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STEP 1 > Antibiotics > Flashcards

Antibiotics Flashcards

1
Q

Penicillin forms

A 
G = IV, IM
V = oral
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2
Q

Mechanism of penicillin

A

bind penicillin-binding proteins (transpeptidases)
block transpeptidase cross-linking of peptidoglycan in cell wall
activates autolytic enzymes

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3
Q

Use of penicillin

A

Mostly used for gram positive organisms (S. aureus - MSSA; Group A strep, Group B strep, Actinomyces)

Some gram negative cocci - N. meningitidis)
Spirochetes (T. pallidum)

Bactericidal for gram-positive cocci, gram-positive rods, gram-negative cocci, and spirochetes that are penicillinase sensitive

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4
Q

Toxicity of penicillin

A

hypersensitivity reactions, hemolytic anemia

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5
Q

Resistance to penicillin

A

penicillinase in bacteria (a type of beta-lactamse) cleaves beta-lactam ring

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6
Q

Mechanism of amoxicillin/ampicillin

A

same as penicillin; wider spectrum; penicillinase sensitive
can combine with clavulanic acid to protect against destruction by beta-lactamase

amoxicillin (more oral bioavailability)

Mech: bind penicillin-binding proteins (transpeptidases)
block transpeptidase cross-linking of peptidoglycan in cell wall
activates autolytic enzymes

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7
Q

Use of amoxicillin/ampicillin

A

Extended-spectrum penicillin (gram-positive cocci, gram-negative cocci, gram-positive rods, spirochetes)

PLUS
H. influenzae, H. pylori, E. coli. Listeria, Proteus, Salmonella, Shigella, enterococci

HHELPSS kill enterococci

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8
Q

Toxicity of amoxicillin/ampicillin

A

Hypersensitivity reactions; rash; pseudomembranous colitis

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9
Q

Resistance to amoxicillin/ampicillin

A

penicillinase in bacteria (a type of beta-lactamase) cleaves beta-lactam ring

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10
Q

Name the penicillinase-resistant penicillins

A

dicloxacillin, nafcillin, oxacillin

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11
Q

Mechanism of dicloxacillin/nafcillin/oxacillin

A

same as penicillin: bind penicillin-binding proteins (transpeptidases); block transpeptidase cross-linking of peptidoglycan in cell wall; activates autolytic enzymes

narrow spectrum
penicillinase resistant because bulky R group blocks access of beta-lactamase to beta-lactam ring

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12
Q

Use of dicloxacillin/nafcillin/oxacillin

A

S. aureus (MSSA only)

MRSA is still resistant to these because of altered penicillin binding protein target site

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13
Q

Toxicity of dicloxacillin/nafcillin/oxacillin

A

Hypersensitivity rxn; interstitial nephritis

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14
Q

Name the antipseudomonal penicillins

A

Piperacillin and ticarcillin

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15
Q

Mechanism of piperacillin/ticarcillin

A

same as penicillin: bind penicillin-binding proteins (transpeptidases); block transpeptidase cross-linking of peptidoglycan in cell wall; activates autolytic enzymes

extended spectrum

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16
Q

Use of piperacillin/ticarcillin

A

pseudomonas spp. and gram-negative rods

susceptible to penicillinase; use with beta-lactamase inhibitors

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17
Q

Toxicity of piperacillin/ticarcillin

A

hypersensitivity rxn

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18
Q

Name the beta-lactamase inhibitors

A

Clavulanic acid, sulbactam, tazobactam

add to penicillin antibiotics to protect the antibiotic from destruction by beta-lactamase (penicillinase)

CAST

Amox/Clav
Amp/Sul
Pip/Tazo

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19
Q

Mechanism of the cephalosporins

A

beta-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases

bactericidal

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20
Q

Organisms that are NOT covered by cephalosporins

A

LAME: listeria, atypicals (chlamydia, mycoplasma), MRSA and enterococci

Exception: ceftaroline covers MRSA

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21
Q

Name the first generation cephalosporins

A

cefazolin, cephalexin

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22
Q

Use of the first generation cephalosporins

A

gram-positive cocci; Proteus, E. coli, Klebsiella (PEcK)

cefazolin used prior to surgery to prevent S. aureus wound infections

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23
Q

Name the second generation cephalosporins

A

cefoxitin, cefaclor, cefuroxime

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24
Q

Use of the second generation cephalosporins

A

gram-positive cocci; H. influenzae, Enterobacter, Neisseria species, Proteus, E. coli, Klebsiella, Serratia (HEN PEcKS)

