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Clinical PK Exam 3 > PK in critical care > Flashcards

PK in critical care Flashcards

1
Q

What are the key factors that can impact extravascular absorption?

A
  1. Hypotension and Vasopressors
  2. Altered gastric emptying
  3. Feeding tube/nutrient effects
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2
Q

What is the physiologic response of critically ill patients in a state of hypotension or shock?

A

shift blood flow to critical organs (brain, heart, etc.)

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3
Q

What will the blood flow to other organs/tissue result in, if the shift of blood flow goes to critical organs?

A

blood flow will decrease as a result

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4
Q

What can reduced blood flow to sites of absorption result in?

A

alter the rate and/or extent of drug absorption

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5
Q

What medications may be used to maintain an adequate blood pressure in patients with hemodynamic shock?

A

Vasopressors (dopamine, epinephrine, norepinephrine)

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6
Q

What delays/slows gastric emptying?

A
  1. Surgery
  2. traumatic brain injury
  3. sepsis
  4. burns
  5. opiates (may cause GI effects)
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7
Q

What can delay gastric emptying result in?

A
  1. Delayed time to peak concentration

2. Decreased drug stability

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8
Q

Some drugs may absorb to the feeding tube material. What does this cause to the total amount of drug delivered?

A

A decrease in the total amount of drug delivered

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9
Q

Drug can become clogged in enteral tubes. What should be performed to minimize accumulation of residual drug?

A

Adequate flushing

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10
Q

Enteral tube feeding can increase gastric pH. What can be altered depending on the chemical characteristics of the drug?

A

the absorption or stability

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11
Q

Enteral nutrition solutions can interact directly with drugs. What are some examples of how enteral solutions can interact directly with drugs?

A

Binding or chelating

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12
Q

Drug/nutrition interactions can reduce the oral bioavailability of certain drugs. What types of drugs can drug/nutrition interactions reduce?

A
  1. Phenytoin
  2. Levothyroxine
  3. Warfarin
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13
Q

How must you administer phenytoin, levothyroxine, and warfarin to avoid drug/nutrient interactions?

A

administer 1-2 hours before and after drug administration

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14
Q

What are the key factors that can impact distribution?

A
  1. IV fluid administration
  2. Plasma protein binding
  3. Tissue perfusion
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15
Q

T/F Lipophilic drugs tend to significantly distribute into tissues and have a smaller apparent volume of distribution?

A

False, larger apparent volume of distribution

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16
Q

T/F Hydrophilic molecules tend to remain in body water and have relatively low volumes of distribution?

A

True

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17
Q

What does plasma protein binding affect?

A

distribution of drugs into tissue

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18
Q

T/F IV fluids can result in an increase in plasma volume and total body water?

A

True

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19
Q

What are the hydrophilic drugs?

A
  1. aminoglycosides

2. beta lactams

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20
Q

What will hydrophilic drugs result in

A

Increased volume distribution

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21
Q

What can an increased volume of distribution do to a loading dose, half-life, and time to steady state?

A

increase

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22
Q

Why is fluid status important?

A

As fluid volume returns to normal levels, the apparent volume of distribution will change as well

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23
Q

What is the primary drug binding plasma protein?

A

Albumin

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24
Q

What are some acidic drugs

A
  1. Phenytoin

2. Diazepam

25
Q

What is the importance of alpha -1 acid glycoprotein

A

important for basic drugs such as lidocaine and diltiazem

26
Q

what can acute stress and trauma result in?

A

increased vascular permeability or increased protein catabolism

27
Q

What may an increased vascular permeability or increased protein catabolism result in

A

loss of circulating plasma albumin and reduction in protein binding and increase unbound fraction of drug (increase fu)

28
Q

What does an increased in unbound fraction in plasma cause?

A

increased volume of distribution and greater access of drug to tissue, prolonged half life, and increased time to attain steady state concentrations

29
Q

What does an increase of alpha-1 glycoprotein levels result in?

A

increased plasma protein binding and a decrease in unbound fraction in plasma

30
Q

What does a decrease in unbound fraction cause

A

decrease in apparent volume, a shortened half-life, and a reduced time to steady state

31
Q

What does hypoperfusion lead to?

