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Therapeutics P3 Spring > Exam 2 lecture 3 > Flashcards

Exam 2 lecture 3 Flashcards

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1
Q

Name the gram positive antibiotics

A

Vancomycin
Quinupristine-dalfopristine
Linezolid
Tedizolid
Daptomycin
Telavancin
Dalbavancin
Oritavancin

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2
Q

Why has the use of vancommycin increased over the past decades

A

Due to the emergence of MRSA and PRSP

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3
Q

What does the large structure of vanc entail

A

Cant be absorbed orally
Cant get into CNS
Does not get removed by hemodialysis membrane

These are common to the otehrs aswell

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4
Q

Vancomycin MOA? bacteriostatic/bactericidal?

A

Inhibits cell wall synthesis at site different than B lactams

It inhibits synthesis and assembly of second stage of cell wall synthesis by binding to D ala D ala on cell wall and preventing cross linking

Time dependent bactericidal activity, slowly kills bacteria (static against enterococcus)

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5
Q

How fast/slow is vanc

A

SLOWEST DRUG is vanc

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6
Q

Mechanism of resistance of vanc

A
  1. Resistance in VRE and VRSA is due to modification of D ala D ala binding site of peptidoglycan. D ala replaced by D lactate. Led to loss of critical H bond and loss of antibacterial activity.
  2. VISA (vancomycin intermediate staph aureus)- They had thickened cell wall
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7
Q

What are the phenotypes that confir resitance to vancomycin (exam)

A

van A is the most important

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8
Q

Spectrum of activity of vancomycin

A

Gram positive bacteria (aerobes and some anaerobes)
-Streptococcus (group, viridians, pneumonia) including PRSP*
- MRSA* and MSSA*
- C diff* and clostridium spp

  • no activity against gram negatives
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9
Q

What should we use in the case of a serious MSSA infection

A

B lactam (nafcillin/cefazolin)

Only used vanc if we have to bc it is a slow killer

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10
Q

Vanc is THE drug of choice in what disease

A

MRSA

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11
Q

What are target organisms for vancomycin

A

MRSA, MSSA, PRSP and c diff

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12
Q

What is the drug of choice for C diff

A

Vancomycin (oral)

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13
Q

What group does vancomycin show synergy with? Give an example

A

Aminoglycoside synergy

Gentamycin + vanc used together

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14
Q

What formulations does vancomycin come in? How is it used

A

Oral and iV

HORRIBLE oral absorption, but we use this to our advantage to target patients with C diff (collitis)

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15
Q

Important point to know about distrubution of vancomycin

A

Takes one hour to distrubute form plasma into tissue compartment (take that into account when looking at pak as it will be falseky elevated)

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16
Q

How is vanc eliminated? half life?

A

Eliminated by kidney

half life depends on renal function

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17
Q

How is hemodialysis going to affect vanc

A

Removed by hemodialysis (30-40% removed per hemodialysis sessions)

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18
Q

When should the peak be drawn for serum concentration in patients on vanc? trough? Target AUC/MIC?

A

60 mins after end of infusion (target 30-40)

Trough- prior to next dose (10-15)

Target AUC/MIC= 400-600

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19
Q

clinical uses of vancomycin (exam)

A

infections due to MRSA (THE DRUG OF CHOICE EXAM)

serious gram positive infection in B lactam allergic patients

PRSP (target organism EXAM)

ORAL vancomycin for C diff collitis (EXAM)

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20
Q

adverse effects of vancomycin (exam)

A
  1. Red man syndorme (AKA red neck syndorme)

Related to RATE of IV infusion, no faster than 15 mg per minute

5-15 mins after infusion
Pretreat with antihistamine
We can give it again if we lengethen infusion

  1. Nephrotoxicity and ototoxicity (rare with monotherapy, more common when administered with other nephro/oto agents)
  2. Thrombophlebitis, interstitial nephritis
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21
Q

What are some risk factors for nephro/ototoxicity with vancomycin (exam)

A

IT is reversible
Risk factors- renal impairement, prolonged therapy, high doses, high serum concentrations, use of other nephro/oto toxic agents

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22
Q

What is synercid a combination of? WHat kind of drug was it?

A

Quinupristine/dalfopristine

It is a streptogramin

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23
Q

What was synercid developed for

A

developed bc of need for antibiotics with activity aganst resistant gram positive bacteria, namely VRE

