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Pharmacology > Antibiotics > Flashcards

Antibiotics Flashcards

1
Q

Which drugs inhibit bacterial cell-wall synthesis

A
  • penicillin
  • cephalosporins
  • monobactams
  • carbapenems
  • bacitracin
  • fosfomycin
  • vancomycin
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2
Q

B-Lactams (4)

A

penicillin
cephalosporins
monobactams
carbapenems

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3
Q

Antitubercular agents

A

isoniazid
rifampin
pyrazinamide
ethambutol

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4
Q

inhibit bacterial cell membrane synthesis

A

daptomycin

colistin

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5
Q

inhibit bacterial protein synthesis

A 
macrolides
tetracycline
aminoglycosides
clindamycin
lenezolid
mupirocin
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6
Q

inhibit nucleic acid synthesis

A

fluoriquinolines
trimethoprim
sulfamethoxazole
metronidazole

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7
Q

30S Subunit protein synthesis blocker

A

tetracyclines

aminoglycosides

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8
Q

50S subunit protein synthesis

A 
macrolides
clindamycin
linezolid
chloramphenicol
stretogramins
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9
Q

Penicillins (MOA)

A

bind to penicillin-binding proteins on cell wall to inhibit further synthesis

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10
Q

Penicillin Bacterial Resistance

A
  • Production of B lactamase enzymes that destroy B lactam ring of penicillin molecule
  • OR mutation of PBP to prevent binding by penicillin
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11
Q

Penicillins (PK)

A

relatively short half-lives

most eliminated by kidney unchanged

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12
Q

Penicillin adverse reactions

A

Hypersensitivity Reactions
immediate: anaphylaxis, articaria, edema
accelerated: 1-72 hrs, urticaria
Delayed: days to weeks, rash, fever, serum sickness
Cross sensitivity exists between all penicillins - avoid if history of immediate or accelerated reaction with any of penicillin group

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13
Q

Penicillin G

A
  • natural penicillin the first penicillin
  • very acid labile and only given IV with 30 min half life
  • dosed in units (1 million units = 0.6 gm)
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14
Q

Procaine penicillin G

A

-suspension given IM that lasts from 1-4 days depending on dose

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15
Q

Benzathine penicillin G

A

suspension given IM that can last up to several weeks

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16
Q

Penicillin V

A

oral form of penicillin that is more acid stable

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17
Q

Natural Penicillins - What is it used for?

A

-Narrow spectrum antibiotic active against Streptococci, Neisseria miningitidis, Clostridium sp and treponema pallidum (syphillis)

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18
Q

aminopenicillins

A

first of semisynthetic penicillins which are all produced from 6-aminopenicillinamic acid

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19
Q

Ampicillin

A
  • an aminopenicillin
  • IV
  • 80 min half life must be given 4 times a day
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20
Q

amoxicillin

A
  • an aminopenicillin
  • most common antibiotic prescribed
  • oral equivalent of ampicillin
  • can be given 2-3 times a day and higher doses used in suspicion of penicillin-resistant pneumococcus
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21
Q

Aminopenicillins - Reactions

A
  • ampicillin rash with both amoxicillin and ampicillin in up to 10 % of individuals
  • 60% incidence of rash in mononucleosis present or taking allopurinol for gout
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22
Q

aminopenicillins - Uses

A
  • active against common upper respiratory tract pathogens
  • S. pyogenes
  • S. pneumoniae
  • hemophilus influenza
  • some activity against enterococcus and common community gram-negative bacteria such as E. coli, and proteus sp
  • NO STAPH AFFECTS
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23
Q

Extended-Spectrum Penicillins

A

Anti-pseudomonal penicillins

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24
Q

Piperacillin

A
  • extended spectrum penicillins
  • most common agents in class
  • given IV
  • usually used in combination with tazobactam (zosyn)
  • excreted via the biliary tract
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25
Q

Carbenicillin, ticarcillin, mezlocillin

A

-extended-spectrum penicillin

E-older agents rarely used now

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26
Q

Extended-Spectrum Penicillins (Adverse Effects)

A
  • sodium overload with high doses

- thrombocytopenia with high doses

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27
Q

Extended-Spectrum Penicillins - What is it used for?

