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Questions and Answers
What is the primary characteristic of the semisynthetic ß-lactamase inhibitors described?
What is the primary characteristic of the semisynthetic ß-lactamase inhibitors described?
Which statement correctly describes the relationship between sultamicillin and its components?
Which statement correctly describes the relationship between sultamicillin and its components?
What is the primary use of Piperacillin combined with Tazobactam?
What is the primary use of Piperacillin combined with Tazobactam?
What is a major limitation of olivanic acids as β-lactamase inhibitors?
What is a major limitation of olivanic acids as β-lactamase inhibitors?
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What is the role of the carbapenem ring in the context of β-lactamase inhibitors?
What is the role of the carbapenem ring in the context of β-lactamase inhibitors?
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What is a characteristic of the side chain described in the content?
What is a characteristic of the side chain described in the content?
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What is the primary mechanism of action discussed for 2-Cephalosporins?
What is the primary mechanism of action discussed for 2-Cephalosporins?
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Which generation of cephalosporins is specifically mentioned as being effective against MRSA?
Which generation of cephalosporins is specifically mentioned as being effective against MRSA?
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Which class of cephalosporins is characterized by a broader strain coverage linked to CNS activity?
Which class of cephalosporins is characterized by a broader strain coverage linked to CNS activity?
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What is a notable feature of the first generation cephalosporins compared to penicillins?
What is a notable feature of the first generation cephalosporins compared to penicillins?
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Which type of Cephalosporins is primarily delivered via injection?
Which type of Cephalosporins is primarily delivered via injection?
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Which functional groups are involved in the process of lactonization in 2-Cephalosporins?
Which functional groups are involved in the process of lactonization in 2-Cephalosporins?
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Which generation of cephalosporins is known for targeting anaerobic bacteria?
Which generation of cephalosporins is known for targeting anaerobic bacteria?
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Which generation of cephalosporins is defined by being more resistant to β-lactamase and more effective against Gram-negative bacteria?
Which generation of cephalosporins is defined by being more resistant to β-lactamase and more effective against Gram-negative bacteria?
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What is a common side effect associated with first generation cephalosporins?
What is a common side effect associated with first generation cephalosporins?
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Which of the following is NOT an indication for the use of first generation cephalosporins?
Which of the following is NOT an indication for the use of first generation cephalosporins?
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Which second generation cephalosporin is noted for its broad spectrum and effectiveness against Gram-negative bacteria?
Which second generation cephalosporin is noted for its broad spectrum and effectiveness against Gram-negative bacteria?
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What is a limitation of second generation cephalosporins regarding their effectiveness?
What is a limitation of second generation cephalosporins regarding their effectiveness?
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Which of the following conditions can be treated with second generation cephalosporins?
Which of the following conditions can be treated with second generation cephalosporins?
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Which property distinguishes cephamycins from traditional cephalosporins?
Which property distinguishes cephamycins from traditional cephalosporins?
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What is the main reason most cephalosporins are administered via injection rather than orally?
What is the main reason most cephalosporins are administered via injection rather than orally?
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What compound was the first cephalosporin derived from?
What compound was the first cephalosporin derived from?
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Which of the following is a disadvantage of cephalosporins?
Which of the following is a disadvantage of cephalosporins?
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Which structural feature is responsible for the reactivity of cephalosporins?
Which structural feature is responsible for the reactivity of cephalosporins?
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What is the first commercial cephalosporin?
What is the first commercial cephalosporin?
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What biosynthetic precursors were initially identified for cephalosporin C?
What biosynthetic precursors were initially identified for cephalosporin C?
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Which of the following is true about the activity against bacteria of cephalosporins?
Which of the following is true about the activity against bacteria of cephalosporins?
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Which property of cephalosporins helps them resist acid hydrolysis?
Which property of cephalosporins helps them resist acid hydrolysis?
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What characteristic feature differentiates cephalosporins from penicillins?
What characteristic feature differentiates cephalosporins from penicillins?
