Advanced Pharmacokinetics

Question 1

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

Answer 1

uncharged, lipid soluble, low pH

Question 2

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

Answer 2

uncharged, lipid soluble, high pH

Question 3

How to treat aspirin overdose?

Answer 3

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

Question 4

Renal clearance depends on? 2 things

Answer 4

Renal blood flow

rate of elimination

Question 5

what is drug metabolism AKA?

Answer 5

biotransformation

Question 6

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

Answer 6

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

Question 7

MEtabolite can be 4 things

Answer 7

active
nonactive
new activity - levo-dopa
toxic -epoxide

Question 8

Phase I metabolism does what

Answer 8

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

Question 9

why do you get drug side effects

Answer 9

Phase I metabolism reactions can alter CYP450 via inhibiting/enhancing

Question 10

what happens in PHase II metabolism?

Answer 10

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

Question 11

Phase II products are nearly always what? 2 things

Answer 11

inactive

more water soluble

Question 12

Renal clearance definition?

Answer 12

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

Question 13

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

Answer 13

more effective the clearance

Question 14

pathway of a drug in the body 6 things

Answer 14

administration
absorption
distribution
elimination(metabolism/excretion)

Question 15

what is ADME?

Answer 15

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

Question 16

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

Answer 16

concentration in the plasma

Question 17

when do you get classic first order kinetics?

Answer 17

rapid IV administration and distribution

Question 18

in first order kinetics, how is the drug eliminated?

Answer 18

exponentially via half-life

Question 19

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

Answer 19

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

Question 20

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

Answer 20

as concentration of drug increases, the elimination also increases

Question 21

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

Answer 21

first order kinetics, half-life decrease

Question 22

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

Answer 22

IV bolus

Question 23

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

Answer 23

good for drugs with small therepeutic windows

Question 24

what is the steady state of IV infusion?

Answer 24

rate infusion = rate elimination

Question 25

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

Answer 25

the concentration will change proportionally

Question 26

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

Answer 26

a two-fold variation in concentration

Question 27

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

Answer 27

loading dose

Question 28

what factors determine volume of distribution?

Answer 28

- 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)

Question 29

What is volume of distribution?

Answer 29

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

Question 30

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

Answer 30

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

Question 31

first order elimination curve, picture it in your head

Answer 31

peak not as high as IV | not all drug is absorbed

Question 32

what is bioavailability?

Answer 32

the amount of active drug that actually enters systemic circulation

Question 33

what are 2 things bioavailability is affected by?

Answer 33

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

Question 34

how to calculate bioavailability from graphs?

Answer 34

Areas under the curves

Question 35

2 complicating factors in pharmacokinetics

Answer 35

``` unusual drug behaviour interpatient variability (narrow therapeutic windows) ```

Question 36

what's bad if bioavailability is low?

Answer 36

more sensitive to variability

Question 37

what's bad if you have slow distribution

Answer 37

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

Question 38

what is zero order kinetics

Answer 38

drug saturates elimination processes, and makes elimination constant

Question 39

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

Answer 39

sites where drug accumulates: prolong terminate slow distribution

Question 40

Common drug reservoirs in the body: 3 places

Answer 40

Plasma proteins cells fat

Question 41

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

Answer 41

may exceed therapeutic window | loading doses to be broken down

Question 42

single dose drug with zero oder elimination a problem?

Answer 42

Nope

Question 43

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

Answer 43

disproportionate increase in concentration because steady state is never reached

Question 44

2 examples of zero order elimination drugs?

Answer 44

aspirin | alcohol

Question 45

2 things that effects pharmacokinetics in the elderly and neonates

Answer 45

reduced renal excretion hepatic metabolism

Question 46

renal clearance of newborn is ___% of adult

Answer 46

20%

Question 47

How long until newborn renal clearance at adult levels?

Answer 47

1 week

Question 48

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

Answer 48

20yrs 75% at 50 50% at 75

Question 49

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

Answer 49

can't do phase II conjugation | 6weeks

Question 50

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

Answer 50

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

Question 51

how is liver metabolism affected in elderly? consequence?

Answer 51

reduced CYP450 | increased half life

Question 52

Drug-Drug interactions: Pharmacodynamic Pharmacokinetic

Answer 52

A affects B without affecting concentration A modifies B concentration at receptor

Question 53

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

Answer 53

narrow therapeutic window | steep concentration-response curve

Question 54

pharmacokinetic drug-drug interactions interact where?

Answer 54

``` ADME absorption distribution metabolism excretion ```

Question 55

pharmacokinetic drug-drug interactions affects absorption how?

Answer 55

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

Question 56

pharmacokinetic drug-drug interactions affects distribution how?

Answer 56

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

Question 57

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

Answer 57

reduced half life | increased bioactivation

Question 58

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

Answer 58

increase half-life and plasma concentration

Question 59

pharmacokinetic drug-drug interactions affects excretion how? 3 things

Answer 59

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