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Lindsey's D&D Unit 3 > Antibacterial Agents III: Protein Synthesis Inhibitors > Flashcards

Antibacterial Agents III: Protein Synthesis Inhibitors Flashcards

1
Q

Clindamycin penetrates most tissues well, especially ____, but not well into ____.

A

bone; CSF

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1
Q

Pts with myasthenia gravis or that take other neuromuscular blocking agents can have respiratory arrest after taking ______.

A

aminoglycosides

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2
Q

What is the mechanism of action for Linezolid?

A

binds to the 23s portion of the 50s ribosome to inhibit early phase protein synthesis

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3
Q

What is the mechanism of resistance in the aminoglycosides?

A

chemical mods to the abx that prevents uptake and ribosomal binding (plasmid mediated)

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3
Q

Where do the aminoglycosides accumulate?

A

the renal cortex and inner ear

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4
Q

_____ are VERY TOXIC!

A

Aminoglycosides

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5
Q

Why do ventricular arrhythmias occur with macrolides?

A

they prolong the QT interval

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5
Q

What are the mechanisms of chloramphenicol resistance?

A

emergence of mutant strains impermeable to drug; inactivation of bacterial enzymes

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5
Q

Why does chloramphenicol cause gray baby syndrome?

A

immature hepatic and renal fxn leads to toxic accumulation of the drug

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6
Q

What impairs the absorption of tetracyclines?

A

milk products, Al, Ca, Mg, and Fe salts

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6
Q

Tx for Borrelia burgdorferi Lyme disease (early)?

A

doxycycline

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6
Q

Quinupristin/Dalfopristin inhibits cytochrome 3A4, which may cause increased plasma levels of _____ (6).

A
  1. benzodiazepines cisapride 2.. calcium channel blockers 3. carbamazepine 4. cyclosporine 5. HMG CoA reductase inhibitors 6. HIV protease inhibitors
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7
Q

Name 3 tetracyclines.

A
  1. tetracycline 2. doxycycline 3. minocycline
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8
Q

Azithromycin is not metabolized; its high tissue penetration and slow release allows _____ dosing.

A

once-daily

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9
Q

_____ in aminoglycoside use is usually reversible when the drug is discontinued.

A

Renal toxicity

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10
Q

How should clindamycin be taken?

A

food doesn’t affect it

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11
Q

Tx for Chlamydia trachoma, C.A. pneumonia, urethritis?

A

azithromycin

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11
Q

Which tetracyclines have the best bioavailability?

A

minocycline, doxycycline

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11
Q

How do antacids and iron supps interact with tetracyclines?

A

decrease bioavail of the tetracyclines by forming insoluble salts

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11
Q

_____ has limited use in the US and is only used for severe infections.

A

Chloramphenicol

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11
Q

Tx of Strep pneumonia (C.A. and nosocomial)?

A

Linezolid, Quinupristin/Dalfopristin

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12
Q

Tx for C. diptheriae diptheria?

A

erythromycin

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13
Q

Avoid _____ if leukopenias, anemia, or thrombocytopenia present bc of bone marrow tox.

A

chloramphenicol

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14
Q

Why does admin of aminoglycosides have to be so carefully monitored?

A

they are subject to wide variation of pharmacokinetics, even in pts with healthy kidney function, and have a narrow therapeutic index

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15
Q

What is Telithromycin/Ketek?

A

a ketolide Abx derived from erythromycin

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16
Q

Describe the hepatotoxicity via macrolides.

A

reversible acute cholestatic hepatitis

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17
Q

Name 6 drugs that can be toxic in combination with a macrolide.

A

theophylline, warfarin, methylprednisolone, cyclosporine, SSRIs, benzodiazepines

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17
Q

Why is there some selective toxicity with tetracyclines?

A

mammalian cells have an active efflux mechanism preventing accumulation of drugs, and lack active transport of drugs into the cell

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17
Q

Tx of Enterococci (including VRE) bacteremia, endocarditis?

A

Linezolid, Quinupristin/Dalfopristin

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18
Q

Tx for Enterococci bacteremia, endocarditis, intra-abd infections?

A

gentamycin + penicillin or vancomycin

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19
Q

What drug can cause gray baby syndrome?

A

chloramphenicol

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20
Q

______ is metabolized in the liver and excreted in the bile.

A

Erythromycin

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21
Q

What is the mechanism of action of clindamycin?

A

inhibits protein synthesis by binding to the 50s ribosome- prevents translocation of peptidyl tRNA and peptide bond formation

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22
Q

How do the tetracyclines work?

