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Pharmacology > ID: cell wall inhibitors > Flashcards

ID: cell wall inhibitors Flashcards

1
Q

Gram +

  • peptidoglycan layer?
  • retain stain?
  • stain color
A

thick peptidoglycan wall

  • retain/absorbs stain
  • purple
  • easier to kill vs negative
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2
Q

gram -

  • peptidogucan layer?
  • retain stain?
  • stain color
A

thin peptidoglycan wall

  • washes away in acid
  • pink
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3
Q

acid fast bacteria

  • can appear how.. + or - ?
  • outer bacterial envelope contains?
A

gram + or -

outer envelope contains glycolipids

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4
Q

what is harder to kill? + or -

A

gram -

  • covered by multiple thin layer of membrane that eject toxins
  • lipopolysaccharide layer
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5
Q

which is quicker to develop resistance?

A

gram -

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6
Q

mycobacteria

  • pos or neg
  • stain on?
A

weakly gram +
but stain on a special stain called acid-fast
-TB

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7
Q

Spirochetes

  • pos or neg
  • how is it visualized
A

gram -
very small and visualized on a darkfield micrscope
-lyme

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8
Q

mycoplasma

  • pos or neg
  • cell wall and membrane?
A

not gram + or -
NO cell wall
only a cell membrane

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9
Q

anaerobic bacteric

  • ex of where to find
  • pos or neg?
  • uni or multi cellular?
A
  • thrive and grow when oxygen is not present
  • mostly unicelluarl
  • can be + or -

EX: GI tract

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10
Q

aerobic bacteria
pos or neg?
-ex dz caused by them

A

live and grow where oxygen is presnt
need it to survive
a
+ or -

EX: tonsillitis

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11
Q

cell wall inhibitors intefere with?

  • work best when ?
  • do not work on?
A

synthesis of bacterial cell wall

  • work best when bacteria are actively proliferating
  • do not work on mycoplasma AND human cells do not have cell walls–>makes them relatively safe abx
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12
Q

why are cell wall inhibs as a class relatively safe?

A

bc they attack the cell wall—- and human cells do not have cell walls

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13
Q

list of cell wall inhibs (5)

A
  1. PCNs
  2. cephalosporins
  3. carbapenenms
  4. monobactams
  5. beta-lactamase inhibitor combinations
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14
Q

cephalosporins start wht

A

CEF-

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15
Q

CEF-

A

cephalosporins

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16
Q

all penicilins have what in their structure

A

beta lactam rings

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17
Q

PCNs inhibt what enzyme

A

Transpeptidase

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18
Q

PCNs are ___ dependent

A

TIME

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19
Q

PCNs are ___ soluble

A

water

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20
Q

PCNs end in?

A

-cillin

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21
Q

PCN G and V

  • which is only PO and only IM/IV
  • spectrum?
  • cover mainly?

DOC for?

A

NATURAL PCNs!!!
V: PO
G: IM/—— comes in depot forms that make t1/2 longer

Spectrum: narrow and penicillinase sensitive

gram (+) cocci (pneumococci, beta-hemolytic streptococcus), gram (+) rods (Listeria),
gram (-) cocci (Neisseria meningitidis) and Treponema pallodum, most anaerobes, *only bacteriostatic for enterococci
beta lactamase sensitive* so does not kill as many staphylococcus bc they produce beta lactamases

INDS:

  1. DOC: Treponema pallodum–syphilis
  2. PCN G Benzathine: prophylaxis for Rheumatic fever.. IM q 21-28 days
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22
Q

Second Generation aminopeniclins

list them and routes

A

Ampicillin–IV

Amoxicillin–PO

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23
Q

Adv rxn to PNCs

A

generally well-tolerated and safe vs other ABX

  • hypersensitivity
  • diarrhea
  • nephritis
  • neurotoxicity
  • hematologic–
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24
Q

what enzyme is involved in construction of cell wall (peptidoglycan layer)

A

transpeptidase or penicillin binding protein

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25
Q

gram pos cell wall:

  • thick or thin
  • lipid content low/high
  • yes/no endotoxin
  • yes/no periplasmic space
  • yes/no porin channels
  • yes/no penetrable by PCN
A

thick cell wall

low lipid content

no endotoxin

no periplasmic space

no porin channel

easily penetrable by PNC

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26
Q

gram neg cell wall:

  • thick or thin
  • lipid content low/high
  • yes/no endotoxin
  • yes/no periplasmic space
  • yes/no porin channels
  • yes/no penetrable by PCN
A

thin cel wall

outer lipopolysaccharide membrane

yes endotoxins

yes periplasmic space

yes porin channel

harder for PCN to access

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27
Q

streptococci pos or neg

A

+

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28
Q

enterococci pos or neg

A

+

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29
Q

staphlyococci pos or neg

A

+

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30
Q

cornebacterium pos or neg

A

+

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31
Q

Listeria pos or neg

A

+

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32
Q

bacillus pos or neg

A

+ and spore forming

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33
Q

Clostridium pos or neg

A

+ and spore forming

34
Q

PCNs kill which type of bacteria

A

Mainly gram +

*harder for them to cross lipopolysaccharide layer surrounding gram -

35
Q

how does the PCNs kill gram -?

A

they have to go through the porins because they cannot cross the lipoplysaccharide layer

36
Q

beta-lactamases are also called?

A

penicillinases

37
Q

Beta lactamases

A

enzymes that break the beta-lactam ring– casing the ABX to lose its bactericidal effect

-some bacteria produce this enzyme

38
Q

PCNs are bacterialcidal or bacteriostatic?

A

bacteriocidal

39
Q

solution to beta-lactamase producitng bacteria?

A

beta-lactamase inhibitors

PCN + BLI added together to make one drug and more effective

40
Q

name the combination drugs that make up beta-lactamase inhibitors (4)

A
  1. Ampicillin + Sulbactam
  2. Amoxicilin + Clavulanate= Augmentin **
  3. Ticarcillin + Clavulanate
  4. Piperacillin + tazobactam
41
Q

list the three ways bacteria are resistant to beta-lactam antibitotics

A
  1. prod of beta-lactamase enzymes
  2. decreased penetration– of cell wall and LPS layer and efflux pumps
  3. Modified penicillin binding proteins (lower affinity of antibiotics to target)
42
Q

list the 5 ways you can classify PCNs

A
  1. source–natural or semi-synthetic
  2. Route of admin: PO only vs PArenteral only
  3. Spectrum of activity: Narrow spectrum to broad to intermediate to extended
  4. Resistance to beta-lactamase or non-resistance
  5. resistance to acids: acid stable vs acid unstable
43
Q

PCN G

  • list the two types
  • routes of admin
A

Procaine PCN G and Benzathine PCN G

IM ONLY**

44
Q

what happens if you give PCN G IV?

A

cardiac arrest

IM ONLY**

45
Q

which drug if given IV can cause cardiac arrest?

A

PCN G benzathine procaine

46
Q

what does PCN G and V fight

A

Gram + cocci: pneumococci, beta-hemolytic streptococcus (strep pharyngitis)

Gram + rods: listeria

Gram - cocci: Neisseria

Most anaerobes

Enterococci: but only has bacteriostatic effect not bacteriocidal

DOC for syphilis

IM PCN G for rheumatic fever prophylaxis

47
Q

which bacteria has become very resistant to PCN G and V

A

staph aureus– over time 90% of the strains have developed beta lactamase

48
Q

Anti Staphylococcal Penicillins

  • list them and routes (4)
  • spectrum?
  • potency compared to natural PCNs
  • resistant to?
  • indications?
  • not effective for?
  • adv rxns
A

Methicillin (not avail in US bc causes acute interstitial nephritis)
Nafcillin (IV ONLY)
Oxacillin (IV, IM)
Dicloxacillin (PO)

