Kardiopii_Pharma_Cysticfibrosisdrgs

Front 1

What are the 2 most common Bacterial Infxs in CF Patiants (CFPT)

Back 1

Pseudomonas Aeruginosa - 53%
S. Aureus - 64% - MRSA 19%

Front 2

What are 2 other Bact. Ifxns

Back 2

Burkolderia cepacia
Stenotrophomonas meltophilia
--both hard to treat and cause death

Front 3

Which infection is more chronic in CFPTs after adolescent

Back 3

P. aerugenosa 70%
surpasses staph at at adolescense

Front 4

What type of bug is pseudomonas

Back 4

Gram neg bacilli

Front 5

Which 2 Beta -Lactam groups and Protein Syn Ibx group have drugs that are anti-pseudomonal

Back 5

1. Penicillins
2. Cephaloporins

3. Amionglycoside (30S Ibx)

Front 6

What are the beta-lactam antipseudomonal drugs used for:
Pens?
Cephs?
Aminoglycs?

Back 6

1. Penicillins: Piperacillin, Ticarcillin (carbenacilllin old/obsolete)
2. Cephaloporins: Ceftazidime 3rd gen, Cefepime 4th
3. Aminoglycosides: Tobramycin

Front 7

For the B-Lacts Anti-Pseud Drgs, what are the AEs for each group
1. Penicillins
2. Cephaloporins
3. Amionglycoside

Back 7

1. Pens: Hypersensitivity, diarrhea, colitis
2. Cephs: Hypersensitivity, diarrhea, colitis
3. AminGlyc: Nephro & Oto Toxicities

Front 8

why are Gram negs harder to treat with antibiotics?
consider beta lacts and PR syn ibx

Back 8

Outer membrane is very hydrophobic and drug must go through Porin (hydrophillic) that puts them in contact with Peptidoglycan
--PR Syn drugs have to further go in through Transporter of PM to get inside, this is O2 dependent, thus with Anaerobics, PR Syn Inb drugs wont work

Front 9

What must Piperacillin, Ticarcillin, Cefepime, Ceftazidime do before they can disrupt the cell wall integrity

Back 9

Bind to PBPs
Penicilin Binding Prs

-Tobromyocin must go inside PM via transporter--requires 02

Front 10

What feature of Piperacilin allows it to both penetrate Outer Mem and build up in quatity that is not a feature of Narrow Spec Pens like Penicillin G/why they DONT' work in Gram Negs

Back 10

Piperacillin (and other modified pens) have Hydrophillic R group which is ionizable and CAN traverse porins to get through outer membrane. (pen G cannot sufficiently get through outer membrane fo gram negs)

Front 11

How does cefepime achieve gram neg activty

Back 11

has quarternary amine, always charged/soluble and hydrophillic enough for Porins,
Also, bad substrate for Beta-Lactamases too, so work on Staphs

Front 12

Which drug is most strongly anti-pseudomonal?
What is it often combined with?

Back 12

Tobramycin (aminoglyc)
--combined with anti-pseud penicillins: piperacillin
-3rd/4th cephs: ceftazidime/Cefpime
-Carbapenem: imipenem/meropenem (not ertapenem)
----dont worry too much about this one
--if resist to Tobra, use amikacin

Front 13

For what Dx is an aminoglyc + pen used together?

Back 13

Synergy Therapy for Endocarditis: gentamicin + pen

-In CF, no synergy effect, but may prevent development of Multi-Drug Resistance (same grounds for TB treatment)

Front 14

For anti-pseudomonal CFPT, how is Tobramycin best used for bactercidal effect?
How is toxicity determined

Back 14

Conc Depen/Hammer, how high peak concentration works--ie bolus injection. single daily dose/ renally cleared
Toxi: short exposure to high levels is best, saftey determined by time below host toxicity threshold, need to be below this level for 12+ hours (ie, less then 12 + hours at high conc)

Front 15

How are Piper, Ticar, Cefe and Cefta best administered for Anti-Psued

Back 15

Time above MIC ensures efficacy
--ie, for the pens, maintain a certain level for extended period of time

Front 16

Mechanisms for bug to have resist to Aminoglycs/Pens/Cephs

Unique for Pens/Cephs with Pseudomonas?

Back 16

Lowered permeability, fewer porins

For Pens/Cephs---altered PBPs
---NOT conferred by overproduction of B-Lactamase in Pseudomonas---that IS the mech for Staph Resis

Front 17

What sort of EnzymaticMods can be used by Pseudomonas on Aminoglycs (tobramycin)

Back 17

Acetylation, Phosphorylation, Adenylation of drug

Front 18

What is unique to pseudomonas coloniization versus infection

Back 18

earlier in life of CFPT, have intermittant infxns, ie, lungs are NOT colonized, so treat (as described above with IVs)
Later in life, they begin to have colonizaiton of pseudomonas and there will be biofilms
--Chronic infextion requires different therapies

Front 19

How are chronic pseudomonal infxns treated

Back 19

Aerosolized Tobramycin
Oral Azithromycin (macrolide)
Aerosol DNA Nuclease (dornase)

Front 20

What are the benefits of the following chronic pseudomonal therapy:
Aerosolized Tobramycin
Oral Azithromycin (macrolide)
Aerosol DNA Nuclease (dornase

Back 20

-Aerosol Tobra: locally effective=low toxicity systemically
-Oral Azithro: has Anti-Inflam property in add to Broad Spec Antibiotic
-DNAse: Mucolytic, degrades neutrophils' dna --an Adjuvant Therapay--ie, effects environment, not infxn

Front 21

Which 3 CF drugs are aerosolized?

