Pmoc semis lesson 9

• Local Anti-infectives


  Drugs used to treat infections at specific sites without affecting the body's overall immune system
• Cell Wall Synthesis Inhibitors


  1. Agents such as beta-lactam antibiotics interfere with bacterial cell wall synthesis by inhibiting enzymes involved in the formation of peptidoglycan

  2. Glycopeptide antibiotics interfere with cell wall synthesis by binding to the D-alanyl-D-alanine terminus of cell wall precursors, preventing their incorporation into the peptidoglycan layer
• Protein Synthesis Inhibitors


  1. Aminoglycoside antibiotics bind to the 30S ribosomal subunit of bacterial ribosomes, leading to misreading of mRNA and inhibition of protein synthesis

  2. Tetracycline antibiotics bind to the 30S ribosomal subunit, inhibiting the binding of aminoacyl-tRNA to the mRNA-ribosome complex, thereby preventing protein synthesis

  3. Macrolide antibiotics bind to the 50S ribosomal subunit, inhibiting translocation and elongation during protein synthesis
• Nucleic Acid Synthesis Inhibitors


  1. Quinolone antibiotics interfere with bacterial DNA gyrase and topoisomerase IV, enzymes involved in DNA replication, transcription, and recombination

  2. Rifamycin antibiotics inhibit bacterial RNA polymerase, thereby blocking transcription and synthesis of RNA
• Other Mechanisms


  • Antifungal agents disrupt fungal cell membrane integrity by inhibiting ergosterol synthesis or targeting cell wall synthesis
  • Antiviral agents may act by inhibiting viral entry into host cells, blocking viral replication, or interfering with viral protein synthesis
• Viruses


  Obligate intracellular parasites, meaning they require a host cell to replicate and produce more virus particles

  
• Antibacterials


  • Polymyxins and Bacitracin exert their antibacterial effects by disrupting bacterial cell membranes
  • The importance of lipophilic and hydrophilic balance for membrane interaction and disruption lies in their ability to effectively target and interact with the bacterial cell membrane, leading to destabilization and eventual cell death
• Lipophilicity


  • The affinity of a molecule for lipid or fat-based structures
  • Lipophilic antibacterial agents can readily penetrate the lipid bilayer of the bacterial membrane, allowing them to reach their target sites within the cell membrane or cytoplasm more efficiently
  • The lipophilic nature of these agents facilitates their ability to disrupt membrane integrity by inserting into the lipid bilayer, causing destabilization and leakage of intracellular contents
• Hydrophilicity


  • The affinity of a molecule for water or aqueous environments
  • Hydrophilicity plays a crucial role in maintaining solubility and dispersibility of the antibacterial agent in physiological fluids or topical formulations allowing for effective delivery and distribution to the site of infection
  • Hydrophilic properties can also influence the extent of interaction with water-soluble components of the bacterial membrane, contributing to the overall antibacterial activity
• Optimal Balance


  • Achieving an optimal balance between lipophilicity and hydrophilicity is crucial for maximizing the efficacy and safety of antibacterial agents
  • Excessive lipophilicity without sufficient hydrophilicity may lead to poor solubility, limited bioavailability, or potential toxicity
  • Conversely, excessive hydrophilicity may compromise the ability of the antibacterial agent to penetrate the bacterial membrane efficiently, reducing its overall efficacy
• Polymyxins


  • Cyclic polypeptide antibiotics that exhibit both lipophilic and hydrophilic properties, allowing them to interact with and disrupt the bacterial cell membrane effectively

  
• Bacitracin


  • A hydrophilic peptide antibiotic that inhibits bacterial cell wall synthesis by interfering with the dephosphorylation of the lipid carrier molecule involved in peptidoglycan precursor transport across the cell membrane
• Antifungals


  • Target fungal cell membranes, exerting their fungicidal or fungistatic effects by disrupting membrane integrity
  • The molecular structure of these antifungals plays a crucial role in their ability to interact selectively with fungal cell membranes while sparing mammalian cell membranes
• Amphipathic Nature


  • Many antifungal agents possess an amphipathic structure, meaning they have both hydrophilic and hydrophobic regions within the same molecule
  • This amphipathic nature allows antifungal agents to interact with the lipid bilayer of fungal cell membranes, which consists of phospholipids and sterols such as ergosterol
• Sterol Binding


  • Many antifungal agents specifically target ergosterol, a sterol unique to fungal membranes
  • Antifungal agents may contain sterol-binding domains or structural motifs that allow them to interact selectively with ergosterol, disrupting its function or causing structural damage to the membrane
• Specificity for Fungal Membranes


  • The molecular structure of antifungal agents often confers specificity for fungal membranes over mammalian cell membranes
  • Differences in membrane composition, particularly the presence of ergosterol in fungal membranes versus cholesterol in mammalian membranes, contribute to the selective targeting by antifungal agents