  • beta lactamase resistant penicillins
  • potency: less potent vs natural PCNs

very narrow spectrum: for staph A infections w/o MRSA

INDS:

  • cellulitis
  • beta-lactamase producing staph infections (NOT MRSA)

NOT FOR:

  • gram neg
  • listeria
  • Enterococci

ADV RXN:

  • N/V/D
  • Neurotoxicity
  • acute interstitial nephritis— from methicillin**
  • thrombocytopenia
  • neutropenia
  • methemoglobinemia
49
Q

which drug causes acute interstitial nephritis

A

Methicillin– anti-staphylococcal penicillin

*why it is no longer avail in US

50
Q

Second Generation Aminopenicillins

  • list them
  • spectrum
  • structure
  • treats?
  • not good for?
  • can be added to?
  • adv eff
A

Ampicillin and Amoxicillin

SPECTRUM: extended/broad

  • great gram + and gram- bacilli coverage
  • including H. influenzae
  • E. coli
  • Listeria
  • Proteus
  • Salmonella
  • respiratory infections
  • dental infections
  • UTI pregnancy
  • otitis media

Semi-synthetic

  • can be added to beta-lactamase inhibitors for better gram - coverage:
    1. ampicillin + sulbactam
    2. Amoxicillin + clavulanate

not good for tx beta-lactamase producing staphylococci

skin rashes with ampicilin– 9%

51
Q

anti-pseudomonal penicillins

  • generatoni?
  • list the drug names
  • which is not avail in us?
  • MOAfor each drgu
  • indications for each drug
A

3rd/4th gen aminopenicillins

Ticarcillin (3rd gen) and Piperacillin (4th gen)

Ticarcillin not avail in US
MOA: can penetrate porin channels of gram- at high doses and resistant to beta-lactamase activity
Indications: Pseudomonas aeurginosa

Piperacillin: aka zosyn

  • Pseudomonas **
  • Klebsiella
  • enterococcus
  • Bacteriodes fragilis

Piperacillin + Tazobactam=zosyn

52
Q 
kinetics of PCNs 
-routes 
-abs
-t 1/2 
-met
eliminatin
A

route depends on whether the drug is acid stable or not

abs: usually rapid

t1/2 is SHORT

well distributed— crosses placenta and into B milk BUT cannot cross BBB unless there is inflammation present

met: kindye, liver
elimin: renal tubules,

53
Q

is dicloxacillin’s absoprtion decreased or increased with food

A

decreased

54
Q

is amoxicillin’s absoprtion decreased or increaesd with food

A

increased

55
Q

can PCNs cross BBB?

A

no, only when there is inflammation present

56
Q

what drug increases excretion and increases levels of PCNs

A

Probenecid

57
Q

adv rxns for PCNs

A

-gen well tol and SAFE compared to other abx

  • hypersensivity
  • diarhea
  • nephritis: only with methicillin
  • neurotoxicity– can lower seizure threshold
  • hematologic: piperacillin, nafcillin, Pen G—can result in decreased coagulation, monitor for cytopenias after prolonged tx
58
Q

which PCN can cause nephritis

A

Methicillin

59
Q 
General MOA for cephalosporins 
ADV rxns for cephalosporins in general 
-abs 
-excretion 
-contraindications 
-which gen is highest cross reactivity
A

-beta-lactam ABX
-Bactericidal
-cell wall inhibs closely related to structure and function of PCN
-1-4 gens
-

Adv rxn: cross reactivity with PCNs— hypersensitivy rxn 0-80%

Poorly absoproed PO– why most is given IV or IM

Excretion: kidney, EXCEPT Ceftriaxone=liver

Generally well tolerated

CONTR:
*severe PCN allg— can develop SJS, anaphy, TEN

*1st gens have the highest cross reactivity with PCN

60
Q

which is more effective against beta- lactamase producting bacteria: PCNs or Cephalosporins