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25
Q

Name the third generation cephalosporins

A

ceftriaxone, cefotaxime, ceftazidime

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26
Q

Use of the third generation cephalosporins

A

serious gram-negative infections resistant to other beta-lactamse

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27
Q

Use of ceftriaxone specifically

A

Neisseria meningitis, gonorrhea; alpha hemolytic streps, disseminated lymes disease

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28
Q

Use of ceftazidime specifically

A

pseudomonas

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29
Q

Name the fourth generation cephalosporins

A

cefepime

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30
Q

Use of fourth generation cephalosporins

A

gram-negative organisms, with increased activity against pseudomonas and gram-positive organisms

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31
Q

Name the fifth generation cephalosporins

A

ceftaroline

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32
Q

Use of the fifth generation cephalosporins

A

broad gram-positive and gram-negative organism coverage, including MRSA; does NOT cover pseudomonas

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33
Q

Toxicity of the cephalosporins

A

hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency

Exhibit cross-reactivity with penicillins

increased nephrotoxicity with aminoglycosides

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34
Q

Resistance to cephalosporins

A

structural changes in penicillin-binding proteins (transpeptidases)

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35
Q

Name the carbapenems

A

imipenem, meropenem, ertapenem, doripenem

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36
Q

Mechanism of imipenem

A

broad-spectrum, beta-lactamase-resistant carbapenem

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37
Q

What is imipenem administered with?

A

also with cilastatin (inhibitor of renal dehydropeptidase I) to decrease inactivation of drug in renal tubules

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38
Q

Which are the newer carbapenems?

A

Ertapenem (limited pseudomonas coverage)

Doripenem

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39
Q

Use of the carbapenems

A

gram-positive cocci, gram-negative rods, and anaerobes

wide spectrum, use in LIFE-THREATENING infections after other drugs have failed

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40
Q

Toxicity of the carbapenems

A

GI distress, skin rash, and CNS toxicity (seizures) at high plasma levels

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41
Q

Specific about meropenem

A

has a decreased risk of seizures and is stable to dehydropeptidase I

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42
Q

Name the monobactams

A

aztreonam

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43
Q

Mechanism of aztreonam

A

less susceptible to beta-lactamases
prevents peptidoglycan cross-linking by binding to penicillin-binding protein 3
synergistic with aminoglycosides
NO cross-allergenicity with penicillins

44
Q

Use of aztreonam

A

gram-negative rods ONLY

use in penicillin-allergic pts and those with renal insufficiency who cannot tolerate aminoglycosides

45
Q

Toxicity of aztreonam

A

usually nontoxic; occasional GI upset

46
Q

Mechanism of vancomycin

A

inhibits cell wall peptidoglycan formation by binding to D-ala D-ala portion of cell wall precursors

bactericidal
not susceptible to beta-lactamases

47
Q

Use of vancomycin

A

gram-positive bugs ONLY
use in serious, multi-drug resistant organisms, including MRSA, S. epidermidis, sensitive Enterococcus species and C. difficile (oral only for pseudomembranous colitis)

48
Q

Toxicity of vancomycin

A

well tolerated in general but NOT trouble free - Nephrotoxicity, Ototoxicity, Thrombophlebitis

diffuse flushing - RED MAN SYNDROME

49
Q

Prevent Red Man Syndrome

A

occurs because of too fast infusion of vancomycin

prevent with antihistamines and SLOW infusion rate

50
Q

Resistant to vancomycin

A

occurs in bacteria via amino acid modification of the D-ala D-ala motif to D-lac D-lac

see this in enterococcus species (VRE)

51
Q

Name the 30S inhibitors

A

aminoglycosides (bactericidal)

tetracyclines (bacteriostatic)

