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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
What other antibiotic shares spectrum similarities with macrolides?
Doxycyclines: both are good for intracellular and lactam-resistant gram(+); azithromycin (macrolide) adds H flu to the spectrum
26
Infection with what virus causes 100% maculopapular eruption in penicillin use?
EBV
27
What is empirical vs definitive antimicrobial selection?
``` empirical = base on clinical suspicion definitive = based on culture/labs ```
28
What bacteria has ESBL and carbapenemase producing strains? What species does it readily exchange plasmids with?
Enterobacter cloacae; E coli and klebsiella
29
Which is more important, eradicating TB or allowing a patient to limit care due to horrid side effect profiles?
Eradicating TB (systemic TB is bad and contagious/public health needs)
30
Adverse effects of rifampin?
Flu/Hypersensitivity with interstitial nephritis, thrombocytopenia, and hemolytic anemia Watch for intermittent dosing regimens
31
Overuse of what three antibiotic classes is driving resistance mechanisms?
Fluoroquinolones, Cephalosporins, and extended spectrum penicillins
32
What are the inhibitors of bacterial nucleic acid synthesis?
fluoroquinolones, rifampin, metronidazole
33
Instantaneous disruption of bacterial translation and survival makes aminoglycosides the DOC for what important clinical scenario?
Gram negative sepsis (especially gram neg rods)
34
What is a macrolide's MOA?
halts translation in the 50S ribosome by inhibiting translocase
35
What are the major allergic manifestations of lactams?
hives, angioedema, stridor, hypotension, interstitial nephritis, toxic epidermal necrolysis, and multi/pancytopenias
36
Where is metronidazole activated in the body? What is the MOA of the active form?
In anaerobic environments it becomes nucleic acid-toxic
37
Adverse effects of pyrazinAMIDE?
increased uric acid levels and gout
38
What adverse events are associated with metronidazole?
inhibition of aldehyde dehydrogenase causing vasodilation and tacharrhythmias; somewhat countered by alcohol in serum
39
Where is clindamycin's antimicrobial action focused?
inhibition of incorporation of new amino acids during translation
40
How do aminoglycosides (gentamicin) disrupt translation?
Interference with 30S ribosome, causing misreading of mRNA and incorporation of incorrect side chains
41
What is the (probably extremely out of date because seriously, MDR-TB anyone?) 4-drug regimen used in treating clinical tuberculosis?
Isoniazid (B6 analog), Rifampin (antiDDRP), Pyrazinamide (?energy limiting), and Ethambutol (anti-arabino? cell wall stuff)
42
Why is vanco slower than lactams in initiating its effects?
It is a competitive inhibitor rather than direct - competes with L-alanine
43
What is the MOA of daptomycin? What is the basis of its gram positive spectrum?
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
How is colistin similar to daptomycin? How is it different?
Its tail inserts in bacterial cell membranes to cause cell death; it interacts with LPS and is gram(-) active
45
What drugs are bacterial cell wall synthesis inhibitors?
Lactams (penicillins, cephalosporins, carbapenem, monobactam) and Glycopeptides (vanco)
46
What part of cell wall synthesis is inhibited by lactams? By vancomycin?
Lactams affect crosslinking by inhibiting transpeptidases | Vanco affect polymerization by inhibiting transglycolases
47
Which antimicrobials inhibit the 50S subunit?
macrolides, linezolid, and clindamycin
48
What rash associated with penicillins/lactams is not a 'true' allergy?
maculopapular rash (IgM, lumpy bumpy); hives is legit - IgE rash raised with central sparing
49
Which lactams do not share allergic manifestations do to structural simplicity?
monobactams (i.e. aztreonam)
50
What lactam antibiotic class is most active against gram negative organisms?
monobactams (i.e. aztreonam)
51
How does the PBP status of Strep pneumo differ from MRSA?
MRSA = PBP 2b AND 2x mutations, Strep pneumo is 2b only
52
Although it has broad Gram (+) efficacy, for what purpose was Linezolid primarily developed?
MRSA and VRSA
53
What side effect of aminoglycosides has made them (improperly) rarely prescribed?
Nephrotoxicity, which is rarely present before 48 hours or even 1 week
54
In what condition is the use of bacteriocidal vs bacteriostatic drugs important?
neutropenic fever
55
Adverse effects of ethambutol?
