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Questions and Answers
What is the primary mechanism through which β-lactam antibiotics induce bacterial cell death?
What is the primary mechanism through which β-lactam antibiotics induce bacterial cell death?
Which structure is essential for the function of β-lactam antibiotics?
Which structure is essential for the function of β-lactam antibiotics?
What distinguishes penicillins from other β-lactam antibiotics?
What distinguishes penicillins from other β-lactam antibiotics?
How do β-lactam antibiotics achieve their bactericidal effect?
How do β-lactam antibiotics achieve their bactericidal effect?
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What is the role of transpeptidases in bacterial cell wall synthesis?
What is the role of transpeptidases in bacterial cell wall synthesis?
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Which of the following penicillins is not susceptible to inactivation by β-lactamases?
Which of the following penicillins is not susceptible to inactivation by β-lactamases?
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What is the main difference between Penicillin G and Penicillin V?
What is the main difference between Penicillin G and Penicillin V?
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Which of the following conditions is NOT indicated for the treatment with natural penicillins?
Which of the following conditions is NOT indicated for the treatment with natural penicillins?
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Which penicillin derivative is effective for prolonged treatment in syphilis?
Which penicillin derivative is effective for prolonged treatment in syphilis?
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What characteristic primarily differentiates aminopenicillins from natural penicillins?
What characteristic primarily differentiates aminopenicillins from natural penicillins?
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Study Notes
Inhibitors of Cell Wall Synthesis
- Beta-lactams are the main group of antibiotics that target bacterial cell walls.
- They work by irreversibly inhibiting enzymes involved in the final stages of cell wall synthesis.
β-lactam Antibiotics
- Beta-lactams include penicillins, cephalosporins, carbapenems, and monobactams.
- They all share a beta-lactam ring structure.
- Bacterial lactamase is an enzyme that hydrolyzes the beta-lactam ring, inactivating the antibiotic.
Bacterial Cell Wall
- The cell wall is a rigid outer layer that surrounds the cytoplasmic membrane, maintaining cell shape and integrity.
- The cell wall prevents cell lysis due to high osmotic pressure by providing structural support.
- Peptidoglycan is the primary constituent of the bacterial cell wall, a complex cross-linked polymer of polysaccharides and polypeptides.
Mechanism of Action of Beta-Lactam Antibiotics
- Beta-lactams interfere with the last step of bacterial cell wall synthesis, which involves cross-linking of adjacent peptidoglycan strands.
- They inhibit transpeptidases, enzymes essential for this process, also known as penicillin-binding proteins (PBPs).
- Beta-lactams bind to the active site of PBPs, preventing cross-linking.
- This weakens the cell wall, leading to cell death.
Penicillins
- The most effective and least toxic drugs known.
- Generally safe, with the exception of allergic reactions.
- Mostly excreted by the kidneys.
- Suffix: -cillin.
- Penicillins have a 6-amino penicillanic acid nucleus with a side chain (R) attached.
- The side chain determines the antimicrobial spectrum, stability to stomach acid, cross-hypersensitivity, and susceptibility to bacterial enzymes.
Classification of Penicillins
- Natural Penicillins: Penicillin G (parenteral) and Penicillin V (oral). Susceptible to inactivation by beta-lactamases. Narrow-spectrum.
- Extended Spectrum Penicillins: Aminopenicillins (Ampicillin and Amoxicillin). Susceptible to inactivation by beta-lactamases.
- Anti-pseudomonal Penicillins: Piperacillin and Ticarcillin.
- Penicillinase Resistant Penicillins: Methicillin, Flucloxacillin, Cloxacillin, Dicloxacillin, and Nafcillin.
Natural Penicillins
-
Penicillin G: (Benzylpenicillin)
- Powder form.
- Given IV (bolus or infusion), IM, or orally, but destroyed by gastric juice.
- Short duration (1-2 hours).
- Used for syphilis, acute tonsillitis, and tetanus.
-
Penicillin V: (Phenoxymethylpenicillin)
- More acid-stable than penicillin G.
- Given orally, every 4 hours.
- Used for tonsillitis and pharyngitis.
Derivatives of Penicillin G
- Procaine Penicillin G: Long-acting, given IM, provides 12-hour duration.
-
Benzathine Penicillin G: Long-acting, given IM, provides 4-week duration.
- Effective in treating syphilis.
- Used prophylactically for rheumatic fever patients.
Extended-Spectrum Penicillins
- Ampicillin: Given IV or orally every 6 hours. Used for listeriosis, otitis media, and urinary tract infections.
- Amoxicillin: Given orally every 8 hours. Better absorbed orally than Ampicillin. Used for bacillary dysentery, prophylaxis in dentistry, and peptic ulcers to eradicate H. pylori.
Beta-Lactamase Inhibitors
- Clavulanate acid is a beta-lactamase inhibitor that doesn't have antibacterial activity itself.
- It binds to beta-lactamase, protecting beta-lactam antibiotics from inactivation.
- It expands the spectrum of beta-lactam antibiotics against beta-lactamase producing bacteria.
- Amoxicillin + Clavulanate Acid: A common formulation.
- Ampicillin + Sulbactam: Another common formulation.
Anti-Staphylococcal Penicillins
- Also known as anti-staph or penicillinase resistance penicillins.
- Methicillin, Flucloxacillin, Cloxacillin, Dicloxacillin, and Nafcillin: Given IV and orally.
- Used to treat infections by penicillinase-producing staphylococci.
- Methicillin-Resistant Staphylococcus Aureus (MRSA): Resistant to these drugs. Commonly treated with Vancomycin.
- Methicillin is no longer used clinically due to nephrotoxicity.
Anti-Pseudomonal Penicillins
- Piperacillin and Ticarcillin: Given parenterally, not orally.
- Pseudomonas aeruginosa is resistant to many antimicrobial agents due to its lack of porins.
- Piperacillin + Tazobactam expands the spectrum to include penicillinase-producing organisms.
Pharmacokinetics of Penicillins
- Absorption: Penicillins vary in acid stability, affecting oral bioavailability.
- Distribution: Most penicillins only cross the blood-brain barrier when the meninges are inflamed.
- Metabolism and Excretion: Most penicillins are excreted unchanged in the urine. Probenecid inhibits this excretion.
- Dosage Adjustment: Required for patients with renal impairment.
Adverse Reactions of Penicillins
- Hypersensitivity Reactions: Most common side effect, ranging from skin rashes to anaphylactic shock.
- Diarrhea: Especially frequent with Ampicillin.
- Nephritis: Potentially caused by penicillins, particularly methicillin.
- Neurotoxicity: Can induce seizures when injected intrathecally or at very high blood levels.
Resistance to Penicillins
- Inactivation by Beta-Lactamase: The most common mechanism.
- Decreased Permeability: Less common, but important for gram-negative bacteria. Caused by absent or downregulated porins, or the presence of efflux pumps.
- Modification of Target PBPs: Low affinity for binding of beta-lactams is the basis of MRSA resistance.
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Description
Test your knowledge on the inhibitors of bacterial cell wall synthesis, focusing on beta-lactam antibiotics. Explore their mechanisms of action, types, and significance in combating bacterial infections. Prepare to dive into the world of antibiotic pharmacology and microbial resistance.
