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Pathology > Antibiotics Final > Flashcards

Antibiotics Final Flashcards

1
Q

Bacteriocidal

A

Kill

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2
Q

Bacteriostatic

A

Prevent growth

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3
Q

Describe penicillin

A

Thiazolidine ring with beta Lactation rings with R groups(for modifications)
Inhibit cell wall synthesis by inhibiting penicillin binding protein/transpeptidase, inhibiting peptidoglycan cell wall cross linking
ONLY WORKS ON ACTIVELY GROWING CELLS

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4
Q

How become resistant to penicillin

A

Alter porins, alter structure of Pbp/transpeptidase, upregulate penicillin pumps

Porins are how they get into bacteri a
Pump get them out

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5
Q

Penicillin G

A

1st
Competitively compete with transpeptidase->bacteriocidal

Many organisms resistant
Use on-S pneumonia, s pyogenes, viridans, N mengitidites, spirochetes, C perfrigens
(Gram positive organisms, gram negative cocci, non beta lactamase producing anaerobes

Can get hypersensitivity reactions

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6
Q

Amino penicillins

A

Increased binding affinity to transpeptidase to increase gram negative coverage
Ampicillin and amoxicillin

Use on E. coli, enteric, W/beta lactamase inhibitor on H influenza, E. coli, klebsiella, protussus, and b fragilis

Hypersensitivity

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7
Q

Penicillinase resistant penicillins

A

Methicillin, nafcillin, oxacilin, dicloxallin

Competitive inhibition of transpeptidase stop cell wall synthesis

Primary antibiotic for staph a and staph e

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8
Q

What is Mersa

A

Methicillin resistant staph a

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9
Q

Antipseudomonal penicillins

A

Competitive inhibitors of pbp and target PSEUDOMONAS A

Piperacillin , usually with tazobactam (beta lactamase inhibitor )

Broadest spectrum of penicillin
Hypersensitivity to beta lactamase ring

Use on staph e and a , enterococcus faecalis, p aeruuginosa

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10
Q

Cephalosporins

A

7 aa cephalosporin acid base with R 1 and R2 to enhance antibacterial
BACTERICIDAL by binding and inhabiting transpeptidase
Resistance-beta lactamase
Can’t use on klebsiella or coli due to b lactamase
Bacteria can alter structure of transpeptidase or upregulate cephalosporin efflux pumps

Broader spectrum than penicillin
1st gen-s aureus +
2nd gen-ok of pos and neg
3rd gen-e coli -

Hypersensitivity to beta lactamase ring rash several days after therapy

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11
Q

1st generation cephalosporins

A 
Cefazolin and cephalexin 
Cell wall synthesis inhibitors 
Get hypersensitivity 
Use on A aureus, enterococcus and s epidermis 
Not MRSA

OK against gram negative

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12
Q

2nd generation cephalosporins

A

Cefotaxime, cefixime, chef dining, ceftibuten, ceftazimide, ceftriaxone,, cefpodoxime proxetil, cefditoren pivoxil

BACTERICIDAL bind transpeptidase
Same as first PLUS gram negative like klebsiella
H influenza, n meningitidis, s pneumonia,
NOT SERRATIA or STAPH A

Cefoxitin and cefotetan against b fragilis and some serratia but not h influenza

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13
Q

3rd generation cephalosporins

A

Ceftizoxime and cefoperazone (prodrugs hydrolyzed to active) FOR NEGATIVE less on positive
Cefpodozime proxetil__>cefpodoxime

Neusseria , haemophilus
NOT enterobacter, citrobacter, serratia, acinobacter (beta lactamase)

Ceftazidime for P aeruginosa
E. coli, h influenza, p miribalis, s pyogenes

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14
Q

Fourth generation cephalosporins

A

Cefepime
Enterobacter and pseudomonas bc resistant to their beta lactamase s
Efflux can make resistant to it though!!

