Botox 

 Introduction 

• rod shap, positive anaerobic bacteria 

1gram enough to wipe out the global human population 

first used in history to treat strabismus 

5 types of botulism 

iatrogenic 

food 

wound 

infant 

inhalational 

has two components - toxins and non toxin bacterial protein 

8 serotypes 

A, B, C, D, E, F, G 

Effects 

1. motor cholinergics - skeletal muscle relaxation, wrinkle reduction 

2. motor non cholinergics - hyperhydrisosi 

3. senosry pain reduction - cervical dystonia, migraine

Approved indications and complications 

1. treat glabellar lines 

-when injected into levator palpabral, can cause brow ptosis 

- So/ST damage 

2. lateral canthal lines 

• can cause alteration of smile if chase the line , it is an accessory muscle to cheek elevation. Therefore, overtreating can sometimes make patients look a little sad because they do not achieve the upward pull in their cheek area when smiling.

"migraine 

3. migraine 

4. axillary hyperhydrosis 

5. cervical dystonia 

Mechanism of action 

Normal NMJ 

• Presynaptic neuromuscular nerve ending has vesicle containing acetylcholine. 

• During action potentional, synaptic vesicle fuses with nerve ending membrane at motor end plate. 

• This fusion process is facilitated by SNARE complex 

• Upon fusion, the synaptic vesicle releases into synaptic cleft by exocytosis. 

• Acetylcholine induces muscle contraction. 

SNARE complex is a 4 helix bundle 

1. v snare 

2. t snare 

3. 2 snap-25 

BONT blocks neuromuscular transmission by binding to sites on motor nerve terminals 

BONT cleaves SNAP-25, and blocks acetylcholine release from vesicles within nerve endings 

BONT produces partial chemical dernevation of muscle, resulting in reduced muscle activity 

axonal sprouting occur, extra junctional actylcholine receptor may develop

BONT

 - prevent release of acetylcholine in NMJ preventing muscle contraction 

- prevent release of pain stimulating neuropeptides in peripheral nerves 

Stages in chemical denervation: 

phase i : nerve muscle communication is blocked ( bind, internalize, block)

phase II: nerve muscle communication is restored ( nerve sprouting, nerve connection re0established ) 

SNARE complex 

 In motor neurons, light chain of BONT core moleculre blocks release of acetylcholine by cleaving SNAP-25, which is eeserntial component of SNARE complex. 

When acetylcholine cannot be released, muscle contraction cnanot occur. 

In sensory neurons, light chain is believed to cleave SNAP 25 by blocking release of neuropeptide neurotrasmitters CGRP and reduce pain sensitization of periphral nerves. 

Phase II : Nerve sprouting 

Effect is temporary 

new nerve endings prout and connect to muscle after oroginal nerve ending is blocked, renewing ability of nerve to cause muscle contraction 

Botox toxin inhibit acetylcholine in all para sympathetic and cholnergic postganglionic sympathetic neurons. 

This has generate interest in its use as treatment for overactive smooth muscle or abnormal gland activity.