A
  • extended activity against gram-negative bacteria
  • pseudomonas aeruginosa activity (combine with aminoglycoside antibiotic for serious P. aeruginosa infections)
  • Bacteremia, pneumonia, neutropenic fever
  • retains activity against enterococcus
  • NO STAPH ACTIVITY
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28
Q

Clavulanic acid

A
  • B-lactamase inhibitor+penicillin combo
  • with amoxicillin = augmentin
  • for diabetic foot wounds, bites, Staphylococcal infections
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29
Q

Sulbactam

A
  • B-lactamase inhibitor+penicillin combinations

- with ampicillin=UNASYN

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30
Q

Tazobactam

A
  • B-lactamase inhibitor+penicillin combo
  • with piperacillin = ZOSYN
  • most widely used IV antibiotic in hospitals
  • active against more gram + and gram - and anaerobic bacteria
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31
Q

B-lactamase Inhibitor/Penicillin Combinations (MOA)

A
  • B-lactamase inhibitors preferentially combine with B-lactamase enzymes produced by bacteria and inactivate them
  • make penicillins more active against previously resistant bacteria - increase activity against Staph, gram - and anaerobic
  • does not increase activity against bacteria that are resistant because of altered PBPs (MRSA)
  • same kinetics, adverse effects, etc as penicillins used alone
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32
Q

Penicillinase-Resistant Penicillins

A

-semisynthetic penicillins specifically developed to treat Staph resistant to penicillins

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33
Q

Methicillin

A

very first penicillinase-resistant penicillins

-MRSA appears in 1961

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34
Q

Nafcillin

A

-penicillinase-resistant penicillin
-IV
-used 4-6 times a day
can cause phlebitis at IV site as well as serum sickness

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35
Q

Dicloxacillin

A
  • penicillinase-resistant penicillin

- oral equivalent of nafcillin

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36
Q

Cephalosporins

A
  • similar to penicillins (sehre B-lactam ring) but more stable to B lactamases
  • similar MOA to penicillin
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37
Q

Cephalosporins - Bacterial Resistance

A
  • bacteria producing variety of B-lactamase enzymes that destroy lactam ring of molecule
  • no activity against MRSA except for new drug ceftaroline
  • no activity against Enterococcus sp or Listeria
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38
Q

Cephalosporins - PK

A
  • half-lives vary from short to very long

- most eliminated by kidney unchanged

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39
Q

Cephalosporins - Adverse Reactions

A
  • hypersensitivity reactions less common than penicillins
  • cross sensitivity with penicillins is minimal unless history of anaphylactic reaction with penicillins
  • bacterial resistance tends to develop quickly with use
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40
Q

Cefazolin

A
  • 1st generation cephalosporin
  • IV
  • given every 8 hours
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41
Q

Cephalexin

A
  • 1st generation cephalosporin
  • oral
  • short half life
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42
Q

Cephradine

A
  • 1st generation cephalosporin

- oral

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43
Q

Cefadroxil

A
  • 1st generation cephalosporin
  • long half life
  • PO
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44
Q

1st Generation Cephalosporins (USES)

A
  • active against steptococcus sp and methicillin-sensitive staphylococcus (MSSA)
  • also active against strains of E. coli and klebsiella sp
  • cefzolin widely used in hospitals for wound infections and surgical prophylaxis
  • cephalexin widely used in community for staphylococcal and streptococcal infections
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45
Q

cefuroxime

A
  • 2nd generation cephalosporins
  • IV
  • for upper respiratory infections
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46
Q

cefaclor

A
  • 2nd generation cephalosporin

- oral

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47
Q

cefprozil

A
  • 2nd generation cephalosporin

- oral

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48
Q

2nd generation cephalosporin - What is it used for?

