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Antibiotics Flashcards

1
Q

What are the 4 main sites of antimicrobial action?

A
  1. Cell wall
  2. Protein synthesis
  3. Cell membranes
  4. Nucleic acid synthesis
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2
Q

How do B-lactams function? What are some examples?

A

Penicillin is one.
B-lactams bind Penicillin Binding Proteins (PBPs), a type of transpeptidase.
This prevents the crosslinking of the peptidoglycan wall.
B-lactams mimic d-ala-d-ala residues on peptide side chains.
This stimulate autolysins to break down the cell wall.

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3
Q

What do B-lactams mimic?

A

The d-ala-d-ala residues on peptide side chains.

This stimulates autolysins –> break down the cell wall.

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4
Q

What type of antibiotic are glycopeptides?

A
  1. Inhibitors of cell wall synthesis, vancomycin, teicoplanin are examples.
  2. Bind terminal d-ala-d-ala on the peptide chain which prevents crosslinking.
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5
Q

How do glycopeptides function as antibiotics?

A

Bind terminal d-ala-d-ala residues on the peptide chain and prevent cross linking.

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6
Q

What are some common glycopeptides?

A

Vancomycin

Teicoplanin

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7
Q

What is the mechanism of action of polymyxins?

A

Inhibit/disrupt the cell membrane. They cause leakage of cytoplasmic contents.

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8
Q

How do nitroimidazoles function?

A

Act on nucleic acid synthesis, affecting DNA.

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9
Q

How does rifampicin function?

A

Act on RNA polymerase.
Rifampicin is used for the treatment of tuberculosis in combination with other antibiotics, such as pyrazinamide, isoniazid, and ethambutol

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10
Q

Vancomycin

A

Glycopeptide

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11
Q

Fluoroquinolones function how?

A

Inhibit DNA synthesis.

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12
Q

What drugs inhibit the metabolic synthesis of nucleic acid?

A

Sulphonamides, trimethoprim.

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13
Q

Colistin

A

Polymyxin

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14
Q

How do ciprofloxacin and levofloxacin function?

A

inhibit nucleic acid synthesis, via inhibiting metabolism.

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15
Q

Teicoplanin

A

Glycopeptide

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16
Q

What is the function of DNA gyrase? what inhibits this?

A

DNA gyrase removes DNA supercoils ahead of the replication fork. It is inhibited by both ciprofloxacin and levofloxacin.

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17
Q

What is topoisomerase IV? what inhibits it?

A

It separates DNA strands after replication.

Inhibited by ciprofloxacin and levofloxacin.

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18
Q

Macrolides, streptogramins and lincosamides all have what in common?

A

They bind to the 50s subunit of DNA and interfere with protein synthesis. They have overlapping binding sites.

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19
Q

Inhibitors of Type II DNA gyrase and/or type IV topoisomerases.

A

Ciprofloxacin and levofloxacin.

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20
Q

Sulphonamide

A

Inhibits nucleic acid synthesis, via inhibiting metabolism

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21
Q

How does fusidic action function as an antibiotic?

A

Fusidic acid works by interfering with bacterial protein synthesis, specifically by preventing the translocation of the elongation factor G (EF-G) from the ribosome. It also can inhibit chloramphenicol acetyltransferase enzymes.

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22
Q

What do aminoglycosides and tetracyclines have in common?

A

Both inhibit 30s subunit of ribosomes.

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23
Q

What three antibiotics share the same mechanism of action and have overlapping binding sites?

A

Macrolides, streptogramins and lincosamides all function by inhibiting the 50s subunit of the ribosome. Prevent protein synthesis.

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24
Q

Trimethoprim

A

Inhibits nucleic acid synthesis, via inhibiting metabolism

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25
Q

Which antibiotic works via preventing the translocation of the elongation factor G (EF-G) from the ribosome?

A

Fusidic acid works by interfering with bacterial protein synthesis, specifically by preventing the translocation of the elongation factor G (EF-G) from the ribosome. It also can inhibit chloramphenicol acetyltransferase enzymes.

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26
Q

These two antibiotics inhibit the 30S subunit of ribosomes.

A

Tetracyclines + aminoglycosides.

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27
Q

Oxazolidinones function how?

A

Oxazolidinones inhibit protein synthesis by binding to the P site at the ribosomal 50S subunit.

