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tcol > Beta-Lactam Antibiotics & Other Cell Wall Synthesis Inhibitors > Flashcards

Beta-Lactam Antibiotics & Other Cell Wall Synthesis Inhibitors Flashcards

1
Q

what are the similarities of bactericidal and bacteriostatic?

A

they are both antimicrobial drugs

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2
Q

What are the differences of bactericidal ang bacteriostatic?

A

Bactericidal - eradicate infection without host defense mechanism
Bacteriostatic - inhibits antimicrobial growth, need host defense mechanism to eradicate infection

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3
Q

Drugs with structures containing a beta-lactam ring: includes the penicillins, cephalosporins and carbapenems. This ring must be intact for antimicrobial action

A

Beta-lactam
antibiotics

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4
Q

Bacterial enzymes (penicillinases, cephalosporinases) that hydrolyze the beta-lactam ring of certain penicillins and cephalosporins

A

Beta-lactamases

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5
Q

Potent inhibitors of some bacterial beta-lactamases used in combinations to protect hydrolyzable penicillins from inactivation

A

Beta-lactamase
inhibitors

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6
Q

Lowest concentration of antimicrobial drug capable of
inhibiting growth of an organism in a defined growth
medium

A

Minimal
inhibitory
concentration
(MIC)

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7
Q

Bacterial cytoplasmic membrane proteins that act as the initial receptors for penicillins and other beta-lactam antibiotics

A

Penicillin-binding
proteins (PBPs)

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8
Q

Chains of polysaccharides and polypeptides that are
cross-linked to form the bacterial cell wall

A

Peptidoglycan

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9
Q

More toxic to the invader than to the host; a property of
useful antimicrobial drugs

A

Selective
toxicity

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10
Q

Bacterial enzymes involved in the cross-linking of linear peptidoglycan chains, the final step in cell wall synthesis

A

Transpeptidase

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11
Q

Types of Microbial resistance:

A

1.Production of antibiotic-inactivating enzymes
2.Changes in the structure of target receptors
3.Increased efflux via drug transporters
4. Decreases in the permeability of microbes’ cellular membrane to antibiotics

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11
Q

Strategies to combat Microbial resistance

A
  1. Use of adjunctive agents that can protect against antibiotic inactivation
  2. Use of antibiotic combinations
  3. Introduction of new chemical derivatives of establish anibiotics
  4. Efforts to avoid indiscriminate use or misuse of anitbiotics
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12
Q

the major antibiotics that
inhibit bacterial cell wall synthesis:

A
  • Penicillins
  • Cephalosporins
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13
Q

Why are they called beta-lactams

A

Because of their 4-member ring

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14
Q

include some of the most
effective, widely used, and well-tolerated agents available for
the treatment of microbial infections.

A

beta-lactams

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14
Q

also inhibit cell wall synthesis but are not nearly as important as the beta-lactam drugs:

A
  • Vancomycin
  • Fosfomycin
  • Bacitracin
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15
Q

The selective toxicity
of the drugs discussed in this chapter is mainly due to specific
actions on the _________ that is unique to the microorganism.

A

synthesis of a cellular structure

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16
Q

how many antibiotics that act as cell wall synthesis inhibitors are currently available, with individual
spectra of activity that afford a wide range of clinical applications

A

More than 50

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17
Q

2 types of Narrow spectrum Penicillins

A
  • Penicillinase susceptible
  • Penicillinase resistant
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18
Q

What generation is included in narrow spectrum cephalosporins?

A

1st generation

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19
Q

What generation is included in wider spectrum cephalosporins?

A

2nd, 3rd, 4th generation

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20
Q

3 miscellaneous Bacterial cell-wall inhibitors

A
  • Carbapenems
  • Aztreonam
  • Vancomycin
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21
Q

Penicillins are derivatives of what?

A

6-aminopenicillanic acid

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22
Q

What does all penicillins contain that is esential for antibacterial activity

A

beta-lactam ring

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23
Q

Penicillin subclasses have additional chemical substituents that confer differences in:

A
  • antimicrobial activity
  • susceptability to acid and enzymatic hydrolysis
  • biodisposition
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24
Q

Pharmacokinetics

Since penicillins vary in their resistance to gastric acid, therfore they vary in their __________

A

Oral Bioavailability

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25
Q

Pharmacokinetics

Why are penicillins not metabolized extensively?