A
  • increased activity against gram negative bacteria including klebsiella pneumoniae, menophilus influenzae, and moraxella catarrhalis
  • for community-acquired penumonia and more resistant upper respiratory infections such as otitis media
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49
Q

Cefotaxime

A
  • 3rd generation cephalosporins
  • IV
  • short half life
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50
Q

Ceftriaxone

A

-3rd generation cephalosporin
-long half line
give once daily IM/IV

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51
Q

Ceftazidime

A
  • 3rd generation cephalosporins
  • only 3rd generation with activity against pseudomonas
  • useful alternative to piperacillin
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52
Q

Cefixime

A
  • 3rd generation cephalosporin

- PO

53
Q

Cefpodoxime

A
  • 3rd generation cephalosporin

- PO

54
Q

3rd Generation Cephalosporins - What are they used for?

A
  • IV forms with wide range of activity against gram (-) bacteria as well as gram (+) bacteria
  • used for nosocomial infections, pneumonia, meningitis, advanced lyme disease
55
Q

Cefepime

A
  • 4th generation cephalosporin
  • only given IV
  • more resistant to chromosomal B-lactamase enzymes
  • good activity against Enterobacteriaceae and Pseudomonas aeruginosa
  • unlike ceftazidime, also good activity against penicillin-resistant Streptococcus pneumoniae
56
Q

Ceftaroline

A
  • 5th generation cephalosporin
  • IV only
  • first beta-lactam approved for treatment of MRSA infections
  • otherwise antibacterial spectrum most similar to 3rd generation cephalosporin, ceftriaxone
  • no activity against pseudomonas or enterococcus species
57
Q

Azteronam

A
  • monobactam
  • only given IV
  • has monocyclic B-lactam ring
  • no cross sensitivity in patients with history of severe penicillin of cephalosporin hypersensitivity reactions
  • activity similar to ceftazidime with activity against many gram-negative bacteria as well as pseudomonas
  • NO ACTIVITY against GRAM POSITIVE
  • used for patients with B-lactam allergies
58
Q

Carbapenems

A
  • broadest spectrum of antibacterial drugs available - reserved for life threatening or multi-resistant infections
  • structurally related to other B-lactam antibiotics
  • all given intravenously
59
Q

Imipenem-cilistatin

A
  • carbapenem
  • cilistatin inhibits the enzyme that hydrolyzes imipenem in kidney - helps increase half life but still give every 8 hours
60
Q

meropenem

A

a carbapenem

61
Q

erapenem

A

carbapenem

longest half life give once daily

62
Q

doripenem

A

carbapenem - preferred agent

-more active against pseudomonas than others

63
Q

carbapenem - uses

A
  • serious polymicrobial and nosocomial infections due to highly resistant bacteria
  • imipenem, doripenem and meropenem (but not ertapenem) also have activity against pseudomonas
64
Q

carbapenems - Adverse

A
  • can be neurotoxic
  • greater chance of superinfections
  • high cost
  • some cross sensitivity in penicillin-allergic patients
  • seizures!
65
Q

Bacitracin

A
  • inhibitors of bacteria cell wall synthesis
  • topical, active against gram positive bacteria only
  • highly nephrotocix if given systemically
  • poor oral absorption
  • used to treat skin infections due to streptococcus and staphylococcus
66
Q

fosfomysin

A
  • inhibitor of bacteria cell wall synthesis
  • oral agent now starting to be recommended for gram-negative urinary infections - if suspected or known resistance to sulfa and fluoroquinolone antibiotics
67
Q

Nitrofurantoin

A
  • bacteria cell wall synthesis inhibitor
  • only used for UTI
  • bactericial against E. coli, enterococcus, and other common UTI organisms
  • commonly causes GI irritation, nausea and vomiting
  • should avoid in elderly due to increased risk of pneumonitis and neuropathy
  • contraindicate in renal failure
68
Q

Vancomycin (MOA)

A
  • glycopeptide molecule with high molecular weight

- inhibits cell wall synthesis by blocking elongation of peptoglycan molecule

69
Q

Vancomycin Bacterial Susceptibility

A
  • bactericidal against most gram-positive bacteria including those resistant to B-lactam antibiotics
  • no activity against gram-negative bacteria
  • some eterococci have become resistant and are known as vancomycin-resistant eterococci or VRE
70
Q