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28
Q

Linezolid works by:

A

Inhibiting protein synthesis by binding to the P site at the ribosomal 50S subunit. Member of the Oxazolidinone class of antibiotics.

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29
Q

Which antibiotic can inhibit chloramphenicol acetyltransferase enzymes?

A

Fusidic acid works by interfering with bacterial protein synthesis, specifically by preventing the translocation of the elongation factor G (EF-G) from the ribosome. It also can inhibit chloramphenicol acetyltransferase enzymes.

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30
Q

Macrolides

A

Macrolides, streptogramins and lincosamides all function by inhibiting the 50s subunit of the ribosome. Prevent protein synthesis.

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31
Q

Most aminoglycosides bind to what?

A

The 30S subunit, decreasing initiation and assembly of the ribosome and decreasing binding of tRNA in the A site and translocation/

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32
Q

Some aminoglycosides bind to what? (same as oxazolidinones)

A

The 50S subunit, decreasing the assembly of the initiation complex.

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33
Q

Doxycycline and minocycline are examples of what?

A

Tetracyclines. 30S subunit binders, decreasing binding of tRNA in the A site.

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34
Q

What is the mechanism of action of chloramphenicol?

A

Disrupts the formation of peptide bonds by binding to the 50s subunit of ribosomes.

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35
Q

Streptogramins

A

Macrolides, streptogramins and lincosamides all function by inhibiting the 50s subunit of the ribosome. Prevent protein synthesis.

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36
Q

Which antibiotics inhibit protein synthesis by binding to the P site at the ribosomal 50S subunit?

A

Oxazolidinones inhibit protein synthesis by binding to the P site at the ribosomal 50S subunit.

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37
Q

Macrolides such as….. function by….

A

Erythromycin, clarithromycin bind to 50S subunit, decreasing the translocation of tRNA from A to P site.

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38
Q

Cycloserine and bacitracin are similar how?

A

Both affect bacterial cell wall synthesis.

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39
Q

Lincosamides

A

Macrolides, streptogramins and lincosamides all function by inhibiting the 50s subunit of the ribosome. Prevent protein synthesis.

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40
Q

Penicillin, cephalosporin, monobactam and carbapenem all have what in common?

A

B-lactam ring.

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41
Q

What does the R group of a penicillin determine?

A 
Solubility,
Stability,
Selectivity,
BA,
B-lactamase resistance.
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42
Q

What are the 4 main classes of penicillin’s?

A
  1. BL sensitive.
  2. BL resistant
  3. Broad spectrum
  4. Anti-pseudomonal.
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43
Q

Which penicillin’s are broad spectrum in activity? [4]

A
  1. Ampicillin
  2. Amoxicillin
  3. Co-amoxiclav
  4. Augmentin
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44
Q

Which penicillin’s are B-lactamase resistant? [3]

A
  1. Flucloxacillin
  2. Co-fluampicil
  3. Temocillin (from G-ve)
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45
Q

Which penicillin’s are B-lactamase sensitive? [3]

A
  1. Benzylpenicillin (PEN G)
  2. Benzathine benzylpenicillin
  3. Phenoxymethylpenicillin (PEN V)
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46
Q

What are the anti-psuedomonal penicillin’s? [3]

A
  1. Piperacillin
  2. Piperacllin + tazobactam: Tazocin
  3. Ticarcillin + Clavulonic acid: Timentin.
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47
Q

Benzathine benzylpenicillin

A

B-lactamase sensitive penicillin

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48
Q

Amoxicillin

A

Broad spectrum penicillin

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49
Q

Temocillin

A

B-lactamase resistant penicillin.

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50
Q

Benzylpenicillin (PEN G)

A

B-lactamase sensitive penicillin

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51
Q

Co-fluampicil

A

B-lactamase resistant penicillin.

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52
Q

Ampicillin

A

Broad spectrum penicillin

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53
Q

Phenoxymethylpenicillin (PEN V)

A

B-lactamase sensitive penicillin

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54
Q

Timentin

A

Ticarcillin + Clavulonic acid: anti-psuedomonal penicillin

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55
Q

Flucloxacillin

A

B-lactamase resistant penicillin.

