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Pharmacology (3) > CH2 | Cell Wall Inhibitors > Flashcards

CH2 | Cell Wall Inhibitors Flashcards

1
Q

List beta-lactam antibiotics.

A
  • Penicillins.
  • Cephalosporins.
  • Carbapenems.
  • Monobactams.
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2
Q

What is the bacterial cell wall composed of?

A

Peptidoglycan strands (polymer of glycan units joined to each other by peptide cross-links).

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3
Q

What condition must bacteria meet for cell wall inhibitors to work?

A

Actively proliferating bacterial cells.

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4
Q

Gram-positive bacteria Vs. Gram-negative bacteria.

A

G+: Thick peptidoglycan layer.
G-: Thin peptidoglycan layer / Outer membrane with porins.

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5
Q

How do penicillins work?

A

Penicillins bind to PBPs, inhibiting transpeptidase enzymes needed for peptidoglycan cross-linking. This weakens the bacterial cell wall, leading to cell death.

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6
Q

Are cell wall inhibitors bacteriostatic or bactericidal?

A

Bactericidal.

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7
Q

What are the two natural penicillins?

A
  • Penicillin V.
  • Penicillin G.
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8
Q

Penicillin V is available…

A

Orally only.

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9
Q

Penicillin G is available…

A

Parenterally only.

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10
Q

Natural Penicillins Antibacterial Spectrum

A
  • Gram+
  • Gram-
  • Spirochetes.
  • Anaerobes.
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11
Q

All types of penicillins are facing increasing resistance due to…

A

Bacterial beta-lactamase production.

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12
Q

Natural penicillins are the drug of choice for…

A
  • Gas gangrene (Clostridium perfringens).
  • Syphilis (Treponema pallidum).
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13
Q

What are the two semisynthetic/amino/extended spectrum penicillins?

A
  • Ampicillin.
  • Amoxicillin.
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14
Q

Semisynthetic Penicillins Antibacterial Spectrum

A
  • Gram+
  • (((EXTENDED))) Gram-
  • Spirochetes.
  • Anaerobes.
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15
Q

Semisynthetic penicillins are the drug of choice for…

A
  • Respiratory infections.
  • Prevention of endocarditis in high-risk dental patients.
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16
Q

Semisynthetic penicillins must be administered with…

A

Beta-lactamase inhibitors:
- Clavulanic acid.
- Sulbactam.

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17
Q

What are the three antistaphylococcal penicillins?

A
  • Methicillin.
  • Nafcillin.
  • Oxacillin.
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18
Q

Which type of penicillins is beta-lactamase resistant?

A

Antistaphylococcal penicillins (methicillin, naficillin, oxacillin).

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19
Q

Antistaphylococcal Penicillins Antibacterial Spectrum

A
  • Restricted to gram-positive penicillinase producing staphylococci, including (((MSSA))).
  • No activity against gram-positive organisms!!!
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20
Q

Antistaphylococcal penicillins are resistant to…

A

MRSA.

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21
Q

What is the only antipseudomonal penicillin?

A

Piperacillin.

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22
Q

Antipseudomonal Penicillins Antibacterial Spectrum

A
  • Inherent antipseudomonal activity, especially against (Pseudomonas aeruginosa).
  • Can be extended to include pencillinase-producing (Enterobacteriaceae) and (Bacteroides species) by using the beta-lactam inhibitor (tazobactam).
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23
Q

How can piperacillin’s spectrum be extended to include (Enterobacteriaceae) and (Bacteroides species)?

A

By coadministering it with the beta-lactamase inhibitor (tazobactam).

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24
Q

What are the three resistance mechanisms to penicillins?

A
  • Beta-lactamase production.
  • Decreased drug permeability.
  • Modified PBPs.
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25
Q

What do beta-lactamases do?

A

They hydrolyze cyclic amide bonds.

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26
Q

How are beta-lactamases produced?

A

Inherently or acquired.

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27
Q

How do Gram+ organisms secrete beta-lactamases?

A

Extracellularly.

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28
Q

How do Gram- organisms secrete beta-lactamases?

A

Periplasmic space.

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29
Q

Drug permeability resistance for gram-positive organisms?

A

Unlikely.

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30
Q

Drug permeability resistance for gram-negative organisms?

A

Common, due to cell wall structure and the presence of porin channels.

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31
Q

Which bacteria lacks high permeability porins?

A

Pseudomonas aeruginosa.

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32
Q

Which bacteria lacks efflux pumps?

A

Klebsiella pneumoniae.

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33
Q

Which bacteria is famous for being resistant due to altering its PBPs?

