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MHD/Pharm Block 3 > Pharm - Antibiotics > Flashcards

Pharm - Antibiotics Flashcards

1
Q

What is the mechanism of action for penicillins and the derivatives of penicillins?

A

Competitive inhibitors of transpeptidase, inhibits cell wall synthesis

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2
Q

What are the different sub-classes of penicillins?

A

Natural, Penicillinase-Resistant, Aminopenicillins, Carboxypenicillins, Ureidopenicillins, and beta lactamase inhibitor combinations

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3
Q

What are the major adverse events associated with penicillin?

A

Allergic hypersensitivity leading to anaphylaxis, hives, and rash. The use of penicillin can also lead to superinfections like C. Diff

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4
Q

Are penicillins bacteriostatic or bacteriocidal?

A

Bacteriocidal

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5
Q

What is the spectrum of activity for Penicillin G?

A

Bacteriocidal against: Gram positive (S. pneumo, S. pyogenes, actinomyces), gram negative cocci (N. meningitidis), anaerobes (Clostridium), spirochetes (T. pallidum)

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6
Q

What are the mechanisms of resistance against penicillin?

A

Resistance developed by preventing entrance to penicillin, enzymatically cleaving beta lactam ring, altering the structure of the transpeptidase enzyme

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7
Q

What is the primary reason for prescribing oral penicillin VK?

A

Strep throat caused by S. pyogenes

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8
Q

What are the main penicillinase resistant penicillins?

A

Nafcillin, Oxacillin and Dicloxacillin

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9
Q

What is the spectrum of activity for penicllinase resistant penicillin?

A

Skin infections when penicillinase producing S. aureus is suspected (Target organism: MSSA)

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10
Q

Name the two aminopenicillins

A

Ampicillin and amoxicillin

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11
Q

What is the spectrum of activity for aminopenicillins?

A

Broad gram negative coverage (P. miribalis, E. Coli, Salmonella, Shigella, H Flu) and enterococcus, listeria

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12
Q

What is the main carboxypenicillin?

A

Ticarcillin

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13
Q

What is the spectrum of activity for ticarcillin?

A

Enhanced gram negative activity (enterobacter, pseudomonas)

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14
Q

What is the main ureidopenicillin?

A

Piperacillin

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15
Q

What is the spectrum of activity for piperacillin?

A

Even more enhanced gram negative activity (enterobacter, pseudomonas, serratia, klebsiella) as well as anaerobes

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16
Q

What is the mechanism of action for the beta-lactamase inhibitor combination drugs?

A

Competitive inhibitor of transpeptidase, inhibits cell wall synthesis AND beta-lactamase inhibitor

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17
Q

List the 3 major beta-lactamase inhibitor combination drugs

A

Ampicillin-Sulbactam (Unasyn)
Amoxicillin-Clavulanate (Augmentin)
Piperacillin-Tazobactam (Zosyn)

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18
Q

What is the spectrum of activity for the beta-lactamase inhibitor combination drugs?

A

Enhanced activity against beta lactamase producing organisms including G+ (S. Aureus), G- (H. flu, Moraxella), and anaerobes (bacteroides)

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19
Q

How are the beta lactams primarily excreted?

A

Primarily elmated by the kidneys (Except nafcillin and oxacillin eliminated by the liver)

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20
Q

What is the general mechanism of action for the aminoglycosides?

A

Bind to 30S ribosomal subunit and inhibits protein synthesis

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21
Q

What class of drugs are aminoglycosides often used with?

A

Cell wall inhibitors (synergy)

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22
Q

List the major aminoglycosides

A

Gentamycin, tobramycin, amikacin and streptomycin

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23
Q

What is the most commonly used aminoglycoside?

A

Gentamycin

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24
Q

What are the major adverse events associated with aminoglycosides?

A

Ototoxicity, nephrotoxicity, neuromuscular blockade

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25
Q

What is the spectrum of activity of gentamycin?

