Penicillins KO

Question 1

How are antibiotics classified based on their structure?

Answer 1

Antibiotics are classified into β-Lactam antibiotics (e.g., Penicillins, Cephalosporins), Aminoglycosides, Tetracyclines, Macrolides, Antifungal antibiotics, Quinolones, and miscellaneous types.

Question 2

How are antibiotics classified based on their structure?

Answer 2

Antibiotics are classified into β-Lactam antibiotics (e.g., Penicillins, Cephalosporins), Aminoglycosides, Tetracyclines, Macrolides, Antifungal antibiotics, Quinolones, and miscellaneous types.

Question 3

What is the β-lactam ring and why is it important?

Answer 3

The β-lactam ring is a four-membered cyclic amide structure crucial for the antibiotic activity of β-lactam antibiotics, including penicillins. Its reactivity and instability are key to its antibacterial effects.

Question 4

What are the subtypes of Penicillins based on their origin?

Answer 4

Penicillins are categorized as Natural Penicillins (e.g., Penicillin G), Semisynthetic Penicillins, Penicillinase-Resistant Penicillins, and Broad Spectrum Penicillins.

Question 5

How did Alexander Fleming discover Penicillin?

Answer 5

In 1928, Alexander Fleming accidentally discovered Penicillin when a mold, Penicillium notatum, contaminated his petri dish of Staphylococcus aureus, inhibiting bacterial growth.

Question 6

What is Penicillin G and how is it produced?

Answer 6

Penicillin G (benzylpenicillin) is the most widely used natural penicillin, produced by growing Penicillium chrysogenum on corn steep liquor rich in phenylacetic acid.

Question 7

Why is Penicillin G acid-unstable, and how can it be stabilized?

Answer 7

Penicillin G is acid-unstable because water / carbonyl group from the side chain can attack the β-lactam ring in acidic environments, breaking it down into inactive compounds. It can be stabilized for oral use by adding electron-withdrawing groups to the amide side chain (e.g., ampicillin).

Question 8

What is the mechanism of penicillinase enzymes, and how do they affect Penicillin G?

Answer 8

Penicillinase enzymes hydrolyze the β-lactam ring of penicillins, rendering them inactive. Bacteria like Staphylococcus aureus produce these enzymes to resist the effects of penicillin.

Question 9

What are the differences between Penicillin G and Penicillin V?

Answer 9

Penicillin V is more acid-stable and can be taken orally, whereas Penicillin G is acid-unstable and usually administered intravenously or intramuscularly.

Question 10

How does ampicillin differ from Penicillin G?

Answer 10

Ampicillin is an acid-stable, broad-spectrum penicillin with a polar side chain that allows it to penetrate the cell walls of Gram-negative bacteria better than Penicillin G.

Question 11

Why should ampicillin be administered either 1 hour before or 2 hours after meals?

Answer 11

Ampicillin absorption is reduced by large meals, especially those rich in phenylalanine, as it competes with amino acid transport systems for absorption in the intestine.

Question 12

What causes the “ampicillin rash,” and how is it related to its structure?

Answer 12

Ampicillin can polymerize due to its amino group, forming antigenic polymers that trigger an immune response, leading to the characteristic ampicillin rash.

Question 13

What is the significance of amoxicillin in terms of absorption and administration?

Answer 13

Amoxicillin is better absorbed than ampicillin and can be taken with food, making it more convenient for patients. It also causes less gastrointestinal disturbance.

Question 14

What are “penicillinase-resistant penicillins,” and provide an example?

Answer 14

Penicillinase-resistant penicillins, like methicillin, have bulky side chains that prevent the penicillinase enzyme from hydrolyzing the β-lactam ring, making them effective against penicillinase-producing bacteria.

Question 15

What is the role of clavulanic acid in antibiotic therapy?

Answer 15

Clavulanic acid is a β-lactamase inhibitor that protects penicillin antibiotics from being broken down by β-lactamase enzymes. It is combined with amoxicillin in the drug Augmentin®.

Question 16

What are “ureidopenicillins” and why are they significant?

Answer 16

Ureidopenicillins, such as piperacillin, have broader antibacterial activity due to their ability to bind to more types of transpeptidase enzymes, making them effective against a wide range of bacteria.

Question 17

Why is ticarcillin often used with an aminoglycoside?

Answer 17

Ticarcillin is used in combination with aminoglycosides like gentamicin to enhance its effectiveness against Pseudomonas aeruginosa. However, they must be administered separately to avoid inactivation in solution.

Question 18

What is the pharmacokinetic importance of the different salts of Penicillin G (e.g., benzathine, procaine)?

Answer 18

Different salts of Penicillin G provide varying durations of action. Benzathine penicillin, for instance, has a longer duration, lasting up to a month, while procaine penicillin lasts about a week.

