Exam 1: Pharmacokinetics/Pharmacodynamics Flashcards Preview

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Flashcards in Exam 1: Pharmacokinetics/Pharmacodynamics Deck (108):
1

Pharmacokinetics vs. pharmacodynamics:

Pharmacokinetics = “what the body does to a drug"

Pharmacodynamics = “what a drug does to the body"

2

Four components of pharmacokinetics:

Absorption
Distribution

Metabolism

Excretion

3

Three components of pharmacodynamics:

Mechanism of effect
Sensitivity

Responsiveness

4

Four commonly measured pharmacokinetic parameters of IV drugs:

1. Elimination half-time

2. Bioavailability

3. Clearance

4. Volume of distribution

5

Define bioavailability

How much of the drug administered is available at the site of action

6

Define volume of distribution

The volume that the drug is able to distribute into

7

Compartments in the two compartment model:

Central
Peripheral

8

Define central compartment:

Highly perfused tissues: kidney, liver, lungs, heart, brain, vessels

9

What pathway does a drug take between the two compartments?

Introduced into central
Distributes into peripheral

Returns to central for clearance

10

What % of CO does the central compartment receive? What % of body mass does it represent?

75% of CO
10% of mass

11

What is the peripheral compartment?

The not highly perfused organs/tissues

12

What are the characteristics of the peripheral compartment?

Large volume
Extensive uptake of drug

13

What type of drugs will transfer easily between plasma and tissues?

Highly lipid soluble

14

How does aging affect the rate of transfer between compartments?

Decreases it, leading to greater plasma concentration

15

What causes a drug to leave the peripheral compartment?

Drop in plasma concentration below peripheral compartment concentration due to clearance

16

How are the duration of effect and elimination half-time related in lipophilic drugs? 

Duration of effect much shorter than elimination half-time



Plasma concentration drops rapidly but drug is slow to leave tissues and get cleared

17

Why do large/repeat doses of a drug prolong duration of action?

Tissues become saturated so clearance depends on metabolism, not redistribution

18

What are the 3 and 4 compartment models?

3: vessel rich, muscle, fat & vessel-poor



4: vessel rich, muscle, fat, vessel-poor

19

Body mass and flood flow % for each compartment (vessel rich to vessel poor):

Body mass: 10%, 50%, 20%, 20%
Blood flow: 75%, 19%, 6%, <1%

20

Special function of lungs r/t drugs:

Serve as a reservoir for basic lipophilic drugs

21

Why does Fentanyl have two peaks?

Lungs sequester initially and then release

22

What type of drugs does the blood-brain barrier block?

Ionized, water-soluble drugs

23

Under what conditions can the blood-brain barrier be overcome?

Large doses of drug in patients with head injury or hypoxemia

24

What populations have weaker blood brain barriers?

Neonates
Elderly

25

Define biophase:

Site of action of drug, aka "effect site"

26

What is the rate constant of drug elimination from effect site?

ke0

27

How do we calculate Vd?

Vd = dose of IV drug / plasma concentration of drug

28

How does lipid solubility affect Vd? Why?

More lipid soluble = higher Vd



Lipid soluble drugs easily cross membranes to enter the peripheral compartment

29

How does protein binding affect Vd? Why?

More protein bound = lower Vd



If drug is bound to proteins, it cannot cross membranes and enter tissues

30

Why does coumadin have such a small therapeutic index?

High protein binding affinity; small changes in [plasma protein] lead to large changes in plasma levels

31

How does molecular size relate to Vd? Why?

Greater molecular size = smaller Vd



Larger molecules have a harder time crossing the membrane and stay in the plasma more

32

Elimination half-time

The time for the plasma concentration of the drug to decrease to 50% during the elimination phase (NOT the total amount of drug in the body)

33

How are elimination half-time and Vd related?

Directly proportional

34

How are elimination half-time and clearance related?

Inversely proportional

35

How are elimination half-time and drug dose related?

They are independent of each other

36

Define elimination half-life:

How long it takes for drug to leave the body by 50%

37

What occurs if dosing intervals are less than elimination half-time?

Drug accumulation

38

% of initial drug eliminated at each of the first 6 half-times:

50%
75%

87.5%

93.8%

96.9%

98.4%

39

Advantages of oral administration:

Convenient and economic

40

Disadvantages of oral administration:

Emesis
Destruction by gastric enzymes/acid

Irregular absorption with food/other drugs

41

What is the first-pass effect?

Drugs absorbed via GI system have to pass through the portal system/liver before systemic circulation and get metabolized

42

What is the advantage of sublingual/transmucosal administration?

Bypasses the liver and the first-pass effect

43

What are the advantages of transdermal administration?

Sustained therapeutic plasma concentration of drug

44

How does absorption occur for transdermal drugs?

Along sweat ducts and hair follicles

45

What is the rate-limiting step for transdermal absorption?

Diffusion across stratum corneum

46

Differences in proximal vs. distal rectal administration:

Proximal: portal system
Distal: caval system

47

What is the advantage of IV administration?

Achieve therapeutic plasma levels precisely and rapidly

48

How acidic/basic are most drugs?

Weak acids and bases

49

Non-ionized drugs are usually (lipid soluble/non lipid soluble):

Lipid soluble

50

Is the ionized or non-ionized fraction of a drug the active part?

Non-ionized

51

How is the ionized fraction of a drug cleared?

By the kidneys, u nchanged

52

Why are drugs with a high ionized fraction a bad idea for renal patients?

Ionized fraction of drugs passes out unchanged via kidneys

53

What two factors determine the degree of ionization?

