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Ch34 Anti-infective Agents Flashcards

1
Q

What is the general spectrum of aminoglycosides? (2)

A
  1. Gram (-)

2. Select aerobic gram (+)

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2
Q

What is the mechanism for aminoglycosides? (2)

A
  1. Inhibit protein synthesis through binding to the 30S ribosomal subunit “3 (common aminoglycosides) 30S”
  2. This irreversibly inhibits bacterial RNA
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3
Q

Are aminoglycosides bactericidal or bacteriostatic?

A

Bactericidal

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4
Q

Which aminoglycosides are minimally absorbed and are used to decrease bacterial content in the bowel? (2)

A
  1. Kanamycin

2. Neomycin

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5
Q

What are important ADRs of aminoglycosides? (3)

A
  1. Nephrotoxicity
  2. Ototoxicity
  3. Neuromuscular blockade
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6
Q

What are risk factors for neuromuscular blockade caused by aminoglycosidses? (3)

A
  1. Myasthenia gravis
  2. Hypocalcemia
  3. Elevated peak concentrations
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7
Q

What nerve is damaged in aminoglycoside induced ototoxicity?

A

Eighth cranial nerve

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8
Q

How are aminoglycosides dosed?

A
  1. Actual body weight

2. Unless patient is obese 20% over ideal use adjusted

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9
Q

What is the equation for ideal body weight (only needed for aminoglycosides to calculate adjusted if obese)?

A

Males: IBW = 50 kg + 2.3 kg for each inch over 5 feet.
Females: IBW = 45.5 kg + 2.3 kg for each inch over 5 feet.
1. My ideal 6ft = 77.6

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10
Q

What is the equation for adjusted body weight?

A

IBW + 0.4(total body weight - ideal)

Ideal is on the outsides

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11
Q

What are the target serum concentrations for amikacin?

A
  1. Peak = 20-30mcg/ml

2. Trough = <10 mcg/ml

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12
Q

What are the target serum concentrations for gentamicin and tobramycin?

A
  1. Peak = 4-10mcg/ml

2. Trough = <2mcg/ml

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13
Q

Which aminoglycoside can be inhaled via nebulization?

A

Tobramycin

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14
Q

What is the rationale for extended interval dosing with aminoglycosides? What trait is helpful in this dosing?

A
  1. Designed to drive the peak very high to max the concentration dependent killing and allow troughs to fall to reduce toxicity
  2. They have a significant postantibiotic effect
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15
Q

What is the mechanism of penicillins?

A

Bind to penicillin binding protein in cell wall

Cell wall synthesis is inhibited

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16
Q

Are penicillins bactericidal or bacteriostatic?

A

Bactericidal

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17
Q

What does the chemical structure of penicillins consist of?

A
  1. Beta-lactam

2. Thiazolidine Ring

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18
Q

How are penicillins eliminated? Name two exceptions.

A
  1. Renal

2. Nafcillin and oxacillin are hepatic

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19
Q

What are examples of “natural penicillins?” (2)

A
  1. Penicillin G

2. Penicillin V

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20
Q

What are examples of “penicillinase-resistant penicillins?” (4)

A
  1. Oxacillin
  2. Nafcillin
  3. Cloxacillin
  4. Dicloxacillin
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21
Q

What are examples of penicillin + beta lactamase inhibitors? (4)

A
  1. Amoxicillin Clavulanic acid (Augmentin)
  2. Ticarcillin Clavulanic acid (Timentin)
  3. Ampicillin Sulbactacm (Unasyn)
  4. Piperacillin Tazobactam (Zosyn)
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22
Q

What is the spectrum of natural penicillins? (5)

A
  1. Viridans Streptococci
  2. Streptococcus pyogenes
  3. 60% Streptococcus Pneumoniae
  4. Clostridium Pefringens (gas gangrene)
  5. Mouth anaerobes
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23
Q

What bacteria are natural penicillins ineffective against?

A

Staphylococcus aureus (penicillinase)

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24
Q

What do aminopenicillins have greater penetration for and higher affinity for?

A
  1. The outer membrane of gram (-) rods

2. Penicillin binding proteins

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25
Q

Are cephalosporins bactericidal or bacteriostatic?

A

Bactericidal

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26
Q

What is the mechanism of cephalosporins?

A
  1. Inhibit mucopeptide synthesis in the bacterial cell wall

2. Formation of defective cell walls

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27
Q

What is a common dose for penicillin G benzathine (Bicillin LA)? For syphilis treatment?

A
  1. 2 million units IM single dose

2. 4 million units IM single dose

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28
Q

What are the first generation cephalosporins? (3)

A
  1. Cephalexin (Keflex) po
  2. Cefadroxil (Duricef) po
  3. Cefazolin (Ancef) IV”
    ALEX tried to keep up with the FADs but they FAZzled out”
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29
Q

What is the general spectrum for first generation cephalosporins?

