ANTIBACTERIALS: BETA LACTAMS Flashcards

1
Q

Name 6 bacterial targets for selective inhibition?

A
  1. Cell wall
  2. Cell membrane (different composition)
  3. DNA synthesis (bacteria use different enzymes used and more DNA is made)
  4. Transcription (different enzymes used and occurs more frequently in bacteria)
  5. Protein synthesis in the cytoplasm (70S not 80S ribosomes)
  6. (Other) metabolism (e.g. folate metabolism - essential for DNA)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Name two types of drugs that attack bacterial cell wall synthesis?

A
  1. Vancomycin
  2. Beta-lactams
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How to determine whether a bacteria is Gram +ve or -ve, using cell well?

A
  • Bacteria is treated with iodine, then acetone (decolourizer)
  • Gram +ve bacteria - purple
  • Gram -ve bacteria - colourless
  • This is because +ve bacteria has more peptidoglycan
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are Norcardiform bacteria (Gram +ve or -ve) and give some examples?

A
  • Norcardiform bacteria are Gram +ve
  • Examples are mycobacteria such as M. tuberculosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Why is it difficult to stain Nocardioform bacteria?

A

Peptidoglycan covalently linked to arabinogalactan, which is esterified to lipids, making it resistant to staining (also resistant to biocides and antibiotics)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe the structure of peptidoglycan

A
  • Alternating NAM and NAG residues
  • Branched peptide chains
  • Peptide chains cross link to form peptidoglycan sheets (cross links are species dependent)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What sort of reaction forms crosslinks on peptidoglycans and what enzyme catalyzes this reaction?

A
  • Formed by a transpeptidation reaction (nucleophillic attack
  • Catalyzed by a membrane-bound transpeptidase (interact with second to last AA of peptide chain = last AA is displaced)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is Carboxypeptidase?

A
  • Found in the cell membrane
  • Involved in cell wall synthesis
  • ONLY displaces the final AA (doesn’t form cross links)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Name some beta-lactams antibiotics? (3)

A
  1. Penicillins
  2. Cephalosporins
  3. Carbapenems
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What was the antibacterial broth prepared from in Flemings discovery of penicillin?

A

Penicillium notatum fungus (Penicillin G was the active ingredient and was purified from the broth)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What amino acid residues are Penicillin G constructed from? (3)

A
  1. Cysteine
  2. Valine
  3. Phenylalanine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What’s the mechanism of action of Beta-lactam antibiotics?

A
  • Lactam ring binds transpeptidase/carboxypeptidase enzymes to prevent cross-linking in the cell wall
  • Cell wall weakened causing cell to rupture
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What five factors affect the efficacy of a Beta Lactam?

A
  • Ability to penetrate the cell wall
  • Resistance to b-lactamases
  • Affinity of various Penicillin Binding Proteins (e.g. transpeptidase and carboxypeptidase)
  • Resistance to stomach
  • Formulation, pharmacokinetics, toxicology etc.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the 5 main penicillins and how susceptible are they to Beta Lactamases?

A
  • Penicillin G (acid labile = injection) and ampicillin (acid srable = oral) - susceptible to Beta Lactamase degradation
  • Amoxicillin - Resistant to class 1 Beta Lactamases
  • Methicillin and Flucloxacillin - Resistant to all Beta Lactamases
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the generations of Cephalosporins?

A
  • 1st, 2nd and 3rd
  • Generation 1 - hardly used
  • Generation 2 - Gram -ve activity and orally administered
  • Generation 3 - Gram -ve activity and injected
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is an example of a 2nd generation cephlasporin and what’s it used to treat?

A
  • Cefaclor
  • Gram -ve infections and Haemophilus (pneumonia causing)
17
Q

What is an example of a 3rd generation cephlasporin and what’s it used to treat?

A
  • Ceftriaxone
  • Used to treat serious infections (often used in combo with a macrolide or an aminoglycoside)
18
Q

What are the advantages of using carbapenems? (2)

A
  • Broad spectrum beta lactam antibiotics
  • Resistant to beta lactamases
19
Q

What are monobactams and which one is in use?

A
  • Gram negative beta lactams
  • Only aztreonam in use
20
Q

What is an example of an carbapenem, and what’s a problem associated with it use and how to avoid this problem?

A
  • Imipenem
  • It is rapidly deactivated in the kidney
  • If administered with cilastatin, this is prevented
21
Q

Describe the structure of Vancomycin and name the organism it’s derived from? (4)

A
  • A non-ribosomal peptide (cyclic peptide)
  • Many unusual amino acids
  • Glycosylated (sugar residues attached)
  • Product of Amycolatopsis orientalis
22
Q

Describe the mechanism of action of Vancomycin?

A

Crystal structure fits between peptidoglycan sheets, preventing cross-linking

23
Q

What Gram bacteria is vancomycin active against?

A
  • Gram +ve infections ONLY (used to treat serious infections)
24
Q

What is the preferred treatment of MRSA?

A

Nafcillin (some trusts use injected rifampicin-vancomycin)

25
Q

Why is vancomycin normally innjected?

A
  • The digestive system hydrolydes vancomycin’s peptide bonds
26
Q

What does oral vancomycin treat?

A

Clostridium diffcile infections

27
Q

What is an alternative drug to vancomycin that has a very similar mode of action?

A

Teicoplanin

28
Q

Name the structure

A

Penicillins

29
Q

Name the structure

A

Cephalosporins

30
Q

Name the structure

A

Carbapenems

31
Q

Name the structure

A

Monobactams

32
Q

Name the structure

A

Vancomycin