor neuropathy
- Myasthenia gravis
- A skeletal muscle disorder
- Progressive muscle weakness with carcinoma
- A condition where one object appears as two or more object
- Double vision
- Blurred vision
- Kidney and renal failure
- Drooping of the upper eyelid
- Pneumonia due to accidental inhalation of vomit
- Decreased lung function
- Hoarseness
- A type of speech disorder called dysarthria
- Trouble breathing
- Difficulty swallowing
- Involuntary leakage of urine
- Allergies to Botulinum Toxin
Warning
- This medication can spread to other parts of the body after your injection, causing serious (possibly fatal) side effects. These can occur hours or even weeks after the injection. However, the chances of such serious side effects occurring when this medication is used for migraines or skin conditions such as wrinkles, eye spasm, or excessive sweating are extremely unlikely.
- Children being treated for muscle stiffness/spasms have the greatest risk of these effects, as well as anyone that has certain medical conditions (see Precautions section). Discuss the risks and benefits of this medication with your doctor.
- Get medical help right away if any of these very serious side effects occur: chest pain, difficulty breathing, excessive muscle weakness, irregular heartbeat, severe difficulty swallowing or speaking, loss of bladder control.
Dosage of BTX-A
Strengths: Not Clear, Dosage may vary according to the condition of disease that is described bellow
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Head/Neck Area | Recommended Dose (Number of Sites) |
Frontalis | 20 Units divided into 4 sites |
Corrugator | 10 Units divided into 2 sites |
Procerus | 5 Units in 1 site |
Occipitalisb | 30 Units divided into 6 sites |
Temporalis | 40 Units divided into 8 sites |
Trapezius | 30 Units divided into 6 sites |
Cervical Paraspinal Muscle Group |
20 Units divided into 4 sites |
Total Dose: | 155 Units divided into 31 sites |
Muscle | Recommended Dose Total Dosage (Number of Sites) |
Biceps Brachii | 100 Units-200 Units divided into 4 sites |
Flexor Carpi Radialis | 12.5 Units-50 Units in 1 site |
Flexor Carpi Ulnaris | 12.5 Units-50 Units in 1 site |
Flexor Digitorum Profundus | 30 Units-50 Units in 1 site |
Flexor Digitorum Sublimis | 30 Units-50 Units in 1 site |
Adductor Pollicis | 20 Units in 1 site |
Flexor Pollicis Longus | 20 Units in 1 site |
Muscle | Recommended Dose Total Dosage (Number of Sites) |
Gastrocnemius medial head | 75 Units divided into 3 sites |
Gastrocnemius lateral head | 75 Units divided into 3 sites |
Soleus | 75 Units divided into 3 sites |
Tibialis Posterior | 75 Units divided into 3 sites |
Flexor hallucis longus | 50 Units divided into 2 sites |
Flexor digitorum longus |
Muscle | Recommended Dose and Number of Sites |
Biceps Brachii | 1.5 Units/kg to 3 Units/kg divided into 4 sites |
Brachialis | 1 Units/kg to 2 Units/kg divided into 2 sites |
Brachioradialis | 0.5 Units/kg to 1 Units/kg divided in 2 sites |
Flexor Carpi Radialis | 1 Units/kg to 2 Units/kg divided into 2 sites |
Flexor Carpi Ulnaris | 1 Units/kg to 2 Units/kg divided into 2 sites |
Flexor Digitorum Profundus | 0.5 Units/kg to 1 Units/kg divided in 2 sites |
Flexor Digitorum Sublimis | 0.5 Units/kg to 1 Units/kg divided in 2 sites |
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Side Effects of BTX-A
The Most Common
- Bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
- Difficult or painful swallowing, dizziness, shortness of breath, or vision changes (when used for cervical dystonia)
- Facial paralysis or persistent eye irritation or pain (when used for eye conditions)
- Falling (when used for spasticity due to cerebral palsy)
- Fever, especially when accompanied by coughing and shortness of breath
- Irregular heartbeat
- Shortness of breath
- Skin rash
- Symptoms of a urinary tract infection (e.g. pain when urinating, urinating more often than usual, low back or flank pain)
- Blurred vision
- Body aches or pain
- Cough producing mucus
- difficulty breathing
- Mild pain, local oedema (fluid buildup) and/or erythema (reddening of the skin) at the injection site.
- Numbness.
- Headache.
- Malaise – feeling generally unwell.
- Mild nausea.
- Temporary unwanted weakness/paralysis of nearby muscles.
- Temporary upper lid or brow ptosis (drooping).
- The weakness of the lower eyelid or lateral rectus (a muscle controlling eye movement).
- Dysphagia – trouble swallowing.
- Neck weakness.
- Flu-like illness.
- Brachial plexopathy – a condition affecting the nerves on either side of the neck and chest.
- Gallbladder dysfunction.
- Diplopia (double vision).
- Bleeding.
- Blurred vision.
- Decreased eyesight.
- Dry mouth.
- Fatigue.
- Wheezing.
- Swelling.
More common
- Signs of an allergic reaction (e.g., hives; difficulty breathing; swelling of the mouth, tongue, or throat)
- Signs of a heart attack (e.g., chest pain or pressure; shortness of breath; jaw, shoulder, or arm pain; nausea; lightheadedness; sweating)
- Difficulty with swallowing
- Dryness of the eyes
- Inability to close the eyelids completely
- Bladder pain
- Bloody or cloudy urine
- Difficult, burning, or painful urination
- Frequent urge to urinate
- Lower back or side pain
- Decreased blinking
- Irritation of the cornea (colored portion) of the eyes
- Turning outward or inward of the edge of the eyelids
- Drooping of the brows and upper eyelids
- Drooping of the upper eyelid
Rare or Less common
- Facial pain
- Muscle weakness
- Partial or slight paralysis of the face
- Swelling of the eyelids
- Body aches or pain
- Ear congestion
- Headache
- Loss of voice
- Nasal congestion
- Sore throat
- Unusual tiredness or weakness
- Dryness or soreness of the throat
- A general feeling of discomfort or illness
- Heavy bleeding from the place where the shot was given
- Joint pain
- Loss of appetite
- Trouble sleeping
- Trouble swallowing
- Drooping of the upper eyelid
- eye pointing upward or downward instead of straight ahead
- drooping of the upper eyelid
- Headache
- Muscle aches and pains
- Difficulty finding the location of objects
- Cough producing mucus
- Difficulty breathing
- Muscle weakness
- Tightness in the chest
Drug Interaction of BTX-A
There may be an interaction between botulinum toxin type A and any of the following:
- aclidinium
- amikacin
- amikacin liposome
- atracurium
- aminoglycoside antibiotics (e.g., gentamicin, neomycin, tobramycin, streptomycin)
- antihistamines (e.g., brompheniramine, diphenhydramine)
- antipsychotics (e.g. clozapine, olanzapine, risperidone)
- gentamicin
- neomycin
- netilmicin
- kanamycin
- metocurine
- mivacurium
- pancuronium
- pipecuronium
- plazomicin
- polymyxin b
- rocuronium
- rapacuronium
Pregnancy Category of BTX-A
FDA Pregnancy Category C
US FDA pregnancy category: Not assigned in some cases
Pregnancy
This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while receiving this medication, contact your doctor immediately. Botulinum toxin also should not be used in pregnant or lactating women, or by people who have had a previous allergic reaction to the drug or any of its ingredients.
Breast-feeding
It is not known if botulinum toxin passes into breast milk. If you are a breast-feeding mother and are receiving this medication, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding. The safety and effectiveness of using this have not been established for children under 18 years of age.
References
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