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Pharmacology MBBS > Cell Wall Synthesis Inhibitors > Flashcards

Cell Wall Synthesis Inhibitors Flashcards

1
Q

Formation of cell wall predecessor

A

NAM NAG complex - GAG
1. NAG + PEP using EPT Enolpyruvate transferase
2. NAM-NAG complex-GAG
Peptide chains ⛓:
1. L-alanine to D-form by alanine racemase
2. To alanine library chain by alanine ligase
3. Glycine added to it to form a T-shaped peptide

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2
Q

Cell wall formation from cell wall precursor

A
  1. Both the precursors joint in cytoplasm
  2. It is transported outside the cell membrane by lipid transporter (bactoprenol)
  3. It is polymerized by transpeptidase
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3
Q

Drugs acting on cell wall synthesis

A
  1. Fosfomycin and fosmidomycin 🅱️ EPT
  2. Cycloserine: 🅱️ alanine racemase, alanine ligase
  3. Bacitracin: 🅱️ lipids transporter
  4. Glycopeptides: vancomycin
    🅱️ D-alanine from forming cross-links
  5. β-lactams: 🅱️ transpeptidase
    Penicillins, cephalosporins, monobactams, carbapenems
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4
Q

Fosfomycin and fosfodomycin

mechanism and pharmacokinetics

A

Analogues of PEP ➡️ competitive 🅱️ of EPT
Pharmacokinetics:
• excreted unchanged in urine ➡️ UTI 3gm single dose
• safe in 🤰

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5
Q

Fosfomycin and fosfodomycin

spectrum

A

Limited spectrum
G-6-P transporter required for transportation into cell ➡️ only gram ➖ve bacteria
Eg., E. coli, klebsiella, serratia

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6
Q

Cycloserine

A

• D-alanine analogue ➡️ 🅱️ alanine racemase, ligase ➡️ cell wall synthesis 🅱️
• Gram ➖ve bacteria
• 2nd line drug for TB
• S/E: neuropsychiatric
Seizure, psychosis, peripheral neuropathy

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7
Q

Bacitracin

A

🅱️ lipids transporter ➡️ cell wall unit transport 🅱️
S/E:
nephrotoxic and bone marrow suppression ➡️ no systemic use
Topical:
• skin infections
• staph nasal carriers (MRSA)
DoC topical mupirocin
Local: GIT
• pseudomembranous enterocolitis
• VRE (vancomycin resistant enterococcus)

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8
Q

Glycopeptides

effects of its size

A

Large in size ➡️ 🔽 oral absorption
Spectrum:
Gram ➕ve bacteria
In gram -ve bacteria, porins allow only small size molecules and water soluble particles to pas

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9
Q

Vancomycin

A

IV route: DoC
1. MRSA
2. Enterococcus faecium
3. Ampicillin resistant enterococcus faecalis
Oral route: DoC
Pseudomrmbranous enterocolitis
• if not responding: fidaxomycin, rifaximin
S/E:
1. 🔼 release of histamine: red neck/man syndrome
2. Nephrotoxic
3. Ototoxic

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10
Q

Recent advances for prophylaxis of pseudomembranous enterocolitis

A
  1. Bezlotoxumab
    Anticlostridium difficile toxin-B antibody
  2. Actozumab:
    Anticlostridium difficile toxin-A antibody
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11
Q

Other glycopeptide drugs

A
  1. Teicoplanin
  2. Dalbavancin: long acting
  3. Telavancin and Oritavancin:
    Disrupts cell membrane ➡️ 🔼bactericidal
    Use: only for SSTI by MRSA
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12
Q

Narrow spectrum penicillins

A 
Penicillin-G
• lipid soluble
• active day
1. G ➕ve 
2. Some G ➖ve bacteria (meningococcus)
Structure: R group present
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13
Q

Broad spectrum

A

• Amidase enzyme ➡️ breaks side chain R
• functional group FG added in place of side chain R
➡️ ionised and water soluble
➡️ active against G ➖ve also

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14
Q

Classification of broad spectrum penicillins

A 
1. Amino (+ve): orally
• amoxicillin, ampicillin
2. Carboxy (-ve): parenteral
• carbenicillin, ticaricillin
3. Ureido (+ve, -ve): parenteral
 Max active against G➖ve organism
 Piperacillin, Azlocillin, Mazlocillin
The last two groups are active against pseudomonas
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15
Q

Amoxicillin

uses

A
  1. Diverticulitis
  2. Cellulitis
  3. Ludwig’s angina
  4. Vincent’s angina
  5. UTI (safe in 🤰)
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16
Q

Ampicillin

uses

A

DoC for:

  1. Meningitis by listeria
  2. H influenza: pneumonia, otitis
  3. Enterococcus faecalis
  4. Shigella infections
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17
Q

Uses of ureidopenicillin like piperacillin, mezlocillin

A

Active against klebsiella and enterococcus

18
Q

Penicillin G

A 
IV route (aqueous)
(IM route ➡️ injection site reaction)
Pharmacokinetics:
1. Poor oral absorption:
 Acid labile unlike acid stable P. V
2. Rapid tubular secretions:
 P-gp pumps ➡️ Very short acting (long acting can be made)
19
Q

Long acting penicillin

A
  1. P-gp
    Probenecid penicillin G
    IM route (not IV, toxicity)
    Measured in IU, 1mg = 1600 IU
  2. 🔼 H2O solubility:
    Given IM:
    • procaine penicillin-G: no pain at injection site (local anesthetic)
    • benzathine penicillin-G: longest acting (28 days)
    DoC: prophylaxis of rheumatic fever (monthly)
20
Q