A

Cephs

61
Q

first generation cephs

  • list drugs and routes
  • spectrum
  • indications
A
  • Cephalexin–PO–KEFLEX
  • Cefazolin–IV
  • Cefadroxil–PO… dont worry about this one…

spectrum: great coverage for gram+ cocci, some anaerobes and gram - rods

indiactions:
- skin and soft tissue infections : staph and strep–NOT MRSA
- surgical prophylaxsis=cefazolin

62
Q

second generation cephs
-spectrum as a class
-indications as a class
-

A

Spectrum:

  • broader gram- coverage since they are resistant to beta lactamases
  • weaker gram + coverage

Indications:
1. Cefoxitin very good coverage for Bacteroids fragilis–anaerobic gram-

  • skin infections
  • respiratory/ENT
  • UTI
  • Cefoxitin is used for anaerobic infections abdominal
63
Q

Third gen Cephs

  • list drugs and routes
  • spectrum
  • indications
  • resistance?
  • can cause?
A
  • Ceftriaxone–IM, IV
  • Ceftazidime–IM, IV +/- avibactam
  • Cefotaxime

spectrum: broader gram- coverage,
GOOD CNS PENETRATION** esp Ceftriaxone*****8
-good coverage for Serratia

Indications:

  • Ceftriaxone, Cefotaxime - DOC Bacterial meningitis, gonorrhea
  • Ceftazidime- Pseudomonas
  • added with macrolide for CAP (but hospitalized)
  • **resistance is building with this class
  • ** can lead to C. Diff
64
Q

Fourth Gen Cephs:

  • drugs and routes
  • spectrum
  • indications
A

*Cefepime (IV)

Spectrum:

  • Gram- for Pseudomonas
  • Gram + for strep and staph only methicillin susceptible organisms

indications:
* Isolated infections with pseudomonas

65
Q

Fith gen ceph:

  • drugs and routes
  • specturm
  • does not cover?
  • indications
A

Ceftaroline IV

spectrum:
* broad spectrum grm + including MRSA and gram-

DOES NOT COVER PSEUDOMONAS OR ANAEROBES

Indications:

  • hosp aquired MRSA infections–skin, CAP
  • never first line tho
66
Q 
Carbapenems 
-drugs and routes 
-MOA 
-spectrum 
-treats? 
-any dose adjustmetns? 
-
A
  • PENEMS
  • Imipenem–IV
  • Meropenem–IV +/- vaborbactam
  • ertapenem–IV, IM

MOA: beta-lactam wall inhibitor

Spectrum: tx beta-lactamase producing organisms that are resistant to other drugs BUT resistance to carbepenams is emerging

  • Broad spectrum and saved only for serious infections:
  • Gram (-)—H. influenzae, N. Gonorrhoeae, Enterobacteriaceae, Pseudomona
  • anaerobes: B. fragilis
  • Gram (+)– Enterococcus, listeria

NOT FOR MRSA or MYCOPLASMA

all need renal dosing**

67
Q

which ABX MUST MUST always be dose-adjusted for renal function?

A

Carbapenems *****

Monobactams aka Aztreonam

68
Q

Imipenem

  • inactivated where and how do we prevent this
  • spectrum?
  • adv rxns
  • avoid in tx of which dz?
A

at the renal tubules
*prevent this by adding cilastatin to it

BROAD BROAD spectrum

  • CNS toxicity–including seizures
  • AVOID IN MENINGITIS**
69
Q

Meropenem

  • adv rxns
  • indications
A

-less CNS toxicity than Imipenem

inds:
- pediatric bacterial meningitis >3 MO of age
- intraabdominal infections

NOT inactivated at renal tubule

70
Q

which carbapenem is inactivated and not inactivated at renal tubules

A

Meropenem NOT

Imipenem YES inactivated

71
Q

Ertapenem

  • t1/2
  • sepctrm
A

narrower spectrum (newer drug)

T1/2 LONG so advantage to taking this is once daily dosing

72
Q

Doripenem

A

discontinued in US

73
Q

Monobactams

  • drugs and routes
  • MOA
  • special dosing?
  • indications
  • does not tx
  • cross allergenicity with?
A