Expand gram - coverage
Enterobacter, p aeruginosa,
Poor b fragilis

Get hypersensitivity

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15
Q

Fifth generation cephalosporins

A

Ceftaroline fosamil—>ceftaroline
Ceftozane ( with tazobactam)

Ceftaroline-MRSA with increased binding to transpeptidase and penicillin resistant S pneumonia
Ceftolozane-pseudomonas

Ok gram negative but not fragilis

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16
Q

Carbapenenems

A

Have beta lactamase ring
Imipenem(first and more severe side effects also needs renal dipeptidase inhibitor, celastatin), ertapenem, meropenem, doripenem

Bind inhibit transpeptidase
RESISTANT TO LACTAMASE DEGRADATION unlike penicillin and cephalosporin
Also smaller structure so can pass through portions better (gram -)
Resistance-lactamase, shrink portions , degrade carbapenem

For gram negative
Impenem-listeria, staph (not mrsa), enterococci(not faecium), strep, enterobacteriacae, acinetobacter, B FRAGILIS,

Not for c deficit like , MRSA, enterococcus faecium

Meropenem and doripenem better with negatives and worse with positive
But NOT DEGRADED by dipeptidase and don’t need dipeptidase inhibitor
Ertapenem no P aeruginosa or acinetobacter or enterococcus

Hypersensitivity to beta lactamase

17
Q

Monobactams

A

Monolithic beta lactamase ring
Aztreonam
Bind transpeptidase
Stable to beta lactamase (still susceptible though)
NOT FOR GRAM POSITIVE OR ANAEROBES (for aerobes)

Same gram - spectrum as ceftazidime since same structure
Enterobacteriacae and P aeruginosa, H influenza
If allergic to penicillin or other can tolerate azetreonam

But caution if giving to a ceftazidime allergic patient

Gram negative bacteria when cant tolerate others
Skin rash or increased serum aminotransferases (hepatoma it you)

18
Q

Glycopeptides and Lipoglycopeptides

A

Glycopeptide vancomycin 1st but not engineer lipoglycopeptides called telavancin, dalbavancin and oritavancin

Cell wall synthesis inhibitor-bind D-alanyl-D-alanine and prevent extension and cross linking of peptidoglycan which also damages cell wall
Lipoglycopeptides further improve this by dimerizing and imbedding in their lipid into the cell membrane for improved binding —rapid (oritavin and telavancin do this more rapid than vancomycin or dalbavancin)

E faecium is resistant since transposoning which changes glycopetpide binding site bind bad
Lipo better at overcoming this resistance

Vancomycin glycopeptide-ampicillin resistant enterococci, penicillin resistant strep, MRSA
Everything else resistant and gram - due to size too big to penetrate gram negative bacteria

Telavancin, dalbavancin and oritavancin -same but ok against some enterococci that are resistant to v

IV given…..orally not absorbed

Nephrotoxicity from fast infusion-hypotension, tachycardia, flushing RED MAN SYNDROME not allergy just direct action with mast cells and degranulation and histamine release
Take antihistamine

19
Q

Beta lactamase inhibitors

A

Not antibiotics, resemble beta lactamase molecules
Weak antibacterial
Clavulanic acid , sulbactam, tazobactam,
Resistance-differ binding affinity

Extend spectrum of aminopenicillins to include h influenza, E. coli and klebsiella, proteus and B fragilis

Piperacillin is always coformuatied with the beta lactamase inhibitor tazobactam to give best gram - coverage

Well tolerated -minimal but sometimes to people with lactamase problem

20
Q

Oxazolidinones

A

Protein synthesis inhibitor (bind to 50s ribosomal subunit, cant protein synthesisinhibit fMET tRNA complex-of AUG no start codon cant be INITIATED)
Linezolid, tedizolid
Gram positive

Bacteriostatic but BACTERICIDAL for strep

Resistance-point mutation 23s rna binding site on 50s , methyltransferase can modify the ribosome and alter binding (TRANSFERABLE BETWEEN BACTERIA_
Gram positive -not for gram negative

For vancomycin resistant enterococci, penicillin resistant s pneumonia, and mrsa
ADVERSE-

Myelosuppression-thrombocytopenia 7-10 days

Lactic acidosis, optic neuritis, peripheral neuropathy from INHIBITION of MITOCHONDRIAL PROTEIN SYNTHESIS
Not used long term is alternate treatment available

Inhibits monomania oxidase -drug drug interactions antidepressants and serotonin reputable inhibitors
Do not coal minister with bc will get serotonin syndome, life threatening headache, palpitations, HTM crisis

21
Q

Macro lines and ketolides

A

Macrocyclic lactose ring with deoxycholic sugars
Erythromycin, clarithromycin, azothromycin, fidaxomicin (C dificile by not systemically absorbed-just fidaxomicin)
Ketaloid-telithromycin

