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Pharmacology Unit 6 > Antibiotics > Flashcards

Antibiotics Flashcards

1
Q

If vancomyin is given IV (rapidly), what is the common adverse event syndrome?

A

“Red man syndrome” with flushing, tachycardia, and hypotension; probably vasodilatory effects

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2
Q

Which class is better for a single, susceptible organism, penicillins or cephalosporins? For a multi-species infection?

A

1) penicillins

2) cephalosporins

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3
Q

In a patient allergic to penicillins, what cephalosporins should be avoided?

A

1st generation only - remember the PBP 2b vs 2x binding sites

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4
Q

What drugs bind PBP 2b? 2x?

A

2b: penicillins and 1st gen cephalosporins;
2x: newer cephalosporins, carbapenems, and monobactams

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5
Q

How do first and second generation fluoroquinolones differ?

A

2nd (levofloxacin) adds anti-bacterial TopoIV activity so has strep pneumo action, unlike 1st gen (cipro) which is gram(-) only

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6
Q

Active TB requires what type of drug regimen? Why? Myco tuberculosis as seen by +PPD only requires what regimen in contrast?

A

4 drug combination therapy to eliminate resitant clonal remnants; +PPD requires isoniazid only due to lower titers and activity

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7
Q

What should doxycycline NOT be given with?

A

A metal - di and trivalent cations chelate the drug

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8
Q

What general adverse effect limits use of antimicrobials against targets unique to bacteria?

A

Allergies (eg against the lactams)

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9
Q

What are the two major resistance mechanisms against vancomycin?

A

altered cell wall (lactone instead of terminal alanine) and thickened peptidoglycan

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10
Q

Which antimicrobials inhibit the 30S subunit?

A

aminoglycosides and tetracyclines

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11
Q

What is clindamycin’s spectrum of efficacy?

A

anaerobes (except C dif), and lactam-resistant pneumococci and MRSA

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12
Q

What are the two major resistance mechanisms against lactams?

A

B-lactamase and altered PBP’s

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13
Q

What is the MOA of doxycycline? What organisms are its primary targets?

A

Block tRNA anticodon-codon binding; intracellular pathogens and lactam-resistant Strep pneumo and MRSA

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14
Q

Clindamycin’s lack of efficacy against what organism leads to its major adverse effect?

A

C dif, causing C dif colitis post-treatment

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15
Q

What lactam antibiotic class has the broadest spectrum?

A

carbapenem - MRSA is the major resistant species

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16
Q

What drug class is best for gram+ pneumonia with diplococci?

A

Ceftriaxone (from cephalosporin gen2+) covers the 30% chance of PBP 2b mutated strep pneumo

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17
Q

What antimicrobial targets can be attacked with high doses of drug?

A

cell walls and their synthesis machinery

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18
Q

What old antibiotic (still used in poorer countries) does Linezolid most resemble? What adverse effect do they share?

A

Chloramphenicol; agranulocytosis

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19
Q

What cell membrane toxin antibiotic is nephrotoxic?

A

Colistin

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20
Q

What antibiotic is used in infected CF patients? Why?

A

Colistin; pseudomonas (gram neg) is highly resistant

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21
Q

What are the bacterial cell membrane toxins?

A

Cyclic lipopeptides and polymixins

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22
Q

What is the probable mechanism of centrilobar hepatitis in TB treatment?

A

CYP induction by rifampin to degreade isoniazid into a toxic metabolite

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23
Q

What are the major mechanisms of bacterial resistance?

A

decreased cell permeability to drug, alteration of target site, drug efflux pumps, and enzyme inactivation of drug

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24
Q

What bacterial protein involved in packing DNA is a prime antimicrobial target?

A

DNA gyrase

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25
Q

What other antibiotic shares spectrum similarities with macrolides?

A

Doxycyclines: both are good for intracellular and lactam-resistant gram(+); azithromycin (macrolide) adds H flu to the spectrum

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26
Q

Infection with what virus causes 100% maculopapular eruption in penicillin use?

A

EBV

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27
Q

What is empirical vs definitive antimicrobial selection?

A 
empirical = base on clinical suspicion
definitive = based on culture/labs
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28
Q

What bacteria has ESBL and carbapenemase producing strains? What species does it readily exchange plasmids with?

A

Enterobacter cloacae; E coli and klebsiella

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29
Q

Which is more important, eradicating TB or allowing a patient to limit care due to horrid side effect profiles?

