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	<title>Pharmacology of Botulinum toxin and its therapeutic uses - Revision history</title>
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		<title>Drtbalu: Created page with &quot;  Category:Laryngology  === Introduction:===  German physician Justinus kerner was the first to conceive the therapeutic uses of botulinum toxin.  He also coined the term...&quot;</title>
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		<updated>2018-10-23T05:03:15Z</updated>

		<summary type="html">&lt;p&gt;Created page with &amp;quot;  &lt;a href=&quot;/index.php/Category:Laryngology&quot; title=&quot;Category:Laryngology&quot;&gt;Category:Laryngology&lt;/a&gt;  === Introduction:===  German physician Justinus kerner was the first to conceive the therapeutic uses of botulinum toxin.  He also coined the term...&amp;quot;&lt;/p&gt;
&lt;p&gt;&lt;b&gt;New page&lt;/b&gt;&lt;/p&gt;&lt;div&gt;&lt;br /&gt;
&lt;br /&gt;
[[Category:Laryngology]]&lt;br /&gt;
&lt;br /&gt;
=== Introduction:===&lt;br /&gt;
&lt;br /&gt;
German physician Justinus kerner was the first to conceive the therapeutic uses&lt;br /&gt;
of botulinum toxin.  He also coined the term &amp;quot;sausage poison&amp;quot; to indicate the toxigenic&lt;br /&gt;
nature of Botulinum.&lt;br /&gt;
&lt;br /&gt;
Botulinum toxin type A has been used as a therapeutic agent to treat:&lt;br /&gt;
&lt;br /&gt;
1. Focal dystonias of head and neck&lt;br /&gt;
&lt;br /&gt;
2. Spasmodic dysphonia&lt;br /&gt;
&lt;br /&gt;
3. Oromandibular dystonia&lt;br /&gt;
&lt;br /&gt;
4. Cervical dystonia&lt;br /&gt;
&lt;br /&gt;
5. Intractable cervical pain&lt;br /&gt;
&lt;br /&gt;
6. Cricopharyngeal dysphagia&lt;br /&gt;
&lt;br /&gt;
7. Gustatory sweating&lt;br /&gt;
&lt;br /&gt;
8. Hyperhiderosis&lt;br /&gt;
&lt;br /&gt;
9. Blepharospasm&lt;br /&gt;
&lt;br /&gt;
10. To treat wrinkles of face&lt;br /&gt;
&lt;br /&gt;
11. Achalasia cardia&lt;br /&gt;
&lt;br /&gt;
12 Paediatric incontinence due to over active bladder&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The basis of using this drug as a therapeutic agent is based on its ability&lt;br /&gt;
to locally block exocytosis from neurons there by blocking the release of&lt;br /&gt;
acetyl choline. Hence this chemical belongs to the neuro toxin group.&lt;br /&gt;
&lt;br /&gt;
=== Secretion of Botulinum toxin: ===&lt;br /&gt;
&lt;br /&gt;
This toxin is synthesized and secreted by a variety of neurotoxigenic C. botulinum.&lt;br /&gt;
Clostridium.  The neurotoxigenic C. Botulinum are divided into 4 groups depending on the&lt;br /&gt;
type of toxin they secrete.  Seven different botulinum neurotoxin serotypes have been identified.&lt;br /&gt;
&lt;br /&gt;
Types of C. Botulinum:&lt;br /&gt;
&lt;br /&gt;
GroupI: This group synthesizes botulinum toxin serotypes A,B and F&lt;br /&gt;
&lt;br /&gt;
Group II: Organisms synthesize serotypes B,E, and F&lt;br /&gt;
&lt;br /&gt;
Group III: Organisms synthesize serotypes C and D&lt;br /&gt;
&lt;br /&gt;
Group IV: Organisms synthesize serotype G&lt;br /&gt;
&lt;br /&gt;
Molecular structure of Botulinum neurotoxin:&lt;br /&gt;
&lt;br /&gt;
These neurotoxins are synthesized as 150 kDa single chain protein molecules.  These molecules&lt;br /&gt;
when secreted are inert and must be cleaved by proteases for them to become active.  These neurotoxin&lt;br /&gt;
botulinum molecule when acted upon by proteases generates a dichain molecule.  This dichain molecule is composed of a heavy chain about 100 kDa  and a light chain which measures about 50 kDa.  These two chains are held together&lt;br /&gt;
by disulfide bond.&lt;br /&gt;
&lt;br /&gt;
The active di-chain molecule is made up of the following functional domains:&lt;br /&gt;
&lt;br /&gt;
1. Binding domain at the C terminal portion of heavy chain&lt;br /&gt;
&lt;br /&gt;
2. Translocation domain at the N-terminal portion of the heavy chain&lt;br /&gt;
&lt;br /&gt;
3. Catalytic domain at the N -terminal portion of light chain&lt;br /&gt;
&lt;br /&gt;
=== Mechanism of action: ===&lt;br /&gt;
&lt;br /&gt;
1. Inhibits calcium dependent neurotransmitter exocytosis.  This is a multistep process.&lt;br /&gt;
&lt;br /&gt;
2. Inhibits release of acetyo choline at the neuromuscular junction&lt;br /&gt;
&lt;br /&gt;
3. Inhibits neurotransmitter release from gamma motor neurons - This can lead to temporary atrophy of muscle fibers.&lt;br /&gt;
&lt;br /&gt;
4. Exhibits antinociceptive action by inhibiting peripheral sensory nerve sensitization to pain&lt;br /&gt;
&lt;br /&gt;
Botulinum toxin binds to the neuronal cells, exclusively to cholinergic neurons.  On binding the botulinum&lt;br /&gt;
toxin is translocated into the neuronal cytosol by a process known as endocytosis.  On reaching the cytosol&lt;br /&gt;
of the neurons, it blocks the release of acetylcholine by closing down the calcium channels.  It has been&lt;br /&gt;
shown that the duration of action of Serotype A is the longest when compared with that of other serotypes.&lt;br /&gt;
&lt;br /&gt;
The effects of Botulinum toxin on the neurotransmitter release is reversible and hence reinjections are necessary&lt;br /&gt;
to sustain the beneficial effects of the drug.  Neurons recover from the effects of botulinum toxin by:&lt;br /&gt;
1. Sprouting of nerve endings - causing temporary re-innervation during early recovery phase&lt;br /&gt;
&lt;br /&gt;
2. Increase in turnover of acetylcholine vesicles with retraction of neuronal sprouts - occurs during late recovery phase.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
=== Uses of Botulinum toxin: ===&lt;br /&gt;
&lt;br /&gt;
1. Due to its blocking effects on the release of acetylcholine it is very useful in the managment of cervical dystonia,&lt;br /&gt;
spasmodic dysphonia, oro mandibular dystonia and Gustatory sweating.&lt;br /&gt;
&lt;br /&gt;
2. It may be used for providing pain releif in patients with cervical dystonia, head ache, migraine and back ache.  This&lt;br /&gt;
effect is produced due to the ability of botulinum toxin to inhibit peripheral sensory nerve sensitization to pain.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
=== Adverse effects: ===&lt;br /&gt;
&lt;br /&gt;
Most common adverse effect caused by this drug is dryness of mouth&lt;/div&gt;</summary>
		<author><name>Drtbalu</name></author>
		
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