Cell Wall Inhibitors and Mechanism of Action
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Questions and Answers

What do cell wall inhibitors selectively interfere with?

Synthesis of the bacterial cell wall

What is the cell wall composed of?

A polymer called peptidoglycan

Which of these are the most important members of the group of cell wall inhibitors?

  • Penicillins
  • Vancomycin
  • Daptomycin
  • All of the above (correct)

    • Penicillins are among the most widely effective and least toxic drugs known.

    <p>True (A)</p> Signup and view all the answers

    What is the key factor that differentiates penicillins within the same family?

    <p>The R substituent attached to the 4 member β-lactamas ring</p> Signup and view all the answers

    What does the nature of the side chain (R substituent) affect in penicillins?

    <p>All of the above (E)</p> Signup and view all the answers

    How do penicillins work?

    <p>Penicillins work by stopping bacteria from building strong cell walls, weakening the cell wall, making it prone to bursting, and allowing the bacterial cell to break open and die.</p> Signup and view all the answers

    Which of the following organisms are NOT effectively treated with penicillin?

    <p>Mycobacteria (B), Fungi (D), Protozoa (E), Viruses (F)</p> Signup and view all the answers

    What two factors determine the ability of penicillins to kill bacteria?

    <p>Crossing the bacterial cell wall and reaching the penicillin-binding proteins (PBPs) in the periplasmic space</p> Signup and view all the answers

    Which of the following factors affect the susceptibility of PBPs to penicillins?

    <p>All of the above (D)</p> Signup and view all the answers

    Gram-positive bacteria are easily susceptible to penicillins.

    <p>True (A)</p> Signup and view all the answers

    Gram-negative bacteria are less susceptible to penicillins.

    <p>True (A)</p> Signup and view all the answers

    What are porins and how do they allow penicillins to enter some gram-negative bacteria?

    <p>Porins are water-filled channels in the outer membrane of some gram-negative bacteria. They allow certain antibiotics, including penicillins, to pass through.</p> Signup and view all the answers

    How are natural penicillins like penicillin G and penicillin V obtained?

    <p>They are obtained from fermentations of the fungus Penicillium chrysogenum.</p> Signup and view all the answers

    How are semisynthetic penicillins, like amoxicillin and ampicillin, created?

    <p>They are created by chemically attaching different R groups to the 6-aminopenicillanic acid nucleus.</p> Signup and view all the answers

    Which of these are β-lactamase (penicillinase)-resistant penicillins?

    <p>All of the above (E)</p> Signup and view all the answers

    The use of penicillinase-resistant penicillins is restricted to the treatment of infections caused by penicillinase-producing staphylococci.

    <p>True (A)</p> Signup and view all the answers

    What is MRSA and why is it a significant concern?

    <p>All of the above (D)</p> Signup and view all the answers

    Penicillinase-resistant penicillins have significant activity against gram-negative infections.

    <p>False (B)</p> Signup and view all the answers

    What is β-lactamase?

    <p>β-Lactamase is an enzyme that breaks down the β-lactam ring of certain antibiotics, rendering them ineffective.</p> Signup and view all the answers

    How does β-lactamase work?

    <p>β-Lactamase hydrolyzes the β-lactam ring, resulting in the loss of bactericidal activity of the antibiotic.</p> Signup and view all the answers

    What are the two main types of β-Lactamase?

    <p>Both of the above (C)</p> Signup and view all the answers

    Flashcards

    Cell Wall Inhibitors

    These drugs target the bacterial cell wall, a structure that mammalian cells lack.

    Peptidoglycan

    A polymer found in bacterial cell walls, composed of glycan units linked by peptide cross-links.

    β-Lactam Antibiotics

    A group of antibiotics sharing a common structure. They are known for their broad effectiveness and low toxicity.

    R substituent

    This refers to any modification on the β-lactam ring, influencing their activity against bacteria.

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    How Penicillins Work

    Penicillins inhibit the synthesis of peptidoglycan, weakening the bacterial cell wall.

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    Penicillin Susceptibility

    The ability of penicillins to enter and reach their target within bacteria.

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    Penicillin-Binding Proteins (PBPs)

    Penicillin-Binding Proteins (PBPs) are the targets of penicillins within the bacterial cell.

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    Lipopolysaccharide Membrane

    This refers to the bacteria's outer layer, which may hinder penicillins from reaching their targets.

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    Porins

    Channels within the bacterial cell wall that allow certain molecules, like penicillins, to enter.

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    Natural Penicillins

    Natural penicillins are obtained from the fungus Penicillium chrysogenum.