52
Q

Name the 50S inhibitors

A

chloramphenicol, clindamycin (bacteriostatic)
erythromycin (macrolides) (bacteriostatic)
linezolid (variable)

53
Q

Name the aminoglycosides

A

Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin

54
Q

Mechanism of aminoglycosides

A

bactericidal
irreversible inhibition of initiation complex through binding of the 30S subunit
can cause misreading of the mRNA
blocks translocation
requires O2 for uptake (therefore ineffective against anaerobes)

55
Q

Use of aminoglycosides

A

severe gram-negative rod infections

synergistic with beta-lactam antibiotics

56
Q

Specific use of neomycin

A

neomycin for bowel surgery

57
Q

Toxicity of aminoglycosides

A

Nephrotoxicity, Neuromuscular blockade, Ototoxicity (esp when used with loop diuretics)

Teratogen

58
Q

Resistance to aminoglycosides

A

bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation or adenylation

59
Q

Name the tetracyclines

A

tetracycline, doxycycline, minocycline

60
Q

Mechanism of tetracyclines

A

bacteriostatic; limited CNS penetration

binds to 30S and prevent attachment of aminoacyl-tRNA

61
Q

Specific pharmacokinetic property of doxycycline

A

it is eliminated fecally and thus can be used in patients with renal failure

62
Q

Interaction of tetracycline and what?

A

Divalent cations

Tetracyclines should not be taken with milk (Ca2+), antacids (Ca2+ or Mg2+) or iron-containing preparations because divalent cations inhibit drugs absorption in the gut

63
Q

Use of tetracyclines

A

Borrelia burgdorferi (lymes), M. pneumoniae

drug can accumulate intracellularly so good against Rickettsia and Chlamydia

also used to treat acne

64
Q

Toxicity of tetracyclines

A

GI distress, discoloration of teeth and inhibition of bone growth in children, photosensitivity

contraindicated in PREGNANCY

65
Q

Resistance to tetracyclines

A

decreased uptake or increased efflux out of bacterial cells by plasmid-encoded transport pumps

66
Q

Mechanism of chloramphenicol

A

blocks peptidyltransferase at 50S ribosomal subunit

bacteriostatic

67
Q

Use of chloramphenicol

A

Meningitis (H. influenzae, Neisseria meningitidis, S. pneumoniae)
Rocky Mountain Spotted Fever (Rickettsia rickettsii)

limited use owing to toxicities, used in developing countries because cheap

68
Q

Toxicity of chloramphenicol

A

Anemia (dose dependent), aplastic anemia (dose independent), gray baby syndrome (in premature infants because they lack the liver UDP-glucoronyl transferase)

69
Q

Resistance to chloamphenicol

A

plasmid-encoded acetyltransferase inactivates the drug

70
Q

Mechanism of clindamycin

A

blocks peptide transfer (translocation) at 50S ribosomal subunit
bacteriostatic

71
Q

Use of clindamycin

A 
ABOVE THE DIAPHRAGM ANAEROBES
anaerobic infections (e.g. Bacteroides, Clostridium perfringens) in aspiration pneumonia, lung abscesses, and oral infections

also effective against invasive group A strep infections

72
Q

Toxicity of clindamycin

A

pseudomembranous colitis (C. diff overgrowth), fever, diarrhea

73
Q

Name the oxazolidinones

A

linezolid

74
Q

Mechanism of linezolid

A

inhibit protein synthesis by binding to 50S subunit and preventing formation of the initiation complex

75
Q

Use of linezolid

A

gram-positive species including MRSA and VRE

76
Q

Toxicity of linezolid

A

bone marrow suppression (esp. thrombocytopenia), peripheral neuropathy, serotonin syndrome

77
Q

Resistance to linezolid

A

point mutation of ribosomal RNA

78
Q

Image of the site of action of the protein synthesis/ribosomal subunit inhibitors

A

insert image

79
Q

Name the macrolides

A

azithromycin, clarithromycin, erythromycin

80
Q

Mechanism of macrolides

A

inhibit protein synthesis by blocking translocation
bind to the 23S rRNA of the 50S ribosomal subunit
bacteriostatic

