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General Description:

Tyrothricin, identified by CAS number 1404-88-2, is a notable compound with significant therapeutic applications. Tyrothricin is an antibiotic peptide complex produced and extracted from the aerobic Gram-positive bacillus Brevibacillus parabrevis which was previously categorized as Bacillus brevis and Bacillus aneurinolyticus . This complex is a mixture comprised of 60% tyrocidine cationic cyclic decapeptides (consisting largely of the six predominant tyrocidines, TrcA/A1, TrcB/B1, TrcC/C1, and other more minor contributors) and 40% neutral linear gramicidins (where valine-gramicidin A is often the major gramicidin present, although the mixture composition can vary) . Moreover, tyrothricin possesses broad spectrum Gram-positive antibacterial and antifungal activity that has not seen many - if any - significant reportings of microbial resistance during the over 60 years of therapeutic use the complex has provided . Nevertheless, as tyrothricin is both cytolytic and hemolytic, it does demonstrate systemic toxicity , although certain formulations that are safe for human use like throat lozenges do exist .

Indications:

This drug is primarily indicated for: Tyrothricin is used as an over the counter topical antibiotic. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Absorption:

The absorption characteristics of Tyrothricin are crucial for its therapeutic efficacy: The lack of water solubility prevents absorption of tyrothricin through the skin. It is not used through other routes due to toxicity concerns . The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Pharmacodynamics:

Tyrothricin exerts its therapeutic effects through: Tyrothricin consists of a mix of tyrocidines and gramcidins which exert a bacteriocidal effect. This clears the area of pathogenic bacteria to allow the body to heal wounds or other damage to the skin. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Tyrothricin functions by: Tyrocidines have a β-sheet structure containing both L and D amino acids . These structural features contribute to the formation of a curved dimer in which most amino acid side chains are located on the convex surface. The dimer orients itself at the membrane-water interface on bacterial cells with the relatively hydrophilic back-bone on the concave side facing the external environment and the many hydrophobic side chains on the convex side facing into the cell's lipid bilayer. The tyrocidine dimer is able to disrupt the cell membrane producing leakage of cell contents but the exact mechanism of this permeabilization is unclear. Tyrocidines appear to act as reversible non-competitive inhibitors of acetylcholinesterase and β-galactosidase . The relation of this to their antibacterial action is unknown. Gramcidins adopt similar β-sheet structures but are capable of forming β-helices . They can either form a double helix, running either parallel or anti-parallel, or a helical dimer wherein the N-termini of each polypeptide meets in the middle of the lipid bilayer. The alternating L and D amino acid structure allows the hydrophobic side chains to point outwards into the lipid bilayer, leaving the more hydrophilic backbone to form the lumen of the pore. The carbonyl oxygen atoms aid in the transport of cations through the pore. In both double helix and helical dimer conformations, gramcidins are capable of transporting monovalent cations through the membrane. Divalent cations result in blockage of the pore or channel when bound. Loss of potassium ions through membrane permeabilization seems to inhibit bacterial growth. Gramcidin also appears to be able to insert into the mitochondial membrane and conduct hydrogen ions . This results in an uncoupling of oxidative phosphorylation from ATP generation due to the loss of the hydrogen ion gradient necessary for H+ATPase function. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Categories:

Tyrothricin is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Anti-Bacterial Agents, Anti-Infective Agents, Anti-Infective Agents, Local, Antibiotics for Topical Use, Cholinesterase Inhibitors, Dermatologicals, Ophthalmologicals, Peptides, Peptides, Cyclic, Sensory Organs, Throat Preparations. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Tyrothricin include:

• Water Solubility: Insoluble