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    Semisynthetic Penicillins

    Modified forms of penicillins, often with broader activity.

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    Penicillinase-Resistant Penicillins

    This refers to penicillins that can overcome the breakdown caused by β-lactamases.

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    Extended-Spectrum Penicillins

    Penicillins that are particularly effective against gram-negative bacteria.

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    β-Lactamase

    A bacterial enzyme that breaks down the β-lactam ring of certain antibiotics, rendering them ineffective.

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    Decreased Permeability

    This mechanism refers to bacteria's ability to reduce the entry of penicillins.

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    Efflux Pumps

    A mechanism of resistance where bacteria pump out penicillins before they can reach their targets.

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    Altered PBPs

    Modifications in the proteins that penicillins bind to, reducing their effectiveness.

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    Pharmacokinetics

    This refers to the process of how the body handles the drug, including absorption, distribution, metabolism, and excretion.

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    Depot Forms

    Depot forms provide sustained low levels of drug for longer periods.

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    Food Impact on Penicillin Absorption

    Food may interfere with the absorption of penicillinase-resistant penicillins.

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    Distribution of Penicillins

    This refers to the drug's journey from the site of administration to the bloodstream.

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    Adverse Reactions to Penicillins

    Adverse reactions beyond hypersensitivity, including gastrointestinal and neurological effects.

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    Cephalosporins

    A class of antibiotics structurally related to penicillins.

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    Cephalosporin Generations

    Cephalosporins are categorized into generations based on their antimicrobial spectrum and resistance to breakdown.

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    β-Lactamase Inhibitors

    These inhibitors are designed to prevent the breakdown of antibiotics by β-lactamases.

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    Vancomycin

    A powerful glycopeptide antibiotic effective against gram-positive bacteria, including MRSA and certain enterococci.

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    Daptomycin

    A cyclic lipopeptide antibiotic known for its ability to disrupt bacterial cell membranes.

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    Telavancin

    A lipoglycopeptide antibiotic with activity against gram-positive bacteria, including MRSA.

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    Fosfomycin

    A phosphonic acid antibiotic used to treat urinary tract infections and some uncomplicated skin infections.

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    Polymyxins

    Polypeptide antibiotics that disrupt bacterial cell membrane function.

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    Importance of Cell Wall Inhibitors

    Cell wall inhibitors have a significant role in treating bacterial infections, particularly in the face of rising resistance.

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    Study Notes

    Cell Wall Inhibitors

    • Cell wall inhibitors are antimicrobial drugs that target bacterial cell walls.
    • Mammalian cells lack cell walls, making these drugs effective against bacteria.
    • Peptidoglycan is the bacterial cell wall polymer, composed of glycan chains linked by peptide cross-links.
    • β-lactam antibiotics, vancomycin, and daptomycin are critical cell wall inhibitors.
    • Penicillins are a key group within β-lactams, differing in R substituents affecting their antimicrobial spectrum, stability, and susceptibility to bacterial enzymes.

    Mechanism of Action

    • Penicillins halt bacterial cell wall construction.
    • Weakening the cell wall makes it vulnerable to bursting.
    • This mechanism is efficient against bacteria with weak cell walls and rapidly growing bacteria.
    • However, penicillins are ineffective against mycobacteria (like TB), protozoa, fungi, and viruses.

    Antibacterial Spectrum

    • Penicillins' antibacterial potency depends on crossing the bacterial cell wall and accessing penicillin-binding proteins (PBPs) in the periplasmic space.
    • Factors influencing susceptibility include antibiotic size, charge, and hydrophobicity.

    Gram-Positive vs. Gram-Negative Bacteria

    • Gram-positive bacteria are generally more susceptible to penicillins, due to their simpler cell walls.
    • Gram-negative bacteria, having an outer lipopolysaccharide membrane, show reduced susceptibility.
    • Some gram-negative bacteria possess porins, facilitating penicillin entry.
    • Natural penicillins like penicillin G and V originate from fungal fermentations.

    Antistaphylococcal Penicillins

    • Methicillin, nafcillin, oxacillin, and dicloxacillin are penicillinase-resistant penicillins, effective against penicillinase-producing staphylococci (e.g., MRSA).
    • Their use is restricted, as some strains are resistant.

    Extended-Spectrum Penicillins

    • Ampicillin and amoxicillin have broader activity against gram-negative bacteria.
    • They treat ailments like gram-positive bacillus Listeria monocytogenes infections and susceptible enterococcal species.
    • Their use may include respiratory infections and prophylactic use in dentistry.