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56
Q

Augmentin

A

Broad spectrum penicillin

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57
Q

Tazocin

A

Piperacillin + tazobactam: anti-psuedomonal penicillin

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58
Q

Piperacillin

A

anti-psuedomonal penicillin

59
Q

Co-Amoxiclav

A

Broad spectrum penicillin

60
Q

What are the typical uses of Pen G?

A 
Throat infections
Endocarditis
Meningitis 
Pneumonia 
Cellulitis 
Osteomyelitis
61
Q

How do we maintain adequate and safe levels of Pen G?

A

Administer large doses, frequently and combine with benzathine benzylpenicillin which has slow release from the IM site.

62
Q

What are the clinical uses of Amoxicillin?

A

Broad spectrum
Throat infections, otits media, sinusitis, oral infections.
Resp tract infections, UTIs, GIT.

63
Q

What are the shared side effects of the penicillins?

A 
Hypersensitivity
Neurotoxicity 
Renal failure 
Diarrhoea and pseudomembranous colitis. 
C.diff
64
Q

What are the properties of Cephalosporins?

A
  1. Resistant to BLs but not ESBLs.
  2. Active against G+ve due to affinity for PBPs, resistance to BLs.
  3. Active against G-ve due to penetration through outer membrane.
65
Q

How do polymyxins function?

A

Act at cell membrane.
Disrupts membrane leading to leakage of cytoplasmic contents.
Binds tightly to lipid A component of LPS in the outer membrane of gram negative bacteria.

66
Q

Cefazolin and cefradine are examples of:

A

1st gen cephalosporins.

67
Q

How did 2nd gen cephalosporins improve upon on 1st generation?

A

Improved gram-ve activity and increased resistance to betalactamases:
Cefuroxime
Cefaclor

68
Q

Cefuroxime and Cefaclor are examples of:

A

2nd gen cephalosporins.

69
Q

How were the 3rd gen cephalosporins an improvement on 2nd generation ones?

A

Improved activity and increased resistance to BLs.

Cefotaxime, Ceftriaxone.

70
Q

4th generation cephalosporins are commonly used against:

A

Psuedomonas.
Many can cross BBB.
Cefepime
Cefpirome

71
Q

Cefepime and Cefpirome are:

A

4th gen cephalosporins.

72
Q

Carbapenems function how?

A 
Inhibition of cell wall synthesis. 
Beta lactam ring containing. 
Meropenem
Doripenem
Imipenem. 
Highly resistant to limited and ESBL. 
Broad spectrum of activity. 
Active against P. aeruginosa.
73
Q

Are carbapenems active against P. aeruginosa?

74
Q

What are carbapenems commonly used to treat?

A 
Sept.
HAP.
Intraabdominal infections. 
Skin and soft tissue infections. 
Complicated UTI.
75
Q

What issues are there with carbapenem use?

A

NDM-1, emerging resistance due to BLs.

76
Q

What is aztreonam?

A

A beta-lactam antibiotic.
Inhibitor of cell wall synthesis.
Less likely to cause hypersensitivity.

77
Q

Meropenem, doripenem and imipenem are what?

A 
Carbapenems. 
Inhibition of cell wall synthesis. 
Beta lactam ring containing. 
Highly resistant to limited and ESBL. 
Broad spectrum of activity. 
Active against P. aeruginosa.
78
Q

Polymyxins bind tightly to what?

A

Lipid A compenent of LPS in the outer membrane of gram negative bacteria.

79
Q

What is the MOA of bacitracin?

A

The CSS lipid molecule carrier transports PG monomers across the cytoplasmic membrane.
Bacitracin binds tightly to CSS-PP.
Blocks CSS-P recycling, decreasing the amount of carrier molecules.

80
Q

How does bacitracin resistance occur?

A

Increased activity of phosphokinase leading to increased carrier molecules.

81
Q

How does resistance to macrolides occur?

A

Altered target site.
Plasmid-mediated methylation of 23S rRNA by erm gene.
Inducible or constitutive.

82
Q

The erm gene contributes to resistance to which antibiotic class?

A

Macrolides

83
Q

How do glycopeptides function as antibiotics?

A

Inhibit cell wall synthesis.
Not active against Gram -ve.
Bind to terminal D-ala.

84
Q

How do the uses of teicoplanin and vancomycin differ?