A

Eradicating TB (systemic TB is bad and contagious/public health needs)

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30
Q

Adverse effects of rifampin?

A

Flu/Hypersensitivity with interstitial nephritis, thrombocytopenia, and hemolytic anemia
Watch for intermittent dosing regimens

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31
Q

Overuse of what three antibiotic classes is driving resistance mechanisms?

A

Fluoroquinolones, Cephalosporins, and extended spectrum penicillins

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32
Q

What are the inhibitors of bacterial nucleic acid synthesis?

A

fluoroquinolones, rifampin, metronidazole

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33
Q

Instantaneous disruption of bacterial translation and survival makes aminoglycosides the DOC for what important clinical scenario?

A

Gram negative sepsis (especially gram neg rods)

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34
Q

What is a macrolide’s MOA?

A

halts translation in the 50S ribosome by inhibiting translocase

35
Q

What are the major allergic manifestations of lactams?

A

hives, angioedema, stridor, hypotension, interstitial nephritis, toxic epidermal necrolysis, and multi/pancytopenias

36
Q

Where is metronidazole activated in the body? What is the MOA of the active form?

A

In anaerobic environments it becomes nucleic acid-toxic

37
Q

Adverse effects of pyrazinAMIDE?

A

increased uric acid levels and gout

38
Q

What adverse events are associated with metronidazole?

A

inhibition of aldehyde dehydrogenase causing vasodilation and tacharrhythmias; somewhat countered by alcohol in serum

39
Q

Where is clindamycin’s antimicrobial action focused?

A

inhibition of incorporation of new amino acids during translation

40
Q

How do aminoglycosides (gentamicin) disrupt translation?

A

Interference with 30S ribosome, causing misreading of mRNA and incorporation of incorrect side chains

41
Q

What is the (probably extremely out of date because seriously, MDR-TB anyone?) 4-drug regimen used in treating clinical tuberculosis?

A

Isoniazid (B6 analog), Rifampin (antiDDRP), Pyrazinamide (?energy limiting), and Ethambutol (anti-arabino? cell wall stuff)

42
Q

Why is vanco slower than lactams in initiating its effects?

A

It is a competitive inhibitor rather than direct - competes with L-alanine

43
Q

What is the MOA of daptomycin? What is the basis of its gram positive spectrum?

A

Its lipophilic tail interacts with the teichoic acid backbone and allows leakage of ions and cell death; the backbone in gram(-) is LPS and is not affected by dapto

44
Q

How is colistin similar to daptomycin? How is it different?

A

Its tail inserts in bacterial cell membranes to cause cell death; it interacts with LPS and is gram(-) active

45
Q

What drugs are bacterial cell wall synthesis inhibitors?

A

Lactams (penicillins, cephalosporins, carbapenem, monobactam) and Glycopeptides (vanco)

46
Q

What part of cell wall synthesis is inhibited by lactams? By vancomycin?

A

Lactams affect crosslinking by inhibiting transpeptidases

Vanco affect polymerization by inhibiting transglycolases

47
Q

Which antimicrobials inhibit the 50S subunit?

A

macrolides, linezolid, and clindamycin

48
Q

What rash associated with penicillins/lactams is not a ‘true’ allergy?

A

maculopapular rash (IgM, lumpy bumpy); hives is legit - IgE rash raised with central sparing

49
Q

Which lactams do not share allergic manifestations do to structural simplicity?

A

monobactams (i.e. aztreonam)

50
Q

What lactam antibiotic class is most active against gram negative organisms?

A

monobactams (i.e. aztreonam)

51
Q

How does the PBP status of Strep pneumo differ from MRSA?

A

MRSA = PBP 2b AND 2x mutations, Strep pneumo is 2b only

52
Q

Although it has broad Gram (+) efficacy, for what purpose was Linezolid primarily developed?

A

MRSA and VRSA

53
Q

What side effect of aminoglycosides has made them (improperly) rarely prescribed?

A

Nephrotoxicity, which is rarely present before 48 hours or even 1 week

54
Q

In what condition is the use of bacteriocidal vs bacteriostatic drugs important?

A

neutropenic fever

55
Q

Adverse effects of ethambutol?

A 
Optic neuritis (Red/Green)
Increased uric acid levels and gout
56
Q

Modification of what site in the 50S ribosome allows macrolide resistance? What 2 organisms are increasingly resistant?

A

P site (where peptidyl tRNA binds); Strep pneumo and Staph aureus

57
Q

What necessary bacterial metabolite competes with sulfonamides in the cell?