* Dissociation constant (pK)

* pH of surrounding fluid

54

Acidic drugs are highly ionized at an _______ pH.

Alkaline

55

Describe ion trapping and an example:

Drug ends up in an acid/basic environment where it becomes ionized and unable to cross back over to equilibrate



Ex. LA accumulating in placenta

56

Main three plasma proteins:

* Albumin-acids

* α 1 acid glycoprotein bases

* Lipoproteins

57

Which fraction of the drug (r/t protein binding) can cross membranes?

The free/unbound fraction

58

How does protein binding affect Vd and effect?

Lower Vd
Lesser effect

59

Name four drugs that are highly protein bound:

Warfarin
Propranolol

Phenytoin

Diazepam

60

Define clearance:

Volume of plasma cleared of drug by metabolism and excretion

61

Define first-order kinetics:

Rate of elimination increases with more of the drug

A constant fraction per unit of time is eliminated

62

Most drugs display ______-order kinetics:

First-order

63

Define zero order kinetics:

A constant amount of drug is eliminated per unit time 

64

What are three common drugs that exhibit zero order kinetics?

ETOH
ASA

Dilantin

65

Define hepatic clearance:

Ratio of hepatic blood flow to hepatic extraction of drug

66

What is perfusion-dependent elimination?

Hepatic extraction ratio > 0.7



Clearance of drug depends on hepatic blood flow

67

Relationship between blood pressure and hepatic extraction ratio:

If ratio is > 0.7, drug is perfusion dependent; low BP means slower clearance

68

Define capacity-dependent elimination:

Hepatic extraction ratio is will not change clearance




Decrease in protein binding -or- increase in enzyme activity will increase hepatic clearance

69

Most important organ for elimination of unchanged drugs or metabolites:

Kidneys

70

Which type of drugs are most efficiently excreted by kidneys?

Water soluble compounds

71

Highly lipid soluble drugs in the kidney:

Get reabsorbed so little to no unchanged drug is excreted

72

Define drug metabolism:

Biotransformation to convert pharmacologically active, lipid soluble drugs into water soluble and often inactive drugs

73

Increased water solubility _____ the Vd for a drug and _____ its renal excretion.

Decreases; increases

74

Four pathways of metabolism:

1. Oxidation
2. Reduction

3. Hydrolysis

4. Conjugation

75

What occurs during phase I of metabolism?

Oxidation, reduction, or hydrolysis

76

What occurs during phase II of metabolism?

Conjugation of drug or metabolite with endogenous substance to form water-soluble compound

77

Sites of drug metabolism in the body (5):

Plasma
Kidneys

Lungs

GI Tract

Liver

78

What is the primary site for drug metabolism? What substance is responsible for metabolism there?

Liver; hepatic microsomal enzymes

79

What is an example of a drug metabolized in the plasma?

Succinylcholine (by plasma esterases)

80

Where are hepatic microsomal enzymes located?

In the hepatic smooth ER

81

What are the protein enzymes that frequently metabolize drugs collectively called?

Cytochrome P-450

82

What are the six CYP isozymes in the Cytochrome P-450 system?

CYP1A2
CYP2C9


CYP2C19

CYP2D6

CYP2E1

CYP3A

83

Define enzyme induction:

Increased enzymatic activity or enzyme concentration, resulting in increased elimination of a drug

84

What class of drugs were mentioned as huge enzyme inducers?

Barbiturates

85

How do nonmicrosomal enzymes typically work?

By conjugation and hydrolysis



(Lesser extent via redox)

86

Where are nonmicrosomal enzymes located?

Liver (mostly)
Plasma

GI tract

87

Which enzymes hydrolize drugs with ester bonds? What are two examples of these drugs?

Nonmicrosomal enzymes



Succinylcholine, esmolol

88

Which type of enzymes can be induced?

Hepatic microsomal enzymes

89

By what mechanism do most drugs exert their effect?

Interaction with cell membrane receptors

90

How do pts on beta-blockers adapt?

Upregulate (increase) the number of beta receptors 

91

Define the state of receptor activation theory:

Non-activated receptors are converted to active by the drug

92

What is the receptor occupancy theory?

The more receptors occupied by the drug, the greater the effect

93

Ex. of a nonreceptor drug action:

Antacids neutralize gastric acid by direct action

Chelating drugs form bonds with metallic cations

94

Agonist drugs work by:

Mimicking cell signalling molecules and activating the same receptors

95

Antagonist drugs work by:

Binding to same receptors as cell signals WITHOUT activating the receptor, therefore blocking the signaling molecules

96

How much does the chemical structure of a drug affect its affinity for a receptor?

Small changes in structure can dramatically change effect

97

Define racemic:

1/2 R isomer, 1/2 L isomer

98

Enantomerism can be produced by:

sp3 hybridized carbon atoms

99

Define efficacy:

The ability of a drug to produce the desired therapeutic effect

100

Define potency:

The relationship between the effect of a drug and the dose necessary to achieve that effect

101

Quickness to effect and amount needed to effect: which is efficacy? Which is potency?

Efficacy: quickness
Potency: amount

102

Define ED50 and LD50:

ED50 is the dose effective in 50% of people

LD50 is the dose lethal in 50% of people

103

Define therapeutic index:

The ratio of LD50 to ED50

104

Define hyperreactivity:

An unusually low dose of drug produces the expected effect

105

Define hypersensitivity:

Allergy

106

Define additive effect:

A second drug acting with the first will produce effect equal to the sum of both

1+1=2

107

Define synergistic effect:

Two drugs interact to produce an effect greater than their sum

1+1=3

108

What type of combined effect do Fentanyl and Versed have?

Synergistic, esp. on respiratory rate