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Jason's GI Block > Advanced Pharmacokinetics > Flashcards

Flashcards in Advanced Pharmacokinetics Deck (59):
1

Acidic drugs and lipid solubility, which ones have good passage?

uncharged, lipid soluble, low pH

2

Basic drugs and lipid solubility, which ones have good passage?

uncharged, lipid soluble, high pH

3

How to treat aspirin overdose?

manipulate tubular reabsorption by administering NaHCO3 to make urine basic and make the acidic aspirin poorly soluble

4

Renal clearance depends on? 2 things

Renal blood flow
rate of elimination

5

what is drug metabolism AKA?

biotransformation

6

what is biotransformation? where does it mostly happen? why does it happen?

chemical change to a drug to a metabolite, happens in liver to increase water solubility for excretion

7

MEtabolite can be 4 things

active
nonactive
new activity - levo-dopa
toxic -epoxide

8

Phase I metabolism does what

creates chemical functional group like -OH, SH, COOH on the drug

9

why do you get drug side effects

Phase I metabolism reactions can alter CYP450 via inhibiting/enhancing

10

what happens in PHase II metabolism?

conjugating water soluble molecule to functional group, like adding sugar to bilirubin or morphine

11

Phase II products are nearly always what? 2 things

inactive
more water soluble

12

Renal clearance definition?

amount of blood from which drug is removed by kidneys per time

13

more drug in the blood, how does what affect clearance?

more effective the clearance

14

pathway of a drug in the body 6 things

administration
absorption
distribution
elimination(metabolism/excretion)

15

what is ADME?

drugs to and from their site of action:
absorption
distribution
metabolism
excretion

16

in first order kinetics, drugs are eliminated at a rate proportional to what?

concentration in the plasma

17

when do you get classic first order kinetics?

rapid IV administration and distribution

18

in first order kinetics, how is the drug eliminated?

exponentially via half-life

19

what does log10(conc) vs. time give you instead of (conc.) vs. time?

give you a gradient, easier to work with and can verify the exponential process

20

in a short term infusion, why does the concentration in the blood plateau?

as concentration of drug increases, the elimination also increases

21

if you stop infusion, what does the drug elimination curve look like?

first order kinetics, half-life decrease

22

Which peak is higher? IV bolus? short term IV infusion?

IV bolus

23

why is it good that the peak for IV infusion is not high?

good for drugs with small therepeutic windows

24

what is the steady state of IV infusion?

rate infusion = rate elimination

25

what happens if you change infusion rate by double or half?

the concentration will change proportionally

26

multiple dosing every hal-life give what in concentration in plasma

a two-fold variation in concentration

27

how do you reach steady state faster in a long term IV infusion?

loading dose

28

what factors determine volume of distribution?

-if drug binds to plasma proteins (greater conc in plasma - VD is small)
-if drugs binds to tissues/taken up by cells (VD is large)

29

What is volume of distribution?

volume of body water in which a drug appears to be dissolved in after it has distributed throughout the body

30

what do you have to take into account re: dosing for oral administration of drugs

first pass metabolism by liver, end up with reduced drug in system

31

first order elimination curve, picture it in your head

peak not as high as IV
not all drug is absorbed

32

what is bioavailability?

the amount of active drug that actually enters systemic circulation

33

what are 2 things bioavailability is affected by?

how much drug absorbed
how much drug is metabolized via:
-first pass
-local metabolism (GI before liver)

34

how to calculate bioavailability from graphs?

Areas under the curves

35

2 complicating factors in pharmacokinetics

unusual drug behaviour
interpatient variability (narrow therapeutic windows)

36

what's bad if bioavailability is low?

more sensitive to variability

37

what's bad if you have slow distribution

drug may be eliminated before it's fully distributed to target areas

38

what is zero order kinetics

drug saturates elimination processes, and makes elimination constant

39

what is a drug reservoir? what can happen to drug?

sites where drug accumulates:
prolong
terminate
slow distribution

40

Common drug reservoirs in the body: 3 places

Plasma proteins
cells
fat

41

what is a bad if you rapid IV admin of slow distributing drug? how to compensate?

may exceed therapeutic window
loading doses to be broken down

42

single dose drug with zero oder elimination a problem?

Nope

43

what's the problem with multiple dosing of zero order elimination drugs?

disproportionate increase in concentration because steady state is never reached

44

2 examples of zero order elimination drugs?

aspirin
alcohol

45

2 things that effects pharmacokinetics in the elderly and neonates

reduced
renal excretion
hepatic metabolism

46

renal clearance of newborn is ___% of adult

20%

47

How long until newborn renal clearance at adult levels?

1 week

48

renal function decreases starting at what age? % at 50
% at 75?

20yrs
75% at 50
50% at 75

49

liver metabolism in newborns are deficient how? how long until 100%?

can't do phase II conjugation
6weeks

50

why can't you give morphine to mom when she's in labour?

baby can't metabolize morphine, no phase II conjugation could be born addicted to morphine...

51

how is liver metabolism affected in elderly? consequence?

reduced CYP450
increased half life

52

Drug-Drug interactions:
Pharmacodynamic
Pharmacokinetic

A affects B without affecting concentration

A modifies B concentration at receptor

53

drug drug interactions, the affect drug needs to be what to be clinically important?

narrow therapeutic window
steep concentration-response curve

54

pharmacokinetic drug-drug interactions interact where?

ADME
absorption
distribution
metabolism
excretion

55

pharmacokinetic drug-drug interactions affects absorption how?

gastric emptying rate (opiates)
formation of pooly absorbed complex in gut (calcium and tetracyclines)

56

pharmacokinetic drug-drug interactions affects distribution how?

displacement from plasma protein binding sites leads to transient toxicity
altering target therapeutic range

57

pharmacokinetic drug-drug interactions affects metabolism via induction of CYP450 can do what? 2 things

reduced half life
increased bioactivation

58

pharmacokinetic drug-drug interactions affects metabolism via inhibition of CYP450 can do what?

increase half-life and plasma concentration

59

pharmacokinetic drug-drug interactions affects excretion how? 3 things

alter:
protein binding
tubular secretion (probenecid olympics)
urine flow/pH (NaCO3 for aspirin overdose)