Btxa
(Botulinum Toxin Type A for Therapy)

Drug Effects

Usage


Although botulinum toxin is a lethal, naturally occurring substance, it can be used as an effective and powerful medication.[34] Researchers discovered in the 1950s that injecting overactive muscles with minute quantities of botulinum toxin type-A would result in decreased muscle activity by blocking the release of acetylcholine from the neuron by preventing the vesicle where the acetylcholine is stored from binding to the membrane where the neurotransmitter can be released. This will effectively weaken the muscle for a period of three to four months.[35]

In cosmetic applications, a Botox injection, consisting of a small dose of botulinum toxin, can be used to prevent development of wrinkles by paralyzing facial muscles.[36] As of 2007, it is the most common cosmetic operation, with 4.6 million procedures in the United States, according to the American Society of Plastic Surgeons. Qualifications for Botox injectors vary by county, state and country. Botox cosmetic providers include dermatologists, plastic surgeons, aesthetic spa physicians, dentists, nurse practitioners, nurses and physician assistants. The wrinkle-preventing effect of Botox normally lasts about three to four months, but can last up to six months.[36]

In addition to its cosmetic applications, Botox is currently used in the treatment of spasms and dystonias, by weakening involved muscles, for the 60–70 day effective period of the drug.[37] The main conditions treated with botulinum toxin are:

  • Cervical dystonia (spasmodic torticollis) (a neuromuscular disorder involving the head and neck)[38]
  • Blepharospasm (excessive blinking)[39]
  • Severe primary axillary hyperhidrosis (excessive sweating)[40][41]
  • Strabismus (squints)
  • Achalasia (failure of the lower oesophageal sphincter to relax)
  • Local intradermal injection of BTX-A is helpful in chronic focal neuropathies. The analgesic effects are not dependent on changes in muscle tone.[42]
  • Migraine and other headache disorders, although the evidence is conflicting in this indication[43]
  • Bruxism: by injecting the toxin into the muscles of mastication, such as the masseter

Other uses of botulinum toxin type A that are widely known but not specifically approved by the FDA (off-label uses) include treatment of:

Treatment and prevention of chronic headache[50] and chronic musculoskeletal pain[51] are emerging uses for botulinum toxin type A. In addition, Botox may aid in weight loss by increasing the gastric emptying time.[52]

Adverse Effect


Side effects, which are generally minor and temporary,[36] can be predicted from the mode of action (muscle paralysis) and chemical structure (protein) of the molecule, resulting, broadly speaking, in two major areas of side effects: paralysis of the wrong muscle group and allergic reaction. Bruising at the site of injection is a side effect not of the toxin, but rather the mode of administration. In cosmetic use, this can result in inappropriate facial expression, such as drooping eyelid,[36] double vision,[36] uneven smile, or loss of the ability to close eyes. This will wear off in around six weeks. Bruising is prevented by the clinician applying pressure to the injection site, but may still occur, and will last around seven to 11 days. When injecting the masseter muscle of the jaw, loss of muscle function will result in a loss or reduction of power to chew solid foods.[53] All cosmetic treatments are of limited duration, and can be as short as six weeks, but usually the effective period lasts from two to three months. At the extremely low doses used medicinally, botulinum toxin has a very low degree of human and animal toxicity.

Other adverse events from cosmetic use include headaches, dysphagia, flu-like syndromes, blurred vision, dry mouth, fatigue, allergic reactions and swelling or redness at the injection site.[53][59]

A petition by Public Citizen to the FDA has requested regulatory action concerning the possible spread of botulinum toxin (Botox, Myobloc) from the site of injection to other parts of the body.[60]

Individuals who are pregnant, have egg allergies or a neuromuscular disorder are advised to avoid Botox.[36]

Botox takes away or dampens the emotional expressions in a particular situation. That may be due to less interaction between facial muscle movement and brain. According to David Neal, a psychology professor at the University of Southern California, “if muscular signals from the face to the brain are dampened, you’re less able to read emotions.”[61]

One way botox might affect emotional feelings is by dampening the relay of signals from the face to the amygdala and brainstem centers for autonomic arousal.[62]

The mental effects of botox may extend beyond emotional feelings to the ability to understand language about emotions. An experimental study suggests the cosmetic use of botulinum toxin for treatment of glabellar lines affects human cognition. Havas and colleagues[63][64] asked subjects to read emotional (angry, sad, happy) sentences before and two weeks after Botox injections in the corrugator supercilii muscle used in frowning. Reading times for angry and sad sentences were longer after injection than before injection, while reading times for happy sentences were unchanged. This finding suggests facial muscle paralysis has a selective effect in human cognition, and shows Botox hinders the ability to understand language. According to the lead researcher in this study, "[B]otox causes a kind of mild, temporary, cognitive blindness to information in the world, social information about the emotions of other people

Mechanism Action


The heavy chain of the toxin is particularly important for targeting the toxin to specific types of axon terminals. The toxin must get inside the axon terminals to cause paralysis. Following the attachment of the toxin heavy chain to proteins on the surface of axon terminals, the toxin can be taken into neurons by endocytosis. The light chain is able to cleave endocytotic vesicles and reach the cytoplasm. The light chain of the toxin has protease activity. The type A toxin proteolytically degrades the SNAP-25 protein, a type of SNARE protein. The SNAP-25 protein is required for vesicle fusion that releases neurotransmitters from the axon endings (in particular acetylcholine).[66] Botulinum toxin specifically cleaves these SNAREs, so prevents neurosecretory vesicles from docking/fusing with the nerve synapse plasma membrane and releasing their neurotransmitters.

Though it affects the nervous system, common nerve agent treatments (namely the injection of atropine and pralidoxime) will increase mortality by enhancing botulin toxin's mechanism of toxicity.[citation needed] Attacks involving botulinum toxin are distinguishable from those involving nerve agent in that NBC detection equipment (such as M-8 paper or the ICAM) will not indicate a "positive" when a sample of the agent is tested. Furthermore, botulism symptoms develop relatively slowly, over several days compared to nerve agent effects, which can be instantaneous.

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