A

Gram negative enterics (E. coli, K. pneumoniae, proteus, serratia, pseudomonas) and gram positive (enterococcus, s. aureus, viridans, s. pyogenes)

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26
Q

What is the difference in spectrum activity between tobramycin and gentamycin?

A

Tobramycin is more active against pseudomonas, but less active against other gram negatives compared to gentamycin

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27
Q

What is the spectrum of activity of amikacin?

A

Amikacin is the broadest spectrum AG.

Most active AG against nosocomial gram negatives (except for Tobra with pseudomonas), mycobacteria, nocardia

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28
Q

How does the aminoglycoside dosing plan differ for treatment of G+ versus G- bacteria?

A

For G- bacteria you want to maximize the peak concentration, but for G+ bacteria low doses are sufficient

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29
Q

Aminoglycoside cell entry requires ________

A

Oxygen

Cell entry of AGs is oxygen dependent

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30
Q

What are the mechanisms of resistance to aminoglycosides?

A

AG modifying enzymes
Altered uptake (porins or efflux pumps)
Target modification

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31
Q

Is the oral absorption of aminoglycosides low or high?

A

AGs have poor oral absorption

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32
Q

How are aminoglycosides eliminated?

A

99% eliminated by the kidney

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33
Q

Aminoglycosides display ______-dependent killing

A

Aminoglycosides display concentration-dependent killing

Want to maximize peak concentration

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34
Q

What is postantibiotic effect?

A

Persistent suppression of bacterial growth after drug concentration falls below the MIC

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35
Q

What are the two dosing strategies associated with aminoglycosides?

A

Traditional dosing: same dose every 8-12 hrs

Extended interval dosing: one large dose given every 24+ hours

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36
Q

What is the general mechanism of cephalosporins?

A

Competitive inhibitor of transpeptidase enzyme, binds to PBPs to inhibit cell wall synthesis

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37
Q

What is the general trend of spectrum of activity across the generations of cephalosporins?

A

With successive generations, G+ activity decreases and G- activity increases

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38
Q

What are the mechanisms of resistance against first generation cephalosporins?

A

Beta lactamase

Altered penicillin binding proteins

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39
Q

What adverse effects are associated with first generation cephalosporins?

A

Allergy causing anaphylactic shock, hives, rash. Delayed rash (cross reactivity with penicillins). Superinfections.

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40
Q

Describe the spectrum of activity of first generation cephalosporins

A

1st gen have best activity against G+ (MSSA, PSSP, strep, viridans) with some G- activity (P. miribalis, E. coli, K. pneumoniae). Excellent for skin infections, surgical prophylaxis

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41
Q

Describe the spectrum of activity of second generation cephalosporins

A

Covers more G-, including anaerobes, than 1st gen, but less active against G+. Coverage: HENPEK

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42
Q

What is the only cephalosporin with activity against anaerobes like B. fragilis?

A

Cephamycins

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43
Q

Describe the excretion of cephalosporins

A

All are excreted renally, except ceftriaxone, which is excreted through the biliary system

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44
Q

Describe the spectrum of activity of 3rd generation cephalosporins

A

Greater activity against gram negative aerobes, including some beta lactamase producing strains. Excellent CSF penetration, used for meningitis (HENPECKSSS)

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45
Q

What are the 4th generation cephalosporins used for?

A

Extended spectrum of activity with combined activity of ceftriaxone and ceftazimidime. Used for pseudomonas

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46
Q

What are the 5th generation cephalosporins used for?

A

MRSA, skin and soft tissue infection, pneumonia

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47
Q

Are cephalosporins bacteriostatic or bacteriocidal?

A

Bacteriocidal

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48
Q

What is cross-allergenicity?

A

Similarities in drug structure or function lead to allergic hypersensitivity in multiple distinct drugs
Example: Pts with penicillin allergy may exhibit reactions to cephalosporins

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49
Q

What is the significance of the MTT side chain found on some cephalosporins?

