lecture 1 - pharmacokinectics Flashcards Preview

pharm1 > lecture 1 - pharmacokinectics > Flashcards

Flashcards in lecture 1 - pharmacokinectics Deck (85):
1

First pass metabolism. what is it?

a phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation. when a drug is absorbed across the GI membrane, it enters the hepatic portal system, which carries the drug molecules directly to the liver.

2

absorption of sublingual/buccal - goes where?

drains to vena cava. (bypasses GI tract)

3

absorption of sublingual/buccal - speed?

rapid

4

sublingual/buccal drugs must be

highly lipid soluble and potent

5

if you have poor blood flow to a cut and put a topical on it you will have poor

absorption

6

p-glycoproteins- where are they?

membranes. they are found all over the kidney, color, BBB, jejunum, liver, pancreas, etc.

7

p-glycoproteins- what are they?

family of transfer proteins. important for med interactions and drug resistance.

8

what do p-gloycoproteins require for transport

ATP

9

total body water

.65L/kg

10

average adult plasma volume is

Vd= 3 liters

11

what does volume of distribution assume?

that a sample of peripheral blood is homogenous throughout the body. sometimes called "apparent" volume of distribution

12

volume of distribution definition

size of compartment necessary to account for the total amount of drug in the body if it were present throughout the body at the same concentration found in the plasma.

13

are SQ and IM lipophilic or hydrophilic ?

lipo

14

injectable meds are absorbed by what process

simple diffusion

15

bioavailability of subcutaneous meds is

100

16

inhaled meds absorption

rapid due to large surface area, avoid first pass, local site of action, difficult to control

17

how does temp affect absorption

increases

18

topical meds need to be

highly lipophilic

19

first pass metabolism

the concentration of a drug is greatly reduced before it reaches the systemic circulation

20

how to figure out new dose if you have the current dose, its bioavailability, and the new dose's bioeval

new dose = f old (current dose) / f (new)

21

concept of bioavailability as a percentage

so (f) is a percentage of the oral dose that is becoming into the general circulation. and because you're giving IV meds right into the circulation pt gets the whole dose

22

100 mcg PO, 75% bioavailable. whats the IV dose?

75mcg

23

salts at the end of the drug like tartrate

can change bioavailability and duration of action

24

100 mcg IV, 50% bioavailable IV-->PO dose?

200mcg

25

factors that affect bioavailability

dissolution and absorption characteristics, route, stability in GI tract, metabolism prior to blood stream

26

absorption definition

the movement of drug molecules a cross membrane and into the bloodstream

27

bioavailability (F) definition

% of med that reaches systemic circulation

28

pharmacodynamics

the effects of a drug on the body

29

pharmacokinetics

the effect of the body on a drug

30

ADME

absorption, distribution, metabolism, excretion

31

oral admin- considerations in GI tract

gastric ph and contents. surface area. blood flow. GI mobility. complete GI tract. flora

32

gastric ph and contents affects what?

absorption of certain meds like ca supplements

33

what limits transport into placental transfer

p-glycoproteins

34

placental transfer -describe fetal plasma

acidic, ion trapping of basic drugs

35

blood brain barrier is made up of

very tight junctions

36

to cross BBB, meds need to be highly

lipophilic

37

CNS inflammation (meningitis) does what to BBB

increases the space between the junctions (look this up more)

38

hydrophillic

water loving water is an ionized. meds need a transport molecule or carrier protein

39

membrane permeability

in order to enter an organ, a drug must permeate all membranes that separate the organ from the site of drug administration

40

tissue binding

where is the drug most likely to be used

41

what meds live in the bones

tetracyclines

42

the less albumin you have

the more unbound medication, and greater risk of toxicity

43

what do basic drugs bind to

Alpha 1 acidic glycoprotein

44

what do acidic drugs bind to

albumin

45

why are free levels drawn

want to know how much of the med is actually active

46

protein binding affects

the amount of free drug that can actually effect the body

47

two compartment model

-redistribution before elimination
-slow rate of administration for secondary re-distribution
-target organ may be in the initial or secondary "compartment"

48

does passive diffusion require energy

no

49

does passive diffusion require a carrier

no

50

what molecules use passive diffusion

rapid for lipophilic, non-ionic, small molecules

51

does facilitated diffusion require energy

no

52

does facilitated diffusion require a carrier

yes

53

what is facilitated diffusion

drugs bind to carrier by noncovalent mechanisms.
chemically similar drugs compete for carrier

54

do aqueous channels require energy

no

55

do aqueous channels require a carrier

no

56

how do aqueous channels work

small hydrophilic drugs diffuse along concentration gradient by passing thru aqueous channels/pores. electrolytes love these

57

does active transport require energy

yes

58

does active transport require a carrier

yes

59

how does active transport work

identical to facilitated diffusion except that ATP powers drug transport against concentration gradient

60

metabolism

breakdown for ease of elimination

61

prodrug

an inactive substance that is converted to a drug within the body by the action of enzymes or other chemicals.

62

phase 1 metabolism

-induce or expose a functional group on the parent compound.
-generally lose activity, rare instances of preserved.

63

phase 1 metabolism - how are they eliminated

often hydrolyzed or ester linked for rapid elimination thru kidneys

64

phase 2 metabolism

conjugation reactions... links parent compound or phase 1 metabolite with a functional group via covalent linkage.

65

most enzymes that break down medications come from

liver

66

cyp450

terminal oxidase in a multicomponent electron transfer chain.
phase 1 type reactions.

"most common enzymes that break down meds into something more ionized, polar water loving, so that they get eliminated"

67

CYP3A4

isoform. responsible for the metabolism of more than 50% of all medications. found in liver and small intestine

68

med metabolized by a CYP is a

substrate

69

inhibition of enzyme

-Will keep the enzyme from
working properly
-Ability to increase amount of parent compound

70

induction of enzyme

- will enhance the capability of the enzyme
- Ability to quickly metabolize the parent compound
so you need more!

71

factors affecting metabolism

genetics, environment, diet, disease factors, age, sex

72

hydrolysis

often provide a site for conjugation, or may inactivate P450 metabolites for excretion. "a chemical process of decomposition involving the splitting of a bond and the addition of the hydrogen cation and the hydroxide anion of water."

73

conjugation

Phase I metabolite joining to another compound.

74

elimination is easier when a med is

polar, hydrophillic

75

3 processes of renal elimination

glomerular filtration, active tubular secretion, passive tubular reabsorption

76

glomerular filtration is for

unbound medications

77

active tubular secretion is for

p-gp and other transport proteins

78

passive tubular reabsorption is for

weak acids and bases via concentration gradients

79

first order kinetics

A constant fraction of the drug in the body is eliminated per unit time. so length of half life is constant.

80

zero order kinetics

half life decreases with decreasing concentration.

81

elimination rate (k)

fraction or % of the total amount of drug in the body removed per unit of time.

82

formula: k= Cl/V

elimination rate = clearance / volume

83

formula: k = ln (C1-C2) / time

elimination rate = natural log times the change in concentration divided by time.

84

how many half lives do you need to get to steady state

5

85

what do half lifes and elimination rates do

-estimate the time to steady state
-estimate the time to eliminate the med from the body
-predict non-steady state plasma levels
-predict steady state from a non-steady state level
-determine dosing intervals