A

Vanc: systemic infections when given via an IV infusions and for C. diff infections when given orally.

Teicioplanin: IM/IV injection or infusion for systemic infections.
B-lactam resistant MRSA etc.

85
Q

What is cycloserine?

A

Broad spectrum antibiotic effective against TB.
Can cause CNS side effects, rashes, liver damage.

As a cyclic analogue of D-alanine, cycloserine acts against two crucial enzymes important in the cytosolic stages of peptidoglycan synthesis.

86
Q

Bacitracin

A

Used alongside poymyxin B in Polyfax. Used topically for skin and eye infections and the prevention of wound infections.

87
Q

How do polymyxins function as antibiotics?

A

Lipid A compenent of LPS in the outer membrane of gram negative bacteria.
Cause membrane disruption and leakage of cytoplasm.

88
Q

Polymyxin B

89
Q

Antibiotic with the side effect of contact allergic dermatitis:

A

Bacitracin.
Used alongside poymyxin B in Polyfax. Used topically for skin and eye infections and the prevention of wound infections.
Side effect of contact allergic dermatitis.

90
Q

A cyclic analogue of D-alanine:

A

As a cyclic analogue of D-alanine, cycloserine acts against two crucial enzymes important in the cytosolic stages of peptidoglycan synthesis.

91
Q

Antibiotic used alongside poymyxin B in Polyfax. Used topically for skin and eye infections and the prevention of wound infections.

A

Bacitracin.

Side effect of contact allergic dermatitis.

92
Q

Daptomycin

A

(Cubicin) is a lipopeptide that causes rapid depolarisation of cytoplasmic membrane leading to loss of function.

93
Q

How are sulphonamides and trimethroprim similar? How do they differ?

A

Both inhibitors of the metabolism needed for NA synthesis.

S inhibits dihydropterate synthetase.

T inhibits dihydrofolate reductase.

Prevent synthesis of purines/pyrimidines.

94
Q

How are sulphonamides and trimethoprim used?

A

S: limited clinical use.
T: orally for G-ve UTI (Not Ps), in combination as Co-trimoxale for pneumocytis pneumonia (PCP).

95
Q

Inhibitor of nucleic acid metabolism found in combination as: Co-trimoxale:

A

Trimethoprim.

Severe side effects: liver damage, bone marrow suppression etc.

96
Q

Which antibiotic is a lipopeptide that causes rapid depolarisation of cytoplasmic membrane leading to loss of function?

A

Daptomycin/cubicin

97
Q

Examples of fluoroquinolone antibiotics:

A

Ciprofloxacin
Levofloxacin
Moxifloxacin
Travafloxacin

98
Q

MOA of fluoroquinolones:

A

Inhibit effective DNA replication.

DNA gyrase + type IV topoisomerase.

99
Q

Which antibiotic has side effects involving tendon damage which can appear months after effective treatment?

A

Ciprofloxacin.

100
Q

Nitroimidazoles:

A

Metronidazole etc:
Fragment DNA.
Can lead to candida superinfection.

101
Q

How are aminoglycosides used in practice?

A

IV for serious infections from aerobic bacteria.

102
Q

Aminoglycosides block what?

A

Block assembly of the initiation complex and binding of tRNA to the A site.
Act at 30s subunit.

103
Q

What are the side effects of Doxycycline?

A

Tetracycline:

causes staining in teeth and a phototoxic reaction.

104
Q

What is clindamycin?

A

Lincosamide.

105
Q

Linezolid is what type of antibiotic?

A

Oxazolidinones.

Binds 23S rRNA in 50s subunit, decreasing assembly of the initiation complex.

106
Q

What spectrum is fusidic acid?

107
Q

True or False:

Chloramphenicol is used topically to treat eye infections

108
Q

True or False:

Fusidic acid is a narrow spectrum antibiotic used to treat skin infections

109
Q

True or False:

Aminoglycosides are a first line drug for community acquired pneumonia

110
Q

True or False:

Macrolides are used as an alternative to penicillins

111
Q

True or False:

Tetracyclines are broad spectrum antibiotics sometimes used to treat respiratory tract infections

112
Q

True or False:

Bacitracin inhibits cell wall synthesis by preventing assembly of the di-peptide D-ala-D-ala.

