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Resp II Exam II > Introduction to antibiotics (pertinent resp drugs) > Flashcards

Introduction to antibiotics (pertinent resp drugs) Flashcards

1
Q

s. pneumoniae and s. aureus general resistance mechanism

A

reduced affinity of penicillin-binding proteins

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2
Q

gram-negative resistance (pseudomonas) to B-lactams occurs via what mechanisms…

A

B-lactamase production

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3
Q

what is empiric therapy

A

provide antimicrobial therapy to a symptomatic patient without identification of infecting organism. Must consider knowledge of microorganisms most likely to cause specific infection/symptoms

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4
Q

what does bacteriostatic mean

A

arrests growth and replication of bacteria (limits spread of infection)
i) In general, bacterial protein synthesis inhibitors

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5
Q

what is bactericidal

A

kills bacterial

examples–> aminoglycosides and fluoroquinolones

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6
Q

MOA of penicillins

A

inhibits the transpeptidation reaction, the last step in peptidoglycan synthesis. Cell wall composed of peptidoglycan which provides rigid mechanical stability. Peptidoglycan composed of two alternating sugars (N-acetylglucosamine and N-acetylmuramic acid). Five-amino-acid peptide linked to final N-acetylmuramic acid which terminates in D-alanyl-D-alanine. Penicillin binding proteins (PBPs) remove the terminal D-alanine in the process of forming the cross-link. B-lactams are structural analogs of D-Ala-D-Ala. B-lactams covalently bind PBPs preventing cross-linking ultimately leading to cell autolysis.

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7
Q

resistance mechanisms of bugs against penicillins

A

structural difference in PBPs (DRSP)

decreased PBP affinity for B-lactams (gram positives)

inability for drug to reach site of action (i.e. gram-negative organisms)

active efflux pumps

drug destruction and inactivation by B-lactamase (Gram negatives)

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8
Q

extended-spectrum

frequently administered with a B-lactamase inhibitor,

extends beyond gram-positive (s. pneumonia and s. pyogenes) to gram-negative (Haemophilus influenzae, Escherichia coli, Proteus mirabilis), Listeria monocytogenes, susceptible meningococci, enterococci

A

Aminopenicillins (ampicillin, amoxicillin)

ampicillin +/- sulbactam

amoxicillin +/- clavulanic acid

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9
Q

what are the anti-pseudomonal penicillins ?

A

extends spectrum to cover pseudomonas aeruginosa, enterobacter, and proteus spp. , klebsiella, and anaerobes!

includes pipercillin (+/- tazobactam- b-lactamase inhibitor)

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10
Q

what are the therapeutic uses of anti-pseudomonal penicillins (pipercillin)

A

: serious gram-negative infections, hospital acquired pneumonia, immunocompromised patients, bacteremia, burn infections, UTI

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11
Q

what are the adverse effects of penicillins

A

allergic rxns

anaphylaxis

interstitial nephritis

nausea/vomiting/mild/severe diarrhea

pseudomembranous colitis

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12
Q

true or false

cephalosporins have activity against methicillin resistant staph aureus (MRSA) , listeria, enterococci

A

false

none of them do!

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13
Q

cetriaxone

A

third generation cephalosporin

DOC for all forms of gonorrhea and severe lyme’s disease, meningitis

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14
Q

ceftazidime

A

third generation cephalosporin

covers pseudomonas

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15
Q

what are cephalosporins the DOC for

A

serious gram negative infections (klebsiella, enterobacter, proteus, providencia, serratia, haemophilus)

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16
Q

cefepime

A

Fourth generation cephalosporin

extends spectrum beyond third generation (useful in serious infections in hospitalized patients)

100% renal excretion

nosocomial infections

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17
Q

major Adverse effects of cephalosporins

A

1% risk of cross reactivity to penicillins (so be careful in patients who have penicillin allergy)

diarrhea

intolerance to alcohol

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18
Q

meropenem

A

carbapenem

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19
Q

ertapenem

A

carbapenem

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20
Q

spectrum of carbapenems

A

aerobics

anaerobics

gram positives (strep, enterococci, staph, listeria)

enterobacteriaceae

pseudomonas

acinetobacter

***Resistant to beta-lactamases

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21
Q

what are the adverse side effects of carbapenems

A

n/v

seizures

hypersensitivty

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22
Q

what are the 3 beta-lactamases inhibitors (combinations)

A

ampicillin- sulbactam

amoxicillin - clavulanic acid

pipercillin - tazobactam

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23
Q

what are the glycopeptides?

