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AU 15 - Pharm Final > Antibacterial Drugs #2 > Flashcards

Antibacterial Drugs #2 Flashcards

1
Q

What drugs Inhibit Nucleic Acid Synthesis

A

Sulfonamides
Trimethoprim
Rifamprin

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2
Q

Sulfonamide Mechanism

A

Competitive Inhibitor of Dihydropteroate synthase - which is required for the synthesis of folic acid

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3
Q

Is Sulfonamide Bacteriostatic or bacteriocidal?

A

Static

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4
Q

Sulfonamide Selectivity

A

Bacteria must synthesize their own folate, while humans utilize dietary folate

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5
Q

Sulfonamide Antibacterial spectrum

A

Gram+ and Gram-

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6
Q

Sulfonamide Clinical uses

A

UTIs
Toxoplasmosis
Malaria
Prophylactive for burns and AIDS patients preventing P jirovecii

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7
Q

Sulfonamide Toxicities

A

Dose related - Crytalluria, Hemolytic anemia, Kernicterus

Dose Unrelated - Hypersensitivity

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8
Q

Trimethoprim Mechanism

A

Inhibitor of Dihydrofolate reductase (DHFR)

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9
Q

Is Trimethoprim Bacteriostatic or Bacteriocidal

A

Static

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10
Q

Trimethoprim Selectivity

A

Bacteria must synthesize their own folate, while humans utilize dietary folate

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11
Q

Trimethoprim Antibacterial Selectivity

A

Gram+ and Gram-

Broader spectrum than Sulfonamides

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12
Q

Trimethoprim Clinical Uses

A

Usually used in combination with Sulfamethoxazole (makes it bacteriocidal)
UTIs
GI infections
P. jarovecii prophylaxis in AIDS patients

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13
Q

Trimethoprim Toxicities

A

Slight blood dyscrasia

Anemia in patients that are folate deficient

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14
Q

Rifamprin Mechanism

A

Binds to an inhibits RNA polymerase

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15
Q

Is Rifamprin Bacteriostatic or Bacteriocidal?

A

Cidal

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16
Q

Rifamprin Selectivity

A

Does not bind to human RNA

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17
Q

Rifamprin Spectrum

A

Potent against M. tuberculosis

Some activity against Stphylococci

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18
Q

Rifamprin Clinical Uses

A

First line anti-tuberculosis in compination with other anto-tubercular drugs (RIPE)

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19
Q

Rifamprin Toxicities

A

Liver damage - Jaundice

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20
Q

Rifamprin Resistance Mechanisms

A

Inductance of resistance is rapid - therefor not used as monotherapy

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21
Q

What drugs are DNA damaging?

A

Quinolones
Nitrofurantoin
Metronidazole
Methenamine

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22
Q

Quinolones mechanism

A

Poison DNA Gyrase A - inhibiting the uncoiling funciton of DNA gyrase ahead of the replication fork

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23
Q

Are Quinolones bacteriostatic or bacteriocidal?

A

Cidal

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24
Q

Quinolones Selectivity

A

Mammalian DNA topoisomerase is not inhibited to the same extent as DNA Gyrase II and Topoisomerase IV in bacteria

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25
Q

Quinolones Spectrum

A

Gram+ and Gram-

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26
Q

Quinolones Clinical Uses

A

UTI
RTI
Anti-tubercular

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27
Q

Quinolones Toxicities

A

Generally well-tolerated

Avoid using with Ciprofloxin with children - leads to potential tendon ruptures

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28
Q

Quinolones Resistance Mechanisms

A

1) Mutations in Gyrase or Topoisomerase targets
2) Increased efflux pumps
3) Altered porins (gram-)

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29
Q

Nitrofurantoin Mechanism

A

DNA damage caused by formation of oxygen free radicals subsequent to reduction of a nitro group

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30
Q

Are Nitrofurantoins Bacteriostatic or bacteriocidal?