A

FALSE

CSS Carrier molecules.

113
Q

True or False:

Acetylated chloramphenicol binds to the 50S ribosomal subunit and prevents protein synthesis.

A

FALSE:
Acetylation is how chloramphenicol is deactivated.
Fusidic acid can inhibit chloramphenicol acetyltransferases.

114
Q

True or False:

Polymyxins act primarily by binding to lipopolysaccharide in the outer membrane.

A

True. Lipid A.

115
Q

True or False:

Ciprofloxacin and clindamycin both inhibit bacterial protein synthesis

A

FALSE.
Ciprofloxacin: DNA gyrase/topoisomerase.
Clindamycin = lincosamide = 50s subunit?

116
Q

True or False:

Trimethoprim and the sulphonamides both inhibit synthesis of tetrahydrofolic acid

117
Q

True or False:

Resistance to b-lactams is often through enzymic inactivation

118
Q

True or False:

Resistance to tetracyclines can occur from efflux pumps

A

True, esp tetracyclines and quinolones.

119
Q

True or False:

Resistance to erythromycin usually results from methylation of 16S rRNA

A

False.

Methylation of 23s caused by erm gene results in macrolide resistance.

120
Q

True or False:

Resistance to vancomycin can result from an altered target site

A

True.

D-ala –> D-lactate = 5Hbonds –> 4Hbonds = unstable.

121
Q

True or False:

Resistance to rifampicin results from mutations in DNA gyrase

A

FALSE.

Results from RNA polymerase mutations.

122
Q

True or False:

Fusidic acid can cause super infections

A

FALSE

Fusidic acid is narrow spectrum.

123
Q

True or False:

Aminoglycosides can cause nephrotoxicity and ototoxicity

124
Q

True or False:

Rifampicin can affect metabolism of the hormonal birth control pill

A

True. Also Isoniazid.

125
Q

True or False:

Chloramphenicol can cause ‘Grey baby syndrome’

126
Q

True or False:

Erythromicin binds motilin receptor and can cause disturbances of the gastro-intestinal tract

127
Q

True or False:

Streptococcus mutans can cause meningitis.

A 
FALSE.
These can cause it:
S. Aureus. 
L. Monocytogenes. 
S. Pneumoniae 
N. Meningitidis
128
Q

True or False:

Penicillin G is given orally to treat tonsilitis

A

False.

Pen G is IV only.

129
Q

True or False:

Tetracycline can be given topically to treat acne vulgaris

130
Q

True or False:

Gentamicin is given orally to treat complicated urinary tract infections

A

False. IV/ antibiotics of last resort.

131
Q

True or False:

Erythromicin is a narrow spectrum antibiotic used to treat ear infections

A

FALSE: broad spectrum.

132
Q

True or False:

Vancomycin is given i.v. to treat serious infections caused by Gram negative bacteria

A

False.

Gram -ve bacteria are intrinsically resistant to large drugs like glycopeptides.

133
Q

True or False:

eicoplanin and bacitracin are inhibtors of cell wall synthesis

134
Q

True or False:

Rifampicin and trimethoprim are inhibitors of nucleic acid synthesis

135
Q

True or False:

Gentamicin and tetracycline bind to the 30S ribosomal subunit and inhibit protein synthesis

136
Q

True or False:

Polymyxin E distorts the outer membrane of Gram positive cocci

A

FALSE

Only Gram -ve have an outer membrane.

137
Q

True or False:

Tetracyclines act on mammalian and microbial ribosomes

138
Q

True or False:

Pulmonary TB is caused by Mycobacterium tuberculosis

139
Q

True or False:

Meningitis can be caused by Streptococcus pneumoniae

140
Q

True or False:

Cellulitis is often caused by Streptococcus bovis

A

False. Staph. Aureus.

141
Q

True or False:

Urinary tract infections can be caused by E. coli

142
Q

True or False:

Community acquired pneumonia can be caused by Haemophilus influenzae

143
Q

Zileuton is to _____ as celecoxib is to _____

A

5-lipoxygenase, COX-2

144
Q

For Gentamicin, what values should be monitored to ensure efficacy and what values should be monitored to avoid toxicity?

A

Peak values should be monitored to ensure efficacy.

Trough values should be monitored to avoid toxicity.

III (24 decks)

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