A

because they are polar compounds

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26
Q

Pharmacokinetics

What are the penicillin parenteral formulations that are available for injections?

A
  • Ampicillin
  • Piperacillin
  • Ticarcillin
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27
Q

Pharmacokinetics

Penicillins are usually unchange in the urine via:

A
  • glomerular filtration
  • tubular secretion
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28
Q

Pharmacokinetics

The tubular secretion of penicillins are inhibited by?

A

Probenecid

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29
Q

Pharmacokinetics

What kind of penicillin is mainly excreted in the bile?

A

Nafcillin

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30
Q

Pharmacokinetics

What kind of penicillin undergoes enterohepatic cycling?

A

ampicillin

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31
Q

Pharmacokinetics

Half life of most penicillins?

A

30 mins to 1 hour

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32
Q

Pharmacokinetics

Forms of penicillin G that are administered intramuscularly and have longer half lives

A
  • procaine
  • benzathine
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33
Q

Pharmacokinetics

Why do procaine and benzathine have longer plasma half-lifes?

A

because the active drug is released vrey slowly to the bloodstream

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34
Q

Pharmacokinetics

When does most penicillins cross the blood-brain barrier?

A

When the meniges are inflamed

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35
Q

Mechanisms of Action

What kind of drugs are beta-lactams?

A

Batericidal drugs

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36
Q

Mechanisms of Action

Steps on how beta-lactams inhibit cell wall synthesis:

A
  1. Bind to specific receptors (penicillin-binding proteins)
  2. Inhibition of transpeptidation reaction
  3. Activation of autolytic enzymes
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37
Q

Mechanisms of Action

Where are PBPs located?

A

in the bacterial cytoplasmic membrane

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38
Q

Mechanisms of Action

the reaction that cross-links the linear pe[tidoglycan chain constituents of the cell wall

A

Transpeptidation reaction

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39
Q

Mechanisms of Action

Enzymes that causes lesions in the bacterial cell wall

A

Autolytic enzymes

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40
Q

Resistance

If this happens to the beta-lactam ring, it will result in the loss of antibacterial activity

A

Enzymatic hydrolysis

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41
Q

Resistance

Is the major mechanism of bacterial resistance

A

Formation of beta-lactamase (penicillinase)

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42
Q

Resistance

What organisms use the formation of penicillinase as resistance?

A
  • staphylococci
  • gram negative organisms
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43
Q

Resistance

What inhibitors of penicillinase are often used in combination with penicillin to prevent their inactivation?

A
  • cluvanic acid
  • sulbactam
  • tazobactam
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44
Q

Resistance

Structural change in target PBPs of staphylococci is responsible for?

A

methicillin resitance

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45
Q

Resistance

Structural change in target PBPs of pneumococci and enterococci is responsible for?

A

penicillin G resistance

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46
Q

Resistance

Example of pneumonococci

A

Penicillin resistant Streptococcus pneumoniae (PRSP)

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47
Q

Resistance

What organisms use changes in the porin structure as resistance

A

Gram negative rods (Pseudomonas aeruginosa)

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48
Q

Resistance

changes in the porin structures in the outer cell wall membrane may contribute to resistance by what?

A

impeding access of penicillins to PBPs

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49
Q

Clinical Uses

Narrow-spectrum penicillinase-susceptible agents

A
  • Penicillin G
  • Penicillin V
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50
Q

Clinical Uses

the prototype of a subclass of penicillins that have a limited spectrum of antibacterial activity and are susceptible to beta-lactamases.

A

Penicillin G

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51
Q

Clinical Uses

Penicillin G theraphy of infections include?

A
  1. common streptococci
  2. miningcocci
  3. gram-positive bacilli
  4. spirochetes
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52
Q

Clinical Uses

Strains of pneumococci that are now resistant to penicillins

A

Penicillin resistant S. pneumoniae (PRSP)

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53
Q

Clinical Uses

Strains that are resistant to penicillin via beta-lactamase:

A
  • Stapphylococcus aureus
  • Neisseria gonorrhoeae
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54
Q

Clinical Uses

Penicillin G is the suitable drug for?

A

Syphilis

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55
Q

Clinical Uses

Penicillin G is not the suitable drug for?