Vancomycin - Route

A
  • usually given IV
  • not absorbed orally
  • oral vancomycin remains in GI tract and only used to treat clostridium difficle colitis
71
Q

Vancomycin - PK

A
  • eliminated by kidney in direct proportion to creatinine clearance
  • narrow therapeutic index - must monitor peak and through levels
72
Q

Vancomycin -Adverse reactions

A
  • Red Man Syndrome - infusion reaction due to massive histamine release if given too fast or in too high a dose -> treat with antihistamine
  • ototoxicity at higher doses
73
Q

Vancomycin - What do you use it for?

A
  • reserved for known or suspected infections due to MRSA
  • also used in combination with aminoglycoside for serious Enterococcus infections
  • oral vancomycin only used to treat pseudomembranous colitis secondary to Clostridium difficile infection
74
Q

Daptomycin

A
  • bacterial cell membrane synthesis
  • unique cyclic lippeptide active against gram-positive bacteria-only available in IV form
  • old drug
  • concentration-dependent activity
75
Q

Colistin

A
  • bacterial cell membrane synthesis inhibitors
  • starting to be used for MDR resistant bacteria such as CRE
  • nephrotoxic like aminoglycosides
  • intravenous
76
Q

Macrolide MOA

A

reversibly bind to 50S ribosomal subunit

77
Q

Macrolide - Bacterial susceptibility

A
  • usually bacteriostatic effect
  • Streptococcus sp and Staphylococcus
  • some activity against hemophilus influenzae and bordetella
  • activity against atypical bacteria (mycoplasma, leionella, chlamydophyla) that cause pneumonia
78
Q

Macrolide - What is it used for?

A
  • for upper and lower respiratory infections potentially due to atyipcal bacteria
  • IV azithromycin used extensively in hospitals for pneumonia
  • for penicillin-allergic patients
  • for chlamydia STD infections
  • clarithromycin for mycobacterium avian complex (MAC)
79
Q

Erythromycin

A
  • macrolide
  • IV form rarely used, orally available as base, stearate, estolate, and ethylsuccinate salts
  • given 3-4 times a day
80
Q

Erythromycin - Adverse Effects

A
  • agonist for motillin receptors leads to abdominal pain and diarhea
  • high IV doses can cause ototocity
81
Q

Erythromycin - drug interactions

A
  • inhibits CYP 450 3A4 enzyme responsible for metabolizing 50% of drugs
  • will increase serum levels of statins, benzodiazepenes, calcium channel blockers, cyclosporine and many more
82
Q

Clartihromycin

A
  • macrolide
  • very similar to erythromycin but better absorbed - higher serum levels and lower GI levels
  • not available as IV, can give twice daily
  • has less GI adverse effects
  • same drug interactions as erythromycin but stronger
83
Q

Azithromycin

A
  • most popular and safest macrolide
  • IV and oral
  • half life of 60 hours requires loading dose and once daily Z Pack ( give 3-5 days)
  • minimal adverse reactions, no drug interactions
84
Q

Tetracyclines

A

MOA: reversibly bind to 30S ribosomal subunit of bacteria
Bacterial susceptibility: bacteriostatic, activity against gram-positive and gram-negative bacteria. Activity against ricketsiae, chlamydiae, mycoplasma and some protozoa

85
Q

Tetracycline - Adverse reactions

A
  • GI irritation
  • photosensitivity
  • discoloration of tooth enamel in children and fetus
  • hepatotoxicity possible with extended use
86
Q

tetracycline - drug interactions

A
  • cations such as calcium will bind to tetracyclines and prevent absorption
  • avoid giving with dairy products or antacids
87
Q

tetracycline - what is it used for?