A

Can cause hypoprothrombinemia by inhibiting Vitamin K metabolism, reducing vitamin K producing bacteria
Also causes ethanol intolerance

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50
Q

What is the general mechanism of action of carbapenems?

A

Inhibit bacterial cell wall synthesis by binding to PBP2

51
Q

What is the spectrum of activity for carbapenems?

A

G+, G- aerobes and anaerobes, including beta lactamase producing strains, Pseudomonas (except for ertapenem)

52
Q

What adverse events are associated with carbapenems?

A

Hypersensitivity, GI (nausea, vomitting), CNS (seizures, confusion, dizziness)

53
Q

What drug must be administered with imipenem? Why?

A

Imipenem is hydrolized by DHP brush border enzyme which must be blocked with cilastatin
“Cilistatin makes it last”

54
Q

Which bacteria are carbapenems not active against?

A

“MVP SACC”

MRSA, VRE, PRSP, Coagulase-negative staph, C diff, atypical bacteria, senotrophomonas maltophilia

55
Q

How are carbapenems excreted?

A

Renal excretion

56
Q

Are carbapenems bacteriostatic or bacteriocidal?

A

Bacteriocidal

57
Q

What are the 4 main carbapenems?

A

Imipenem, meropenem, ertapenem, doripenem

58
Q

What are the mechanisms of resistance against carbapenems?

A

beta lactamase production
decreased permeability
alteration of PBPs

59
Q

What class of drug is considered the broadest spectrum agent available?

A

Carbapenems

60
Q

What are the target organisms of carbapenems?

A

MSSA, Pseudomonas, and Bacteroides

61
Q

Are carbapenems functional in the presence of beta lactamase?

A

Yes. They are resistant to beta lactamase degradation

62
Q

What is the major monobactam drug?

A

Aztreonam

63
Q

What is the mechanism of action of monobactams?

A

Inhibits bacterial cell wall synthesis by binding to PBP3

64
Q

Do monobactams exhibit cross reactivity with penicillin?

A

No. Patients allergic to penicillin do not have hypersensitive reactions to aztreonam

65
Q

What is the spectrum of activity of aztreonam?

A

G- aerobes (including Pseudomonas), little to no activity against G+ or anaerobes

66
Q

Are monobactams bacteriocidal or bacteriostatic?

A

Bacteriocidal

67
Q

What are the mechanisms of resistance of monobactams?

A

Beta lactamase hydrolysis

Decreased permeability

68
Q

What adverse events are associated with monbactams?

A

Nausea and diarrhea

69
Q

What is the mechanism of action of vancomycin?

A

Inhibits synthesis of G+ peptidoglycan by inhibiting transpeptidation of D-alaninne

70
Q

How does the elimination of vancomycin differ between oral and IV administration?

A

IV –> renal excretion, Oral –> not absorbed well, high stool concentration

71
Q

What are the adverse events associated with vancomycin?

A

Ototoxicity
Nephrotoxicity
Red man syndrome: due to rate of IV infusion

72
Q

What is the spectrum of activity of vancomycin?

A

All gram positive organisms, C. Diff (oral)

73
Q

What is the main mechanism of resistance to vancomycin?

A

Increasing resistance to vancomycin recently due to modification of D-ala D-ala bindng site
VISA: thickened cell wall

74
Q

What is the spectrum of activity of dalbavancin?

A

Used for resistant G+ organisms, MRSA, VISA, VRE (vanB, vanC)

75
Q

What is the mechanism of action of Linezolid?

A

Binds to 50S preventing formation of 70S initiation complex, inhibiting protein synthesis

76
Q

What adverse events are associated with linezolid?

A

Lactic acidosis, peripheral neuropathy, thrombocytopenia, anemia
Possible serotonin storm with SSRIs/MAOIs

77
Q

What is the spectrum of activity of linezolid?

