EXAM #1: PHARMACOKINETICS Flashcards Preview

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Flashcards in EXAM #1: PHARMACOKINETICS Deck (96):
1

What is absorption?

Movement of the agent from the site of administration into the circulation

2

What is the difference between enteral and parenteral administration?

Enteral= drug delivery via the GI tract

Parenteral= non-GI drug delivery

3

What are the four routes of enteral administration?

1) Oral
2) Sublingual
3) Buccal
4) Rectal

4

What are the pros of oral administration?

Highest levels of compliance

5

What is the con of oral administration?

- GI tract breaks down drug
- enters portal circulation
- liver breaks down drug

Thus, delivery can be a challenge

6

What are the disadvantages of sublingual and buccal administration?

Mucosal irritation

7

What are the advantages of sublingual and buccal administration?

Drug is delivered directly into the venous system, BYPASSING the liver

8

What is the disadvantage to rectal administration?

- Inconvenient
- Non-compliance
- Incomplete absorption in rectal tissue can make it difficult to predict dosing

9

What are the advantages of rectal administration?

- Unconscious patients
- 50% of drug goes to liver, partially bypassing first-pass metabolism

10

What are the general cons of enteral administration?

1) Must pierce the skin, leading to non-compliance
2) Break in skin increases risk of infection

11

What is the advantage of IV drug administration?

Bypass metabolism b/c the entire dose is placed directly into the blood/ circulation

12

What is the disadvantage of IV drug administration?

If a mistake is made in dosing, the drug cannot be "recalled" i.e. can't correct the mistake

*****Margin of error significantly reduced

13

What are the pros of IM & subcutaneous injections?

- Dosing is less frequent
- Slow diffusion from tissuee that mirrors taking the medical regularly

14

What are the cons of IM & subcutaneous injections?

- Pain that leads to poor compliance
- *Especially for subcutaneous tissue, change in tissue composition with repeated administration*

15

Where is an intrathecal administration delivered?

Subarachnoid space

16

What are the advantages of intrathecal and epidural administration?

Bypass the BBB and delivery of drug directly into the CNS

17

What are the disadvantages of intrathecal and epidural administration?

The CNS is a very delicate tissue that is prone to damage

18

What types of drugs are best given transdermally?

Lipophillic drugs b/c they need to pass through the lipid membrane of the epidermis

19

What is the con of transdermal drugs?

Skin is a difficult barrier to bypass

20

What is the pro of inhalation?

- Direct administration into lungs
- Very rapid absorption

21

What are the cons of inhalation?

1) Irritation of lung tissue
2) Direct delivery of drug to the heart following inhalation, which is especially detrimental if the drug is cardiotoxic

22

Which form of drug is able to cross barriers, ionized or unionized?

Unionized

23

What form should weak acid and bases be in to best cross a lipid membrane?

Weak acid= protonated= unionized

Weak base= unprotonated= unionzed

Why? These forms are UNIONIZED

24

Write the Henderson-Hasselbach equation.

N/A

25

What is the pKa?

pH at which 50% if the drug is ionized, 50% is unionzed

26

If the pH is greater than pKa , what form will the drug be in?

pH > pKa= DEPROTONATED

27

If the pH is less than pKa, what form will the drug be in?

pH

28

Where is the body are weak acids and weak bases favored for absorption?

Stomach= low pH= protonated= weak acids more readily absorbed

Intestine= high pH= unprotonated= weak bases more readily absorbed

29

What pH favors absorption of Salicylic acid, pKa = 3?

Less than 3

*****Protonated and unionized

30

What pH favor absorption of Amphetamine, pKa= 10?

Greater than 10

*****Unprotonated and unionized

31

How much salicylic acid, pKa=3, will be absorbed from the small intestine, which has a pH of 7?

N/A

See ppt.

32

In the stomach (at pH=2), what is the ratio of unionized to ionized ASA?

N/A

See ppt.

33

At a pH of 8, what is the ratio of unionized to ionized amphetamine (pKa=10)?

N/A

See ppt.

34

What is the antilog of -4?

0.0001

35

What is the antilog of -3?

0.001

36

What is the antilog of -2?

0.01

37

What is the antilog of -1?

0.1

38

What is the antilog of 0?

1

39

What is the antilog of 1?

10

40

What is the antilog of 2?

100

41

What is the antilog of 3?

1,000

42

What is the antilog of 4?

10,000

43

What is distribution?

Process by which a drug leaves the circulation and enters the tissues perfused by the blood

44

What are the four general factors that affect drug distribution?

1) Cardiovascular factors
2) Tissue binding
3) Drug molecule size
4) Lipid solubility

45

What are the four cardiovascular factors that affect drug absorption?

1) CO
2) Regional blood flow
3) Capillary permeability
4) Binding to plasma proteins

46

What is drug metabolism?

Biotransformation--making a drug more soluble for elimination from the body

47

What is Phase I of biotransformation?

Generation of a more polar molecule by exposing a functional group

48

What is Phase II of biotransformation?

Conjugation of a drug to yield a more water soluble product to be excreted

49

What enzymes mediate Phase I biotransformation?

Cytochrome P450's or "CYPs"

50

What are the most common reactions of Phase II biotransformation?

Glucuronidation
Sulfation
Acetylation

*****Know that these are conjugation processes that are making the drugs more polar and water soluble for excretion.*****

51

What are the key sites of biotransformation?

GI
Lungs
Skin
Kidneys
Brain

52

What is the "first-pass" effect?

