Pharmacokinetics

Question 1

pharmacokinetics (3)

Answer 1

absorption
distribution
elimination

Question 2

IV meds vs PO meds

Answer 2

IV onset of action is immediate. Tmax is immediate. PO is not because it had to travel through multiple different organ systems before systemic circulation.

Question 3

Bioavailability

Answer 3

the fraction of an administered dose of drug that reaches the systemic circulation unchanged

Question 4

bioavailability % of PO meds vs IV meds

Answer 4

PO meds <1 or <100% (typically 15-95%), IV meds 1 or 100%

Question 5

factors that affect PO bioavailability (4)

Answer 5

1. solubility/ability of drug to resist breakdown in stomach
2. ability of drug to permeate and resist metabolism in the GI epithelium
3. ability of drug to resist metabolism in portal circulation
4. ability of drug to resist metabolism within the liver, hepatic vein, lungs, etc.

Question 6

first pass effect

Answer 6

when the concentration of a med is greatly reduced before entering systemic circulation. typically PO meds.

Question 7

process of first pass effect

Answer 7

PO meds are absorbed in GI tract and circulated to liver via hepatic portal vein. liver metabolizes part of the med before it reaches systemic circulation. this combination results in first pass effect.

Question 8

factors affecting distribution from plasma: endothelial cell fenestration

Answer 8

a high degree of fenestration, like in the liver and kidney, facilitates more distribution. low degree of fenestration, like in the brain, prevents distribution.

Question 9

factors affecting distribution from plasma: blood flow

Answer 9

high blood flow like in major organ systems facilitates distribution. low blood flow, like in joints or fat or bones, leads to less distribution.

Question 10

factors affecting distribution from plasma: lipophilicity and molecular weight

Answer 10

lipophilic drugs will pass through the membrane much easier, as will drugs with a lower molecular weight.

Question 11

factors affecting distribution from plasma: protein bound

Answer 11

protein bound meds will have a harder time crossing the cell membrane.

Question 12

factors affecting distribution from plasma: ionization

Answer 12

uncharged passes easier.

Question 13

blood brain barrier purpose and components

Answer 13

the barrier that protects the CNS from outside medications. this is achieved through low fenestration, encapsulated cells, efflux transporters on the barrier (pgp transporter).

Question 14

ion trapping

Answer 14

distribution of meds based on pH

Question 15

if a drug is a weak acid…

Answer 15

it will want to go toward a more basic environment (plasma).

Question 16

if a med is a weak base…

Answer 16

it will want to go towards a more acidic environment (neurons)

Question 17

volume of distribution. what is it and what is the equation?

Answer 17

it is a proportionality constant.
equation is
amount of drug in the body divided by the concentration of drug in plasma.

Question 18

Vd < 5 L

Answer 18

most of med is confined to plasma

Question 19

Vd is between 5 - 10 L

Answer 19

medication is distributed throughout the blood

Question 20

Vd > 42 L

Answer 20

med is distributed to all tissues in the body

Question 21

protein bound drugs remain in

Answer 21

the bloodstream

Question 22

drug elimination

Answer 22

irreversible removal of medication from the body

Question 23

two categories of elimination

Answer 23

metabolism and excretion

Question 24

drug metabolism

Answer 24

the enzymatic conversion of a medication to its metabolites

Question 25

drug excretion

Answer 25

the removal of unchanged medication from the body

Question 26

phase I reactions

Answer 26

anything that goes through cytochrome p450 or a cyp enzyme oxidation reduction hydrolysis

Question 27

phase II reactions (5)