Question 19

What is the therapeutic significance of Penicillin G’s excretion rate?

Answer 19

Penicillin G has a fast excretion rate (t½ = 1 hour), so frequent administration or continuous IV infusion is required to maintain therapeutic levels.

Question 20

Why is the β-lactam ring highly reactive?

Answer 20

The β-lactam ring is a four-membered ring that is fused to a five-membered ring, creating significant ring strain. This strain makes the β-lactam ring more reactive and prone to nucleophilic attack, which is key to its antibacterial activity.

Question 21

What is the significance of the pharmacophore in penicillins?

Answer 21

The pharmacophore in penicillins is the 6-aminopenicillanic acid structure. Modifications to this structure’s side chain can alter the activity, stability, and spectrum of the penicillin, but changes to the core structure lead to loss of activity.

Question 22

How is ampicillin structurally different from Penicillin G, and what are its benefits?

Answer 22

Ampicillin has an amino group in its side chain, making it more polar, acid-stable, and effective against both Gram-positive and some Gram-negative bacteria.

Question 23

What are the limitations of ampicillin?

Answer 23

Ampicillin is penicillinase-sensitive, so it can be hydrolyzed by bacterial penicillinases. It also has low absorption from the gastrointestinal tract (30-55%) due to its zwitterionic nature.

Question 24

How does the structure of methicillin make it resistant to penicillinase?

Answer 24

Methicillin has two bulky methoxy groups attached to the side chain’s aromatic ring, preventing the β-lactam ring from fitting into the active site of the penicillinase enzyme, thereby protecting it from hydrolysis.

Question 25

Why can’t methicillin be taken orally?

Answer 25

Methicillin is acid-unstable due to its electron-donating methoxy groups, making it degrade in acidic environments like the stomach. Therefore, it must be administered parenterally.

Question 26

What is the mechanism behind the acid-stability of oxacillin?

Answer 26

Oxacillin contains an isoxazole ring with nitrogen, which reduces the electron density on the side chain’s carbonyl group, decreasing intramolecular hydrolysis and making it acid-stable for oral use.

Question 27

How do polar side chains affect the spectrum of penicillins like ampicillin?

Answer 27

Polar side chains increase the ability of penicillins to penetrate the cell walls of Gram-negative bacteria, expanding their antibacterial spectrum beyond Gram-positive bacteria.

Question 28

What is the primary advantage of amoxicillin over ampicillin?

Answer 28

Amoxicillin is absorbed more efficiently than ampicillin, has fewer gastrointestinal side effects, and can be taken with food without reducing its absorption.

Question 29

What is the role of clavulanic acid in combination antibiotics like Augmentin®?

Answer 29

Clavulanic acid inhibits β-lactamase enzymes produced by resistant bacteria, allowing the penicillin (e.g., amoxicillin) to remain effective.

Question 30

Why are ureidopenicillins like piperacillin used for broader antibacterial coverage?

Answer 30

Ureidopenicillins contain a urea moiety that allows them to bind more strongly to penicillin-binding proteins, increasing their effectiveness against a wider range of bacteria, including Gram-negative bacteria.

Question 31

Why is ticarcillin often combined with clavulanate (Timentin®)?

Answer 31

Ticarcillin is sensitive to penicillinase enzymes, and combining it with clavulanate, a β-lactamase inhibitor, protects it from being inactivated by bacterial enzymes.

Question 32

What is the significance of benzathine penicillin’s long duration of action?

Answer 32

Benzathine penicillin is very sparingly soluble, leading to a slow release of the drug over a month, making it useful for long-term treatment without frequent dosing.

Question 33

Why must ticarcillin and aminoglycosides be administered separately?

Answer 33

When mixed together, ticarcillin and aminoglycosides can chemically react, forming inactive compounds, reducing their effectiveness. Therefore, they must be administered at different times or through separate IV lines.

Question 34

How does the urea moiety in ureidopenicillins enhance their binding to penicillin-binding proteins?

Answer 34

The urea moiety strengthens the interaction with a larger number of penicillin-binding proteins (PBPs), enhancing their antibacterial potency, especially against Gram-negative bacteria.

Question 35

What is the importance of protein binding in the effectiveness of antibiotics like ampicillin?

Answer 35

Low protein binding increases the concentration of free drug in the bloodstream, which enhances its effectiveness against bacteria. Ampicillin has lower protein binding than Penicillin G, resulting in higher bioavailability.

Question 36

What is the difference between benzathine penicillin and procaine penicillin in terms of duration?

Answer 36

Benzathine penicillin has a longer duration of action (up to one month), while procaine penicillin has a shorter duration (about one week), making benzathine more suitable for long-term treatments.