A

gonorrhea

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56
Q

Clinical Uses

Activity of penicillin G against enterococci is enhanced by?

A

coadministration of aminoglycosides

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57
Q

Clinical Uses

oral drug mainly used in oropharyngeal infections

A

Penicillin V

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58
Q

Clinical Uses

Very-narrow-spectrum penicillinase-resistant drugs:

A
  • methicillin
  • nafcillin
  • oxacillin
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59
Q

Clinical Uses

Very-narrow-spectrum penicillinase-resistant drug that is a prototype but rarely used because of its nephrotoxic potential

A

methicillin

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60
Q

Clinical Uses

The primary use of Very-narrow-spectrum penicillinase-resistant drugs is in the treatment of known or suspected _________

A

staphylococcal infections

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61
Q

Clinical Uses

are resistant to all penicillins and are often resistant to multiple antimicrobial drugs.

A

Methicillin-resistant (MR)
staphylococci
- S. aureus (MRSA)
- S. epidermis (MRSE)

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62
Q

Clinical Uses

Wider-spectrum penicillinase-susceptible drugs:

A
  • Ampicillin and Amoxicillin
  • Piperacillin and Ticarrcillin
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63
Q

Clinical Uses

Ampicillin and amoxicillin therapy of infections include?

A
  1. similar to penicillin G
  2. enterococci
  3. Listeria monocytogenes
  4. Escherichia coli
  5. Proteus mirabilis
  6. Haemophilus influenzae
  7. Moraxella catarrhalis
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64
Q

Clinical Uses

Piperacillin and ticarcillin have activity
against:

A

gram-negative rods
- Pseudomonas
- Enterobacter
- Klebsiella sps

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65
Q

Clinical Uses

Most drugs in this subgroup have synergistic actions with aminoglycosides against such organisms.

A

Piperacillin and ticarcillin

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66
Q

Clinical Uses

What penicillinase inhibitors are used with piperacillin and ticarcillin to ennhance their activity?

A
  • tazobactam
  • clavulanic acid
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67
Q

Toxicity

Allergic reactions to penicillin include:

A
  • urticaria
  • severe pruritus
  • fever
  • joint swelling
  • hemolytic anemia
  • nephritis
  • anaphylaxis
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68
Q

Toxicity

How many percent of people with history of penicillin reaction have a allergic response when given penicillin again?

A

5-10%

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69
Q

Toxicity

Methicilin causes?

A

interstitial nephritis

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70
Q

Toxicity

nafcillin is associated with?

A

neutropenia

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71
Q

Toxicity

Ampicillin frequently causes?

A

maculopapular skin rash

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72
Q

Toxicity

What are the antigenic determinants that causes allergic reactions to penicillin

A

Penicilloic acid

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73
Q

Toxicity

Degration product of penicillin

A

penicilloic acid

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74
Q

Toxicity

occur with oral penicillins, especially with ampicillin.

A

Nausea and diarrhea

75
Q

Toxicity

Toxicity of penicillins:

A
  • Allergy
  • Gastrointestinal disturbances
76
Q

Toxicity

Gastrointestinal upsets from penicillin may be caused by:

A
  • direct irritation
  • overgrowth of gram + organisms or yeast
77
Q

Toxicity

Ampicillin has been implicated in what disease?

A

pseudomembranous colitis

78
Q

The cephalosporins are derivatives of what?

A

7-aminocephalosporanic acid

79
Q

1st generation Cephalosporins

A
  1. cephalexin
  2. cefazolin
  3. cefadroxil
  4. cephalotin
  5. cephadrine
  6. cephapirin
80
Q

2nd generation cephalosporins

A
  1. cefuroxime
  2. cefoxitin
  3. cefotetan
  4. cefamandole
  5. cefaclor
81
Q

3rd generation cephalosporins

A
  1. ceftriazone
  2. cefotaxime
  3. cefoperazone
  4. ceftazidime
  5. cefixime
  6. cefnidir
  7. moxalactam
82
Q

4th genaration cephalosporins

A
  1. cefepime
  2. ceftaroline
83
Q

Pharmacokinetics

Several cephalosporins are administered via

A

oral

84
Q

Pharmacokinetics

Most cephalosporin are administered via?

A

parenterally

85
Q

Pharmacokinetics

Major elimination mechanism of cephalosporins?