A

Static

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31
Q

Nitrofurantoins Selectivity

A

Bacteria cause reductive activation more extensively than mammalian cells

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32
Q

Nitrofurantoins Antibacterial spectrum

A

Broad spectrum against Gram+ and Gram-

Not effective against P. aeruginosa

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33
Q

Nitrofurantoins Clinical Uses

A

UTI
RTI
Anti-tubercular

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34
Q

Nitrofurantoin Toxicities

A

Poor renal function leads to toxicity - fever, rashes, urticaria, and eventually pulmonary fibrosis

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35
Q

Metronidazole Mechanism

A

Reductive activation of nitro group specifically in anaerobic bacteria leads to free radical species and reactive intermediates that bind to and effect DNA function

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36
Q

Is Metronidazole bacteriostatic or bacteriocidal?

A

Cidal

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37
Q

Metronidazole selectivity

A

Bacteriocidal agent against most obligate anaerobic gram+ bacteria

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38
Q

Metronidazole spectrum

A

Gram+ anaerobic

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39
Q

Methenamine Mechanism

A

Hydrolyzed at acidic pH to form formaldehyde - which has been shown to damage DNA

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40
Q

Is Methenamine bacteriostatic or bactericidal?

A

Cidal

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41
Q

Methenamine antibacterial spectrum

A

Gram-

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42
Q

Methenamine Clinical Uses

A

Only for prophylaxis of UTIs

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43
Q

Which drugs Inhibit Cell Wall synthesis?

A 
Beta-Lactams
-Penicillins
-Cephalosporins
-Monobactams
-Carbapenems
B-lactamase inhibitors
Vancomyocin
Bacitracin
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44
Q

Penicillin mechanisms

A

Mimics D-ala-D-ala structure of pentapeptide on peptidoglycan and ties up transpeptidase

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45
Q

Is penicillin bacteriostatic or bactericidal?

A

Cidal

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46
Q

Penicillin selectivity

A

Inhibits cell wall synthesis - there is no cell wall in eukaryotic cells

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47
Q

Penicillin clinical uses

A

Streptococcus pneumoniae

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48
Q

Penicillin resistance mechanisms

A

1) B-lactmases (Gram+ and gram-)
2) Altere PBPs
3) Altered porins (gram-)
4) Increases efflux (enhanced pump mechanisms)

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49
Q

Are penicillins Time dependent or Concentration dependent?

A

Time dependent

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50
Q

Cephalosporins Mechanisms

A

Mimics D-ala-D-ala structure of pentapeptide on peptidoglycan and ties up transpeptidase

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51
Q

Are Cephalosporins bacteriostatic or bacteriocidal?

A

Cidal

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52
Q

Cephalosporin Selectivity

A

Inhibits cell wall synthesis - there is no cell wall in eukaryotic cells

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53
Q

Cephalosproin toxicities

A

Relatively nontoxic, but direct toxic effect in the kidney have been noted as well as hypersensitivity

54
Q

B-lactamase Mechanism

A

Inhibits B-lactamase - binds to serine at the active site of lactamase

55
Q

Are B-lactamases bacteriostatic or bactericidal?

56
Q

B-lactamases selectivity

A

Inhibits cell wall synthesis - there is no cell wall in eukaryotic cells

57
Q

B-lactamase clinical use

A

Used in combination with beta-lactam antibiotics (extends their spectrum)

58
Q

Vancomyocin Mechanism

A

Binds to the carboxyl terminus of D-ala-D-ala and thereby:

1) Inhibits Peptidoglycan synthase
2) Inhibits transpeptidation reaction (so there’s no cross-linking)

59
Q

Is Vancomyocin bacteristatic or bactericidal

60
Q

Vancomyocin selectivity

A

Inhibits cell wall synthesis - there is no cell wall in eukaryotic cells

61
Q

Vancomyocin Antibacterial spectrum

A

Narrow spectrum - active against Gram+ staph and strep

62
Q

Vancomyocin Toxicities

A

Hearing loss (dose related) often relate to renal impairment
Some renal toxicity has been noted
Red neck syndrome

63
Q

Vancomyocin Resistance Mechanism

A

Resistance is a major issue

Due to altered D-ala-D-ala peptide structures causing Vancomyocin to not bind as avidly

64
Q

Bacitracin Mechanism

A

Binds to isoprenyl-phosphate lipid carrier, inhibiting dephosphorylation and utilization

65
Q

Is Bacitracin bacteriostatic or bactericidal?

