penicilins

Question 1

What is the widely cited definition of antibiotics proposed by Waksman in 1942?

Answer 1

An antibiotic or antibiotic substance is a substance produced by microorganisms, which has the capacity of inhibiting the growth and even of destroying other microorganisms.

This definition restricts antibiotics to metabolic products of microorganisms.

Question 2

How did Benedict and Langlykke define antibiotics in 1947?

Answer 2

A chemical compound derived from or produced by a living organism, which is capable, in small concentration, of inhibiting the life processes of microorganisms.

This definition broadens the sources of antibiotics to include higher plants and mammals.

Question 3

What are the key characteristics that classify a substance as an antibiotic?

Answer 3

A substance is classified as an antibiotic if it meets the following conditions:
* It is a product of metabolism.
* It is a synthetic product as a structural analog of a naturally occurring antibiotic.
* It antagonizes the growth or survival of one or more species of microorganisms.
* It is effective in low concentrations.

Question 4

Who discovered penicillin and when?

Answer 4

Sir Alexander Fleming discovered penicillin from a fungal colony in 1928.

Question 5

What are some examples of penicillin produced by fungi?

Answer 5

Examples include benzyl penicillin and phenoxymethylpenicillin.

Question 6

What significant developments occurred in the history of penicillin from 1938 to 1944?

Answer 6

• Isolated and purified by Florey, Chain, and Abraham at Oxford University (1938).
• First successful clinical trial (1941).
• Produced by large-scale fermentation (1944).

Question 7

What is the structure of penicillin established by X-ray crystallography?

Answer 7

The penam ring, which consists of a β-lactam fused to a thiazolidine.

Question 8

What is the significance of 6-Aminopenicillanic acid (6-APA) in penicillin development?

Answer 8

6-APA is a core structure used for the development of semi-synthetic penicillins.

Question 9

What does the folded structure of the β-lactam ring in penicillin indicate?

Answer 9

The β-lactam ring and thiazolidine ring are not co-planar, which suppresses normal amide resonance.

Question 10

Why is the β-lactam ring highly reactive and unstable?

Answer 10

It is highly strained due to the four-membered ring and is susceptible to nucleophilic attack.

Question 11

What are the transformations of penicillins caused by gastric acid?

Answer 11

Gastric acid can lead to the formation of penillic acid.

Question 12

What are the properties of Penicillin G?

Answer 12

• Active vs. Gram +ve bacilli and some Gram -ve cocci.
• Non-toxic.
• Limited range of activity.
• Not orally active - must be injected.
• Sensitive to β-lactamases.
• Some patients are allergic.

Question 13

What are the goals of drug development for penicillins?

Answer 13

• To increase chemical stability for oral administration.
• To increase resistance to β-lactamases.
• To increase the range of activity.

Question 14

What is the mechanism of action of penicillins?

Answer 14

Penicillins inhibit a bacterial enzyme called transpeptidase, involved in bacterial cell wall synthesis.

Question 15

What happens to bacteria when penicillin inhibits transpeptidase?

Answer 15

Inhibition leads to a weakened cell wall, causing cells to swell and burst (lysis).

Question 16

What structural feature of penicillin mimics D-Ala-D-Ala?

Answer 16

Penicillin’s structure mimics acyl-D-Ala-D-Ala.

Question 17

What is a key reason for resistance to penicillins in Gram -ve bacteria?

Answer 17

Gram -ve bacteria have a lipopolysaccharide outer membrane preventing access to the cell wall.

Question 18

What role do porins play in penicillin resistance?

Answer 18

Porins allow small hydrophilic molecules, including penicillins, to cross the outer membrane.

Question 19

How do β-lactamases contribute to penicillin resistance?

Answer 19

β-lactamases hydrolyze the β-lactam ring, rendering penicillins ineffective.

Question 20

What is the primary location of β-lactamases in bacteria?

Answer 20

Periplasmic space

Question 21

What mechanism do bacteria use to pump penicillin out of the periplasmic space?

Answer 21

Efflux mechanisms

Question 22

What is the significance of 6-aminopenicillanic acid (6-APA) in penicillin synthesis?

Answer 22

It serves as a precursor for the synthesis of semisynthetic penicillins

Question 23

What is Penicillin G also known as?

Answer 23

Benzylpenicillin

Question 24

What are the key problems associated with Penicillin G?

Answer 24

• Sensitive to stomach acids
• Sensitive to β-lactamases
• Limited range of activity

Question 25

What is the purpose of activating the side chain in penicillin synthesis?

Answer 25

To make it more reactive

Question 26

True or False: Penicillin V is more acid-stable than Penicillin G.

Answer 26

True

Question 27

What type of penicillins are significantly more stable in acid solutions?

Answer 27

Semi-synthetic penicillins

Question 28

What is the role of β-lactamase enzymes in bacterial resistance?

Answer 28

They inactivate penicillins by opening β-lactam rings

Question 29

Fill in the blank: The mechanism of action for lactamases is identical to the mechanism of inhibition for the target enzyme, __________.

Answer 29

transpeptidase

Question 30

What are the two main strategies to combat β-lactamase activity?