A

Used for serious/complicated G+ infections.

Activity against resistant G+ including VRE, MRSA and VISA

78
Q

If a patient is on SSRIs, what drug can be perscribed instead of linezolid?

A

Tedizolid is also an oxazolidinone like linezolid, but does not react with SSRIs

79
Q

What is the mechanism of action for daptomycin?

A

Binds bacterial membranes causing rapid depolarization that inhibits DNA, RNA and protein synthesis, leadiing to cell death

80
Q

What is the spectrum of activity for daptomycin?

A

Serious/complicated infections caused by resistant bacterias (MSSA, MRSA, S. pyogenes, S. aureus bacteremia).
No G- activity

81
Q

What are the adverse effects associated with daptomycin?

A

myopathy
CPK elevation
pneumonia

82
Q

Is linezolid bacteriostatic or bacteriocidal?

A

Bacteriostatic (except against S. pneumo)

83
Q

True or false: daptomycin can be used to treat pneumonia

A

FALSE

Daptomycin should NOT be used in the treatment of pneumonia

84
Q

What is the general mechanism of action of tetracyclines?

A

Reversibly binds to 30S ribosomal subunit and inhibits protein synthesis

85
Q

What is the spectrum of activity for tetracyclines?

A

G+ (primarily MSSA), G- (burkholderia) , Rickettsia, chlamydia, legionella, mycoplasma

86
Q

Describe the absorption of tetracyclines

A

Oral absorption from the stomach, which can be impaired by food, milk, divalent cations

87
Q

What adverse events are associated with tetracyclines?

A

GI (nausea, vomiting, diarrhea), hypersensitivity, photosensitivity, renal failure (Fanconi syndrome)
Category D drug for pregnant women: discolored teeth and bone growth abnormalities

88
Q

What are the mechanisms of resistance to tetracyclines?

A

Resistance can develop due to efflux pumps, ribosomal protection proteins, or enzymatic inactivation

89
Q

What is the difference between tigecycline and the tetracyclines?

A

Tigecycline has broader coverage than teracyclines, but not covering Proteus or psedomonas

90
Q

What is the mechanism of action of sulfonamides?

A

Inhibits DNA synthesis by Inhibiting dihydropteroate synthesis, preventing PABA from incorporating into tetrahydropteroic acid
Bacterostatic

91
Q

What is the spectrum of activity of Trimethoprim-Sulfamethoxazole?

A

Acute, chronic, recurrent UTIs, prostatitis, skin infections from CA-MRSA, Nocardia

92
Q

What adverse events are associated with TMP-SMX?

A

GI (nausea, vomiting, diarrhea), leukopenia, thrombocytopenia, hypersensitivity, renal toxicity

93
Q

What is the mechanism of action of Chloramphenicol?

A

Inhibits protein synthesis by binding to the 50S ribosome

94
Q

What adverse events are associated with chloramphenicol?

A

Bone marrow depression, gray baby syndrome

95
Q

What is the spectrum of activity of chloramphenicol?

A

Broad spectrum, kiills G+ (except s. aureus and enterococcus), G- (except P. aerugnosa), including anaerobes

96
Q

What is the mechanism of action of nitrofurantoin?

A

Binds ribosomal proteins, inhibits translation, bacterial respsiration, and pyruvate metabolism

97
Q

Describe the absorption and elimination of nitrofurantoin

A

Some absorbed in small intestine, large urine concentration, eliminated via urine

98
Q

Spectrum of activity of nitrofurantoin

A

Acute, uncomplicated UTIs

99
Q

What is the mechanism of action of methenamine?

A

Broken into ammonia and formaldehyde in acidic pH leading to denatured proteins and nucleic acids

100
Q

What is methenamine used for?

A

Suppression or prophylaxis against recurrent UTIs

101
Q

Are tetracyclines bacteriostatic or bacteriocidal?

A

Bacteriostatic

102
Q

What are the two gram negative aerobes that tigecycline does not cover?