A

More gram (+) than gram negative coverage

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30
Q

What are the second generation cephalosporins? (5)

A
  1. Cefaclor (Ceclor) po
  2. Cefuroxime (Ceftin, Zinacef) IV IM po
  3. Cefoxitin (Mefoxin) IV
  4. Cefotetan (Cefotan) IV IM
  5. Cefprozil (Cefzil) po
    “The FACt is the FURry FOX crossed the TETANs like a PRO”
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31
Q

What is the general spectrum for second generation cephalosporins?

A

Enhanced gram (-) over 1st gen

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32
Q

What are the third generation cephalosporins? (7)

A
  1. Cefpodoxime (Vantin) po
  2. Ceftazidime (Fortaz, Tazicef) IV IM
  3. Cefixime (Suprax) po
  4. Cefdinir (Omnicef) po
  5. Ceftriaxone (Rocephin) IV IM
  6. Cefibuten (Cedax) po
  7. Cefotaxime (Claforan) IV
    “Listening to his iPOD, TAZ was so FIXed on DINIR he fell off his TRIke onto his BUT and had to pay TAXes
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33
Q

What is the general spectrum for third generation cephalosporins?

A
  1. More gram (-) than positive coverage

2. Cerebrospinal fluid penetration

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34
Q

What is the general spectrum for third generation cephalosporins?

A
  1. More gram (-) than positive coverage

2. Cerebrospinal fluid penetration

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35
Q

What is the fourth generation cephalosporin?

A

Cefepime (Maxipime) IV IM

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36
Q

What is the fifth generation cephalosporin?

A

Ceftaroline (Teflaro) IV

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37
Q

What cephalosporins have antipseudomonal activity?

A
  1. Ceftazidime

2. Cefepime

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38
Q

Which cephalosporin has no gram (+) activity?

A

Ceftazidime

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39
Q

What cephalosporins have anaerobic coverage? (4)

A

Cefotetan 2nd
Cefoxitin 2nd
Cefprozil 2nd
Cefpodoxime 3rd

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40
Q

Which cephalosporin has bleeding (hypoprothrombinemia) which is attributable to the presence of a N-methylthiotetrazole side chain?

41
Q

What cephalosporin can cause a disulfiram-like reaction with ingestion of alcohol?

42
Q

Which cephalosporins should be adjusted in renal insufficiency?

A

All but ceftriaxone (renal and via bile cleared)

43
Q

What mechanism can cause bacterial resistance to cephalosporins?

A

Beta-lactamases

44
Q

Are carbapenems beta-lactams?

A

They are beta-lactam-like

Structurally similar to penicillins

45
Q

What is the mechanism for carbapenems?

A

Bind to penicillin binding proteins and inhibit peptidoglycan synthesis

46
Q

Carbapenems are the DOC for what?

A

ESBL producing Enterobacteriaceae species

47
Q

What is ESBL?

A

Extended Spectrum Beta-Lactamases

48
Q

What is the general spectrum for carbapenems? (5)

A
  1. Gram (+)
  2. Gram (-)
  3. Anaerobes
  4. Atypical (Mycobacterium and chlamydia)
  5. Pseudomonas Acinetobacter (not ertapenem)
49
Q

What are the most common ADRs reported with imipenem? (2)

A
  1. GI NVD (C.diff)

2. Seizures reported in 0.4%

50
Q

Why is cilastatin needed with imipenem?

A

It increases the AUC and urinary concentrations of imipenem

51
Q

What is a difference in ADRs of meropenem and doripenem compared to imipenem?

A

Meropenem and doripenem have decreased CNS toxicity

52
Q

What is a common dose for ertapenem?

A

1000 mg q24h

53
Q

What type of bacterial killing do aminoglycosides have?

A

Concentration dependent

54
Q

What type of bacterial killing do penicillins and cephalosporins have?

A

Time above the MIC dependent

55
Q

What type of bacterial killing do fluoroquinolones have?

A

Concentration dependent

56
Q

What condition cannot be treated with daptomycin?

57
Q

What condition should not be treated with linezolid?

A

Endovascular infections

58
Q

What is the spectrum of clindamycin?

A

Anaerobes
Gram (+)
MRSA

59
Q

What conditions are tetracyclines the DOC for? (2)

A
  1. Lyme disease

2. Rocky Mountain spotted fever

60
Q

What is the general spectrum for macrolides?

A
  1. Gram (+)

2. Atypical

61
Q

What is a BBW for telithromycin?

A

Hepatotoxicity

62
Q

Why is aztreonam less likely to have cross-reactivity with penicillin allergy?

A

It does not have a beta lactam ring

63
Q

What is the spectrum for aztreonam?

64
Q

Name two bacteria that linezolid is active against?

A

Enterococcus faceium and faecalis

65
Q

What are some serious ADRs to linezolid? (3)

A
  1. Myelosuppression
  2. Neurotoxicity (peripheral neuropathy, and optic neuritis)
  3. Lactic Acidosis
66
Q

When are myelosuppression ADRs to linezolid more common to occur?