A

reversibly bind to 30s ribosome to prevent access of aminoacyl-tRNA to site

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22
Q

Aminoglycosides have ____ killing and a _____ which allows their admin in a single, large daily dose.

A

concentration-dependent; postantibiotic

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22
Q

What are the adverse affects of Linezolid?

A

minor GI, thrombocytopenia, drug interaction with MAO and SSRI

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23
Q

Choose: The macrolides ARE/ARE NOT excreted in breast milk and ARE/ARE NOT ok to use in breastfeeding women.

A

ARE; ARE

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25
Q

When should Telithromycin/Ketek be prescribed?

A

ONLY in community acquired pneumonia due to Strep. pneumoniae

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26
Q

Choose: Chloramphenicol is BACTERIOCIDAL/BACTERIOSTATIC.

A

normally static, but cidal against bacteriodes, H. influenzae, N. meningitidis

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27
Q

How is Linezolid metabolized/distributed/excreted?

A

nonenzymatic oxidation; well-perfused tissues; renally

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28
Q

Tx for Chlamydia trachoma, C.A. pneumonia, urethitis?

A

doxycycline

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28
Q

Name 6 general adverse rxns for the tetracyclines.

A
  1. teeth and bone 2. GI upset 3. photosensitivity 4. yeast/candida overgrowth 5. liver/kidney toxicity 6. drug interactions
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29
Q

Aplastic anemia, although rare, can be fatal and appears weeks to months post-_____ treatment.

A

chloramphenicol

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30
Q

What drugs does Linezolid interact with?

A

MAOs, SSRIs

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31
Q

Choose: Linezolid is BACTERIOSTATIC/BACTERIOCIDAL.

A

static

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32
Q

Tx for Richettsia rocky mtn spotted fever, Q fever?

A

doxycycline, chloramphenicol

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33
Q

Which tetracycline is choice for pts with renal disease or for breastfeeding mothers?

A

doxycycline

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34
Q

_____ should be used to treat severe anaerobic infections.

A

Clindamycin

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36
Q

Tx for Strep and Pneumococci pneumonia and pharyngitis?

A

any macrolide

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37
Q

Tx for Myco. avium pneumonia?

A

clarithromycin, azithromycin

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38
Q

Name 3 adverse rxns for clindamycin.

A
  1. pseudomembranous colitis 2. GI upset or skin rashes 3. impaired liver function, neutropenia (rare)
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38
Q

Aminoglycosides have concentration-dependent killing and a postantibiotic effect which allows their admin in a ______.

A

single, large daily dose

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39
Q

Azithromycin and clarithromycin accumulate in higher concentrations in _____ and ____.

A

certain tissues (skin, lungs, tonsils, cervix, sputum); macs

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40
Q

Tx for Bacillus anthracis anthrax?

A

doxycycline

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41
Q

Tetracyclines can lead to disturbance of normal gut flora, leading to ____ and _____.

A

thrush, vaginitis

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41
Q

Tx for MRSA localized cutaneous infection?

A

clindamycin

42
Q

Tx for Strep. pneumonia, pharyngitis?

A

clindamycin

43
Q

What are the s/s of gray baby syndrome?

A

vomiting, abnormal respirations, cyanosis, vasomotor collapse and ashen-gray color

44
Q

Tx for Myco. tuberculosis Tb?

A

streptomycin + anti-Tb drugs

45
Q

Is clindamycin bacteriocidal or bacteriostatic?

A

static, but can be cidal against certain orgs and high concentrations

47
Q

Which of the macrolides causes the most GI upset? How?

A

erythromycin; directly stimulates gut motility

48
Q

How do the aminoglycosides work?

A

inhibits initiation of protein synthesis by interacting with mRNA on the 30s ribosome- breaks up the polysomes, misreads the code

48
Q

Why does chloramphenicol have a diminished selective toxicity?

A

it inhibits mammalian mitochondrial protein synthesis in the bone marrow

49
Q

Tx for Bacteriodes fragilis intra-abd. and brain abscesses?

A

clindamycin, chloramphenicol

50
Q

Choose: Macrolides are BACTERIOSTATIC/BACTERIOCIDAL.

A

bacteriostatic at normal concentrations

51
Q

Tx for Salmonella typhi typhoid fever?

A

chloramphenicol

52
Q

_______ inhibits metabolism of phenytoin, oral anticoagulants, and 1st gen oral hyperglycemic agents.

A

Chloramphenicol

53
Q

What is the absorption, distribution, metabolism, and excretion of chloramphenicol?