66
Q

Bacitracin Selectivity

A

Inhibits cell wall synthesis - there is no cell wall in eukaryotic cells

67
Q

Bacitracin Antibacterial spectrum

A

Gram+ cocci

Some Gram- activity

68
Q

Bacitracin Clinical uses

A

Superficial skin and opthalmic infections

69
Q

What drugs damage the cell membrane?

A

Polymyxins

Daptomycin

70
Q

Polymixin Mechanism

A

Acts as a cationic detergent

71
Q

Are polymixins bacteriostatic or bactericidal?

72
Q

Polymixins Spectrum

73
Q

Polymixins Clinical uses

A

Particularly useful in hospital settings against pan-resistant (multi-drug resistant) Gram- infections

74
Q

Polymixins toxicities

A

Dose related nephrotoxicity in patients with renal disease

75
Q

Daptomycin mechanism

A

Insertion of lipophylic tail into cell membrane, causing membrane depolarization, K efflux, and disruption to DNA and RNA synthesis
Works very quickly (~1 hour)

76
Q

Is Daptomycin bacteriostatic or bactericidal?

77
Q

Daptomycin Antibacterial spectrum

A

Gram+

Because it binds to the LPS layer in gram- bacteria, it can never reach the cell membrane

78
Q

Daptomycin clinical uses

A

Effective against most Gram+ pathogens (includin MRSA)

Can’t use on lung infections because it gets inactivated by pulmonary surfactant

79
Q

What drugs are inhibitors of protein synthesis?

A 
Aminoglycosides
Tetracyclines
Tigecyclines
Chlorophenicol
Macrolides
Ketolide
Clindamycin
Linezoid
Quinupristin/Dalfopristin
80
Q

Aminoglycosides Mechanism

A

Bind to proteins in the interface between 30S and 50S -

  • interfere with tRNA attachment
  • block activity of initiation complex
  • distorting of mRNA triplet codon - leading to mispairing
81
Q

Are Aminoglycosides bacteriostatic or bactericidal?

82
Q

Aminoglycosides Selectivity

A

Don’t bind to mammalian ribosomes (80S)

83
Q

Aminoglycosides Antibacterial spectrum

84
Q

Aminoglycosides Clinical Uses

A

Streptomyocin - used in the past for TB

Neomucin - topical use for treatment of burns and wounds

85
Q

Aminoglycosides Toxicities

A

Ototoxicity - cochlear hair cell death
Nephrotoxicity
Neuromuscular blockade - leading to muscle weakness and respiratory depression

86
Q

Are aminoglycosides time or concentration dependent?

A

Concentration

Exhibit a considerable post-antibiotic effect

87
Q

Tetracycline Mechanism

A

Bind to 30S and bind blocking of tRNA

88
Q

Are tetracyclines bacteriostatic and bactericidal

89
Q

Tetracycline Selectivity

A

Concentrated to a greater extent in bacterial cells compared to mammalian cells by a specific carrier protein not found in mammalial cells

90
Q

Tetracycline Antibacterial spectrum

A

Broad spectrum against Gram+ and Gran-

91
Q

Tetracycline toxicities

A

Photosensitivity

Binds to bone and teeth - can stain teeth and retard bone growth

92
Q

Tetracycline Resistance mechanisms

A

Decreased influx
Increases efflux pump
Decreased binding to ribosomes

93
Q

Tigecycline Mechanism

A

Bind to 30S and block binding of tRNA

94
Q

Is Tigecycline bacteriostatic or bactericidal?

