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Pharm test #3 > vancomycin, linezolid, and daptomycin > Flashcards

vancomycin, linezolid, and daptomycin Flashcards

1
Q

vancomycin belongs in which family of drugs

A

glycopeptides

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2
Q

glycopeptides affect what types of bacteria

A

gram + aerobes and some anaerobes

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3
Q

how does vancomycin work

A

inhibits cell wall synthesis by binding D-alanyl-D-alanine portion of cell wall precursors to
prevent cross-linking and further elongation of peptidoglycan

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4
Q

how can cells confer resistance to vancomycin

A

i. Resistance in VRE and VRSA due to modification of D-alanyl-D-alanine
binding site of peptidoglycan
ii. Terminal D-alanine replaced by D-lactate
iii. Loss of critical hydrogen bond
iv. Loss of antibacterial activity
v. 3 phenotypes - vanA, vanB, vanC
vi. VISA – thickened cell wall

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5
Q

vancomycin spectrum of activity

A

i. Gram-positive bacteria - Methicillin-Susceptible AND MethicillinResistant
S. aureus and coagulase-negative staphylococci*
ii. Streptococcus pneumoniae (including PRSP), viridans streptococcus, Group streptococcus, Enterococcus spp.
iii. Corynebacterium, Bacillus. Listeria, Actinomyces Clostridium spp. (including C. difficile), Peptococcus, Peptostreptococcus
iv. No activity vs gram-negative organisms

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6
Q

clinical uses

A

i. Infections due to methicillin-resistant staph including bacteremia, empyema, endocarditis, peritonitis, pneumonia, skin and soft tissue
infections, osteomyelitis, meningitis
ii. Serious gram-positive infections in -lactam allergic patients
iii. Infections caused by multidrug resistant bacteria (PRSP)
iv. Endocarditis or surgical prophylaxis in select cases
v. Oral vancomycin for moderate to severe C. difficile colitis

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7
Q

when do you give vancomycin orally

A

for C. difficile (not absorbed well so it stays in the gut/colon)

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8
Q

Red-Man Syndrome

A
  • due vancomycin administration
  • Flushing, pruritus, erythematous rash on face, neck, and upper torso within 5 to 15 minutes of starting infusion due to Histamine release from mast cell degranulation;
  • Related to RATE of intravenous infusion;
  • Resolves spontaneously after discontinuation
  • May lengthen infusion (over 2 to 3 hours) or pre-treat with antihistamines in some cases
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9
Q

Nephrotoxicity and Ototoxicity with vancomycin use

A
  • Rare with vancomycin monotherapy, more common when administered with other nephro- or ototoxins , such as aminoglycosides
  • Risk factors include renal impairment, prolonged therapy, high doses, ? high serum concentrations, use of other nephro- or ototoxins
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10
Q

adverse effects of vancomycin use

A
  • red man syndrom
  • nephrotoxicity and ototoxicity
  • Dermatologic - rash (later onset)
  • Hematologic - neutropenia and thrombocytopenia with prolonged therapy
  • Thrombophlebitis – related to rate of infusion. Recommend slow infusion at least over 60 minutes.
  • interstitial nephritis
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11
Q

old name for vancomycin

A

mississippi mud - had a brown color - purification lead to less adverse effects

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12
Q

main uses for vancomycin

A

MRSA and PRSP

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13
Q

is vancomycin bactericidal or static

A

time dependent bactericidal except for enterococcus which it is bacteriostatic

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14
Q

timing of vancomycin effects

A

can take days after beginning therapy to see the effects clinically

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15
Q

vancomycin elimination

A

unchanged via the kidney

1/2 life depends on renal function normally 6-8 hr but can be very very long with renal disease

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16
Q

vancomycin absorption and distribution

A

slow - peak concentrations are measured 1 hr after infusion

not absorbed well orally

widely distributed to all tissues - variable CSF penetration but increased when inflamed (used for strep pneumo menigitis)

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17
Q

Dalbavancin belongs to which drug group

A

2nd generation gycopeptide

A semisythetic lipoglycopeptide.

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18
Q

Dalbavancin mechanism of action

A

binds to C terminal D-ala-D ala interfering with cross-linkage and polymerization.

•It can attach (anchors) to the cell membrane from its lipophilic moiety, making it more potent than vancomycin*

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19
Q

Dalbavancin is used against

A

resistant gram + bacteria
MRSA, VISA
VRE with the vanB or vanC gene
MRSE (epi), streptococcus

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20
Q

how is dalbavancin given?