A

rapid and complete from GI tract; widely distributed in all tissues and fluids, inc CNS and CSF; metabolized by glucuronidation or reduction except in fetus and neonate; excreted in breast milk

55
Q

Tx for H. pylori peptic ulcers?

A

tetracycline

56
Q

______ have concentration-dependent killing and a postantibiotic effect which allows their admin in a single, large daily dose.

A

Aminoglycosides

58
Q

How should each of the macrolides be taken?

A
  1. erythromycin = depends on salt form 2. clarithromycin = doesn’t matter- food may help absorb 3. azithromycin = take on empty stomach
59
Q

Tx for H. influenzae URI/bronchitis?

A

azithromycin, clarithromycin

61
Q

Tetracyclines should be used with caution in pts with ____.

A

impaired liver function

62
Q

Tx for Vibrio cholera cholera?

A

doxycycline

63
Q

How does resistance to the macrolides occur?

A

methylation of the 50S ribosome, preventing binding of drug

65
Q

Tx for Myco. pneumoniae C.A. pneumonia?

A

any macrolide

66
Q

How does resistance to tetracyclines work?

A
  1. changes in protein receptors or transporters 2. produce proteins to block and protect the ribosome
66
Q

_____ penetrates most tissues well, especially bone, but not well into CSF.

A

Clindamycin

66
Q

What are the important drug interactions with Quinupristin/Dalfopristin?

A

inhibits cytochrome 3A4

68
Q

____ is short-acting (t1/2 of 6-8 hours); ____ and _____ are long-acting (t1/2 of 16-18 hours).

A

tetracycline; doxycycline, minocycline

70
Q

What are the macrolides?

A
  1. erythromycin 2. clarithromycin 3. azithromycin
71
Q

What is the mechanism of action for Quinupristin/Dalfopristin?

A

inhibits bacterial protein synthesis by binding to the 50S ribosome to inhibit elongation

72
Q

Tx for Clost. perfringens gas gangrene, food poisoning?

A

clindamycin

73
Q

Tx for Pseudo. aeruginosa (any)?

A

gentamycin, tobramycin, amikacin

74
Q

Does tetracycline cross into the placental/fetal circulation?

A

yes

75
Q

Tetracycline is short-acting (t1/2 of ____); doxycycline and minocycline are long-acting (t1/2 of _____).

A

6-8 hours; 16-18 hours

77
Q

Aminoglycosides are _____ at low concentrations and _____ at high concentrations (clinically).

A

bacteriostatic, bactericidal

79
Q

Tx for Prop. acnes acne?

A

minocycline, doxycycline, clindamycin

81
Q

Which drug requires oxygen and is therefore ineffective in anaerobic organisms?

A

aminoglycosides

82
Q

Name the 6 aminoglycosides.

A
  1. streptomycin 2. tobramycin 3. gentamycin 4. amikacin 5. kanamycin 6. neomycin
83
Q

How are the aminoglycosides absorbed, distributed, metabolized, and excreted?

A

highly polar, so not sig. absorbed after oral admin- use IM- distributed into extracellular fluid- excluded from CNS but accumulates in the renal cortex and inner ear; not metabolized; excreted thru kidneys

84
Q

Tx for H. influenzae otitis media, C.A. pneumonia?

A

doxycycline

85
Q

Tx of Staph (including MRSA) complicated skin infections?

A

Linezolid, Quinupristin/Dalfopristin

86
Q

______ should be avoided in pregnancy and breastfeeding because it cannot be conjugated by the fetal and neonate liver, causing toxicity.

A

Chloramphenicol

88
Q

Tx for MSSA osteomyelitis?

A

clindamycin

89
Q

Pts with myasthenia gravis or that take other neuromuscular blocking agents can have _____ after taking aminoglycosides.

A

respiratory arrest

90
Q

What happens when an aminoglycoside and penicillin are given together?

A

the aminoglycoside is inactivated

92
Q

Clarithromycin is ____ eliminated.

A

renally

93
Q

What is the distribution of the macrolides?

A

widely except brain and CSF; crosses placenta

94
Q

Tx for H. influenza meningitis?

A

chloramphenicol

95
Q

How do the macrolides work?

A

inhibit protein synthesis by binding to the 50s subunit and block translocation of peptidyl tRNA and peptide bond formation

97
Q

Tx for E. coli, Klebsiella, Serratia, Proteus, Enterobacter UTIs, lower RIs, bacteremias, post-surg bowel sterilization, wound infections?