A

vancomycin

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24
Q

MOA of glycopeptides

A

inhibits cell wall synthesis binding with high affinity to D-alanyl-D-alanine terminal of cell wall precursor units. Due to large size, unable to penetrate outer membrane of gram-negative bacteria

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25
Q

what are the mechanisms of bacterial resistance to glycopeptides?

A

alteration of D-alanyl-D-alanine target to D-alanyl-D-lactate or D-alanyl-D-serine which binds glycopeptides poorly.

Intermediate resistance may occur if small proportion of cells growing with vancomycin present or if they have abnormally thick cell wall.

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26
Q

what is the spectrum of coverage of glycopeptides (Vancomycin)

A

broad gram positive coverage (s aureus (MRSA)

s. epidermidis (MRSE)

streptococci

bacillus

corynebacterium spp.

actinomyces

clostridium

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27
Q

what bugs are resistant to vancomycin

A

all gram negative

mycobacterium

28
Q

what are the adverse effects of glycopeptides (Vancomycin)

A

macular skin rashes

chils, fever

Red man syndrome
-extreme flushing
-tachycardia
-hypotension
(this is not an allergic rxn just a direct toxic effect of vancomycin on mast cells causing them to release histamine)

ototoxicity

nephrotoxicity

29
Q

what are the fluoroquinolones

A

levofloxacin
moxifloxacin
ciprofloxacin

30
Q

what is special about moxifloxcain

A

doesn’t need to be dose adjusted in renal dysfunction b/c it is metabolized in the liver

31
Q

MOA of fluoroquinolones

A

direct inhibitor of nucleic acid synthesis

inhibits DNA gyrase and topoisomerase IV (responsible for separation of replicated DNA during cell division)

DNA must be separated to permit DNA replication or transcription

32
Q

mechanisms of bacterial resistance to FQ’s

A

mutation in bacterial chromosome genes encoding DNA gyrase or topoisomerase IV

active transport of drug out of cell

33
Q

what is the spectrum of coverage of FQ’s

A

Pseudomonas

S. aureus (NOT MRSA)

coverage of strep. spp.

H. influenzae

Moraxella

M. pneumoniae

C. pneumoniae

Legionella

Levofloxacin covers DRSP (HAP)

34
Q

what are the adverse effects of FQ’s

in what patients are FQ’s contraindicated ?

A

GI - most common. mild nausea, vomiting, abdominal discomfort

CNS- mild headache, dizziness, delirium, rare hallucinations

rash

photosensitivity

Achilles tendon rupture

*** Contraindicated in children

35
Q

what are the 30S inhibitors of protein synthesis ?

Buy AT 30

A

AT

Aminoglycosides- Gentamicin

Tetracyclines - Doxycycline

36
Q

what are the 50S inhibitors of protein synthesis?

A

macrolides –> Azithromycin

Lincosamides–> Clindamycin

oxazolidinones –> Linezolid

Chloramphenicol

37
Q

aminoglycoside example drug

A

gentamicin

38
Q

MOA of aminoglycosides (gentamicin)

A

concentration-dependent, binds 30S ribosomal subunit and disrupts normal cycle of ribosomal function by interfering with initiation of protein synthesis.*** Abnormal initiation complexes and aberrant proteins (due to misreading of mRNA template) accumulate. Aberrant proteins inserted into cell membrane leading to altered permeability.

39
Q

bacterial Mechanisms of resistance against aminoglycosides *3

A

AG metabolizing enzymes

impaired transport of drug into the cell

altered ribosome

40
Q

spectrum of aminoglycosides coverage

what does it NOT work on

A

aerobic gram negative

limited action against gram positive

does NOT work on anaerobes b/c it requires O2

used when there is resistance to other agents or in seriously ill patients

HAP

41
Q

what are the adverse effects of aminoglycosides (gentamicin)

A

ototoxicity (may be as high as 25%)

nephrotoxicity (8-26%)

neuromuscular block and apnea

42
Q

what is the tetracycline drug relevant to respiratory infections

A

doxycycline

43
Q

MOA of tetracyclines (doxycycline)

A

bacteriostatic, inhibits bacterial protein synthesis by binding 30S bacterial ribosome and preventing access of aminoacyl tRNA to acceptor (A) site on mRNA ribosome complex.

i) Enters outer membrane via passive diffusion through porin proteins and cytoplasmic membrane via active/energy-dependent transport

44
Q

what are the mechanisms of bacterial resistance of bugs against tetracyclines

A

decreased influx

acquisition of energy dependent efflux

ribosomal protection proteins

enzymatic inactivation

45
Q

spectrum of coverage of tetracyclines

A

aerobic and anaerobic gram positive and gram negatives

Mycoplasma pneumoniae

atpyical mycobacerium

MRSA

H. influenzae

46
Q

what bugs are resistant to tetracyclines

A

pseudomonas

47
Q

do tetracylines require adjustments in renal impairment ?