A

decreased delivery of drugs to target tissues and tissues into which drugs may distribute

32
Q

What are the key factors of affecting metabolism

A
  1. Alterations in hepatic blood flow
  2. Alterations in protein binding
  3. Alterations in intrinsic liver clearance
  4. Alterations in intrinsic clearance - high extraction ration and low extraction ratio drugs
33
Q

What is the primary organ of drug metabolism?

A

the liver

34
Q

What are the high extraction ratio drugs?

A

drugs highly metabolized by hepatic enzymes

35
Q

What are examples of high extraction ratio drugs?

A
  1. Diltiazem
  2. Fentanyl
  3. Haloperidol
  4. lidocaine
  5. propofol
36
Q

What are the low extraction ratio drugs

A

clearance independent of hepatic blood flow

37
Q

What are examples of low extraction ratio drugs?

A
  1. Diazepam
  2. phenytoin
  3. warfarin
  4. valproic acid
38
Q

When does hepatic blood flow increase?

A

during earlier stages of sepsis or with administration of vasodilators (nitroglycerin)

39
Q

What can a decrease blood flow occur with?

A

cirrhosis or with vasopressors used for hypotension and shock can reduce hepatic blood flow

40
Q

What are alterations in liver blood flow expected to have minimal of?

A

impact on drugs with a lower extraction ratio

41
Q

Alterations in protein binding of high extraction ratio drugs will affect what type of concentrations?

A

unbound concentrations of high extraction ratio drugs

42
Q

What will an increase of unbound fraction cause in high extraction ratio drugs?

A

increase unbound concentrations that will interact with therapeutic targets or targets associated with adverse effects

43
Q

What will alterations in protein binding have on low extraction ratio drugs and protein binding

A

minimal impact on unbound concentrations of a low extraction ratio drug, total concentration will be affected

44
Q

Because unbound concentrations are not altered in low extraction ratio drugs, will there be a change in the amount of drug reached to its target?

A

No

45
Q

What factors can alter the intrinsic clearance (CLi) of drugs from the liver?

A
  1. severe burns or cholestasis may decrease cytochrome p450 activity
  2. renal impairment can be associated with decrease hepatic clearance. As a result, clearance can be decreased even when a drug is not primarily eliminated by the kidneys
  3. Cirrhosis is associated with a decreased drug metabolism due to a reduced number of functional hepatocytes
  4. Therapeutic hypothermia may decrease CYP activity, and blood flow (enzyme inducers and inhibitors need to be considered)
46
Q

what organ is responsible for non metabolic drug elimination?

A

the kidney

47
Q

What are the three main factors involved in renal clearance of a drug?

A
  1. glomerular filtration
  2. secretion
  3. reabsorption
48
Q

What are the key factors that impact renal clearance?

A
  1. AKI
  2. increased renal blood flow
  3. tubular secretion and reabsorption
49
Q

Reduction in doses for patients receiving renally cleared drugs is often required in what type of patients?

A

patients with AKI

50
Q

What can renal impairment be associated with?

A

decreased protein binding of highly bound drugs. Which can result in an increased Vd or alteration in hepatic clearance

51
Q

What is the primary determinant of loading doses

A

Vd

52
Q

what is tubular secretion?

A

the process by which drugs are actively secreted into the renal tubules for elimination in urine

53
Q

Does tubular secretion enhance or reduce renal clearance?

A

enhance

54
Q

What is tubular reabsorption

A

the process by which drugs re-enter the systemic circulation after being filtered at the glomerulus

55
Q

Does tubular reabsorption enhance or reduce renal clearance?

A

reduce

56
Q

Does basic drugs increase or decrease renal clearance

A

decrease

57
Q

Does acidic drugs increase or decrease renal clearance

A

increase

58
Q

when monitoring renal function in patients, how should Cockroft gault be monitored?

A
  1. measuring 24-hour creatine elimination in urine as a direct measure of crcl
  2. measurement of renal function based on plasma cystatin c

Clinical PK Exam 3 (5 decks)

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