  
• Mechanisms of Action


  Once bound to fungal membranes, antifungal agents can exert their effects through various mechanisms, including membrane disruption, alteration of membrane permeability, or interference with membrane-associated enzymes or transporters
• Structural modifications in antiviral agents


  Can play a significant role in enhancing specificity for viral enzymes or replication processes, thereby improving their efficacy while minimizing off-target effects
• Targeting Viral Enzymes


  1. Many antiviral agents target specific viral enzymes essential for viral replication, such as viral polymerases, proteases, or integrases

  2. Structural modifications can be introduced to the antiviral agent to enhance its binding affinity and specificity for the active site of the viral enzyme
• Acyclovir


  • Used to treat infections caused by the herpes simplex virus (HSV), including genital herpes, cold sores (oral herpes), and shingles (herpes zoster)
  • Works by interfering with the replication of the virus, thereby reducing the severity and duration of symptoms
  • Enters cells infected with HSV or VZV through passive diffusion
  • Once inside the infected cell, acyclovir is phosphorylated by viral thymidine kinase to form acyclovir monophosphate
  • By interfering with viral DNA synthesis, acyclovir prevents the replication of herpesviruses
• Preservatives


  • Purpose: To prevent contamination and growth of microorganisms in pharmaceuticals, cosmetics, and food products
  • Common Preservatives: Alcohols, Phenolics, Quaternary Ammonium Compounds, Parabens
• Alcohols (Ethanol, Isopropanol)


  • Ethanol and isopropanol are both alcohols commonly used as antiseptics and disinfectants due to their antimicrobial properties
  • The relationship between chain length (molecular structure) and antimicrobial activity in alcohols can be explained by their ability to disrupt microbial cell membranes and denature proteins
• Molecular Size


  Generally, longer chain alcohols like cetyl and stearyl alcohols have larger molecular sizes. This affects their ability to penetrate microbial cell walls. Short
• Acyclovir


  Antiviral drug that is phosphorylated by viral thymidine kinase to form acyclovir monophosphate, which is essential for its antiviral properties
• Acyclovir mechanism of action

  1. Phosphorylation by viral thymidine kinase

  2. Formation of acyclovir monophosphate

  3. Interferes with viral DNA synthesis

  4. Prevents replication of herpesviruses
• Preservatives


  Substances added to pharmaceuticals, cosmetics, and food products to prevent contamination and growth of microorganisms
• Common preservatives


  • Alcohols
  • Phenolics
  • Quaternary Ammonium Compounds
  • Parabens
• Alcohols (Ethanol, Isopropanol)


  • Antimicrobial properties due to ability to disrupt microbial cell membranes and denature proteins
  • Shorter chain alcohols like ethanol and isopropanol can easily penetrate bacterial and fungal cell walls
• Molecular size of alcohols

  Longer chain alcohols have larger molecular sizes, affecting their ability to penetrate microbial cell walls
• Hydrophobicity of alcohols


  Longer chain alcohols are more hydrophobic, enhancing their ability to disrupt microbial cell membranes
• Microbial susceptibility to alcohols

  Ethanol and isopropanol are effective against a broad spectrum of bacteria, fungi, and some viruses
• Ethanol


  Produced by fermentation of sugars, used as a solvent, fuel additive, antiseptic, and disinfectant
• Isopropyl Alcohol (IPA)


  Typically produced from propene, used as a solvent, antiseptic, and disinfectant
• Phenolics (Phenol, Cresols)


  • Aromatic compounds with one or more hydroxyl groups, position and number of hydroxyl groups impact antibacterial potency and toxicity
  • Ortho-substituted phenolics tend to be more effective as antimicrobial agents
  • Compounds with multiple hydroxyl groups (polyphenolics) generally exhibit increased antibacterial potency
• Toxicity of phenolics


  Increased antibacterial potency is often associated with increased toxicity, as mechanisms of action can also lead to toxicity in mammalian cells
• Quaternary Ammonium Compounds (Benzalkonium Chloride)

  • Widely used as disinfectants and antiseptics, longer alkyl chains enhance ability to disrupt microbial cell membranes and other cellular structures
• Parabens


  • Antimicrobial preservatives used in cosmetics, pharmaceuticals, and food products
  • Balance between water solubility and lipophilicity is crucial for effective antimicrobial activity while maintaining safety and stability
  • Water solubility allows even distribution and effectiveness against waterborne microorganisms
  • Lipophilicity enables penetration of microbial cell membranes
• Some studies have suggested a potential link between parabens and certain health concerns, including cancer, due to their ability to mimic estrogen
• Parabens have been detected in human tissues, including breast tissue, leading to concerns about their potential to mimic estrogen and promote the growth of some types of breast cancer cells
• The presence of parabens in breast cancer tumors does not necessarily mean they caused the cancer