A

NO

48
Q

what are the therapeutic uses of doxycycline

A

CAP

atypical CAP

MRSA

49
Q

what are the adverse effects of doxycycline ?

A

GI - epigastric burning, abdominal discomfort, nausea, vomiting, diarrhea

superinfections of C. difficile

photosensitivity

tooth discoloration ***

thrombophlebitis

50
Q

liconsamide?

A

clindamycin

inhibitor of 50S

51
Q

macrolide?

A

azithromycin

inhibitor of 50S

52
Q

MOA of macrolides (azithromycin)

A

bacteriostatic, binds reversibly to 50S ribosomal subunit, inhibits translocation*** where a newly synthesized peptidyl tRNA molecule moves from acceptor site on ribosome to peptidyl donor site

53
Q

what are the mechanisms of resistance against macrolides

A

drug efflux

ribosomal protection proteins

hydrolysis

ribosomal mutations

54
Q

what is the spectrum of coverage of macrolides?

A

Wide spectrum (gram positive and negatives)

note- staphylococcus not reliably susceptible

H. influenzae

bordetella pertussis

m. pneumoniae

some atypical mycobacterium

legionella

55
Q

therapeutic uses of azithromycin ?

A

CAP–> strep pneumoniae, h. influenzae

atpyicals (mycoplasma, chlamydophilia, legionella)

otitis media, sinusitis, bronchitis alternative

pertussis

56
Q

what are the adverse effects of macrolides (azithromycin)

A

GI (epigastric distress)

hepatotoxicity

arrythmia

QT prolongation

DRUG INTERACTIONS–> CYP3A4 inhibition which prolongs the effects of digoxin, valproate, warfarin

57
Q

MOA of lincosamides

A

Clindamycin

binds exclusively to 50S subunit of bacterial ribosome and suppresses protein synthesis

58
Q

what are the mechanisms of resistance of bugs against lincosamides (clindamycin)

A

ribosomal methylation

59
Q

what is the spectrum/therapeutic use of clindamycin (a lincosamide)

what bugs are resistant to clindamycin

A

pneumococci

s. pyogenes

viridans strep

MSSA

anaerobes *** (fragilis)

all aerobic gram negative bacilli are resistant

therapeutic use?

  • lung abscess
  • anaerobic lung and pleural space infection
60
Q

what are the adverse effects of lincosamides (clindamycin)

A

GI - diarrhea (2-20%)

pseudomembranous colitis due to c.difficile ***

skin rashes

reversible increase in aminotransferase activity

may potentiate neuromuscular blockade

61
Q

what is the drug under class oxazolidinone?

A

Linezolid

62
Q

MOA of linezolid?

A

inhibits protein synthesis by binding P site of 50S ribosome subunit preventing formation of initiation complexes

63
Q

what is the mechanism of resistance against linezolid ?

A

ribosomal mutation

64
Q

spectrum of use of linezolid ?

A 
gram positive :
staph
-MSSA
-MRSA
-VRSA

streptococcus
-penicillin resistant strep pneumoniae

enterococci (VRE)

gram positive anaerobic cocci

gram positive rods (corynebacterium, L. monocytogenes)

65
Q

what is the therapeutic use of linezolid

what is it reserved for…

A

VRE

nosocomial pneumonia caused by MSSA and MRSA

CAP

DO NOT use when other agents are likely to be affective!! should be reserved for multiple - drug resistant organisms

66
Q

what are the adverse effects of linezolid?

A

myelosuppression

  • anemia
  • leukopenia
  • pancytopenia
  • thrombocytopenia

headache

rash

drug interactions!!! –> nonspecific inhibitor of monoamine oxidase –> concomitant adrenergic serotoninergic (SSRI’s) may lead to serotonin syndrome ( palpitations, headache, hypertensive crisis )

Resp II Exam II (11 decks)

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