    Antipseudomonal Penicillins

    • Piperacillin and ticarcillin specifically target Pseudomonas aeruginosa and other gram-negative bacilli.
    • These are administered parenterally (intravenously or intramuscularly) only, given their potency and limitations.
    • A combination with clavulanic acid or tazobactam broadens their spectrum to encompass penicillinase-producing organisms.

    β-lactamase

    • β-lactamase is an enzyme that deactivates β-lactam antibiotics.
    • It hydrolyzes the β-lactam ring, rendering the antibiotic ineffective.
    • β-lactamase types include constitutive (produced by the bacterial chromosome) and acquired (obtained through plasmid transfer).

    Decreased Permeability to the Drug

    • Reduced penetration of the antibiotic through the bacterial outer membrane limits access to its target (PBPs).
    • The presence of bacterial efflux pumps can diminish intracellular drug concentrations.
    • Altered PBPs exhibit decreased affinity to β-lactams, necessitating higher concentrations for effective inhibition.

    Pharmacokinetics

    • Administration routes of β-lactams depend on their stability to stomach acid and the infection's severity.
    • Some penicillins (e.g., piperacillin with tazobactam, nafcillin) require intravenous or intramuscular administration.
    • Oral administration is restricted to certain penicillins, such as penicillin V and amoxicillin.

    Absorption of Penicillins

    • Many penicillins are partially absorbed orally, with unabsorbed portions affecting intestinal flora.
    • Food diminishes penicillinase-resistant penicillin absorption due to delayed gastric emptying and increased drug exposure to stomach acid.

    Distribution & Metabolism

    • Penicillins typically distribute widely throughout the body, crossing the placental barrier without teratogenic effects.
    • They have limited penetration into bone, cerebrospinal fluid (unless inflamed), and the prostate.
    • Host metabolism of penicillins is usually insignificant, but some penicillin G metabolism may occur in patients with renal impairment.

    Excretion of Penicillins

    • The primary route of excretion is through the kidneys into the urine.
    • Secondary routes include bile, saliva, and sweat.

    Adverse Reactions

    • Penicillins can cause hypersensitivity reactions.
    • Gastrointestinal symptoms like nausea, vomiting, and diarrhea can also occur.
    • Neurological effects including seizures (high doses), confusion, and hallucinations are rare adverse reactions. ,

    Cephalosporins

    • Structurally and functionally related to penicillins, affecting bacterial cell wall synthesis similarly.
    • Cephalosporins are classified into generations based on their antibacterial spectrum and resistance to β-lactamases.
    • They generally work against gram-positive bacteria, but their capability varies between generations.

    Vancomycin

    • A glycopeptide antibiotic targeting bacterial cell wall synthesis.
    • Effective against gram-positive bacteria, including MRSA and enterococci.
    • Administered intravenously or orally for specific infections like C. difficile.
    • Resistance is increasing, especially among enterococci.

    Daptomycin

    • A cyclic lipopeptide antibiotic targeting bacterial cell membrane function.
    • Works against gram-positive bacteria including MRSA and vancomycin-resistant strains.
    • Administered intravenously only.

    Telavancin

    • Lipoglycopeptide antibiotic targeting bacterial cell wall synthesis and membrane function.
    • Has wide effectiveness against gram-positive bacteria.
    • Vancomycin-susceptible strains.
    • Administered intravenously for complicated skin and skin structure infections.

    Fosfomycin

    • Phosphonic acid antibiotic inhibiting bacterial cell wall synthesis.
    • Broad-spectrum against both gram-positive and gram-negative bacteria.
    • Used to treat urinary tract infections.

    Polymyxins

    • Polypeptide antibiotics disrupting bacterial cell membrane function.
    • Effective against gram-negative bacteria, especially Pseudomonas aeruginosa and multidrug-resistant strains.
    • Administered intravenously, via inhalation, or topically, used for severe infections (e.g., pneumonia, sepsis).

    Conclusion

    • Cell wall biosynthesis inhibitors are a historically important class of antibiotics.
    • Their effectiveness stems from targeting bacterial cell walls.
    • β-lactams and glycopeptides represent significant examples within this class.

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    Cell Wall Inhibitors - BS (Surgical Technology) PDF

    Description

    This quiz covers the importance of cell wall inhibitors, particularly penicillins, and their mechanisms in targeting bacterial cells. It discusses the structure of bacterial cell walls, the role of β-lactam antibiotics, and the spectrum of antibacterial activity. Understand how these drugs effectively combat infections while considering their limitations against certain pathogens.

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