penicillin Flashcards
What is the definition of an antibiotic proposed by Waksman in 1942?
A substance produced by microorganisms that inhibits the growth and destroys other microorganisms
This includes bacteria, mycobacteria, fungi, protozoa, or viruses.
How did Benedict and Langlykke define antibiotics in 1947?
A chemical compound derived from or produced by a living organism that inhibits life processes of microorganisms in small concentrations.
What are the main conditions for a substance to be classified as an antibiotic?
- 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.
Who discovered penicillin and in what year?
Sir Alexander Fleming in 1928.
What are the two types of penicillins produced by fungi?
- Benzyl penicillin
- Phenoxymethylpenicillin.
What significant developments related to penicillin occurred in 1938?
Isolation and purification by Florey, Chain, and Abraham at Oxford University.
What structural feature of penicillin contributes to its reactivity?
The β-lactam ring is highly reactive and unstable.
What is 6-Aminopenicillanic acid (6-APA)?
A key intermediate in the synthesis of penicillins.
What is the shape of the β-lactam ring in penicillin?
Folded structure with an angle of 117° between the two rings.
Fill in the blank: The β-lactam ring is susceptible to _______.
[nucleophilic attack].
What happens to penicillin in the presence of gastric acid?
It transforms into penillic acid.
What is the role of β-lactamase enzymes?
They hydrolyze the β-lactam ring, leading to antibiotic resistance.
What is the mechanism of action of penicillins?
They inhibit the transpeptidase enzyme involved in bacterial cell wall synthesis.
What is the result of penicillin inhibiting transpeptidase?
Weakened cell wall leading to cell lysis.
True or False: Penicillins are equally effective against Gram-positive and Gram-negative bacteria.
False.
What structural components are essential for penicillin’s activity?
- Amide
- Carboxylic acid
- Bicyclic system.
What does the term ‘semi-synthetic penicillins’ refer to?
Penicillins modified from natural penicillin to improve properties.
What is the significance of the carboxylate group in penicillin?
It is essential for penicillin activity.
What are the challenges penicillins face when targeting Gram-negative bacteria?
- Lipopolysaccharide outer membrane
- Low affinity of transpeptidase for penicillins
- Presence of β-lactamases.
Fill in the blank: Penicillin mimics the structure of _______.
[D-Ala-D-Ala].
What is the clinical significance of penicillin’s limited range of activity?
It necessitates the development of new antibiotics.
What can be a result of high levels of β-lactamases in bacteria?
Increased resistance to penicillins.
What is the role of porins in Gram-negative bacteria regarding penicillin?
They allow small hydrophilic molecules to cross the outer membrane.
What is the first orally active penicillin?
Penicillin V.
What type of reaction leads to the transformation of penicillins in acidic conditions?
Alkaline hydrolysis to penicilloic acid.
What is the role of β-lactamases in bacterial resistance?
Enzymes that inactivate penicillins by opening β-lactam rings
This allows bacteria to be resistant to penicillin and can be transferred between bacterial strains.
What are the problems associated with Penicillin G?
- Sensitive to stomach acids
- Sensitive to β-lactamases
- Limited range of activity
How does Penicillin V differ from Penicillin G?
Better acid stability and orally active
However, it is still sensitive to β-lactamases and slightly less active than Penicillin G.
What is 6-aminopenicillanic acid (6-APA)?
A core structure used for the synthesis of semi-synthetic penicillins
Fill in the blank: The first system used to classify penicillins is designated according to the Chemical Abstracts system as ______.
5-acylamino-2,2-dimethylpenam-3-carboxylic acids
What is the significance of hydrophobic side chains in penicillin activity?
Result in high activity vs. Gram +ve bacteria and poor activity vs. Gram -ve bacteria
Why is the β-lactam ring essential for penicillin activity?
It must be retained for the antibiotic to be effective
What are some strategies to combat the sensitivity of penicillins to β-lactamases?
- Use of steric shields
- Introduce bulky groups to the side chain
True or False: Ampicillin and amoxicillin are effective against Gram-negative bacteria that produce β-lactamases.
False
What modifications can improve the pharmacokinetic properties of penicillins?
Vary the acyl side group (R) to make it electron-withdrawing to stabilize the β-lactam ring
What is the mechanism of action for lactamases?