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24
Q

ROA synercid? CNS action? Hemodialysis removal

A

TOO big for oral

No CNS

Not removed by hemodualysis membranes

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25
MOA of synercid? Where does it bind? Bacteriostatic/cidal?
Each agent acts individually on 50S ribosomal unit t inhibit early and late stages of protein synthesis Binds to 50s ribsosme near site where macrolides and clindamycin bind bacteriostatic (may be cidal against some bacteria)
26
Mechanism of resistance of synercid
alteration in ribsosme binding site Enzymatic inactivation
27
spectrum of activity of synercid
Gram positive bacteria -ENterococcus Faecium* ONLY -PRSP* -MSSA and MRSA - Coagulase negative staphylococcus
28
What is one of the short comings of synercid
ONLY works on VRE enterococcus faecium, VRE enterococcus Faecallis
29
is synercid time dependent of concentration dependent? Distribution?
Time dependent bactericidal MINIMAL CSF PENETRATION
30
When do we need to adjust synercid
Not in renal but in hepatic
31
Clinical use of synercid
VRE (faecium) bacterium where we can not use linezolid or daptomycin
32
drug interactions of synercid (exam)
3A4 inhibitor HMG CoA reductase (lovastatin, simvastatin, atorvastatin) cyclosporin carbamezapine
33
adverse effects of synercid
Venous irritation (only use central vein) (66%) Myalgias, arthralgias (22%)
34
What are oxazolidinone drugs? ROA?
Linezolid and tedizolid PO and IV
35
What is the reason they developed linezolid
needed for antibiotics with activity against resistant gram positives (VRE, MRSA, VISA) also is effective against enterococcus faecium and Faecalis
36
MOA of linezolid
Bind to 50S ribosomal subunit near surface of 30S subunit (unique binding site). Causes inhibition of 70S initiation complex
37
Are oxazolidinones bacteriocidal or bacteriostatic
Bacteriostatic (cidal against some)
38
Mechanism of resistance of oxazolidinones
Alteration in ribosomal binding site (rare) Cross resistance with protein synthesis inhibitors is unlikely
39
spectrum of activity of linezolid and tedizolid
Gram positive bacteria Group, viridians and pneumoniae streptococcus (including PRSP*) - enterococcus faecium AND faecalis (including VRE)* - MSSA, MRSA and VRSA*
40
For MSSA, what do we use before linezolid? MRSA?
Linezolid is bacteriostatic so we use other drugs before it. MSSA- nafcillin, cephazolin and Vanc MRSA- Vancomycin, dapto
41
What are linezolid and tedizolids oral bioavailability? CSF penetration? eliminated by? Renal adjustment?
91% tedizolid and 100% linezolid Linezolid CSF penetration= 30% Removed renally and non renally No renal adjustments removed by HD
42
Clinical use of linezolid/tedizolid
- reserved for serious/complicated infections caused by resistant gram positive bacteria - VRE bacteremia or UTI - Nosocomial pneumonia due to MRSA and serious infections due to MRSA
43
drug interactions of linezolid and tedizolid
Serotonin syndrome with SSRIs/SNRIs
44
adverse effects of linezolid and tedizolid
Optic and peripheral neuropathy Thrombocytopenia or anemia most often with prolonged tx
45
Name lipopeptide drug? Why was it developed
Daptomycin Developed bc of the need for antibiotics with activity against VRE, MRSA, VISA
46
How big/small is daptomycin? How does this affect the ROA? does it get into CSF? Hemodialysis removal?
Huge molecule, not oral No CSF or HD removal
47
MOA of daptomycin? Time or concentration dependent? Static or cidal?
Binds to bacteria and inserts lipophilic tail into cell wall to form trans membrane channel. Causes leak of cellular contents. Concentration dependent bactericidal activity
48
mechanism of resistance of daptomycin
Rarely reported in VRE and MRSA due to altered cell membrane binding
49
spectrum of activity of daptomycin
Gram positive -Group, viridians, pneumo Strep (PRSP*) -Both enterococcus faecium and facialis* (including VRE) - MSSA, MRSA and VRSA*
50
elimination of daptomycin? Would dosage adjustment be required?
Excreted primarily in kidney Dosage adjustments required in presence of RI
51
clinical uses and dosing of dapotmycin? When should it not be used?
Reserved for serious/complicated infections caused by resistant bacteria 6 mg/kg/day Daptomycin should not be used in tx of pneumonia and left sided endocarditis
52
adverse effects and drug interactions of daptomycin
-myopathy and CPK elevation <2% - Acute eosinophilic pneumonia Drug i/a - HMG CoA reductase inhibitors (statin) may lead to increased myopathy
53
Why were lipoglycoeptides developed? What are the drug names?
lipoglycopeptides were developed to address the need for antibiotics with activity against VRE, MRSA, VISA Televancin Dalbavancin Oritavancin
54
How big/small are lipoglycopeptides? How does this affect ROA? CSF penetration? HD removal?
Huge Not available orally Not getting into CSF Not removed by HD
55
Mechanism of action of lipoglycopeptides? Time/concentration dependent? Bacteriostatic/cidal?
All 3 interfere with polymerization and cross linking of peptidoglycan by binding D ala D ala Televancin and oritavancin can bind to bacterial membranes and insert lipophilic tail to form transmembrane channel. leakage. COncentration dependent bacteriocidal activity
56
mechanism of resistance of lipoglycopeptides (televancin oritavancin dalbavancin)
Alteration in peptidoglycan terminus (oritavancin still maintains activity)
57
Spectrum of activity of lipoglycopeptides
Gram positive - group, viridians and pneumoniae strep Enterococcus AND faecalis * MSSA, MRSA and VISA*
58
Some strains of enterococcus faecalis and faecium are resistant to which lipoglycopeptides
televancin and dalbavancin
59
How are lipoglycopeptides eliminated? Which ones need dosage adjustments and which ones dont?
Televancin- excreted by kidneys. Dosage adjustment needed Dalbavancin- 33% unchanged in urine, dosage adjustment needed Oritavancin- ONLY ONE no adjustment needed
60
clinical uses of lipoglycopeptide
serious/complicated infections caused by resistant bacteria
61
What are some interactions lipoglycopeptides have?
Televancin and oritavancin interfere with coagulation tests (PT, INR, aPTT) by binding to artificial phospholipid surfaces
62
Adverse effects of lipoglycopeptides? Black box?
Televancin- Nephrotoxicity, QTc prolongation, taste disturbances All- Infusion related rxn (red man) Televancin black box warning on use during pregnancy.
63
What is drug of choice for unfections due to MRSA
Vancomycin
64

Therapeutics P3 Spring (33 decks)

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