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Block 6 Week 2 > Pharmokinetics II > Flashcards

Pharmokinetics II Flashcards

1
Q

How does vancomycin act?

A

it inhibits proper cell wall synthesis in gram-positive bacteria.

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2
Q

When do you use vancomycin?

A

for treatment of serious or severe infections cused by methicillin resistant (beta-lactam resistant) staphylococci

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3
Q

Vancomycin is primarily effective against (blank)

A

gram-positive cocci

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4
Q

Staph aureus and staph epidermis including (MRSA and MRSE) are usually sensitive to vancomycin with MIC less than (blank).

A
  1. 5 mcg/ml

* most strains of strep are sensitive to vancomycin*

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5
Q

(blank) is an event occurring in 2% of patients receiving vancomycin. Toxicity is associated with both high peak and trough levels although a minimal toxic level has not been clearly established

A

Ototoxicity

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6
Q

In vancomycin what can happen if you adminster it by IV to quickly and reach peak serum concentration?

A

you can get a histamine-mediated reaction called “red man syndrome” involves a rash over the upper body somtimes accompanies by hypotension

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7
Q

How do you prevent red man syndrome?

A

dilute solution to less than 10 mg and minutes for 60 minutes

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8
Q

Higher vancomycin doses carry a substantial risk for (blank). How much is too much?

A

nephrotoxicity

greater than 4 grams a day

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9
Q

Who are at particular risk for vancomycin-induced nephrotoxicity?

A

critically ill patients receiving concomitant nephrotoxic agents (aminoglycosides) and patients with already compromised renal function (CLcr <60 ml/minute)

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10
Q

In medicine, a (blank) level is the lowest level that a medicine is present in the body. In a medicine that is administered periodically, the trough level should be measured just before the administration of the next dose in order to avoid overdosing. It should be contrasted with a (blank), which is the highest level of the medicine in the body, and the “average level”, which is the mean level over time. It helps in therapeutic drug monitoring. It’s widely used in clinical trials for newer medicines for its therapeutic effectiveness and safety.

A

trough

peak level

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11
Q

When is the risk for vancomycin toxicity incrementally higher?

A

with higher trough levels and longer duration of vancomycin use

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12
Q

Vancomycin has a kill rate that is (blank) as long as the concentration is above the MIC.

A

concentration-independent

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13
Q

What is the post-antibiotic effect like for vancomycin?

A

intermediated -> therefore serum levels may be allowed to drop below the MIC for a short period

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14
Q

How should you use vancomycin?

A

max exposure time during which the plasma conc. exceeds MIC

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15
Q

What is the ideal dosing regimen for vancomycin?

A

max amount of drug recieved. 24-AUC/MIC ration correlated with efficacy. A 24h AUC/MIC ratio of greater than 125 is necessary (greater than 400 for problem bugs)

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16
Q

When given vancomycin by IV infusion over 60 minutes, vancomycin follows a (blank) comparment pharmacokinetic model.

A

2

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17
Q

When given by IV infusion over 60 minutes, vancomycin follows a 2-compartment pharmacokinetic model; alpha (distribution) and beta (elimination); (blank) is relatively long, averaging two hours.

A

alpha

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18
Q

When should you check for peak serum levels when giving someone vancomycin via IV?

A

during the elimination phase

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19
Q

(blank) for vancomycin is highly variable (0.2 -1.5 L/Kg) making treatment difficult

A

Vd

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20
Q

Can you predict Vdfor vancomycin?

A

No

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21
Q

How is vancomycin primarily cleared?

A

by glomerular filtration

22
Q

Correlation of vancomycin clearance to creatinine clearance typically gives vales for slope of between (blank) and (blank) and y intercept of up to (blank)

A

0.5 and 0.8

15 ml/min

23
Q

There is a strong correlation between vancomycin (blank) and (blank)

A

clearance

creatinine

24
Q

What is a standard dose of vancomycin?

A

500 mg/ 6 hr

25
Q

The terminal elimination half-life of vancomycin is prolonged and the total body clearance is reduced in patients with (blank)

A

impaired renal function.

26
Q

How do you change a drug dose if it is too high?