Bind 50s prevent translocation of tRNA from a site to p site also cause conformational change in ribosome
Which indirectly inhibit pbp
Bacteriostatic

Resistance-efflux, ribosome can make methylated enzymes which modify binding site on ribsome, degradation(esterases by enterobacteriacae), 50s mutations (campylobacter and bacillus )

Erythromycin-streptococci, pneumococci, staphylococci, C jejuni, M pneumonia, C trachomatis, H pylori, gram positive bacilli, bartonalle, neisseria, rickettsia, treponema pallidus

Not for aerobic gram negative bacilli

Azithromycin-moraxella catarrhalis , chlamydia, , h pylori ,

Clarithromycin-better for strep and staph and h influenza

Fidaxomicin-c difficult

Ketolide-withstand resistance to S pneumonia and S aureus bc poor substrates for drug efflux

Adverse-diarrhea nausea vomiting anorexia —erythromycin acts on motility receptors that stimulate GI motility , prolonged hepatotoxicity
Hypersensitivity skin eruptions , eosinophilia, fever

22
Q

Streptogramins

A

Streptogramin a-dalfopristin 70%
Streptogramin b-quinupristin 30%
COMBINED - bind 50s SYNERGYSTICALLY
Q bind 50s induces early termination of protein synthesis
D-enhance bind 50s nearby conformational change enhance binding of Q
BACTERICIDAL
Resistance-enzymatic deactivation D, binding site altered, efflux,

Gram positive cocci (resistant strep, penicillin resistant s pneumonia, MRSA)
M pneumonia, C pneumonia, Legionella
Staph strep BACTERICIDAL 
Bacteriostatic with E faecium 
Not foR -

Well tolerated pain at infusion site

23
Q

Tetracyclines and glycycylines

A

T-four membered ring -doxycycline, minocycline, tetracycline, demeclocycline
G-broader spectrum in tetracycline resistant -tigecycline

Bind 30s prevent aminoaciduria tRNA from entering a site
Bacteriostatic

Resistance-influx reduced or efflux up , (glycylcylines overcome the efflux sometimes), upregulationof a preotein that dislodges tetracyclines or glycylcylines(. G have higher affinity bind0, enzymatically deactivated

Tetracyclines0gram positive anaerobes, chlamydia, mycoplasms, rickettsias, MRSA, strep pyogenes UREAPLASMA, mycoplasma pneumonia’s, rickettsia, chlymidia legionells plasmodium , t pallidus spirochete

G-all and enterococci, enterobacteriacae, acinobacter, b fragilis,
Pseudomonas proteus are resistant

Adverse-GI irritation and bone and teeth bind calcium deform, enamel
Can get C dificille

24
Q

Aminoglycosides

A

Streptomycin, gentamicin, tobramycin, amikacin, neomycin, paromycin, kanamycin, netilmicin

Often combined
Bind 30s inhibit initiation, continuation, premature termination

BACTERICIDAL
Enter gram - by porin and then electrical gradient which needs o2 don’t work on anaerobes
Synergy if add penicillin or vancomycin on getting in there
SYNERGYYYY

Resistant-enzymatic inactivation , decreased transport from porin change, (streptomycin)gram negative aerobes
Enterobacter, E. coli, klebsiella, pneumonia, pseudomonas, serratia, acinetobacter

Not used alone to treat gram positive add with beta lactamase antibiotic to exapsd coverage to gram negative
To work on listeria, viridans, streptococci enterococci staphylococci

Adverse-nephrotoxic and ototoxic
Balance ataxia

25
Q

Fluoroquinolones

A

Morflaxin and ciproflacin second group better for gram positive cocci
Gemifloaxin, moxifocin, gatifloxacin-gram positive
Moxifloxacin-anaerobes

Inhibit transcription and replication of bacterial dna by inhibiting bacterial topoisomerase 2 (gyrase)and bacterial topoisomerase 4. We have 2 but ok and dna gyrase

Resistance- mutation in quinolone binding region on dNA grasses or topoisomerase , efflux

Gram pos and neg
Gram negative aerobes
Not gram positive cocci

Well tolerated GI side effects C dificille induced colitis tendon rupture, AT prolongation from moxifloxacin

