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B. Anti-microbials > 2. Bacterial Cell Wall Synthesis Inhibitors > Flashcards

2. Bacterial Cell Wall Synthesis Inhibitors Flashcards

1
Q

Classification of bacterial cell wall synthesis inhibitors

A

Beta lactams:

a. Penicillins
1. Natural penicillins
2. Penicillinase resistant penicillins
3. Aminopenicillins + BL inhibitors
4. Anti pseudomonal pencillins + BL inhibitors

b. Cephalosporins
c. Carbapenems
d. Monobactam

Glycopeptide: Vancomycin

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2
Q

MOA of beta lactams

A
  1. Interfere with the synthesis of the bacterial cell wall peptidoglycan
  2. They act by binding to the active site of the enzyme, transpeptidase, which catalyses the cross-linking of the terminal peptide components of the linear polymer chains
  3. In actively growing cell → results in weakening of the cell wall structure → build up in intracellular osmotic pressure and lysis of the bacterial cells → bactericidal to actively growing cells
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3
Q

Types of natural penicillins

A
  1. Penicillin G

2. Penicillin V

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4
Q

Examples of penicillinase-resistant penicillins

A

Cloxacillin, Oxacillin, Flucloxacillin

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5
Q

Types of aminopenicillins

A
  1. Ampicillin
  2. Amoxicillin
  3. Piperacillin
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6
Q

MOA of beta-lactamse inhibitors

A
  1. They work primarily by inactivating serine beta-lactamases, which are enzymes that hydrolyse and inactivate the beta-lactam ring
  2. Strong affinity for beta-lactamases → allow them to either bind and inactivate it thus protecting beta-lactams from being targeted by the beta-lactamases
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7
Q

Types of beta-lactamse combination drugs

A
  1. Amoxicillin clavulanic acid
  2. Ampicillin sulbactam
  3. Piperacillin tazobactam
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8
Q

Mechanism of resistance to penicillin

A
  1. Transpeptidase can be altered → reduced affinity for penicillin
  2. Production of beta-lacatamase → hydrolysis of beta-lacatam ring
  3. Decreased ability of the antibiotic to reach the transpeptidase when the bacteria decreases porin production → decrease in intracellular drug conc.
  4. Presence of efflux pumps
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9
Q

Adverse reactions to penicillins

A
  1. Allergy / hypersensitivity
    - Steven Johnson syndrome (SJS)
    - Toxic Epidermal Necrolysis (TEN)
  2. Clostridium difficile-associated diarrhoea (CDAD) (with ampicillin, co-amoxiclav)
  3. Neurotoxicity
  4. Hepatotoxicity (penicillinase-resistant penicillin)
  5. Anosmia
  6. High dose penicillins in renal failure → seizures
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10
Q

Examples of 1st Gen Cephalosporins

A
  1. Cefazolin

2. Cephalexin

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11
Q

Examples of 2nd Gen Cephalosporins

A

Cefuroxime

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12
Q

Examples of 3rd Gen Cephalosporins

A
  1. Cefotaxime
  2. Ceftriaxone
  3. Ceftazidime
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13
Q

Examples of 4th Gen Cephalosporins

A

Cefepime

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14
Q

Examples of 5th Gen Cephalosporins

A
  1. Ceftaroline

2. Ceftobiprole

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15
Q

1st to 4th Gen Cephalosporins lack activity against?

A 
LAME 
Listeria monocytogenes 
Atypicals (mycoplasma, chlamydia, legionella spp.)
MRSA
Enterococcus spp.
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16
Q

Adverse reactions to cephalosporins

A
  1. Hypersensitivity - as with penicillin
    * patients with a history of anaphylaxis with penicillin should not be given a cephalosporin*
  2. GIT - diarrhoea, CDAD
  3. Thrombophlebitis
17
Q

Types of Carbapenems

A
  1. Imipenem and Cilastatin
  2. Meropenem
  3. Ertapenem
18
Q

Adverse effects of carbapenems

A
  1. GIT-related symptoms (nausea, vomiting, diarrhoea)
  2. Rashes
  3. Neurotoxicity at high blood conc.
  4. Cross-hypersensitivity with penicillin
19
Q

Example of monobactam

A

Aztreonam

20
Q

Example of glycopeptide

A

Vancomycin

21
Q

MOA of vancomycin

A

Binds with high affinity to the D-ala-D-ala terminus of pentapeptide of NAM component of peptidoglycan and interferes with transglycosylation of the cell wall precursor units, hence inhibiting bacterial cell wall synthesis

22
Q

Adverse effects of vancomycin

A
  1. Thrombophlebitis with fever, chills
  2. “Red-neck” or “Red man syndrome”
  3. Nephrotoxicity and ototoxicity
  4. Pregnancy: Cat C (for parental formation), Cat B (for oral capsules)
23
Q

Vancomycin resistance

A
  1. Enterococcal resistance → due to expression of enzymes that modify cell wall precursor by substituting the terminal D-alanine, for D-lactate or D-serine → reducing vancomycin binding affinity
  2. Emergence of S. aureus that expresses reduced or “intermediate” susceptibility to vancomycin → major concern

B. Anti-microbials (7 decks)

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