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What significant feature does the α-position of the acyl side chain in oximinocephalosporins provide?
What significant feature does the α-position of the acyl side chain in oximinocephalosporins provide?
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Which third generation cephalosporin is specifically noted for its poor bioavailability when administered orally?
Which third generation cephalosporin is specifically noted for its poor bioavailability when administered orally?
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Which of the following infections are third generation cephalosporins NOT typically effective against?
Which of the following infections are third generation cephalosporins NOT typically effective against?
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How do fourth generation cephalosporins compare to third generation in terms of resistance to beta-lactamases?
How do fourth generation cephalosporins compare to third generation in terms of resistance to beta-lactamases?
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Which of the following statements about third generation cephalosporins is TRUE?
Which of the following statements about third generation cephalosporins is TRUE?
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What is a notable character of fourth generation cephalosporins regarding their spectrum of activity?
What is a notable character of fourth generation cephalosporins regarding their spectrum of activity?
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Which of the following is a common use for third generation cephalosporins?
Which of the following is a common use for third generation cephalosporins?
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What key structural feature enhances the ability of fourth generation cephalosporins to penetrate Gram negative bacteria?
What key structural feature enhances the ability of fourth generation cephalosporins to penetrate Gram negative bacteria?
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What is the primary activity of cefepime?
What is the primary activity of cefepime?
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Which component is crucial for the activity of fifth generation cephalosporins against MRSA?
Which component is crucial for the activity of fifth generation cephalosporins against MRSA?
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What is a key property of the combination of amoxicillin and clavulanic acid?
What is a key property of the combination of amoxicillin and clavulanic acid?
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Which feature of clavulanic acid contributes to its role as a β-lactamase inhibitor?
Which feature of clavulanic acid contributes to its role as a β-lactamase inhibitor?
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What is the role of the alkoximino group in the ceftolozane/tazobactam combination?
What is the role of the alkoximino group in the ceftolozane/tazobactam combination?
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Which statement about β-lactamase inhibitors is accurate?
Which statement about β-lactamase inhibitors is accurate?
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What distinguishes ceftolozane in its treatment application?
What distinguishes ceftolozane in its treatment application?
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Which component of clavulanic acid affects its stereochemical properties?
Which component of clavulanic acid affects its stereochemical properties?
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Study Notes
Lecture 7: B-Lactamase Inhibitors & Cephalosporins
- The lecture covers B-lactamase inhibitors and cephalosporins, a class of antibiotics.
- Course learning outcomes include outlining the relationship between chemical structure and biological activity in the design of chemotherapeutic agents, and identifying pharmacological properties such as mechanisms of action, uses, adverse reactions, and physicochemical properties of studied chemotherapeutic agents.
2-Cephalosporins
- The first cephalosporin (cephalosporin C) was derived from a fungus (Acremonium chrysogenum) found in sewer water in Sardinia in the mid-1940s.
- Its structure wasn't determined until 1961.
- Biosynthetic precursors include valine and cysteine.
- Cephalosporin C has limited use due to its weak activity.
- Cephalothin is the first commercial cephalosporin.
- Key structures include penicillins, penems, cephalosporanic acids, and 7-amino cephalosporanic acid (7-ACA).
- B-lactam ring is less strained than in penicillin.
- Reactivity is due to 1-Olifenic linkage at C3 and 2-acetoxymethyl groups (activating group).
Advantages & Disadvantages of 2-Cephalosporins
- Advantages: Activity against Gram-negative and Gram-positive bacteria, greater resistance to acid hydrolysis and b-lactamases, and less likely to cause allergic reactions.
- Disadvantages: 1/1000 the activity of penicillin G, 3-acetoxymethyl group undergoes lactonization in the gastrointestinal tract (GIT) leading to inactivation, high polarity of the side chain causing difficulty in isolation, purification and poor gastrointestinal absorption.
Mechanism of Action of Cephalosporins
- Cephalosporins bind to and inhibit bacterial enzymes involved in cell wall synthesis.