Aztreonam (IV)

  • beta lactam cell wall inhibitor– binds to penicilin-binding proteins
  • effective against gram(-) and aerobes (enterobacteriaceae, Pseudomonas)

DOES NOT work on anaerones or gram+

yes renal dosing required

-cross allergenicity with Ceftazidime

good alterntive for PCN allergy

74
Q

Vancomycin

  • routes
  • MOA/structure
  • spectrum/indications
  • adv rxns
A

IV, PO

*glycopeptide that binds to peptidoglycan precursors–interferring with polymerization and cross linking requried for stable bacterial cell wall

Spectrum:

  • Gram + only
  • mostly staphlyococci and streptococci–BACTERICIDAL
  • bacteriostatic for enterococci

Indications:

  • MRSA***** IV also bacteremia/sepsis, pneumonia
  • C Diff ***** PO

ADV RXN:

  • Vancomycin flushing syndrome aka red man syndrome
  • flushing
  • erythema
  • pruritis of face/neck–>goes to lower body
  • rarely cause cardiovascular collapse
  • due to rapid infusion rates
  • thrombophlebitis
  • Nephrotoxicity–always check renal functions and check troughs
75
Q

Lipoglycopeptides

  • drugs
  • MOA
  • ____ dependent
  • potency compared to vancomycin
  • spectrum
  • adv rxn
  • t 1/2
A
  • Telavancin
  • Olivanic–inferes with cell wall synthesis
  • Dalbavancin
  • Bactericidial
  • concentration dependent
  • more potent than vancomycin

Spectrum: gram+

  • staphylococci
  • streptococci
  • VRE
  • MRSA
  • VRSA

ADV RXN:
*Telavancin– nephrotoxicity, teratogeniciy, coagulation disturbance, prolonged QTc

t 1/2 of Oritavancin and Dalbavancin– very long half lives=— 200 hours!!

76
Q

Daptomycin

  • rotue
  • MOA
  • spectrum
  • cannot tx?
  • adv rxn
A

IV

Cyclic lipopeptide causes rapid depol of the cell membrane and inhibits DNA, RNA and protein synthesis

Bactericidal and [ ] dependent

SPectrum:

  • gram+
  • MRSA
  • VRE (vancomycin resistant enterococci)
  • Skin infections
  • bacteremia

Do not use for pneumonia bc it is inactivated by pulmonary surfactant

ADV RXN:

  • elevated transaminases
  • myalgia
  • rhabdomyolysis
77
Q

Fosfomycin

  • routes
  • MOA/structure
  • bacteriostatic or cidal?
  • inds
  • dosing?
  • abs?
  • distrubtion
  • ADV rxn
A

PO, IV

Phosphonic acid derivative, inhibits peptodoglycan synthesis needed for bacterial cell wall synthesis

bactericidal

INDS:
-UTIs caused by E. coli and E. Faecalis
SINGLE DOSE

abs: rapidly
distributed: kidneys well

ADV RXN

  • gen well tol
  • diarrhea/nausea
  • vaginitis
  • HA
78
Q

Polymyxin B

  • routes
  • moa
  • spectrum and inds
A

IM, IV, topical

  • *IV: great risk of nephrotoxicity and neurotoxicity
  • *topical not abs in GI tract

MOA: cation polypeptide binds to lipopolysaccharide membrane of gram-
*causing cell contents to leak out— cell death

Spectrum:

  • narrow: primarily gram- organisms
  • Hops acquired multi-drug resistance organisms (i.e resistance to carbapenems)—-PSEUDOMONAS, ACINETOBACTER
  • topical is MC used–ophthalmic
79
Q

adv rxn to Telavancin

A

nephrotoxicity, teratogeniciy, coagulation disturbance, prolonged QTc

80
Q

-vancin

A 
Lipoglycopeptides 
*televancin 
*olivanic 
*delevancin
gram+ coverage

Pharmacology (28 decks)

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