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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
what are the mechanisms of bacterial resistance to glycopeptides?
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.
26
what is the spectrum of coverage of glycopeptides (Vancomycin)
broad gram positive coverage (s aureus (MRSA) s. epidermidis (MRSE) streptococci bacillus corynebacterium spp. actinomyces clostridium
27
what bugs are resistant to vancomycin
all gram negative mycobacterium
28
what are the adverse effects of glycopeptides (Vancomycin)
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
what are the fluoroquinolones
levofloxacin moxifloxacin ciprofloxacin
30
what is special about moxifloxcain
doesn't need to be dose adjusted in renal dysfunction b/c it is metabolized in the liver
31
MOA of fluoroquinolones
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
mechanisms of bacterial resistance to FQ's
mutation in bacterial chromosome genes encoding DNA gyrase or topoisomerase IV active transport of drug out of cell
33
what is the spectrum of coverage of FQ's
Pseudomonas S. aureus (NOT MRSA) coverage of strep. spp. H. influenzae Moraxella M. pneumoniae C. pneumoniae Legionella Levofloxacin covers DRSP (HAP)
34
what are the adverse effects of FQ's in what patients are FQ's contraindicated ?
GI - most common. mild nausea, vomiting, abdominal discomfort CNS- mild headache, dizziness, delirium, rare hallucinations rash photosensitivity Achilles tendon rupture *** Contraindicated in children
35
what are the 30S inhibitors of protein synthesis ? Buy AT 30
AT Aminoglycosides- Gentamicin Tetracyclines - Doxycycline
36
what are the 50S inhibitors of protein synthesis?
macrolides --> Azithromycin Lincosamides--> Clindamycin oxazolidinones --> Linezolid Chloramphenicol
37
aminoglycoside example drug
gentamicin
38
MOA of aminoglycosides (gentamicin)
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
bacterial Mechanisms of resistance against aminoglycosides *3
AG metabolizing enzymes impaired transport of drug into the cell altered ribosome
40
spectrum of aminoglycosides coverage what does it NOT work on
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
what are the adverse effects of aminoglycosides (gentamicin)
ototoxicity (may be as high as 25%) nephrotoxicity (8-26%) neuromuscular block and apnea
42
what is the tetracycline drug relevant to respiratory infections
doxycycline
43
MOA of tetracyclines (doxycycline)
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
what are the mechanisms of bacterial resistance of bugs against tetracyclines
decreased influx acquisition of energy dependent efflux ribosomal protection proteins enzymatic inactivation
45
spectrum of coverage of tetracyclines
aerobic and anaerobic gram positive and gram negatives Mycoplasma pneumoniae atpyical mycobacerium MRSA H. influenzae
46
what bugs are resistant to tetracyclines
pseudomonas
47
do tetracylines require adjustments in renal impairment ?
NO
48
what are the therapeutic uses of doxycycline
CAP atypical CAP MRSA
49
what are the adverse effects of doxycycline ?
GI - epigastric burning, abdominal discomfort, nausea, vomiting, diarrhea superinfections of C. difficile photosensitivity tooth discoloration *** thrombophlebitis
50
liconsamide?
clindamycin inhibitor of 50S
51
macrolide?
azithromycin inhibitor of 50S
52
MOA of macrolides (azithromycin)
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
what are the mechanisms of resistance against macrolides
drug efflux ribosomal protection proteins hydrolysis ribosomal mutations
54
what is the spectrum of coverage of macrolides?
Wide spectrum (gram positive and negatives) note- staphylococcus not reliably susceptible H. influenzae bordetella pertussis m. pneumoniae some atypical mycobacterium legionella
55
therapeutic uses of azithromycin ?
CAP--> strep pneumoniae, h. influenzae atpyicals (mycoplasma, chlamydophilia, legionella) otitis media, sinusitis, bronchitis alternative pertussis
56
what are the adverse effects of macrolides (azithromycin)
GI (epigastric distress) hepatotoxicity arrythmia QT prolongation DRUG INTERACTIONS--> CYP3A4 inhibition which prolongs the effects of digoxin, valproate, warfarin
57
MOA of lincosamides
Clindamycin binds exclusively to 50S subunit of bacterial ribosome and suppresses protein synthesis
58
what are the mechanisms of resistance of bugs against lincosamides (clindamycin)
ribosomal methylation
59
what is the spectrum/therapeutic use of clindamycin (a lincosamide) what bugs are resistant to clindamycin
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
what are the adverse effects of lincosamides (clindamycin)
GI - diarrhea (2-20%) pseudomembranous colitis due to c.difficile *** skin rashes reversible increase in aminotransferase activity may potentiate neuromuscular blockade
61
what is the drug under class oxazolidinone?
Linezolid
62
MOA of linezolid?
inhibits protein synthesis by binding P site of 50S ribosome subunit preventing formation of initiation complexes
63
what is the mechanism of resistance against linezolid ?
ribosomal mutation
64
spectrum of use of linezolid ?
``` gram positive : staph -MSSA -MRSA -VRSA ``` streptococcus -penicillin resistant strep pneumoniae enterococci (VRE) gram positive anaerobic cocci gram positive rods (corynebacterium, L. monocytogenes)
65
what is the therapeutic use of linezolid what is it reserved for...
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
what are the adverse effects of linezolid?
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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