``` Optic neuritis (Red/Green) Increased uric acid levels and gout ```
56
Modification of what site in the 50S ribosome allows macrolide resistance? What 2 organisms are increasingly resistant?
P site (where peptidyl tRNA binds); Strep pneumo and Staph aureus
57
What necessary bacterial metabolite competes with sulfonamides in the cell?
PABA (for folate synthesis)
58
Mutations at what site convert MSSA to MRSA? Is this more prevalent nosocomially or in the community?
PBP 2b and 2x - nosocomial >> community
59
What is the rational drug choice for severe gram (+) endocarditis, penicillins or cephalosporins?
penicillins
60
What enzyme transfers the translational peptide chain from the A site to the P site? What antibiotic inhibits it?
Peptidyl transferase; Linezolid
61
Overuse of antibiotics is combined with what molecular mechanism to increase bacterial resistance?
plasmid exchange
62
What organisms are 'ESBL' carriers? What does that mean?
Pseudo aeruginosa and Enterobacter cloacae; B-lactamase activity agaisnt ALL lactams
63
Which compound should be given with isoniazid to prevent peripheral neuropathy and be an antidote in overdose-driven status epilepticus?
Pyridoxine (remember isoniazid is a B6 analog)
64
What part of aminoglycoside action limits its use?
Requires active O2 uptake, thus only in aerobes or facultative anaerobes
65
What unique adverse reaction is associated with daptomycin?
Rhabdomyolysis
66
What antibiotic inhibits DNA dependent RNA polymerase? What side effect may be seen (esp. in combination with isoniazid)?
Rifampin; centrilobular hepatitis
67
Bactrim acts on what bacterial spectrum? Anything non-bacterial?
``` Staph aureus (even a little MRSA), saprophyticus, E coli, Klebsiella, and H flu Remember Pneumocystis and Toxoplasmosis too ```
68
What 2 organisms are completely penicillin resistant? How?
Staph aureus and B fragilis (H flu is 20%); penicillinase
69
What is the Lehman approved aminoglycoside method?
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
What 2 mechanisms are used to limit beta lactamase activity?
steric hindrance with aromatic groups (penicillinase-resistant class) and adding a clavam suicide inhibitor (i.e. augmentin/amoxicillin and zosyn/piperacillin)
71
What organisms cause the majority of skin and soft tissue infections? What is the DOC?
Strep pyogenes (Group A) and MSSA; penicillin or cephalosporin
72
Why is the slower MOA of vanco of clinical relevance?
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
What are the enzymes inhibited by Bactrim?
Sulfas: Dihydropteroate synthetase Trimethoprim: Dihydrofolate reductase *I keep them straight by remembering that sulfa=synthetase
74
What activity will not be enjoyed by a doxycycline user?
Tanning - photosensitivity reactions are frequent
75
What part of the lactam structure is responsible for the majority of drug allergies in this class?
the lactam-adjacent ring and its penicillinoic acid metabolite
76
Fluoroquinolones have some activity against what close structural homolog to DNA gyrase? What human molecular mechanism is affected by this?
Topoisomerase IV - fluoroquinolones can block generation of the daughter strand
77
What do macrolides have in common with fluoroquinolones?
Torsades de pointes!!! (GI distress with oral intake is another macrolide adverse effect)
78
Structural similarity with ____ and trimethoprim causes ____ in cases of renal failure.
Triamterene (K-sparing diuretic); Hyperkalemia
79
What are the bacterial antimetabolites?
trimethoprim/sulfamethoxazole (folic acid) and anti-tuberculars
80
Where is Bactrim considered the DOC? Which one of these is bad per Lehman?
Uncomplicated UTIs (E coli), Immunocompromised (pneumocystis & toxo), and cellulitis (MRSA, but no action on Strep means ER visits)
81
What is the primary driver of therapeutic index for antimicrobials?
uniqueness of the microbial target
82
How does the extended spectrum of 2nd gen fluoroquinolones affect toxicity?
unlike cipro, levofloxacine can cause polymorphic ventricular tachycardia (torsades de pointes)
83
What common antibiotic has little to no effect on organisms with a P site mutation?
Z-pack (zithromycin)

Pharmacology Unit 6 (6 decks)

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