Answer 30

* Use of steric shields * Vary the acyl side group

Question 31

Which semi-synthetic penicillin is known for being orally active and acid-resistant?

Answer 31

Oxacillin

Question 32

What is the relationship between the size of steric shields and β-lactamase activity?

Answer 32

Size is crucial to inhibit reaction of penicillins with β-lactamases

Question 33

What are the characteristics of ampicillin and amoxicillin?

Answer 33

* Active vs Gram +ve and Gram -ve bacteria * Acid resistant and orally active * Sensitive to β-lactamases

Question 34

What is the effect of introducing an ionized or polar group into the side chain of penicillin?

Answer 34

It confers activity against Gram-negative bacilli

Question 35

What is the first system used to classify penicillins according to Chemical Abstracts?

Answer 35

5-acylamino-2,2-dimethylpenam-3-carboxylic acids

Question 36

What factors contribute to the range of activity of penicillins?

Answer 36

* Cell wall structure * Presence of β-lactamases * Excess transpeptidase enzymes * Resistant transpeptidases

Question 37

What happens to penicillin when it encounters stomach acids?

Answer 37

It undergoes acid-catalyzed degradation

Question 38

Fill in the blank: The introduction of __________ at the β-benzyl carbon atom of penicillin G extends the spectrum of activity.

Answer 38

an acidic substituent

Question 39

What is a common limitation of many penicillins regarding their effectiveness?

Answer 39

They are inactive against Gram-negative bacteria

Question 40

What is the clinical effectiveness of carboxybenzylpenicillin against Gram-negative bacilli attributed to?

Answer 40

Incorporation of an acidic substituent

Question 41

What is the significance of the acyl side group (R) in penicillin derivatives?

Answer 41

It influences pharmacological properties and activity spectrum

Question 42

True or False: Methicillin is resistant to β-lactamases.

Answer 42

True

Question 43

What is a characteristic of penicillins that contain methoxy groups?

Answer 43

They block access to β-lactamases but not transpeptidases

Question 44

What are the characteristics of the penicillin that is acid resistant and orally active?

Answer 44

Non toxic, sensitive to β-lactamases, increased polarity due to extra amino group, poor absorption through the gut wall, disruption of gut flora leading to diarrhoea, inactive vs. Pseudomonas aeruginosa.

Question 45

What is the clinical effectiveness of a-carboxybenzylpenicillin (carbenicillin)?

Answer 45

Active against ampicillin-sensitive Gram-negative species and additional Gram-negative bacilli of the genera Pseudomonas, Klebsiella, Enterobacter.

Question 46

What happens to the polar carboxylic acid group in the increased cell membrane permeability formulation?

Answer 46

It is masked by the ester, which is metabolised in the body by esterases to give the free drug.

Question 47

What is carfecillin and its significance?

Answer 47

Prodrug for carbenicillin, active over a wider range of Gram-negative bacteria than ampicillin, effective vs. Pseudomonas aeruginosa, resistant to most β-lactamases.

Question 48

How does ticarcillin compare to carbenicillin?

Answer 48

Identical antibacterial spectrum, smaller doses required, more effective against P. aeruginosa, fewer side effects, can be administered with clavulanic acid.

Question 49

Which penicillins are generally more active than carboxypenicillins vs. streptococci and Haemophilus species?

Answer 49

Azlocillin, Mezlocillin, Piperacillin.

Question 50

What is the role of β-lactamase inhibitors in combination therapy?

Answer 50

Used in combination with a β-lactamase-sensitive penicillin to treat infections caused by β-lactamase-producing bacterial strains.

Question 51

What are the three key factors that may contribute to the failure of β-lactamase inhibitor combinations?

Answer 51

* Failure of lipophilic penicillinase-resistant penicillins to penetrate Gram-negative bacilli * Reversible binding of penicillinase-resistant penicillins to β-lactamase * Induction of β-lactamases by some penicillinase-resistant penicillins.

Question 52

What is the significance of clavulanic acid in β-lactam therapy?

Answer 52

It is a naturally occurring, mechanism-based inhibitor that causes potent and progressive inactivation of β-lactamases.

Question 53

What is the pKa range for most penicillins?

Answer 53

2.5 to 3.0.

Question 54

Fill in the blank: Salts of penicillins with organic bases, such as benzathine and procaine, have limited water solubility and are useful as _______ forms.

Answer 54

depot.

Question 55

What are the classifications based on the properties of penicillins?

Answer 55

* Biosynthetic, semisynthetic, or synthetic * Acid-resistant or not * Orally or parenterally active * Resistant to β-lactamases or not * Narrow, intermediate, broad, or extended spectrum of activity.

Question 56

What is the clinical use of benzylpenicillin?

Answer 56

Multipurpose.

Question 57

What type of penicillin is methicillin and what is its resistance profile?

Answer 57

Semisynthetic, resistant to β-lactamases.

Question 58

What is the absorption percentage of ampicillin?

Answer 58

20-25%.

Question 59

True or False: Piperacillin can be administered alongside tazobactam.

Answer 59

True.