A

hold the next dose long enough to allow the trough level to drop down to normal then decrease the maintenance dose but dont make a 100% change

27
Q

(blank) have bactericidal activity against most gram-negative bacteria including Acinetobacter, Citrobacter, Enterobacter, E. Coli, Klebsiella, Proteus, Providencia, Pseudomanas, Salmonella, Serratia and Shigella.

A

Aminoglycosides

28
Q

The MIC’s of gram negative bacteria are usually less than (blank) for gentamicin and tobramycin and (blank) for amikacin

A

2 mcg/ml

8 mcg/ml

29
Q

Aminoglycosides are associated with (blank) and (blank), both of which are associated with elevated trough levels and sustained elevated peak levels.

A

nephrotoxicity

ototoxicity

30
Q

What is the average Vd of aminoglycosides in healthy adults?

A

0.26 L/Kg (range: 0.2-0.3)

31
Q

Do aminoglycosides distribute into adipose tissue?

A

no but it does distribute into extracellular adipose fluid

32
Q

Obese patients require a correction in the weight used for Vd calculation. T or F

A

T
LBW + 40% of weight above LBW.
LBW-lean body weight

33
Q

Patients with cystic fibrosis have an increased Vd of (blank) due to increases in extracelular fluid.

A

0.35 L/kg

34
Q

Patients with ascites have additional extracellular fluid which increases the Vd to approx. (blank)

A

0.32 L/kg

35
Q

ICU patients may have a Vd (blank) above norma

A

25-50%

36
Q

T or F

Aminoglycoside elimination exhibits a close linear correlation with creatinine clearance.

A

T

37
Q

CF patients show a (blank) increase in elimination rate of aminoglycosides

A

50%

38
Q

A major body burn increases the (blank) resulting in a MARKED increase in aminoglycoside elimination

A

basal metabolic rate

39
Q

(blank) can cause permanent vestibular and/or auditory ototoxicity.

A

Aminoglycosides

40
Q

Factors associated with otoxicity include …….?

A

increasing age,
duration of therapy,
elevated peak and trough levels,
concurrent loop diuretics or vancomycin,
underlying disease states and previous exposure to aminoglycosides.

41
Q

(blank) is the most common single known cause of bilateral vestibulopathy, accounting for 15-50% of all cases.

A

genatmicin toxicity

42
Q

Recent studies indicate a genetic predisposition to aminoglycoside ototoxicity due to an inherited mutation, the (blank) mutation in the (blank) 12S ribosomal RNA gene; 17-33% of patients with aminoglycoside ototoxicity carry this mutation

A

A1555G

mitochonrial

43
Q

When given by IV infusion over 30 minutes, aminoglycosides follow a (blank) pharmacokinetic model; alph (distribution), beta (elimination), and gamma (tissue release).

A

3-compartment

44
Q

When is the distribution phase of aminoglycosides not observed?

A

when infused over one hour

45
Q

When does the gamma phase (tissue release) of aminoglycosides occur?

A

app. 16 hours post infusion

46
Q

T or F
The amount released from tissue is very small, but does accumulate over time, contributing to toxicity.
(for aminoglycosides)

A

T

47
Q

Factors associated with nephrotoxicity for aminoglycosides…….are?

A

Factors associated with nephrotoxicity include duration of treatment, increasing age, compromised renal function, volume depletion, elevated peak and trough levels, concurrent nephrotoxic drugs (NSAIDs, loop diuretics, Vancomycin) and previous exposure to aminoglycosides.

48
Q

Aminoglycosides eliminate bacteria quickest when their concentration is appreciably above the MIC for an organism; this is (blank) activity

A

concentration dependent activity.

49
Q

(blank) exhibit a persistant suppression of bacterial growth following antibiotic exposure. What does this mean?

A

Aminoglycosides
This means that trough levels can drop below the MIC of targeted bacteria for a sustained period without decreasing efficacy

50
Q

What is the ideal dosing regiment for aminoglycosides?

A

The ideal dosing regimen would maximize concentration, because the higher the concentration, the more extensive and faster is the degree of killing.

51
Q

What would you use to predict efficacy for aminoglycosides?

A

peak/MIC ratio

eradicate best at ration of 8-10

Block 6 Week 2 (7 decks)

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