A

-lyme disease, erlichiosis, rocky mountain spotted fever, atypical pneumonia, pelvic inflammatory disease, tetracycline and minocycline for acne

88
Q

Tetracycline

A

-rarely used now because of lower bioavailability and short half life - have to give 4x daily

89
Q

doxycycline

A
  • most popular tetracycline
  • given both IV and oral (good bioequivalence)
  • has long half life and can be given once or twice a day depending on infection
90
Q

minocycline

A
  • tetracycline
  • popular for acne due to high distribution in skin
  • very expensive
91
Q

Tigecycline

A
  • new tetracycline, IV drug for complicated skin and intra-abdominal infections
  • bacteriostatic
  • active against gram-positive (including MRSA), gram-negative, and anaerobic bacteria
  • not active against pseudomonas or proteus species
  • reserve for antibiotic-resistant infections
  • Adverse: frequent naseau and vomiting
92
Q

aminoglycoside MOA

A

IRREVERSIBLY binds to 30S ribosomal subunit of bacteria

93
Q

aminoglycoside - bacterial susceptibility

A
  • bactericidal activity against most gram-negative bacteria, including pseudomonas
  • streptococci are resistant to agents when used alone
  • synergystic activity when combined with B-lactam antibiotics
94
Q

aminoglycoside - what is it used for?

A

bacteremia, pneumonia, intra-abdominal infections, and other serious infections due to gram-negative bacteria

95
Q

aminoglycoside - PK

A
  • only available for IV or IM use - unable to be absorbed orally
  • short half life of 2-3 hours
  • give high dose once daily due to concentration-dependent effect on bacterial killing
  • eliminated renally and accumulate in renal failure
  • monitor peak and through levels due to narrow therapeutic window
96
Q

aminoglycoside - adverse reactions

A
  • very nephrotoxic - can accumulate in renal tubules and cause acute renal failure
  • also ototoxic at high doses for extended periods of use
97
Q

Tobramycin

A

-aminoglycoside - inhaled form for cystic fibrosis patients with pseudomonas pneumomniae

98
Q

neomycin

A
  • aminoglycoside
  • most toxic and never used as IV
  • used in topical formulas in combination with other antibiotics
  • oral form sometimes used for prophylaxis before elective bowel surgery
99
Q

streptomycin

A
  • aminoglycoside (1st one)

- used IV or IM as second-line therapy for active tuberculosis

100
Q

clindamycin MOA

A
  • aminoglycoside

- binds to same 50S ribosomal subunit as macrolide antibiotics

101
Q

clindamycin - bacterial susceptibility

A
  • bacteriostatic activity
  • inhibits Streptococci, staphylococci, and pneumococci
  • inhibits anaerobic bacteria such as bacteroides fragilis and clostridium perfinges
102
Q

Clindamycin - what is it used for?

A
  • anaerobic infections such as intra-abdominal wounds, gynecologic infections, abscesses, and aspiration penumonia
  • for gram-positive infections in penicillin-allergic patients
  • for newly discovered community-acquired MRSA
103
Q

clindamycin - PK

A
  • can be given IV or orally

- metabolized by liver

104
Q

Clindamycin - adverse reactions

A
  • GI upset such as nausea and diarrhea

- primary antibiotic to cause antibiotic -associated pseudomembranous colitis

105
Q

Linezolid (MOA)

A

oxazolidinedione with unique activity against bacterial 50S subunit of bacteria

106
Q

Linezolid - Bacterial susceptibility

A
  • bacteriostatic activity
  • active against most gram-positive bacteria, including most strains resistant to other antibiotics
  • resistance may occur with overuse
107
Q

Linezolid - USES

A

should be reserved for infections caused by mutli-drug resistant bacteria such as VRE and MRSA

108
Q

Linezolid - PK

A
  • oral or IV with 100% F

- metabolized by the liver with half life of 4-6 hours

109
Q

Linezolid - Adverse reactions

A

hematologic toxicity - can cause thrombocytopenia and neutropenia with extended use

110
Q

Mupirocin

A
  • bactroban
  • unrelated to other antibiotics only used in topical preparations for treating staphylococcal infections
  • should be reserved for suspected for definite MRSA to avoid development of resistance
  • also used for impetigo caused by streptococci or staphylococci
  • special nasal formulation available to eliminate carriage of MRSA
111
Q

fluoroquinolone (MOA)

A

inhibit DNA gyrase and topoisomerase that are essential for maintaining bacterial DNA structure and function

112
Q

fluoroquinolone (Bacterial Susceptability)

A
  • bactericidal activity against most gram-negative bacteria
  • active against atypical bacteria
  • 3rd generation agents also have good activity against gram-positive bacteria (except staphylococci)
113
Q

fluoroquinolone - what is it used for?