A

PABA (for folate synthesis)

58
Q

Mutations at what site convert MSSA to MRSA? Is this more prevalent nosocomially or in the community?

A

PBP 2b and 2x - nosocomial&raquo_space; community

59
Q

What is the rational drug choice for severe gram (+) endocarditis, penicillins or cephalosporins?

A

penicillins

60
Q

What enzyme transfers the translational peptide chain from the A site to the P site? What antibiotic inhibits it?

A

Peptidyl transferase; Linezolid

61
Q

Overuse of antibiotics is combined with what molecular mechanism to increase bacterial resistance?

A

plasmid exchange

62
Q

What organisms are ‘ESBL’ carriers? What does that mean?

A

Pseudo aeruginosa and Enterobacter cloacae; B-lactamase activity agaisnt ALL lactams

63
Q

Which compound should be given with isoniazid to prevent peripheral neuropathy and be an antidote in overdose-driven status epilepticus?

A

Pyridoxine (remember isoniazid is a B6 analog)

64
Q

What part of aminoglycoside action limits its use?

A

Requires active O2 uptake, thus only in aerobes or facultative anaerobes

65
Q

What unique adverse reaction is associated with daptomycin?

A

Rhabdomyolysis

66
Q

What antibiotic inhibits DNA dependent RNA polymerase? What side effect may be seen (esp. in combination with isoniazid)?

A

Rifampin; centrilobular hepatitis

67
Q

Bactrim acts on what bacterial spectrum? Anything non-bacterial?

A 
Staph aureus (even a little MRSA), saprophyticus, E coli, Klebsiella, and H flu
Remember Pneumocystis and Toxoplasmosis too
68
Q

What 2 organisms are completely penicillin resistant? How?

A

Staph aureus and B fragilis (H flu is 20%); penicillinase

69
Q

What is the Lehman approved aminoglycoside method?

A

Start aminoglycosides early on gram negative rods, and switch to another antibiotic when the sensitivity testing comes back in order to clean up the infection

70
Q

What 2 mechanisms are used to limit beta lactamase activity?

A

steric hindrance with aromatic groups (penicillinase-resistant class) and adding a clavam suicide inhibitor (i.e. augmentin/amoxicillin and zosyn/piperacillin)

71
Q

What organisms cause the majority of skin and soft tissue infections? What is the DOC?

A

Strep pyogenes (Group A) and MSSA; penicillin or cephalosporin

72
Q

Why is the slower MOA of vanco of clinical relevance?

A

Strep pyogenes and Staph aureus are both fast moving (from skin to fascia and hematologic respectively), so only resistant strains should get non-lactams

73
Q

What are the enzymes inhibited by Bactrim?

A

Sulfas: Dihydropteroate synthetase
Trimethoprim: Dihydrofolate reductase
*I keep them straight by remembering that sulfa=synthetase

74
Q

What activity will not be enjoyed by a doxycycline user?

A

Tanning - photosensitivity reactions are frequent

75
Q

What part of the lactam structure is responsible for the majority of drug allergies in this class?

A

the lactam-adjacent ring and its penicillinoic acid metabolite

76
Q

Fluoroquinolones have some activity against what close structural homolog to DNA gyrase? What human molecular mechanism is affected by this?

A

Topoisomerase IV - fluoroquinolones can block generation of the daughter strand

77
Q

What do macrolides have in common with fluoroquinolones?

A

Torsades de pointes!!! (GI distress with oral intake is another macrolide adverse effect)

78
Q

Structural similarity with ____ and trimethoprim causes ____ in cases of renal failure.

A

Triamterene (K-sparing diuretic); Hyperkalemia

79
Q

What are the bacterial antimetabolites?

A

trimethoprim/sulfamethoxazole (folic acid) and anti-tuberculars

80
Q

Where is Bactrim considered the DOC? Which one of these is bad per Lehman?

A

Uncomplicated UTIs (E coli), Immunocompromised (pneumocystis & toxo), and cellulitis (MRSA, but no action on Strep means ER visits)

81
Q

What is the primary driver of therapeutic index for antimicrobials?

A

uniqueness of the microbial target

82
Q

How does the extended spectrum of 2nd gen fluoroquinolones affect toxicity?

A

unlike cipro, levofloxacine can cause polymorphic ventricular tachycardia (torsades de pointes)

83
Q

What common antibiotic has little to no effect on organisms with a P site mutation?

A

Z-pack (zithromycin)

Pharmacology Unit 6 (6 decks)

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