Neuromuscular Transmission and Botox

This assignment delves into the complex process of neuromuscular transmission, focusing on the role of acetylcholine receptors and SNARE proteins. It then explores how botulinum toxin disrupts this process, leading to muscle paralysis. The document examines the therapeutic uses of botulinum toxins in conditions like myofascial pain and facial synkinesis, as well as its application in cosmetic procedures for wrinkle reduction. Finally, it discusses potential complications associated with botulinum toxin injections.

Running head: ANESTHETICS
ANESTHETICS
Name of the Student
Name of the University
Author note

1ANESTHETICS
Table of Contents
Answer a:.............................................................................................................................2
Answer b:.............................................................................................................................2
Answer c:.............................................................................................................................4
Answer d:.............................................................................................................................5
Answer e:.............................................................................................................................6
Answer f:.............................................................................................................................7
REFERENCES:...................................................................................................................8

2ANESTHETICS
Answer A:
The stages of neuromuscular synaptic transmission can be summarized as follows (1): a)
The action potential reaches the presynaptic membrane (2). This opens the voltage gated calcium
channels, causing the influx of Ca2+ ions. b) The secretory vesicles are excited, and exocytosis
occurs, releasing acetylcholine into the synapse. c) Acetylcholine binds to the ligand
/neurotransmitter gated channel on the post synaptic membrane. d) This causes influx of Na+ and
efflux of K+ ions, resulting in depolarization of membrane (change from -70mV to +30mV inside
the cell). e) Once the threshold potential is achieved, other voltage gated channels across the
membrane are opened. f) Ca2+ is released from the terminal cisternae of smooth ER that binds to
troponin, inhibits tropomyosin and exposes active site of actin. g) Myosin pulls the actin filament
towards the centre of sarcomere, and contraction occurs (3).
Botulin toxin can cleave key proteins that take part in neuronal activation (4). The toxin
binds to the presynaptic neurons that has acetylcholine transmitters, and is taken up into a vesicle
inside the cytosol and then cleavs the SNARE protein (5). This prevents the release of the
neurotransmitter, causing paralysis
Botulin toxin is a two chain protein (Heavy chain: 100kDa and Light chain: 50kDa) and
disulfide bond joins them. Based on the structure and sequence of the chain, it can be of the
following types: A, B, C1, C2, D, E, F, and G (6).

3ANESTHETICS
Answer B:
Common botulinum toxin type A brands: Botox (Vistabel), Xeomin (Bocouture) and
Dysport (Azzalure). These neurotoxins cleave SNAP-25 protein needed for the docking and
release of secretory vesicles containing acetylcholine.
Xeomin contains no additives, and is pure injectible (7). This greatly reduces the chances
of developing immunity against it. Also, it does not require refrigeration (8).
Volume of preservative
free 0.9% NaCl
50 unit vial: Resulting
dose per 0.1 mL
100 unit vial: Resulting
dose per 0.1 mL
0.25 mL 20 units --
0.5 mL 10 units 20 units
1 mL 5 units 10 units
2 mL 2.5 units 5 units
4 mL 1.25 units 2.5 units
8 mL -- 1.25 units
[Source: FDA]
Dysport contains human albumin, and the recommended dose frequency should not be
exceeded (9).
Dilutent per 500
unit vial
Resulting dose
units per 0.1 mL
Dilutent per 300
unit vial
Resulting dose
units per 0.1 mL
1 mL 50 units 0.6 mL 50 units
2 mL 25 units -- --
2.5 mL 20 units 1.5 mL 20 units
-- -- 2.5 mL 12 units

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5 mL 10 units 3 mL 10 units
.[Source: FDA]
Botox also contains human albumin. Dosage is in form of single use, sterile 50/ 100/ 200
units of vacuum dried powder with 0.9% NaCl Injection, USP (non preserved and sterile).
Diluten
t added to 50
unit vial
Resulti
ng dose units
per 0.1 mL
Diluten
t added to 100
unit vial
Resulti
ng dose units
per 0.1 mL
Dilute
nt added to 200
unit vial
Resulti
ng dose units
per 0.1 mL
1 mL 5 units 1 mL 10
units
1 mL 20
units
2 mL 2.5
units
2 mL 5 units 2 mL 10
units
4 mL 1.25
units
4 mL 2.5
units
4 mL 5 units
8 mL 1.25
units
8 mL 2.5
units
10 mL 2 units
[Source: FDA]
Answer C:
Botulinum toxin administration for reducing glabellar, forehead, periocular and perioral
lines are associated with few complications (10). The most common Complications of botox
injections include: ptosis (2% occurrence) (drooping of eyelid), Keratitis (inflammation of

