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Pharmacology > Antibacterials > Flashcards

Antibacterials Flashcards

1
Q

how do you select for appropriate antibacterial drug

A 
look at toxicity
type of organism
anatomical location (will drug go there?, -cidal or -static?)
host status (age, pregnancy, allergies, renal/hepatic fxn, host defenses)
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2
Q

MIC

A

minimal inhibitory (static) concentration

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3
Q

MBC

A

minimal bactericidal concentration to kill 99.9% of bacteria

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4
Q

infections in which -cidal drugs would have an advantage

A

immunocompromised

in immunocompetent: meningitis, endocarditis, deep bone infections, artificial device implants (in these cases, immune system has hard time eradicating the bug b/c hard to get at)

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5
Q

time dependent killing

A

drugs work most effectively when concentration is above 4x MIC for more than 50% of the time

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6
Q

example of time dependent killing drug

A

beta lactams

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7
Q

concentration dependent killing

A

want to maximize the peak concentration

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8
Q

example of concentration dependent killing

A

aminoglycosides

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9
Q

concentration x time dependent killing

A

calculated as AUC(over 24 hr)/MIC

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10
Q

example of concentration x time killing drug

A

quinolones

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11
Q

properties of beta lactams

A

bactericidal

get maximal activity on growing bacteria

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12
Q

MOA of beta lactams

A

covalent binding to PBP-irreversible, competitive

prevents PBP from cross linking cell wall

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13
Q

what kinds of resistance are there to beta lactams?

A

beta lactamase
altered PBP
beta lactam unable to reach PBP

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14
Q

how can bacteria that are sensitive to a beta lactam be resistant when in the presence of bacteria that have beta lactamase?

A

bacteria that have beta lactamase release it out of the cell membrane, so the beta lactamase can degrade the beta lactam

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15
Q

how many different beta lactamases are there

A

over 400, with different substrates

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16
Q

half life of beta lactams

A

short, so dosing intervals are short to keep the drug 4x MIC for more than 50% of the time

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17
Q

properties of penicillins

A

well distributed (low penetration into CSF, BUT increases when you have meningitis)

renal elimination-anion transport

short half lives (30 min-3 hr)

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18
Q

what can you do to predict severe penicillin allergies

A

pt history

pre-pen-a skin test

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19
Q

penicillins’ side effects

A 
allergies
fever (even in normal pts w/o an infection)
diarrhea
enterocolitis
elevated liver enzymes
hemolytic anemia
seizures

ALL antibacterials could cause enterocolitis

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20
Q

MOA of beta lactamase inhibitors

A

beta lactam mimics that bind irreversibly to beta lactamase

21
Q

Examples of beta lactam resistance that is NOT due to beta lactamase

A

penicillin resistant Strep pneumo: actually a change in PBP

MRSA: resistance due to obtaining a new PBP2a

22
Q

properties of cephalosporins

A

distributed well, but only some get to the CSF

most require injection

mechanism same as penicillins

resistance comparable to penicillins

23
Q

what is notable about the 3rd gen cephalosporins

A

effective for many gram neagtives

E coli
Klebsiella
Enterobacter

Works in presence of many gram negative beta lactamases

24
Q

how are cephalosporins metabolized

A

renal

25
Q

side effects of cephalosporins

A

allergies
nausea, vomiting, diarrhea, enterocolitis
hepatocellular damage

26
Q

rationale for developing drugs against extended spectrum beta lactamase containing bacteria

A

some gram negative species have beta lactamases that inactivate penicillin but also prove resistant against drugs “considered” beta lactamase resistant like the 3rd gen cephalosporins and monobactams

27
Q

what is the treatment of choice for extended spectrum beta lactamse bacteria

A

carbapenems

28
Q

MOA of quinolones

A

inhibits DNA gyrase (interferes with DNA replication and repair)

29
Q

properties of quinolones

A

bactericidal

killing predicted by AUC24/MIC

30
Q

side effects of quinolones

A 
nausea vomiting, abd pain, enterocolitis
dizziness, headache, restlessness, depression
rare seizures
rashes
EKG irregularities, arrhthymias
peripheral neuropathy
arthropathy, tendon rupture

caution: seizure hx, pregnancy, children (may cause cartilage damage)

31
Q

What antibacterials cause C diff enterocolitis?

A

all of them can

32
Q

antibacterial treatment for c diff enterocolitis

A

metronidazole (1st choice, esp for mild to moderate)
vancomycin (moderate to severe)
vancomycin and metronidazole (very severe)
fidaxomicin

33
Q

properties of aminoglycosides

A

bactericidal (the ONLY protein synthesis inhibitors that are)

IV, IM, topical

post-antibiotic effect–gets into bacteria and there is sustained activity for hours after the aminoglycoside concen. has gone below effective levels (concentration dependent killing)

narrow therapeutic window,
use only for serious infections

34
Q

MOA of aminoglycosides

A

taken up into bacteria by an energy-requiring aerobic process

binds to several locations on ribosomes:

  • prevents initiation and induces release of ribosome from mRNA
  • leads to mRNA misreading
35
Q

uses of aminoglycosides

A

PRIMARILY gram negative aerobic bacilli (usually used in combo with cell wall inhibitors or quinolones for synergy)

poorly effective against anaerobes

gram positive requires drug combos (cell wall inhibitors increase the permeability of aminoglycosides)

36
Q

what kind of killing do aminoglycosides exhibit?

A

concentration dependent

37
Q

side effects of aminoglycosides

A

narrow therapeutic window

nephrotoxicity (usually reversible)

ototoxicity (usually irreversible)

neuromuscular blockade

38
Q

MOA of tetracyclines

A

transported into cells

prevents attachment of aminoacyl-tRNA to 30S ribosome subunits

39
Q

how does resistance to tetracycline occur?

A

drug efflux pumps in bacteria–resistance to 1 tetracycline usually means resistance to all of them

40
Q

uses of tetracyclines

A

unusual bacteria:
rickettsia
Lyme disease
Chlamydia, mycoplasma, Ureaplasma

41
Q

properties of tetracyclines

A

bind Ca2+ and inhibits tetracycline absorption

42
Q

Side effects of tetracyclines

A

GI disturbances, enterocolitis
Candida superinfection in colon
photosensitization with rash
teeth discoloration (avoid in children younger than 8, contraindicated in preg)

43
Q

H pylori treatments

A

Clarithromycin and amoxicillin and omeprazole

Metronidazole and tetracycline and bismuth subsalicylate and proton pump inhibitor

44
Q

MOA of sulfonamides

A

competitive analog of p-aminobenzoic acid, precursor in folate synthesis

45
Q

sulfonamide use

A

mostly combined with other antibacterials

46
Q

treating uncomplicated cystitis (UTIs)

A

1st choice: TMP-SMX

others: nitrofurantoin
fosfomycin

47
Q

reasons for antibac failure

A 
drug choice
host factors (abscess, host immune status important for finishing the job with static drugs, foreign bodies are hard to get at)
48
Q

quinolone resistance in gram negatives

A

has gone up concurrently w/ its use

49
Q

drugs used for MRSA

A 
hospital acquired:
vancomycin
linezolid
daptomycin
tigecycline
community:
linezolid
doxycycline, minocycline
clindamycin
TMP-SMX

Pharmacology (10 decks)

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