Identical to the mechanism of inhibition for the target enzyme (transpeptidase)
What is the result of incorporating an acidic substituent at the β-benzyl carbon atom of penicillin G?
Imparts clinical effectiveness against Gram-negative bacilli
What are methoxy groups used for in penicillin structure?
Block access to β-lactamases but not to transpeptidases
Fill in the blank: The introduction of an ionized or polar group into the α-position of the side chain benzyl carbon atom of penicillin G confers activity against ______.
Gram-negative bacilli
What is the impact of bulky side chains on penicillin’s effectiveness?
They can block access to the active site of β-lactamases
What is a characteristic of semi-synthetic penicillins like ampicillin?
Orally active and acid resistant
What does the presence of a neighboring group in the hydrolysis mechanism indicate?
Contributes to the sensitivity of penicillins to hydrolysis
What is the effect of hydrophilic groups at the α-position in penicillins?
Increase activity vs. Gram-negative bacteria
What is the significance of the term ‘penam’ in penicillin nomenclature?
Describes the bicyclic structure of penicillins
True or False: Ampicillin is inactive against Pseudomonas aeruginosa.
True
What are the three main problems leading to the limited effectiveness of penicillins?
- Sensitivity to stomach acids
- Sensitivity to β-lactamases
- Limited range of activity
How did the introduction of ionized groups affect the spectrum of activity for penicillins?
Extended the spectrum to include organisms resistant to ampicillin
What is the acid resistance property of most penicillins?
Most penicillins are acids with pKa values in the range of 2.5 to 3.0.
Most penicillins are not suitable for oral or parenteral administration in their free acid form.
What are the characteristics of carbenicillin?
Active against ampicillin-sensitive Gram-negative species and additional Gram-negative bacilli such as Pseudomonas, Klebsiella, Enterobacter.
Carbenicillin is an example of a penicillin with an acidic substituent that increases its effectiveness.
What does the term ‘prodrug’ refer to in the context of carfecillin?
Carfecillin is a prodrug for carbenicillin.
Prodrugs are inactive compounds that become active when metabolized in the body.
What is the absorption characteristic of penicillin?
Poor absorption through the gut wall.
This characteristic can lead to disruptions in gut flora and diarrhea.
Which penicillin is more effective against Pseudomonas aeruginosa, Ticarcillin or Carbenicillin?
Ticarcillin is more effective against Pseudomonas aeruginosa.
Ticarcillin requires smaller doses compared to carbenicillin.
True or False: Clavulanic acid is a -lactamase inhibitor.
True.
Clavulanic acid is a naturally occurring, mechanism-based inhibitor that inactivates -lactamases.
What is the significance of the ester in the context of drug metabolism?
The ester is metabolized in the body by esterases to give the free drug.
This mechanism increases cell membrane permeability.
Fill in the blank: The sodium and potassium salts of most penicillins are soluble in water and readily absorbed _______.
[orally or parenterally].
What are some factors that contribute to the failure of penicillin combinations against resistant strains?
- Failure of lipophilic penicillinase-resistant penicillins to penetrate Gram-negative bacilli
- Reversible binding of penicillinase-resistant penicillins to -lactamase
- Induction of -lactamases by some penicillinase-resistant penicillins.
These factors limit the effectiveness of combination therapy.
What is the classification of penicillins based on their resistance to -lactamases?
Penicillins may be resistant or sensitive to -lactamases (penicillinases).
This classification impacts their clinical use.
What is the clinical use of Benzylpenicillin?
Multipurpose.
Benzylpenicillin has intermediate spectrum activity.
What is the absorption characteristic of Penicillin V?
Good absorption (60%).
Penicillin V is biosynthetic and has a good acid resistance.
What is the activity spectrum of Piperacillin?
Extended spectrum.
Piperacillin can be administered alongside tazobactam, a -lactamase inhibitor.
What is a characteristic of the methyl ester of ampicillin?
Not hydrolyzed in the body.
This characteristic affects its stability and effectiveness.
What is the relationship between stereochemistry at the a-position and carfecillin?
Stereochemistry at the a-position is important as C02H at this position is ionized at blood pH.
This ionization affects the drug’s activity.