81
Q

Use of macrolides

A

atypical pneumonia (Mycoplasma, chlamydia, legionella), STIs (chlamydia), gram-positive cocci (strep. pneumo/strep viridans esp in pts allergic to penicillins), and B. pertussis

82
Q

Toxicity of macrolides

A

MACRO: gi Motility issues, Arrhythmia caused by prolonged QT interval, acute Cholestatic hepatitis, Rash, eOsinophilia

increases serum concentration of theophyllines, oral anticoagulants

clarithromycin and erythromycin inhibit cytochrome p450

83
Q

Resistance to macrolides

A

Methylation of 23S rRNA-binding site prevents binding of drug

84
Q

Mechanism of trimethoprim

A

inhibits bacterial dihydrofolate reductase

bacteriostatic

85
Q

Use of trimethoprim

A

used in combination with sulfonamides (TMP-SMX), causing sequential block of folate synthesis

Combination used for UTIs, shigella, salmonella, pneumocystis jirovecii pneumonia treatment and prophylaxis, toxoplasmosis prophylaxis

86
Q

Toxicity of trimethoprim

A

Megaloblastic anemia, leukopenia, granulocytopenia (may alleviate with supplemental folinic acid)

TMP Treats Marrow Poorly

87
Q

Name the sulfonamides

A

sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine

88
Q

Mechanism of sulfonamides

A

inhibit folate synthesis
para-aminobenzoic acid (PABA) antimetabolites inhibit dihydropteroate synthase
bacteriostatic (bactericidal when with TMP)

89
Q

What is a closely related drug to sulfonamides and what is it used to treat?

A

Dapsone and it also inhibits folate synthesis

used for lepromatous leprosy

90
Q

Use of sulfonamides

A

gram-positives, gram-negatives, Nocardia, chlamydia

Triple sulfas or SMX for simple UTI

91
Q

Toxicity of sulfonamides

A

hypersensitivity reactions, hemolysis if G6PD deficient, nephrotoxicity (tubulointerstitial nephritis), photosensitivity, kernicterus in infants, displace other drugs from albumin (e.g. warfarin)

92
Q

Resistant to sulfonamides

A

altered enzyme (bacterial dihydropteroate synthase), decreased uptake or increased PABA synthesis

93
Q

Name the fluoroquinolones

A

ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, moxifloxacin, gemifloxacin, enoxacin

94
Q

Mechanism of fluoroquinolones

A

inhibit prokaryotic enzymes topoisomerase II (DNA gyrase) and topoisomerase IV
bactericidal
must NOT be taken with antacids

95
Q

Use of fluoroquinolones

A

gram-negative rods of urinary and GI tracts (including pseudomonas), Neisseria, some gram-positive organisms

96
Q

Toxicity of fluoroquinolones

A

GI upset, superinfections, skin rashes, headache, dizziness

less common: leg cramps and myalgias

may prolong QT interval
may cause tendonitis or tendon rupture in people >60 years old and in patients taking prednisone

97
Q

Contraindications to fluoroquinolone use

A

pregnant women, nursing mothers, and children

98
Q

Resistance to fluoroquinolones

A

chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps

99
Q

Mechanism of daptomycin

A

lipopeptide that disrupts cell membrane of gram-positive cocci

100
Q

Use of daptomycin

A

S. aureus skin infections (especially MRSA), bacteremia, endocarditis, VRE

101
Q

Do not use daptomycin in?

A

pneumonia because avidly binds to and is inactivated by surfactant

102
Q

Toxicity of daptomycin

A

myopathy and rhabdomyolysis

103
Q

Mechanism of metronidazole

A

Forms toxic free radical metabolites in the bacterial cell that damage DNA

bactericidal, antiprotozoal

104
Q

Use of metronidazole

A

BELOW THE DIAPHRAGM ANAEROBES

treats Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes (Bacteroides, C. difficile)

used with PPIs and clarithromycin for “triple therapy” against H. Pylori

GET GAP on the metro

105
Q

Toxicity of metronidazole

A

disulfiram-like reaction (severe flushing, tachycardia, hypotension) with alcohol; headache, metallic taste

STEP 1 (26 decks)

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