A

MRSA.

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34
Q

How are penicillins administered?

A
  • Orally.
  • Parenterally (IV/IM).
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35
Q

Which penicillins are available as depot forms for slow IM absorption and longer duration of action?

A
  • Procaine penicillin G.
  • Benzathine penicillin G.
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36
Q

How is the absorption of penicillins like, generally?

A

Poorly absorbed orally due to stomach acid instability.

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37
Q

How’s the oral bioavailability of penicillin V?

A

Poor.

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38
Q

Which penicillin is taken on an empty stomach?

A

Dicloxacillin.

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39
Q

Which penicillin is stable in stomach acid and is therefore readily absorbed from the GIT?

A

Amoxicillin.

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40
Q

How is the distribution of penicillins like, generally?

A
  • Distributed well.
  • Cross the placental barrier.
  • No teratogenic effects.
  • Insufficient bone and CSF penetration, except during inflammation.
  • Insufficient prostate penetration.
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41
Q

How is the metabolism of penicillins like, generally?

A

Insignificant in healthy individuals.

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42
Q

Which penicillin faces increased metabolism in renally impaired patients?

A

Penicillin G.

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43
Q

Which penicillins are metabolized in the liver?

A
  • Nafcillin.
  • Oxacillin.
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44
Q

How are most penicillins excreted primarily and secondarily?

A

Primarily, renally, via organic acid tubular secretory system and glomerular filtration.
NOTE: Dose adjustments are recommended for renally impaired patients.

Secondarily, through breast milk.

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45
Q

Which penicillins are excreted in the liver?

A
  • Nafcillin.
  • Oxacillin.
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46
Q

Adverse Effects of Penicillins.

A
  • Hypersensitivity.
  • Cross-allergic reactions.
  • Diarrhea.
  • Nephritis.
  • Neurotoxicity.
  • Hematologic toxicities.
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47
Q

How’s the hypersensitivity of penicillins?

A

Ranges from mild rashes to fatal angioedema and anaphylaxis.

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48
Q

What is the cross-reactivity profile of penicillins?

A

Cross-allergic with other beta lactams.

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49
Q

What is the mechanism of action of cephalosporins?

A

Same as penicillins.

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50
Q

What are the resistance mechanisms to cephalosporins?

A
  • Beta-lactamase production.
  • Reduced PBP affinity.
    Generally, same as penicillins.
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51
Q

Which cephalosporins induce their own resistance?

A
  • Second generation cephalosporins.
  • Third generation cephalosporins.
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52
Q

How many generations of cephalosporins exist?

A

5 generations.

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53
Q

List the first generation cephalosporins.

A

Cephalexin (taken orally).
Cefadroxil (taken orally).
Cefazolin (taken parenterally; long duration of action).

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54
Q

What is Cephalexin used for?

A

Pharyngitis.

55
Q

First Cephalosporin Generation Antibacterial Spectrum

A
  • Gram+
  • Gram-
  • MSSA.
56
Q

List the second generation cephalosporin.

A
  • Cefuroxime axetil (taken orally).
  • Cefuroxime sodium (taken parenterally).
57
Q

Cefuroxime Antibacterial Spectrum

A
  • Greater Gram+ activity.
  • Weaker Gram- activity.
  • MSSA.
58
Q

Which gram-positive bacteria do second generation cephalosporins target?

A
  • H. influenzae.
  • Klebsiella species.
  • Proteus species.
  • E. coli.
  • Moraxella catarrhalis.
59
Q

Cephamycins Antibacterial Spectrum

A

Gram- anaerobes, but still not considered a first-line treatment.

60
Q

What are the cephamycins?

A
  • Cefotetan.
  • Cefoxitin.
61
Q

What is cefuroxime sodium’s half-life?

A

Longer than similar agents.

62
Q

How’s cefuroxime sodium absorption?

A

Can cross the blood-brain barrier.

63
Q

What is cefuroxime sodium used for?

A
  • Community-acquired bronchitis.
  • Pneumonia in the elderly and immunocompromised agents.
64
Q

List the third generation cephalosporins.

A
  • Cefdinir (taken orally).
  • Cefixime (taken orally).
  • Cefotaxime (taken parenterally).
  • Ceftazidime (taken parenterally).
  • Ceftriaxone (taken parenterally).
65
Q

What is Cefotaxime used for?

A

Treating meningitis; because it can cross the blood-brain barrier.

66
Q

Which third generation cephalosporin is the only drug of its kind that acts against Pseudomonas aeruginosa?

A

Ceftazidime.

67
Q

Which cephalosporin has the longest half-life of its kind?