A

via IV with once a week dosing
half life is 9-12 days

(decrease dose with renal insufficiency)

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21
Q

dalbavancin side effects

A

Hematologic, headaches
Pruritus, anaphylaxis, skin reactions
Increased ALT
Flushing with rapid infusion (red man syndrom)

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22
Q

telavancin is used for

A

MRSA and GPOs (resistant gram + organisms

SSSI, HAP, VAP (all S. aureus

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23
Q

telavancin toxicity

A

higher renal toxicity than vancomycin

shown to be teratogenic in animals

24
Q

telavancin delivery

A

IV only

25
Q

Oritavancin used for

A

MSSA, MRSA, enterocococcus, strep

possible some bacillus anthacis

26
Q

oritavancin mechanism of action

A

disrupts cell membrane and cell well

27
Q

oritavancin dosing

A

IV - single dose

28
Q

oritavancin belongs to which group

A

semisynthetic glycopeptide (for GPOs)

29
Q

what drug is an Oxazolidinones

A

Linezolid

30
Q

Mechanism of Action of Linezolid

A

Binds to the 50S ribosomal subunit near the surface interface of 30S subunit – causes inhibition of 70S initiation complex (unique binding site), **which inhibits protein synthesis

• Bacteriostatic (bactericidal against Strep pneumoniae)

31
Q

Linezolid dosing

A

same given IV or orally

has a 100% bioavailability when given orally

32
Q

linezolid is used for

A
  • Methicillin-Susceptible, Methicillin-Resistant AND VancomycinResistant Staph aureus* and coagulase-negative staphylococci
  • Streptococcus pneumoniae (including PRSP*), viridans streptococcus, Group streptococcus
  • Enterococcus faecium AND faecalis (including VRE)*
  • Bacillus. Listeria, Clostridium spp. (except C. difficile), Peptostreptococcus, P. acnes

no gram neg activity

33
Q

linezolid elimination

A

both renal and non-renal

* adjustment is NOT needed for renal insufficiency

34
Q

clinical uses for linezolid

A

VRE bacteriemia (NOT UTIs)
nosocomal pneumonia due to MRSA
comilicated skin and soft tissue infections due to MRSA, MSSA, or strep pyrogens

35
Q

drug interactions with linezolid

A

interacts with adrenergic or serotonergic agents

enhances the pressor response to Epi and dopamine

  • serotonin syndrome with SSRIs and MAOIs
    • hyperpyrexia, diarrhea, cognitive dysfunction, restlessness, seizures, coma (may need 2 week washout period before starting linezolid)
36
Q

adverse effects of linezolid

A

GI- lactic acidosis
Headache
peripheral neuropathy
**Thrombocytopenia (platlets drop- most often after 10 days) or anemia

37
Q

Tedizolid advantages

A

can be given IV or Oral, more potent than linezolid, no SSRI interaction**

38
Q

Tedlizolid uses

A

Staph, strep, enterococcus, skin and skin structure infections

39
Q

adverse effects of Tedlizolid

A

headache, dizzy
hematologic (similar to linezolid)
neuropathy (peripheral and optic) (linezolid)

40
Q

Daptomycin belongs to which drug group

A

lipopeptides

41
Q

Daptomycin struture

A

very large molecule

42
Q

Daptomycin is used for

A

resistant gram +ives –VRE, MRSA, VISA

43
Q

Mechanism of Action of daptomycin

A

Binds to bacterial membranes causing rapid depolarization of membrane potential, inhibition of protein, DNA, and RNA synthesis

concentration dependent bactericidal activity

44
Q

daptomycin resistances

A

rare in VRE and MRSA but can be due to altered cell membrane binding

45
Q

Daptomycin spectrum of activity

A

gram +

MRSA, VISA, VRE

46
Q

daptomycin distribution

A

only available IV

distributed into well profused tissue

47
Q

daptomycin elimination

A

mainly kidney - dose needs to be adjusted based on kidney function

48
Q

daptomycin in inactivated by

A

surfactant - therefore do not give for pneumonia

49
Q

MRSA pneumonia treatment

A

vancomycin or linezolid (NOT daptomycin)

50
Q

adverse effects of daptomycin

A 
GI
headache
injection site reaction
rash
**myopathy and CPK elevation
51
Q

daptomycin drug interactions

A

HMG CoA-reductase inhibitors - may lead to increased incidence of myopathy

52
Q

Quinupristin-Dalfopristin (aka synercid)

A

individually they are static but together they have a cidal effect on bacteria

53
Q

Quinupristin-Dalfopristin (aka synercid) mechanism

A
  • dalfopristin enhances binding of quinupristin. Inhibits peptidyltransferase
  • quinupristin prevents elongation of the pp chain and coauses incomplete chain release
54
Q

Quinupristin-Dalfopristin (aka synercid) elimination

A

cleared by the liver

55
Q

Quinupristin-Dalfopristin (aka synercid) adverse effects

A

server GI intolerance – not tolerated well

56
Q

Quinupristin-Dalfopristin (aka synercid) spectrum of activity

A

gram positive resistant bacteria – end of the line if nothing else works

Pharm test #3 (17 decks)

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