A

neomycin

99
Q

Chloramphenicol inhibits metabolism of ____, ____, and _____.

A

phenytoin, oral anticoagulants, and 1st gen oral hyperglycemic agents

100
Q

What is the main adverse rxn for clindamycin?

A

pseudomembranous colitis

101
Q

______ is not metabolized; its high tissue penetration and slow release allows once-daily dosing.

A

Azithromycin

102
Q

_____, although rare, can be fatal and appears weeks to months post-chloramphenicol treatment.

A

Aplastic anemia

103
Q

How is Quinupristin/Dalfopristin administered?

A

IV only

105
Q

Which drugs interact negatively with tetracyclines?

A
  1. antacids and iron supps 2. phenytoin/barbs/carbamazipines 3. oral anticoagulants
106
Q

How do the aminoglycosides get into the bacterium?

A

active transport

107
Q

Tx for Staph. aureus cutaneous infections, pneumonia, food poisoning?

A

doxy, tigecycline

108
Q

How do the tetracyclines affect bones and teeth?

A

temporarily depresses bone growth and permanently discolors teeth

109
Q

How is clindamycin metabolized and excreted?

A

metabolized by the liver, then into biliary excretion- also excreted into breast milk

110
Q

Erythromycin is metabolized in the ____ and excreted in the ____.

A

liver; bile

111
Q

Name 5 adverse rxns to chloramphenicol.

A
  1. bone marrow tox 2. gray baby syndrome 3. GI upset 4. oral or vaginal candidiasis 5. drug interactions
113
Q

Tx for Legionella community-acquired pneumonia?

A

azithromycin

114
Q

How is Quinupristin/Dalfopristin metabolized and excreted?

A

hepatic conjugation rxns; biliary excretion into the feces

116
Q

Tx for Moraxella catarrhalis otitis media, c.a. pneumonia?

A

doxycycline

117
Q

______ is renally eliminated.

A

Clarithromycin

118
Q

What drug do the aminoglycosides interact with?

A

the β-lactams and penicillin

119
Q

Why are the macrolides only selectively toxic?

A

they don’t bind to the 60S ribosome

120
Q

Where is tetracycline metabolized and excreted?

A

concentrated in the liver, secreted into bile, excreted into the urine (except doxycycline and minocycline)

121
Q

How does chloramphenicol work?

A

reversible binding of the 50S ribosome, blocking peptidyl transferase action and incorporation of aas in to the newly formed peptide

122
Q

Tx for N. meningitides meningitis?

A

chloamphenicol

123
Q

Which macrolides can potentially cause toxicity via drug-drug interactions and why?

A

erythromycin, clarithromycin- inhibit CYP450- increase plasma drug levels

124
Q

Tx for H. pylori peptic ulcer disease?

A

clarithromycin plus PPI or H2 antagonist

125
Q

____ and ____ accumulate in higher concentrations in certain tissues and macs.

A

Azithromycin; clarithromycin

126
Q

How is Linezolid administered?

A

orally, food doesn’t matter

127
Q

What are the common side effects of Quinupristin/Dalfopristin?

A

infusion site irritation, arthralgia/myalgia, GI upset, skin rashes

128
Q

_____ in aminoglycoside use is irreversible and happens at high frequency in elderly pts and those with impaired renal function.

A

8th nerve damage

129
Q

What must be monitored in aminoglycoside-receiving pts?

A
  1. plasma drug conc 2. 8th cranial nerve function 3. kidney function
130
Q

Tx for Myco. pneumoniae C.A. pneumonia?

A

doxycycline

131
Q

______ and _____ should only be used for life-threatening infections.

A

Linezolid and Quinupristin/Dalfopristin

133
Q

What are the 4 main adverse rxns of macrolides?

A
  1. GI upset 2. hepatotoxicity 3. ventricular arrhythmias 4. inhibition of CYP450 causing drug/drug interactions
134
Q

Choose: Tetracyclines are BACTERIOCIDAL/BACTERIOSTATIC.

A

bacteriostatic

135
Q

Linezolid and Quinupristin/Dalfopristin should only be used for _____.

A

life-threatening infections

136
Q

How should tetracycline be administered?

A

on an empty stomach

137
Q

What sensitivity rxns can occur with aminoglycoside use?

A

contact dermatitis, skin rashes, bone marrow depression

138
Q

Tx for B. pertussis whooping cough?

A

any macrolide

139
Q

Macrolides enter the cell via ____.

A

passive diffusion

Lindsey's D&D Unit 3 (12 decks)

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