A

Ceftriaxone.

68
Q

Which cephalosporin has high concentration levels in the blood, CSF, and bones?

A

Ceftriaxone.

69
Q

What is Ceftriaxone used for?

A

Treating meningitis; because it can cross the blood-brain barrier.

70
Q

Which is the drug of choice for treating genital, anal, and pharyngeal Neiserria gonorrhoeae?

A

Ceftriaxone.

71
Q

General Antibacterial Spectrum of Third Generation Cephalosporins

A
  • Less potent than first generation cephalosporins for treating MSSA.
  • Enhanced activity against Gram- bacilli, including beta-lactamase producing H. influenzae and Nesseria gonorrhoea.
  • Acts against Gram+.
  • Acts against Gram-.
72
Q

Why should third generation cephalosporins be used cautiously?

A
  • Increased resistance.
  • C. difficile infection.
73
Q

What is the fourth generation cephalosporin?

A

Cefepime (taken parenterally).

74
Q

Which fourth generation cephalosporin acts against Pseudomonas aeruginosa?

A

Cefepime.

75
Q

General Antibacterial Spectrum of Fourth Generation Cephalosporins

A
  • Pseudomonas aeruginosa.
  • Same as third generation cephalosporins.
  • Acts against methicillin susceptible streptococci and staphylococci.
  • Greater stability to beta-lactamases.
76
Q

What is the fifth (advanced) generation cephalosporin?

A

Ceftaroline (taken parenterally).

77
Q

Which is the only beta-lactam active against MRSA?

A

Ceftaroline.

78
Q

Which cephalosporin is active against Streptococcus pneumoniae?

A

Ceftaroline.

79
Q

What is ceftaroline used for?

A

Complicated skin structure infections and community-acquired pneumonia.

80
Q

General Antibacterial Spectrum of Fifth Generation Cephalosporins

A
  • Broad gram+ spectrum.
  • Same gram- spectrum as third generation cephalosporins.
81
Q

Which bacteria has developed resistance to fifth generation cephalosporin ceftaroline?

A

Pseudomonas aeruginosa.

82
Q

How are cephalosporin administered?

A
  • Orally.
  • Parenterally (IV/IM).
83
Q

How are cephalosporin distributed into body fluids?

A

Very well.

84
Q

Which cephalosporins are used to treat CSF infections, especially neonatal and childhood meningitis caused by H. influenzae?

A

Ceftriaxone and cefotaxime.

85
Q

Which cephalosporin is used for surgical prophylaxis?

A

Cefazolin.

86
Q

Which cephalosporin is used for penicillinase-producing S. aureus?

A

Cefazolin.

87
Q

How are cephalosporins metabolized generally?

A

Renally (tubular secretion and/or glomerular filtration).

88
Q

Which cephalosporin is excreted through the bile in the feces?

A

Ceftriaxone.

89
Q

Adverse Effects of Cephalosporins

A
  • As well-tolerated as penicillins.
  • Allergic reactions.
90
Q

How is the cross-reactivity between cephalosporins and penicillins?

A

3% to %5; determined by side chain similarity.

91
Q

Where does the highest cephalosporin cross-reactivity rate exist?

A

Between penicillins and first generation cephalosporins.

92
Q

For which kind of patients are cephalosporins used cautiously?

A

Penicillin allergic patients.

93
Q

List the carbapenems.

A
  • Doripenem.
  • Imipenem.
  • Meropenem.
  • Ertapenem (different coverage than similar agents).
94
Q

What is the mechanism of action of carbapenems?

A

Same as penicillins.

95
Q

Carbapenem Antibacterial Spectrum

A

Broad spectrum:
- Acts on Beta-lactamase producing Gram+ and Gram- organisms.
- Acts on anaerobes.
- Acts on Pseudomonas aerugionsa.

96
Q

How is the resistance of carbapenems to bacteria?

A

They resist normal beta-lactamases, but not metallo-beta-lactamases.

97
Q

How are carbapenems administered?

A

All of them are administered parenterally.

98
Q

How are carbapenems excreted?

A

Renally; through glomerular filtration.

99
Q

How’s the penetration of carbapenems, generally?

A

Carbapenems penetrate body fluids well; including the CSF when the meninges are inflamed.

100
Q

Which carbapenem can reach therapeutic CSF levels without meningeal inflammation?

A

Meropenem.

101
Q

Which carbapenem is coadministered with cilastatin to prolong its activity?

A

Only imipenem.

102
Q

Why is imipenem coadministered with cilastatin?

A

To inhibit proximal renal tubule dehydropeptidase hydrolyzation.