A

When therapy exceeds 14 days

67
Q

What is an important drug interaction with linezolid? (4 classes, 1 agent involved)

A
  1. It is a weak MAO inhibitor

2. Caution with Sympathomimetics (Pseudoephedrine, NE, DA), SSRIs, TCAs, Triptans, Meperidine)

68
Q

Where does linezolid achieve higher concentrations (tissue vs plasma)?

A

In tissue rather than plasma

69
Q

What is the mechanism of daptomycin?

A
  1. Causes rapid depolarization to bacterial cell membranes “rap depo dapto anagramish”
  2. Loss of membrane potential inhibits protein, DNA, and RNA synthesis
70
Q

What are 2 serious ADRs with daptomycin?

A
  1. Rhabdomyolysis (increased creatine phosphokinase)

2. Nephrotoxicity

71
Q

What is the dose for daptomycin in treating pneumonia?

A

It cannot be used. It is inactivated by the surfactant in the lung

72
Q

What is the mechanism of vancomycin? (2)

A
  1. Inhibition of peptidoglycan synthesis polymerization and cross-linking
  2. May also inhibit RNA synthesis
73
Q

What is “red-man syndrome”?

A

Caused my histamine release associated with rapid IV infusion of vancomycin

74
Q

How can the risk of “red-man syndrome be minimized?

A
  1. Slow IV infusion of vancomycin

2. NTE 500mg/30 mins

75
Q

What is the volume of distribution of vancomycin?

A

0.7 L/kg (total body weight)

76
Q

Are fluoroquinolones bactericidal or bacteriostatic?

A

Bactericidal

77
Q

What is the mechanism of fluoroquinolones?

A

Inhibition of bacterial DNA gyrase and topoisomerase

78
Q

What is an important counseling point fluoroquinolones

A
  1. Ca, Mg, iron decrease absorption

2. Antacids, dairy, and multivitamins should not be taken for at least 2 hours after dose

79
Q

What is a BBW for fluoroquinolones?

A
  1. Increased risk of tendinitis and tendon rupture (increased risk >60 years, children)
  2. Avoid in myasthenia gravis
80
Q

Are macrolides bactericidal or bacteriostatic?

A

Bacteriostatic

81
Q

What is the mechanism for macrolides?

A

Bind to 50S RNA subunit thereby inhibiting RNA synthesis

82
Q

What is the PO to IV conversion of azithromycin?

83
Q

Macrolides are the DOC in what diseases? (2)

A
  1. Atypical pneumonia

2. Chlamydia

84
Q

What is the difference between tetracyclines and tigecycline?

A

Same MOA but tigecycline has a structural modification that increases affinity and binding to the bacterial ribosome and decreases efflux from the cell

85
Q

What are counseling points for tetracycline?

A
  1. Best to take without food. Food interferes with absorption. However, food can minimize GI ADRs
  2. Photosensitivity
  3. Antacids, Dairy, Iron, Multivitamin should be avoided for several hours before and after (decrease tetracycline concentration)
86
Q

What is an important serious ADR for sulfamethoxazole?

A

Dermatologic reactions (Steven-Johnson syndrome, rash, urticaria)

87
Q

What antibiotic can induce clostridium difficile enterocolitis at higher rates?

A

Clindamycin

88
Q

What miscellaneous antibiotic causes a disulfiram-like reaction?

A
  1. Metronidazole

2. Alcohol should be avoided 3 days before and after

89
Q

What should be considered as an alternative to ceftriaxone in treating meningitis in patients with a life threatening b-lactam allergy? Why

A
  1. Chloramphenicol

2. It penetrates CNS

90
Q

What is the mechanism which explains why chloramphenicol has limited use?

A

It’s toxicities are caused by inhibition of mammalian protein synthesis

91
Q

What is the BBW for chloramphenicol? (3)

A
  1. Can cause life-threatening blood dyscrasias (abnormal blood condition)
  2. Aplastic anemia (bone marrow does not produce sufficient new blood cells) and Hypoplastic anemia (decreased RBCs)
  3. Thrombocytopenia and granulocytopenia
92
Q

What agent can cause gray baby syndrome?

A

Chloramphenicol

93
Q

What are the components of prokaryotic ribosomes? (3)

A
  1. 70S
  2. Large subunit = 50S (5S, 23S)
  3. Small subunit = 30S (16S)
94
Q

What are two indications for rifaximin?

A
  1. Traveler’s diarrhea caused by E coli

2. Hepatic encephalopathy

95
Q

What are three examples of echinocandins?

A
  1. Caspofungin
  2. Micafungin
  3. Andulafungin
96
Q

When should caspofungin be dose adjusted?

A

Severe liver dysfunction

97
Q

Are azole antifungals inducers or inhibitors of CYP?

98
Q

What is a cardiovascular ADR of azole antifungals?

A

QT prolongation

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