A

renal exretion via active tubular secretion

86
Q

Pharmacokinetics

What kind of elimination mechanism cephalosporins with side chains may undergo?

A

hepatic metabolism

87
Q

Pharmacokinetics

Type of cephalosporin excreted mainly in the bile?

A
  • cefoperazone
  • ceftriazone
88
Q

Pharmacokinetics

What generation of cephalosporins do not enter the cerebrospinal fluid even when the miniges are inflamed?

A

First and second generation

89
Q

Resistance

Structural differences from penicillins render cephalosporins
less susceptible to penicillinases produced by __________

A

staphylococci

90
Q

Resistance

Many bacteria are still resistant to cephalosporins through?

A

production of other beta-lactamase that can inactivate cephalosporins

91
Q

Resistance

Resistance to cephalosporins can also resukt from:

A
  • decrease of permeability to cephalosporins
  • changes in PBPs
92
Q

Resistance

Are Methicillin-resistant staphylococci resistant to cephalosporins?

A

yups

93
Q

Clinical Uses

Cefazolin is administered via

A

parenteral

94
Q

Clinical Uses

cephalexin is administered via?

A

oral

95
Q

Clinical Uses

First generation drugs are active againts:

A
  • Gram positive cocci (staphylococci and common streptococci)
  • E. coli
  • K. pneumoniae
96
Q

Clinical Uses

Clinical uses of 1st generation drugs

A
  • treatment of infection
  • surgical prophylaxis (selected conditions)
97
Q

Clinical Uses

First generation drugs have limited activity against:

A
  • gram-negative cocci
  • enterococci
  • methicillin-resistant staphylococci
  • gram negative rods
98
Q

Clinical Uses

Drugs in this subgroup usually
have slightly less activity against gram-positive organisms than the first-generation drugs but have an extended gram-negative coverage.

A

Second-generation drugs

99
Q

Clinical UsesClinical Uses

Second generation drugs that can treat infections caused by the anaerobe Bacteroides fragilis

A
  • cefotetan
  • cefoxitin
100
Q

Clinical Uses

Second-generation drugs that can treat sinus, ear, and respiratory infection caused by H. influenzae or M catarrhaliss

A
  • cefamandole
  • cefuroxime
  • cefaclor
101
Q

Clinical Uses

Feature of this subgroup include increased activity against gram-negative organisms resistant to other beta-lactam drugs and ability to penetrate the blood-brain barrier

A

Third generation drugs

102
Q

Clinical Uses

3rd generations drugs that cannot penetrate the blood-brain barrier

A
  • cefoperazone
  • cefixime
103
Q

Clinical Uses

3rd generation drugs are active against:

A
  • Providencia
  • Serratia marcescens
  • beta-lactamase producing strains (H. influenza and Neisseria)
104
Q

Clinical Uses

3rd generation drugs are less active against?

A

Enterobacter strains that produce extended-spectrum beta-lactamases

105
Q

Clinical Uses

Currently the most active cephalosporins against penicillin-resistant pneumonococci (PRSP strains)

but resistance is reported

A

Ceftriaxone and cefotaxime

106
Q

Clinical Uses

3rd generation drugs that have activity against Pseudomonas

A
  • cefoperazone
  • ceftazidime
107
Q

Clinical Uses

3rd generation drugs that have activity against B. fragilis

A

ceftizoxime

108
Q

Clinical Uses

Drugs in this subclass should
usually be reserved for treatment of serious infections

A

3rd generation drugs

109
Q

Clinical Uses

Ceftriaxone is adminstered via?

A

parenteral

110
Q

Clinical Uses

cefixime is administered via?

A

oral

111
Q

Clinical Uses

Drugs of choice for gonorrhea?

A
  • ceftriaxone
  • cefixime
112
Q

Clinical Uses

In acute otitis media, a single injection of ceftriaxone is usually as effecetive as?

A

10-day course treatment of amoxicillin

113
Q

Clinical Uses

Cefepime is more resistant to
beta-lactamases produced by gram-negative organism including:

A
  • Enterobacter
  • Haemophilus
  • Neisseria
  • penicillin-resistant pneumococci
114
Q

Clinical Uses

combines the gram-positive
activity of first-generation agents with the wider gram-negative spectrum of third-generation cephalosporins

A

Cefepime

115
Q

Clinical Uses

has activity in infections caused by methicillin-resistant staphylococci.