Back 21

-Tobramycin, Colistin, Dornase (dnase)
--note: about 25x Aminoglyc higher MIC given for aerosolized

Front 22

What sort of drugs is Azithromycin (same family as erythromycin

Back 22

-50S Ribosomal PR Syn Inbx
-Macrolide
-Broad Spectrum & Atypical organisms
-0ral bioavail-good,
-Biliary Excretion

Front 23

What is unique feature for Azithromycin for Pseudomanl therapy?

Back 23

Azithro CONCENTRATES in Sputum ~ 10-100x higher than plasma
--Prevents biofilm formation
-Anti Inflam effects by suppressing some cytokines
--allows healing

Front 24

What drug is reserved for severe cases of MDR Pseudomonas?

Back 24

Colistin (IV)---only therapeutic option
-binds to LPS and disrupts outer membrane
-has Ototox & Neprhotoxicity--watch CrCl--for dose adjustment

Front 25

What is first question for Staph A. infxn for CFPT?

Back 25

is it MSSA (meth sensitive)
or MRSA--requires Vanco

-Generally, though not all, most/correct answer is that all Staph Infxns are Pen G/V resistant (narrow spec)

Front 26

What sort of drug is Vancomycin?
MOA?

Back 26

NOT a beta-lactam--ie not susceptable for b-lactamase
--IS a Bucket 1/Ibx Cell Wall Syn
---blocks elongation of cell wall
---IS Bactericidal

Front 27

What if Staph CFPT has MRSA that doesnt respond to Vanc (VRSA)?
What drug is called for
What type of drug is it?

Back 27

Linezolid (an Oxazolidinone)
--bacterioSTATIC
--Bucket 2, PRot Syn Ibx

Front 28

What is MOA for Linezolid

Back 28

Binds to 50S Subunit of Ribosome
--disrupts Peptidyl Transferase Center---esp in Mitos

Front 29

Clearance and AEs of Linezolid

Back 29

Renal Clearance: NOT a CYP450
AEs
--so long term use has inc. ALT (??)
--decrease Platelets, MAO interaction, Peripheral Neruopathy

Front 30

What does MSSA indicate about bug?

Back 30

Secretes B-lactamases

MRSA - may secreat lactamases, but Mainly means it has altered PBProts. = Vanco

Front 31

Is Vanco used for MSSA

Back 31

ehh. for MSSAs, do use a b-lactam (vanco is not), they will work better for MSSAs

Front 32

What is therapy for MSSA in CFPT who also has Pseudomonas

Back 32

Ticarcillin-Clavulanate (ibx b-lactamases) tica kills
Piperacillin-tazobactam (same as above, but Piper kills bugs)

Front 33

If Pseudomonas is Not Resistant, treat with what

Back 33

Piperacillin, Ticarcillin

Front 34

If Pseudomonas is Not Resistant, but PT has coinfection with MSSA OR MRSA

Back 34

Cant use Piper/Tica (MSSA inactivates, MRSA has altered PBPs)

Front 35

What is therapy for NON-Res Pseudomonas + MSSA

Back 35

Piperacillin (pseudom) + Tazobactam (ibx lactamase)
--Piper will kill MSSA with Tazobactam

--Same reasoning with:
Ticarcillin + Clavulanate

Front 36

What drugs are added to to make Penicillin drugs more efficacious in Pseudo + MSSA

Back 36

Clavulanate or Tazobatam are added to the Pencillin (not V or G)

Front 37

What is therapy for MSSA with OR without a NON-Res Pseudomonas

Back 37

same as if there were a Non-Res Pseudo
--Piperacillin + Tazobactam
--Ticarcillin + Clavulanate

Front 38

List drugs that a "Pen Resistant" Staph A is resistant to?

Back 38

Pen G/V
Ampicillin, Amoxicillin
Ticarcillin, Peperacillin (unles Clavu/Tazobactam added)

Front 39

What are drugs to Staph A that IS "Pen" Resistant, but Methicillin Sensitive (MSSA)?

Back 39

Previous drugs + lactamase ibx (except for Pen V/G)
=Ampi-sulbactam, Amoxi-clavul
Ticar-clavul, Piper-tazo
PLUS
Oxacillin, Cloxacillin, Dicloxacillin, Nafcillin

Front 40

What is drug for Burholderia cepacia

Back 40

Colistin, but OFTEN resistant to it
--some TRY Sulfamethoxazole-trimethoprim
with little success