Penicillin uses

A
  1. Syphilis
  2. Streptococcus infection
  3. Gas gangrene
  4. Yaws
  5. Leptospirosis
  6. Rat bite fever
21
Q

Benzathine penicillin G

2.4 million IU once

A

• 1° syphilis
• 2° syphilis
S/E: Jarisch Herxheimer reaction (hypersensitivity reaction)
🤒, arthralgia, myalgia, worsening of cutaneous lesion
• Early latent syphilis

22
Q

Benzathine penicillin G

2.4 million IU 3 doses once/week

A
  1. Tertiary syphilis (without CNS involvement)
  2. CNS involvement
  3. Late latent
23
Q

Neurosyphilis

DoC

A

Aqueous penicillin G
18-24 million IU
Continuous IV infusion (10-14 days)

24
Q

Mechanism of resistance of penicillin in gram ➖ve bacteria

A
  1. Decreased porin production
    Eg., pseudomonas
  2. Drug efflux
    Eg., pseudomonas, E. coli, gonococcus
25
Q

Mechanism of resistance of penicillin in gram ➖ve & gram ➕ve bacteria

A
  1. Altered transpeptidase (protein binding protein)
    Eg., Staphylococcus ➡️ MRSA ➡️ mec A gene
  2. β-lactamase production: Ambler production
26
Q

Ambler classification of β-lactamase production

A

Class A: ESBL enzymes
DoC carbapenems
• penicillinase
• cephalosporinase
• monobactams
Class B: all enzymes except monobactamase
Class C: cephalosporinase
Class D: cloxacillinase
NDM-1 (New Delhi metalo-1) β lactamase breaks
β lactams/fluoroquinlones, macrolides, Chloramphenicol
Rx: Tigecycline, colistin

27
Q

β lactamase inhibitors

A
  1. Clavulanic acid: with amoxicillin
  2. Sulbactam: with ampicillin
    Rx: acinetobacter
  3. Tazobactam: piperacillin
  4. Avibactam: with ceftazidime
  5. Vaborbact: with meropenem
  6. Relebactam: with imipenem + cilastatin
28
Q

Oral penicillinase resistant penicillins

A
  1. Cloxacillin: DoC mastitis
  2. Dicloxacillin:
    Most active PRP‘S agonist Staph
  3. Oxacillin: hepatotoxic
29
Q

Parental drugs

A 
1. Nafcillin:
 Most active PRP (other microbes)
 S/E: neutropenia
2. Methicillin:
 S/E: interstitial nephritis
30
Q

Cephalosporins

spectrum according to generation

A 
1st generation:
• Most G➕, some G➖
• anaerobes except bacteriodes 
2nd generation:
• both G ➕&➖
• anaerobes and bacteroides
3rd gen: only G➖
4th gen:
• both G➕&➖ 
• pseudomonas, enterobacter
5th gen:
• both G➕&➖
• Staph, Strept, MRSA
31
Q

First generation cephalosporins

examples

A

Cefadroxil
Cefradin
Cephalexin
Cefazolin-IV others are oral

32
Q

Cefazolin IV uses

(1st gen cephalosporin)

A
  1. Staph infections
  2. Strept infections
  3. DoC: surgical prophylaxis;
    • 1 hr before incision
    • 24 hr after surgery
33
Q

Uses of cefadroxil and cephalexin

(1st gen cephalosporins)

A

UTI
active against E. coli, klebsiella
Well concentrated in urine

34
Q

Second generation cephalosporins

examples

A 
Follow Maur taxi par
Fa cefaclor
Lo loracarbef
Ma cefamandole
Ur cefuroxime
Ta cefotetan
Xi cefoxitin
Par cefprozil
Follow oral par 
Maur IV/IM
35
Q

Uses of ‘follow maur’ of second generation cephalosporins

A 
Not active against bacteroides 
Uses:
1. Pneumonia 🫁 
2. Otitis 👂 
3. Surgical prophylaxis
4. Sinusitis
36
Q

Uses of cefotetan and cefoxitin

A 
Cefotetan:
• most active against anaerobes
• prophylaxis of anaerobic infection ➡️ Used in colorectal surgeries
Cefoxitin:
• 2nd most active against anaerobes
• use: Rx off PID, lung abscess
37
Q

Third generation cephalosporins

A 
Delhi PMT Xam
Delhi: orally
 Cefdinir
 Cefditoren
 Cefpodoxime
P. Cefoperazone
M. Moxalactam
T: IV/IM
 Ceftriaxone (longest acting)
 Ceftizoxime
 Cefotaxime (shortest acting)
 Ceftazidime
Xam: Cefixime - orally
38
Q

Ceftriaxone

uses

A 
DoC:
1. Gonorrhea:
 current ToC: ceftriaxone + Azithromycin/doxycycline
2. E. coli infections
3. Klebsiella
4. Providencia
5. Typhoid (oral DoC cefixime)
6. Meningitis caused by: except listeria
• H influenza
• meningococcus
• empirical 
7. Osteomyelitis
39
Q

Ceftazidime

uses

A
  1. DoC for pseudomonas, add aminoglycoside
  2. Melioidosis
  3. Febrile neutropenia
40
Q

Ceftolozane

A 
Derivative of ceftazidine (3rd generation cephalosporin)
 Used:
1.  against pseudomonas
With Tazobactum against:
2. Complicated abdominal infections
3. UTI

Pharmacology MBBS (19 decks)

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