A

Ceftaroline

116
Q

Toxicity

Allergic reaction of cephalosporins:

A
  • skin rashes
  • anaphylactic shock
117
Q

Allergic reactions occur less frequently in penicillins than with cephalosporins

A

that is not factual

118
Q

Does complete cross-hypersensitivy exist in different cephalosporins

A

yups

119
Q

Does complete cross-reactivty exist between penicillins and cephalosporins?

A

nope

120
Q

Should patients with history of anaphylaxis to penicillins be treated with cephalosporins?

A

no way

121
Q

Cephalosporins may cause pain
at __________

A

intramuscular injection sites

122
Q

Cephalosporins may cause _______ after intravenous administration

A

phlebitis

123
Q

What will happen if you administer cephalosporin with aminoglycosides?

A

increase nephrotoxicity

124
Q

may cause hypoprothrombinemia and disulfiram-like reactions with ethanol.

A

Drugs containing a methylthiotetrazole group
- cefamandole
- cefoperazone
- cefotetan

125
Q

Is a monobactam that is resistant to beta-lactamases produced by certain gram-negative rods

A

Aztreonam

126
Q

What are the certain gram negative rods that aztreonam are resistant to

A
  • Klebsiella
  • Pseudomonas
  • Serratia
127
Q

Aztreonams have no activity against?

A

Gram-positive bacteria or anaerobes

128
Q

Where does aztreonam prefer to bind?

A

PBP3

129
Q

Aztreonam are synergistic with what?

A

Aminoglycosides

130
Q

Aztreonam is administered via?

A

IV

131
Q

Aztreonam is eliminated via?

A

Renal tubular secretion

132
Q

Aztreonam’s half life is prolonged in what situation?

A

Renal failure

133
Q

Adverse effects of aztreonam:

A
  • gastrointestinal upset with possible superinfection
  • vertigo
  • headache
  • hepatoxicity (rare)
134
Q

Can Skin rash occur in aztreonam?

A

Yeah

135
Q

Cross-allergenity of aztreonam with penicillin is possible?

A

Nope

136
Q

Examples of carbapenems

A
  • imipenem
  • doripenem
  • meropenem
  • ertapenem
137
Q

Drugs that are chemically different from penicillins but retaining the betalactam ring structure with low susceptanility to beta-lactamases

A

Carbapenems

138
Q

Carbapenems have wide activity against:

A
  • gram-positive cocci (penicillin resistant pneumococci)
  • gram-negative rods
  • anerobes
139
Q

Carbapenems are used in combination with what in pseudomonal infections

A

Aminoglycosides

140
Q

Carbapenems are administered via?

A

Parenterally

141
Q

Drugs that are useful for infections caused by organisms resistant to other antibiotics

A

Carbapenems

142
Q

Organisms that are resistant to carbapenems

A

MRSA strains of staphylococci

143
Q

Carbapenems are currently co-drugs of choice for infections caused by:

A
  • enterobacter
  • citrobacter
  • serratia
144
Q

Imipenem is rapidly inactivated by what?

A

Renal dehydropeptidase I

145
Q

An inhibitor of the enzyme renal dehydropeptidase

A

Cilastatin

146
Q

Imipinem is always administered with this

A

Cilastatin

147
Q

Increases the half life of imipenem and inhibits the formation of a potentially nephrotoxic metabolite

A

Cilastetin

148
Q

Adverse effects of imimpenem-cilastetin:

A
  • gastrointestinal distress
  • skin rash
  • very high plasma levels
  • cns toxicity (confusion, enchepalopathy, seizures)
149
Q

Does Imipenem-cilastatin have partial allergenicity with penicillins

A

Yups

150
Q

Is similae to imipenem except that it is not metabolized by renal dehydropeptidases and is less likey to cause seizures

A

Meropenem

151
Q

Type of carbapenem that has a long half life but is less active against enterococci and Pseudomonas and its intramuscular injection causes pain and irritation

A

Ertapenem

152
Q

Examples of beta-lactamase inhibitors

A
  • clavulanic acid
  • sulbactam
  • tazobactam
153
Q

Are used in fixed combinations with certain hydrolyzable penicillins

A

Beta-lactamase inhinbitors

154
Q

Beta-lactamase inhibitors are most active against:

A

Plasmid-encoded beta-lactamase produced by:
- gonococci
- streptococci
- e. coli
- h. influenzae

155
Q

Beta-lactamse inhibitors are not good inhibitors of what?