A
  • complicated urinary tract infections and prostatitis
  • serious infections secondary to gram0negative bacteria such as bacteremia and intra-abdominal infections
  • 3rd generation agents used for severe pneumonia
  • infectious diarrhea secondary to salmonella and shigella
  • for penicillin-resistant anthrax
114
Q

fluoroquinolone - PK

A
  • most available as both IV and oral forms
  • distribute very well into most tissues
  • renal excretion
115
Q

Fluoroquinolone - Adverse Reactions

A
  • causes arthropathy in developing animals - avoid in children less than 18 years old and during pregnancy
  • neurotoxic in high doses (irritability, seizures)
116
Q

Fluoroquinolone - drug interactions

A
  • absorption of oral dosage forms inhibited by cations such as calcium, magnesium, iron and zinc (multivitamins and antacids)
  • inhibit metabolism of caffein and theophylline
117
Q

ciprofloxacin

A
  • 2nd generation fluoroquinolone (most commonly used)
  • only quionolone with activity against pseudomonas aeruginosa
  • poor activity against gram-positive bacteria, shorter half life requires 2x a day - IV or oral
118
Q

Norfloxacin

A

still used for urinary tract infections - doesnt achieve high enough serum levels for systemic infections

119
Q

3rd Generation Fluoroquinolones

A
  • known as respiratory fluoroquinolones
  • active against most bacteria responsible for respiratory infections including atypical bacteria and multidrug-resistant streptococcus pneumoniae
120
Q

Levofloxacin

A

-3rd generation fluoroquinolone
-most common; used for serious infections
-renal elimination with normal half life = 7 hrs
given once daily IV or oral

121
Q

moxifloxacin

A
  • 3rd generation fluoroquinolone
  • has better activity against anaerobic bacteria than levofloxacin
  • metabolized by liver so should not be used for urinary tract infections
  • given once daily IV or oral
122
Q

gemifloxacin

A
  • 3rd generation fluoroquinolone
  • oral only
  • hepatic metabolism
  • greater incidence of rash
  • twice as expensive as other 2nd generation agents
123
Q

Bactrim - Bacterial Susceptibility

A
  • bactericidal activity against most gram-positive and gram-negative bacteria including CA-MRSA
  • active against nocardia, penumocystic, jiroveci
  • no activity against enetrococci, atypical bacteria, anaerobic bacteria or pseudomonas aeruginosa
124
Q

Bactrim - Uses

A
  • primary drug for urinary tract infections
  • secondary drug for upper and lower respiratory tract infections, sepsis, meningitis, travelers-diarrhea, typhoid, cholera
125
Q

bactrim - PK

A
  • can be given both oral and IV
  • well distributed in tissues including CSF
  • 50% excreted by kidneys
  • half life 12 hours can be dosed 2x a day
126
Q

Bactrim - adverse reactions

A
  • hypersensitivity
  • exfoliative dermatitis adn stevens johnson syndrome
  • high doses for P. jiroveci infections in AIDS: can cause thrombocytopenia and neutropenia, high incidence of allergic reactions and hyperkalemia
127
Q

Bactrim - imp. drug interactions

A

-can increase serum levels ad toxicity of warfarin, phytoin and oral sulfonylureas

128
Q

Metronidazole

A
  • both antibacterial and antiprotozoal
  • nitromidazole that is readily taken up only by anaerobic bacteria and then reduced to a toxic metabolite
  • disrupts DNA helical structure only in anaerobic bacteria
  • best single agent to treat anaserobic infections, including abdominal infections and C. difficile colitis
  • available oral or IV - Avoid alcohol

Pharmacology (2 decks)

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