5ANESTHETICS
cornea). Additional complications like: pruritus, abdominal pain, brachial plexopathy, blurred
vision, reduced hearing, diarrhea, ringing of ears, focal facial paralysis, malaise, myaglia,
glaucoma, localized numbness, myasthenia gravis, sweating, syncope, retinal vein occlusion,
erythema multiforme, vertigo, vomiting, psoriasiform eruption, and loss of appetite. Patients with
pre existing breathing or swallowing problems are especially vulnerable to these complications.
Risk of ptosis can be lowered by: a) Desist injection in areas adjoining levator palpebrae
superioris (especially for patients having larger bow depressor complexes). b) Lateral corrugators
injection 1 cm above the supraorbital. c) Administering minimally accurate dosage. d) Avoiding
injections less than 1cm above central eyebrow. Ecchymosis can be averted by the application of
compression at the injection site, post injection. Bruising, pain and pruritus can be avoided by
slow and precise injections, and applying cold compress after injecting. Proper skin preparation
with antiseptics can prevent infections and development of biofilms or erythematous nodules.
Imperfections due to superficial placement of product can be managed by Local massage,
aspiration and using hyaluronidase.
Answer D:
The facial anatomy includes the ensuing components. The superficial fat compartments
comprised of: naso labial compartment, medial, middle, and latral-temporal-cheek fat pads, and
superior, inferior, lateral orbital fat pads. The superficial musculoaponeuric system (SMAS) -
this is a collagenous network containing fat cells and elastic fibers connecting the dermis to the
mimetic muscles, and is vital for facial expression. Retaining ligaments connects the underlying
periosteum to dermis. For example: Zygomatic, lateral orbital thickening and orbicularis
retaining ligament, Masseteric ligaments, Platysma-auricular ligament. Mimetic muscles include

6ANESTHETICS
the muscles for facial expression. They include: Supercilii, Frontalis, Corrugator, Depressor
Orbicularis Oculi and Procerus representing periorbital facial muscles. Levator muscle,
Zygomaticus major & minor, risorius, depressor anguli oris, orbicularis oris, depressor labii, and
mentalis representing the perioral muscles. Compressor naris, Depressor septi and Dilator naris,
representing nasal group. Nerves innervating the face include the seventh cranial nerve (Facial
nerve) providing motor control to the facial muscles. The nerve divides into temporal,
Zygomatic, buccal, marginal mandibular and cervical branches in the parotid gland. The sensory
nerve innervations to the face are via three branches of fifth cranial nerve (Trigeminal nerve):
ophthalmic, maxillary, and mandibular. Facial arteries include external carotid artery that
innervates the facial skin and tissues via facial, maxillary, and superficial temporal arteries. The
central forehead, eyelids, upper part of nose through internal carotid system via ophthalmic
arteries (11).
Answer E:
Contradictions to botulinum treatment are applicable in the following cases: a) patients
having a history of hypersensitivity to any type of botulinum toxin preparation or any
components in the formulation. b) Patients suffering from infection at the proposed site of
injection. c) Patients suffering from infection of the urinary tract or urinary retention. The
hypersensitive reaction can include: anaphylaxis, urticaria, serum sickness, dyspnea and soft
tissue edema. Administration of botulinum toxoid should be discontinued in such cases.
Botulinum treatment or administration is mainly directed towards treating various facial
lines that is caused due to the ageing process. The toxin paralyses the muscles that are
responsible for the ageing lines, thereby removing those lines. For example: Glabellar facial and

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frown lines, horizontal lines or pleats, lateral orbital lines, peri oral lines, marionette lines and
chin dents. Consequently, usage of botulinum toxoid is prevalent among individuals who would
like to hide the ageing process as it shows on the face for professional or personal preferences.
Therefore relevance to the patient’s occupation is rather limited, as far as the treatment goes.
Facial asymmetries (temporary and permanent) and spasms can also be treated by
botulinum toxin. This is generally done by injections into opposite functioning frontalis muscles
of patients with unilateral frontal nerve paralysis. Contra lateral hypertrophy can also cause facial
asymmetry. Such condition can be treated with Botox A injection (13).
Answer F:
Facial wrinkles are are particularly formed in those areas subjected to repeated
movements of facial muscles (14). It can cause 2 types of wrinkles:
Static wrinkling: these are caused due to the loss of skin elasticity. This is caused when
the skin’s collagen breaks, and laxation of tissues occur. Genetics, poor diet, smoking, can
accelerate this process. Examples: lines in the corner of mouth and along cheeks, neck wrinkles.
These can be smoothened by using dermal fillers like Restylane, Juvederm, and Radiesse. They
comprise of hyaluronic acid, and it boosts collagen production in the body.
Dynamic wrinkling: these are facial creases and wrinkles caused due to repetitive
movements of muscles. Example: continued squinting, worrying, frowning, and smiling that can
cause deep lines on the skin. They can develop into: frown lines, forehead wrinkles, crow’s feet.
It can be treated by botox injection. Since it paralyzes the local muscles, that underlie the
wrinkles, it can make them smooth.

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