- The mechanism involves a crucial serine (Ser) enzyme.
Lactonization
- Spontaneous lactonization of part of a cephalosporin molecule can render it inactive.
- A good-leaving group is vital for this process.
Structure-Activity Relationship (SAR) of Cephalosporins
- Structural modifications (e.g., replacing a group with 7a-methoxy group) can alter the effectiveness and resistance of cephalosporins to b-lactamases.
- Factors influencing the Spectrum of Cephalosporins includes: affinity & potency (good leaving group), duration of action, and oral bioavailability. Important aspects of chemical stability also strongly affect the choice of oral route.
Classes of Cephalosporins
- Classification based on route of administration (oral or parenteral).
- Classification also based on generation (1st, 2nd, 3rd, 4th, and 5th).
- Each generation has varying degrees of activity against gram-negative and gram-positive bacteria. Some are active against anaerobic bacteria, and some are active against Pseudomonas.
- Varying generations are effective against certain CNS infections such as meningitis.
First Generation Cephalosporin
- Lower activity compared to comparable penicillins but with a more extended range of uses, mostly for injections.
- Examples : Cephalothin & cephalexin
- Uses: uncomplicated skin and soft-tissue infections, uncomplicated urinary tract infections, and streptococcal pharyngitis (strep throat).
Second Generation Cephalosporin
- Introduced in the 1970s.
- More active against Gram-negative bacteria, including Hemophilus Influenza.
- More resistant to beta-lactamases than first-generation cephalosporins.
- Uses: upper and lower respiratory tract infections, acute sinusitis and otitis media. They aren't effective against CNS infections.
- Cephamycins & Oximinocephalosporins
- Examples: Cefoxitin & Cefaclor
Third Generation Cephalosporin
- Increased penetration through the outer membrane of Gram-negative bacteria.
- Increased affinity for the transpeptidase enzyme.
- Broader spectrum than second-generation cephalosporins.
- Active against anaerobic bacteria and some Pseudomonas (e.g., Ceftazidime and cefoperazone).
- Administered intravenously (I.V.) or intramuscularly (I.M.).
- Uses: Treatment of Gram-negative bacillary meningitis, serious Enterobacteriaceae infections, upper respiratory tract infections, otitis media, pyelonephritis, and skin and soft-tissue infections.
Fourth Generation Cephalosporin
- Oximinocephalosporins.
- Enhanced ability to penetrate the outer membrane of Gram-negative bacteria.
- Broad spectrum, including similar activity to first-generation cephalosporins against Gram-positive organisms.
- Effective against CNS infections.
- Increased resistance to beta-lactamases compared to third-generation cephalosporins.
- Includes Cefepime
Fifth Generation Cephalosporin
- Active against various strains of MRSA (methicillin-resistant Staphylococcus aureus) and Streptococcus pneumoniae MDRSP (multi-drug-resistant-Streptococcus-pneumonia).
- 1,3-thiazole ring crucial for activity against MRSA.
- Examples: Ceftaroline
Beta-Lactamase Inhibitors
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Used in combination with beta-lactamase-sensitive penicillins to treat infections caused by beta-lactamase-producing bacteria.
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Types: Clavulanic acid, Sulbactam/Tazobactam, and Olivanic acids.
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Clavulanic acid is a natural product.
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Sulbactam and Tazobactam are semi-synthetic.
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Olivanic acids have higher potency than clavulanic acid, but less stability.
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Amoxicillin & Clavulanic acid (Augmentin®) combination: decrease amoxicillin dose and increase spectrum of activity
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Piperacillin + Tazobactam (Tazocin®): enhances piperacillin's effectiveness by inhibiting beta-lactamases— but not MRSA. Used for hospital-acquired infections.
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Description
This quiz explores B-lactamase inhibitors and cephalosporins, essential antibiotics in pharmacology. Understand their chemical structures, mechanisms of action, and clinical uses. Dive into the historical background and properties that distinguish this class of chemotherapeutic agents.
