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Questions and Answers
What do cell wall inhibitors selectively interfere with?
What do cell wall inhibitors selectively interfere with?
Synthesis of the bacterial cell wall
What is the cell wall composed of?
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?
Which of these are the most important members of the group of cell wall inhibitors?
Penicillins are among the most widely effective and least toxic drugs known.
Penicillins are among the most widely effective and least toxic drugs known.
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What is the key factor that differentiates penicillins within the same family?
What is the key factor that differentiates penicillins within the same family?
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What does the nature of the side chain (R substituent) affect in penicillins?
What does the nature of the side chain (R substituent) affect in penicillins?
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How do penicillins work?
How do penicillins work?
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Which of the following organisms are NOT effectively treated with penicillin?
Which of the following organisms are NOT effectively treated with penicillin?
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What two factors determine the ability of penicillins to kill bacteria?
What two factors determine the ability of penicillins to kill bacteria?
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Which of the following factors affect the susceptibility of PBPs to penicillins?
Which of the following factors affect the susceptibility of PBPs to penicillins?
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Gram-positive bacteria are easily susceptible to penicillins.
Gram-positive bacteria are easily susceptible to penicillins.
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Gram-negative bacteria are less susceptible to penicillins.
Gram-negative bacteria are less susceptible to penicillins.
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What are porins and how do they allow penicillins to enter some gram-negative bacteria?
What are porins and how do they allow penicillins to enter some gram-negative bacteria?
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How are natural penicillins like penicillin G and penicillin V obtained?
How are natural penicillins like penicillin G and penicillin V obtained?
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How are semisynthetic penicillins, like amoxicillin and ampicillin, created?
How are semisynthetic penicillins, like amoxicillin and ampicillin, created?
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Which of these are β-lactamase (penicillinase)-resistant penicillins?
Which of these are β-lactamase (penicillinase)-resistant penicillins?
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The use of penicillinase-resistant penicillins is restricted to the treatment of infections caused by penicillinase-producing staphylococci.
The use of penicillinase-resistant penicillins is restricted to the treatment of infections caused by penicillinase-producing staphylococci.
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What is MRSA and why is it a significant concern?
What is MRSA and why is it a significant concern?
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Penicillinase-resistant penicillins have significant activity against gram-negative infections.
Penicillinase-resistant penicillins have significant activity against gram-negative infections.
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What is β-lactamase?
What is β-lactamase?
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How does β-lactamase work?
How does β-lactamase work?
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What are the two main types of β-Lactamase?
What are the two main types of β-Lactamase?
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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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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.