A

Proteus and pseudomonas

103
Q

What are the 3 major tetracyclines?

A

Tetracycline, doxycycline and minocycline

104
Q

Is chloramphenicol bacteriostatic or bacteriocidal?

A

Bacteriostatic except for H. influenzae, S. pneumoniae, and N. meningitidis

105
Q

What is the mechanism of action of fluoroquinolones?

A

Inhibit DNA gyrase leading to breakage in bacterial DNA, inhibited DNA synthesis

106
Q

What is the spectrum of activity of fluoroquinolones?

A

G+ (MSSA, S. pneumo PRSP), and excellent G- coverage (enterobacteriaceae, H flu, neisseria, Pseudomonas), Legionella, Chlamydia, mycoplasma

107
Q

What are the names of the major fluoroquinolones?

A

Ciprofloxacin, levofloxacin, moxifloxacin, gemifloxacin

108
Q

What is unique about moxifloxacin?

A

It is the only FQ that treats anaerobes

109
Q

What are the adverse effects associated with fluoroquinolones?

A

GI (nausea, vomiting, diarrhea, dyspepsia, C. diff), CNS problems in elderly, hepatotoxicity, phototoxicity, cardiotoxicity (prolonged QT), tendon rupture, divalent and trivalent cations decrease absorption

110
Q

What is the mechanism of action of clindamycin?

A

Binds to 50S ribosomal subunit and inhibits protein synthesis

111
Q

What is the spectrum of activity of clindamycin?

A

Anaerobes not in the CNS (bacteroides), G+ (MSSA, CA-MRSA, PSSP, group and viridans strep), and for pts with penicillin allergy

112
Q

Is clindamycin bacteriostatic or bacteriocidal?

A

Bacteriostatic

113
Q

What adverse events are associated with clindamycin?

A

Nausea, vomiting, diarrhea, dyspepsia

Can cause pseudomembranous colitis, which can lead to C. Diff

114
Q

What are the three major macrolides?

A

Erythromycin, clarithromycin, azithromycin

115
Q

What is the mechanism of action of the macrolides?

A

Binds to 50S ribosomal subunit and inhibits protein synthesis

116
Q

Which macrolides are time-dependent and which are concentration dependent?

A

Erythro and Clarithro are time dependent

Azithromycin is concentration dependent

117
Q

How are macrolides metabolized?

A

CYP450. This can lead to drug interactions if other meds are also metabolized by CYP450

118
Q

What is the difference between the spectrum of activity of macrolides and clindamycin?

A

Macrolides also cover gram negative aerobes (Neisseria, M. cattarhalis), and atypical bacteria (legionella, chlamydia) in addition to the G+ aerobes (MSSA, PSSP, group and viridans strep, Bacillus, Corynebacterium)

119
Q

Which macrolide has the best activity against G+ bacteria? Which has the best for G-?

A

Clarithromycin has the best activity against G+

Azithromycin has the best activity against G-

120
Q

What are the mechanisms of resistance against macrolides?

A 
Active efflux (mef gene)
Altered ribosomal target sites (erm gene)
121
Q

What is the mechanism of action of Quinupristin-dalfopristin (Synercid®)?

A

Inhibits 50S ribosomal subunit to inhibit early and late stages of protein synthesis

122
Q

What s the spectrum of activity for Quinupristin-dalfopristin (Synercid®)?

A

G+ bacteria
Primarily used to treat VRE
Also has activity against MRSA, S. epi, S. sap, PRSP

123
Q

Is Quinupristin-dalfopristin (Synercid®) bacteriostatic or bacteriocidal?

A

bacteriostatic

124
Q

What adverse events are associated with Quinupristin-dalfopristin (Synercid®) ?

A

Venous irrtation, GI (nausea vomiting, darrhea), myalgias, arthralgias, rash

MHD/Pharm Block 3 (2 decks)

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