A

Inducible chromosomal beta-lactamases formed by
- enterobacter
- pseudomonas
- serratia

156
Q

Is a bactericidal glycoprotein that binds to the D-Ala-D-Ala terminal of nascent peptidoglycan pentapeptide side chain

A

Vancomycin

157
Q

Drug that inhibit transglycosylation

A

Vancomycin

158
Q

Drug that prevents elongation of the peptidoglycan chain and interferes with cross linking

A

Vancomycin

159
Q

Strains that are resistan to vancomycin

A
  • vancomycin-resistant enterococci (VRE)
  • vancomycin-resistant S. aureus
160
Q

How does VRE and VRSA resist vancomycin?

A

Replacement of the terminal D-ala by D-lactate

161
Q

Vancomycin are used for serious infections caused by?

A

Drug-resistant gram-positive organisms
- methicilin-resistan staphylococci (MRSA)
- penicillin-resistan pneumococci
- c. difficile

162
Q

Vancomycins are used in combination with what for treatment if penicillin resistan pneumococci (PRSP)?

A

3rd generation cephalosporin (ceftriaxone)

163
Q

Vancomycin is also a backup drug for treatment of infections caused by?

A

Clostridium difficile

164
Q

Drugs that similar characteristics to vancomycin

A

Teicoplanin and telavancin

165
Q

Vancomycin is not absorbed from the

A

Gastrointestinal tract

166
Q

Vancomycin may be given orally for what disease?

A

Bacterial enterocolitis

167
Q

When given this way, vancomycin penetrates most tissues and is eliminated unchanged in the urine

A

Parenterally

168
Q

This mandatory in patients with renal impairment taking vancomycin

A

Dosage modification

169
Q

Toxic effects of vancomycin:

A
  • chills
  • fever
  • phlebitis
  • ototoxicity
  • nephrotoxicity
170
Q

Rapid intavenous infusion of vancomycin may cause

A

Diffuse flushing (red man syndrome) from histamin release

171
Q

Is an antimetabolite inhibitor of cytosolic enolpyruvate transferase

A

Fosfomycin

172
Q

Prevent formation of N-acetylmuramic acid

A

Fosfomycin

173
Q

An esential precursor molecule for peptidoglycan chain formation

A

N-acetylmuramic acid

174
Q

Resistance to fosfomycin occurs via

A

Decreased intracellular acumulation of the drug

175
Q

Fosfomycin is excreted via?

A

Kidney

176
Q

Fosfomycin urinary levels exceed what for many urinary tract pathogens

A

Minimal inhibitory concentrations (MICs)

177
Q

In a single dose, this drug is less effective than a 7-day course of treatment with flouriquinolones

A

Fosfomycin

178
Q

With multiple dosing of this drug, resistance emerges rapidly and diarrhea is common

A

Fosfomycin

179
Q

Fosfomycin may be synergistic with these drug in specific infections

A

Beta-lactam and quinolone antibiotics

180
Q

Is a peptide antibiotic that interferes with a late stage in cell wall synthesis in gram-positive organisms

A

Bacitracin

181
Q

Because of its marked nephrotoxicity, the drig is limited to topical use

A

Bacitracin

182
Q

An antimetabolite that blocks the incorporation of D-ala into the pentapeptide side chain of peptidoglycan

A

Cycloserine

183
Q

Bacause of its potential neurotoxicity, it is only used to treat tuberculosis caused by organisms resistant to first line antituberculosis drugs

A

Cycloserine

184
Q

Is a novel cyclic lipopeptide with spectrum similar to vancomycin but active against vancomycin-resistant strains of enterococci and staphylococci

A

Daptomycin

185
Q

Daptomycin is eliminated via

A

Kidney

186
Q

This should be monitored since daptomycin may cause myopathy

A

Creatine phosphokinase

187
Q

CYLCOSERINE toxic effects

A

potential neurotoxicity
- tremors
- seizure
- psychosis

tcol (10 decks)

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