103
Q

Adverse Effects of Carbapenems

A
  • Nausea, diarrhea, vomiting.
  • Eosinophilia and neutropenia.
  • Seizures.
  • Cross-reactivity.
104
Q

Which carbapenems cause nausea, diarrhea, and vomiting?

A

Imipenem and colistatin.

105
Q

Which carbapenems cause seizures?

A

Imipenem.

106
Q

Cross-reactivity of Carbapenems and Penicillins

A

Less than 1%; still used cautiously with penicillin allergic patients.

107
Q

List the only monobactam available.

A

Azretonam.

108
Q

What is the mechanism of action of monobactams?

A

Same as penicillins.

109
Q

Monobactam Antibacterial Coverage

A
  • Only gram-negative bacteria, including (Enterobacteriaceae) and (Pseudomonas aeruginosa).
  • No activity against gram-positive bacteria or anaerobes.
110
Q

How are monobactams excreted?

A

Renally.

111
Q

How are monobactams administered?

A

Parenterally (IV/IM).

112
Q

Adverse Effects of Monobactams

A
  • Phlebitis.
  • Skin rash.
  • Abnormal liver test results.
113
Q

How is monobactams’ cross-reactivity with penicillins?

A

Minimal; making them safe for penicillin, cephalosporin, and carbapenem allergic patients.

114
Q

List the four most commonly used beta-lactamase inhibitor combinations.

A
  • Amoxicillin + Clavulanic Acid (taken orally).
  • Ceftolozone + Tazobactam (Taken IV).
  • Ceftazidime + Avibactam (taken IV).
  • Meropenem + Vaborbactam (taken IV).
115
Q

What is the mechanism of action of vancomycin?

A

Cell wall synthesis by binding to D-Ala-D-Ala terminus of nascent peptidoglycan pentapeptide. This disrupts cross-linking and results in cell death.

116
Q

When is vancomycin used?

A
  • Skin and soft tissue infections.
  • Infective endocarditis.
  • Nosocomial pneumonia.
117
Q

How is vancomycin administered?

A

IV or orally.

118
Q

What does orally administered vancomycin treat?

A

Clostridium diffcile infections; due to its poor oral absorption.

119
Q

Adverse Effects of Vancomycin

A
  • Nephrotoxicity.
  • Infusion-related toxicity.
  • Ototoxicity.
120
Q

Vancomycin Resistance Mechanisms

A

Bacteria changes D-Ala-D-Ala to D-Ala-D-Lactate, rendering vancomycin useless.

121
Q

Bacitracin Mechanism of Action?

A

Interferes with dephosphorylation in cycling of the lipid carrier that transfers peptidoglycan to the growing cell wall.

122
Q

Why is bacitracin only administered topically?

A

Because it is highly nephrotoxic.

123
Q

Bacitracin Antibacterial Spectrum

A

Acts only against gram-positive bacteria.

124
Q

Fosfomycin Antibacterial Spectrum

A

Acts against gram-positive and gram-negative bacteria.

125
Q

Fosfomycin Mechanism of Action?

A

Inhibits the cytoplasmic enzyme (enol pyruvate transferase), which is required for the formation of (NAM), a component of the bacterial cell wall (peptidoglycan).

126
Q

Polymyxins’ Antibacterial Spectrum

A

Active against gram-negative bacteria only.

127
Q

List the polymyxins.

A
  • Polymyxin B.
  • Polymyxin E (colistin).
128
Q

Polymyxins Mechanism of Action?

A

They bind to the phospholipids present on the bacterial cell membrane, creating a detergent-like effect that causes leakage; ultimately resulting in cell death.

129
Q

Why are Polymyxins used as a last resort (salvage therapy for multi-drug resistant patients)?

A

Because of their nephrotoxicity and neurotoxicity.

130
Q

How is Polymyxin B administered?

A
  • Parenterally.
  • Ophthalmically.
  • Otically.
  • Topically.
131
Q

How is Polymyxin E (colistin) administered?

A

IV or inhalation.

132
Q

Antibacterial Spectrum of Daptomycin?

A

Same as vancomycin. It is used for strains that are resistant to vancomyin.

133
Q

How is Daptomycin administered?

A

Parenterally.

134
Q

Daptomycin Mechanism of Action

A

Daptomycin binds to bacterial cell membranes in the presence of calcium, inserting its lipid tail into the membrane. This forms channels that allow potassium ions to leak out, causing membrane depolarization and rapid loss of membrane potential. As a result, essential cellular processes fail, leading to bacterial cell death.

Pharmacology (3) (15 decks)

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