Entrance into the portal circulation and initial metabolism of a drug by the liver

53

What is the primary mechanism of drug elimination? Secondary?

Primary= renal excretion

Secondary= fecal via hepatic secretion into bile

54

What are the factors that alter renal excretion of a drug?

- GFR (glomerular filtration rate)
- Binding to plasma proteins
- Urine pH

55

What is the "Volume of Distribution (V)?"

Measure of the space in the body available for the drug

*****Amount of drug in body/ Concentration of drug in blood or plasma*****

56

What is "Clearance (CL)?"

Measure of the ability of the body to eliminate a drug

*****Rate of elimination/ concentration of drug*****

57

Generally, what does a large V mean?

Greater extent to which the drug distributes to the extravascular tissue

58

What does a V similar to the blood volume mean?

Majority of the drug is located in the vasculature

59

What does a V 100x the volume of the blood mean?

Majority of the drug is located in the extravascular tissue e.g. fat

60

What is zero-order elimination?

A specific amount of drug is eliminated of a specific period of time INDEPENDENT of drug concentration

*****E.g. 20mg of drug eliminated per 2 hours*****

61

When is zero-order kinetics/ elimination observed?

When the body's capacity to eliminate the drug is saturated

62

Draw an example of zero-order elimination graphically.

N/A

63

What is first-order elimination?

A constant fraction of drug is eliminated per unit time b/c the system is NOT saturated

*****E.g. Half the drug is eliminated from the body per 2 hours*****

64

Draw an example of first-order elimination graphically.

N/A

65

What is capacity-limited elimination?

A point at which the concentration of drug has saturated the elimination capacity of the system

*****Zero-order process*****

66

What is flow-dependent elimination?

When the system to eliminate drug is NOT saturated, the limiting factor in elimination is how fast blood can get to the organ/system

*****E.g. how fast can you get blood to the liver?*****

67

What is the consequence of continuous dosing with a drug that undergoes capacity-limited elimination?

Dangerous toxic levels of drug will accumulate

68

What drugs are associated with capacity-limited elimination?

Phenytonin
ASA
Alcohol

69

What drug is associated with flow limited elimination?

Propanolol

70

What is the half-life of a drug?

Time required for the plasma concentration of a drug to decrease by 50%

71

What is the half-life a drug dependent on?

- Volume of distribution (V)
- Clearance (CL)

72

After two half-lives, how much drug has been eliminated?

75%

73

How many half-lives does it take for a drug to be "fully eliminated?"

4-5 half-lives

74

What happens to the half-life of a drug if you reduce the clearance of the drug e.g. from renal insufficiency/failure?

Half-life INCREASES

75

How does increasing the Volume of Distribution (V) impact the half-life of the drug?

Increases the half-life

76

How is the initial plasma concentration calculated?

- Plot drug plasma concentration vs. time (semi-log)
- Slope= rate of elimination
- Extrapolate the line of best fit to find the y-intercept, the Cp0

*****Note that Cp0= Dose/V*****

77

What is the impact of calculating the initial plasma concentration in a one compartment vs. a two compartment model?

- B/c Cp0= Dose/V, the method works well for a one compartment model with a LOW volume of distribution V
- In the two-compartment model, Cp0 is much HIGHER than the Cp0 in a one-compartment model


*****If you use a one compartment model to give a loading dose, you could give a toxic/lethal initial dose*****

78

What is an accumulation factor?

= 1/fraction of drug lost in one dosing interval

*A factor used to predict the ratio of steady-state concentrations to the dose seen following the first dose*

79

When does accumulation of a drug become detectable?

If the dosing interval is shorter than 4 half-lives

80

What is bioavailability? What is the equation for bioavailability?

The amount of drug that reaches the systemic circulation

F= f x (1-ER)

f= extent of absorption from gut

81

What is the bioavailability of a drug given IV? How does this compare to a drug given PO?

IV= 100%
PO= much less

82

What is the extraction ratio (ER)?

Effect of first-pass metabolism on bioavaliability

83

What are the determinants of the extraction ratio?

ER= Hepatic Clearance/ Hepatic Blood Flow

84

What is the TC?

Target concentration

85

What is the MEC?

Minimum effective concentration

86

What is the Css?

"Steady State concentration"

= Dosing Rate/Clearance

The point at which elimination of a drug is equal to the bioavaliability i.e. in and out are balanced

87

How long will it take to reach the Css?

4-5 half-lives

88

What is the therapeutic window?

Concentration range between the MEC for the desired effect and the MEC for the toxic effect

89

If the clearance of a drug decreases from renal insufficiency or failure, what happens to the Css?

Css INCREASES

90

What is the effect of an increased dosing rate of the Css?

Css INCREASES

91

What is a maintenance dose?

The dose needed to maintain the Css (Steady State Concentration)

92

What value do you need to calculate first to determine the maintenance dose?

Dosing rate at steady state

Dosing Ratess= CL x TC

93

What is the equation for maintenance dose?

Dosing rate x dosing interval

94

What is a loading dose?

An initial dose that can be given to reach target concentrations (TC) rapidly

= V x TC/F

95

What are the advantages of a loading dose?

Useful when it would take a long to reach steady state, but you need to rapidly reach the TC
- E.g. in a drug with a long half-life

96

What are the disadvantages of a loading dose?

- Abrupt high concentration may be v.toxic
- Calculation takes into final volume of distribution, but inital dose is restricted to the blood

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