26
Q

Sulfonamides and benzylpyrimidines

A

Co formulated
Sulfamethoxazole and trimethoprim
TMP/SMX
Synergistic -disrupt different steps of THF biosynthetic pathway
For purine synthesis
PABA-THF-purine
Trimethoprim-dihydrofolatereductase inhibitor
Sulfamethoxazole-analog of PABA competitive inhibitor for dihydropteroate synthesis

Resistance-change in THF synthetic path , overproduce PABA, upregulate mutated dihydropteroate synthase that has reduced binding for sulfamethoxazole. Permeability

Permeability, upregulate DHF reductase,

Combo-staph epidermidis, s aureus, MRSA, S pyogenes, viridans, strep, serratia, shigella, salmonella, enterobacter, proteus m, nocardia, p jiroveci, haemophilus

Anemia leukoplakia
Nausea vomit urticaria rash Stevens Johnson syndrome -mucous membrane skin eruption

27
Q

Polymyxins

A

Basic peptides
Polymyxin B and colistin (polymixin E)

Polymyxin E-topical
Adverse effects not used as much
Gram negative
But used again to combat resistance
Disrupts membrane cationic detergent due to amphipathic properties
Disrupt outer membrane gram negative
And can inactivate endotoxins!!!! Prevent fever, diarrhea, shock, BACTERICIDAL

Resistance is rare-klebsiella and acinetobacter , p aeruginosatopical on scrape well tolerated. But systemic parenteral administration is toxic NEPHROTOXICITY slurred speech, vertigo, parenthesis, apnea, muscle weakness

Only for gram negative

28
Q

Why are penicillins called “beta-Lactam antibiotics”?

A

They all have a beta-Lactation ring

29
Q

Is penicillin bateriostatic or bactericidal?

A

Bactericidal

30
Q

Steps in penicillin action

A
  1. Penetrate cell layers
  2. Keep beta-Lactam ring in tact
  3. Bind transpeptidase (Pbp)
31
Q

How can a bacteria be resistant to penicillin

A
  1. Outer membrane (gram negative) must be right size and charge to enter
  2. Beta lactamase(gram - and +) cleave CN bond in the beta Lactation ring (staph a secretes penicillinase, NOTE: gram negative with beta lactamase destroy in the periplasmic space)
  3. Later transpeptidase
  4. Pump it out with the “effluent pump”
32
Q

Sensitivity to penicillin

A

Anaphylactic “allergic” reaction
IgE mediated
Bronchospasm, urticaria, anaphylactic Shock)

C. difficile

33
Q

Type G penicillin

A

Fleming original
Mold penicillium notatum made a chemical that inhibited Steph a growth
1941
Oral (penicillin V is acid stable), IM, IV (cryastalline to increase HL)

USE ON : streptococcus pharygitis (oral )

34
Q

Aminopenicillins

A

Better coverage of gram -
Better penetration through outer membrane and better binding to transpeptidase
Still problems with penicillinase
‘USE ON : E. coli, proteus, salmonella, shigella) ENTEROCOCCUS

Resistance: H influenza and many gram - have penicillinase

Ampicillin(oral) , amoxicillin(oral, better absorbed so for bronchitis, otitis media, sinusitis)
DRUG OF CHOICE FOR LISTERIA

*AMP-GENT IV ampicillin with others (gentamicin) for broad spectrum gram ———-UTI bc often has gram negative enteric or enterococcus

35
Q

Penicillinase resistant penicillins

A

Wider gram - (including pseudomonas )

Methicillin, nafcillin, oxacilin (IV)
(I met a nasty ox)
Staph Aureus, but not MRSA

Naficillin-S. Aureus (cellulitis, endocarditis, sepsis)

36
Q

Cloxacillin and dicloxacillin

A

Oral beta lactamase resistant penicillins

Only for gram + (staph a)

37
Q

Patient has cellulitis or impetigo?

A

Staph a or b hemolytic steptococcus

CLOCK

Penicillin g or v-not for staph a
Penicillinase resistant agents-give bc cover staph a (produces beta lactamase)

38
Q

Anti pseudomonas penicillins (carboxypenicillins and ureidopenicillins )

A

Expanded gram - rod coverage

Pseudomonas a, b fragilis, and many gram +

Pathology (36 decks)

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