95
Q

Tigecycline Selectivity

A

Doesn’t bind to mammalian ribosomes (80S)

96
Q

Tigecycline Antibacterial Spectrum

A

Broad spectrum against Gram+ and gram-

97
Q

Tigecycline Clinical uses

A

Complicated intra-abdominal and skin infections

Not used in bacteriemias because of low serum levels

98
Q

Tigecycline toxicities

A

Doesn’t have the toxicities associated with Tetracyclines

99
Q

Chlorophenicol Mechanism

A

Binds to 50S - inhibiting peptidyl transferase by preventing the attachment of amino acid end of aminoacyl-tRNA to the “A” site

100
Q

Is Chlorophenicol bacteriostatic or bactericidal?

101
Q

Chlorophenicol Selectivity

A

Doesn’t bind to mammalian ribosomes (80S)

102
Q

Chlorophenicol Clinical uses

A

Extremely limited clinical use because of potentially Aplastic Anemia

103
Q

Chlorophenicol Antibacterial spectrum

A

Broad spectrum against Gram+ and Gram-

104
Q

Chlorophenicol toxicities

A

Aplastic Anemia

Grey baby syndrome

105
Q

Macrolides Mechanism

A

Binds to 50S - inhibiting translocation and causes the release of oligo-peptidyl tRNA

106
Q

Are macrolides bacteriostatic or bactericidal?

A

Bacteriostatic against most

Bactericidal against some Gram+

107
Q

Macrolides Selectivity

A

Doesn’t bind to mammalian ribosomes (80S)

108
Q

Macrolides Antibacterial spectrum

A

Bacteriostatic against most

Bactericidal against some Gram+

109
Q

Macrolides Clinical Uses

A 
M. pneumoniae
Legionnaire's
Chlamydia
Pneumonias
Middle ear and sinus infections
110
Q

Macrolides Toxicities

A

Fairly safe - some GI issues and hypersensitivity

111
Q

Ketolide Mechanism

A

Binds to 50S - inhibiting translocation and causes the release of oligo-peptidyl tRNA

112
Q

Is Ketolide bacteriostatic or bactericidal?

113
Q

Ketolide Antibacterial spectrum

A

Gram+ and Gram-

114
Q

Ketolide Clinical uses

A

Effective against Macrolide-resistant strains (efflux pumps don’t effect them)
RTIs

115
Q

Ketolide toxicities

A

Liver toxicity

116
Q

Clindamycin Mechanism

A

Binds to 50S

117
Q

Is Clindamycin bacteriostatic or bactericidal?

118
Q

Clindamycin Selectivity

A

Doesn’t bind to mammalian ribosomes (80S)

119
Q

Clindamycin Antibacterial Spectrum

A

Gram+ and anaerobes

120
Q

Clindamycin Clinical Uses

A

Against penicillin-resistant anaerobic infections

Topical acne treatment

121
Q

Clindamycin toxicities

A

Pseudomembranous colitis caused by toxin from C. dificile - which is resistant to Clindamycin

122
Q

Linezolid Mechanism

A

Binds to 50S - blocks formation of initiation complex

123
Q

Is Linezolid bacteriostatic or bactericidal?

124
Q

Linezolid selectivity

A

Doesn’t bind to mammalian ribosomes (80S)

125
Q

Linezolid Antibacterial Spectrum

126
Q

Linezolid Clinical uses

A

Useful against vancomyocin-resistant Enterococcus faecium and MRSA

127
Q

Quinupristin/Dalfopristin Mechanism

A

Both bind to 50S
Quin = stimulates dissociation of peptidyl-tRNA
Dal = prevents binging of aa-tRNA

128
Q

Are Quinupristin/Dalfopristin bacteriostatic or bactericidal?

A

Static alone

Cidal when used together

129
Q

Quinupristin/Dalfopristin Selectivity

A

Doesn’t bind to mammalian ribosomes (80S)

130
Q

Quinupristin/Dalfopristin Antibacterial Spectrum

131
Q

Quinupristin/Dalfopristin Clinical uses

A

Useful against vancomyocin-resistant Enterococcus faecium and MRSA

AU 15 - Pharm Final (7 decks)

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