Answer 27

``` glucuronidation sulfation acetylation peptide conjugation glutathione conjugation ```

Question 28

phase 1 and phase 2

Answer 28

meds may go through none, one, or both.

Question 29

cytochrome p450 and CYP enzymes are largely found in

Answer 29

the liver

Question 30

active parent compound

Answer 30

active from ingestion to metabolism from liver, then metabolized into inactive metabolites.

Question 31

prodrug

Answer 31

the med is inactive UNTIL it is metabolized by the liver. when metabolized, the med is transformed into an active metabolite which exhibits the therapeutic effect.

Question 32

metabolism of acetaminophen

Answer 32

goes through both phase I and phase II CYP mediated reaction (phase I) and then sulfation and glutathione conjugations (phase II). After CYP mediated reaction, you have NAPQI. This is a toxic metabolite and needs to be converted and eliminated. This is where you need a glutathione conjugation (phase II) to convert NAPQI into a less toxic metabolite.

Question 33

acetaminophen toxicity

Answer 33

if you can't go through the steps of metabolizing acetaminophen. after acetaminophen is metabolized through phase I and II, phase I converts acetaminophen into NAPQI. Glutathione has to then conjugate the NAPQI because it's toxic. if not, you'll have serious AEs like hepatocyte death.

Question 34

purpose of acetylcystine

Answer 34

in acetaminophen overdose....provides your body with glutathione to break down NAPQI.

Question 35

Half life

Answer 35

parameter defined by the time it takes for the concentration of a med to reach half of its present concentration

Question 36

what can half life be used to determine?

Answer 36

how long a med will last in the body.

Question 37

how many half lives to steady state?

Answer 37

~ 4 - 5

Question 38

How many half lives to ~99% drug removal?

Answer 38

5 half lives.

Question 39

First order kinetics

Answer 39

constant elimination of med per unit of time, proportional to amount of med in the body. same proportion is eliminated per unit of time, meaning the amount is variable based on plasma conc. as the conc drops, the elimination rate drops as well.

Question 40

zero order kinetics

Answer 40

constant elimination of med in mg/hr, regardless of amount of med in body. the same amount is eliminated per unit of time regardless of plasma concentration.

Question 41

elimination mechanism is saturated in ____ order kinetics

Answer 41

zero

Question 42

phenytoin elimination and considerations.

Answer 42

follows zero order kinetics. as you dose pts, you will reach a point where all receptor sites are saturated. elimination continues at same fixed rate but an increase in therapeutic effect will be seen bc of buildup of the med waiting to bind as receptors desaturate. As you get to higher concentrationss, even small changes can have big impact on therapeutic effects.

Question 43

clearance (CL) equation

Answer 43

the rate of elimination of a drug divided by the plasma concentration of a drug

Question 44

clearance equation

Answer 44

clearance in L/hr = elimination in mg/hr OVER concentration in mg/L

Question 45

rate of elimination

Answer 45

clearance x concentration

Question 46

steady state definition

Answer 46

rate of absorption is equal to the rate of elimination of given med

Question 47

dosing rate equation

Answer 47

clearance x steady state conc

Question 48

creatinine clearance

Answer 48

measurement used to determine level of kidney function by looking at how well your kidneys are clearing creatinine from the blood.

Question 49

creatinine clearance Cockcroft-gault equation

Answer 49

creat clearance ml/min = (140-age) x weight in kg OVER serum creatinine mg/dl x 72 ALL MULTIPLIED BY 0.85 if female

Question 50

at what creatinine clearance do you need to make renal adjustments?

Answer 50

below 30 or 40.

Question 51

drug-drug interactions at pharmacokinetic level can happen during what 4 stages?

Answer 51

absorption, distribution, metabolism, excretion

Question 52

what happens when there is a drug-drug interaction between two drugs metabolized by the same enzyme

Answer 52

competition between the two drugs for the enzyme to metabolize them. the one that loses out on being metabolized will have high concentrations of free drug.

Question 53

drug-drug interactions: GI absorption (3 points)

Answer 53

- absorption of other drugs can be delayed by drugs that inhibit gastric emptying, like opiates - absorption of other drugs can be increased by drugs that speed up gastric emptying, like erythromycin. - absorption can be slowed or completely inhibited by formation of physical complexes (iron and tetracyclines)

Question 54

drug-drug interactions at the level of distribution is typically related to

Answer 54

protein binding drugs and albumin

Question 55

hypoalbuminemia and protein bound drugs

Answer 55

increased concentrations of free drug in circulation bc less protein is available to bind to. increased clinical effect/potential side effects. not guaranteed to be a problem.

Question 56

changes in hepatic metabolism are a common cause of

Answer 56

drug-drug interactions

Question 57

2 factors that affect hepatic metabolism in the context of drug-drug interactions

Answer 57

enzyme inhibition | enzyme induction

Question 58

when analyzing enzyme inhibition/induction interactions, it is important to know what about a drug?

Answer 58

if it is an APC or a prodrug

Question 59

enzyme inhibition

Answer 59

occurs when a medication reduces the activity of a metabolic enzyme, decreasing its metabolic capacity.

Question 60

enzyme induction

Answer 60

occurs when a med enhances a metabolic enzyme, increasing its activity.

Question 61

if a med is an inducer of a CYP3A4 enzyme and another med, normally metabolized by CYP3a4 is given, what will happen?

Answer 61

it will be metabolized faster

Question 62

if an APC med metabolized by CYP3A4 is given with a med which induces CYP3a4, what will you expect?

Answer 62

the APC will be converted into an inactive metabolite at a faster rate. less of a clinical effect will be seen.

Question 63

if a prodrug, normally metabolized by CYP3A4, is given with a med that induces CYP3a4, what will you expect?

Answer 63

the prodrug will be converted to an active metabolite quicker and a greater clinical effect will be seen.

Question 64

if you have a med that inhibits CYP3A4 and then an APC given that is metabolized by cyp3a4, you should expect

Answer 64

a greater clinical effect/concentration because the APC will not be metabolized into an inactive metabolite as quickly. the active form of the drug will remain active for longer.

Question 65

if you have a med that inhibits CYP3A4 and a prodrug metabolized by CYP3A4, what will you expect?

Answer 65

diminished effect. the inactive drug will not be metabolized into its active metabolite at the rate it normally would.

Question 66

atorvastatin is a prodrug and CYP3A4 substrate. ketoconazole is a moderate inhibitor of CYP3A4. give them together - what is the expected outcome?

Answer 66

moderately diminished effect. inactive parent form would not be metabolized into its active metabolite as it normally would be.

Question 67

diltiazem is an APC and known substrate of CYP3A4. St John's Wort is a CYP3A4 inducer. Give them together - what do you expect?

Answer 67

diltiazem would have a diminished effect because its active parent compound would be metabolized quickly

Question 68

absorption of medications is based on

Answer 68

route of administration

Question 69

volume of distribution is a

Answer 69

proportionality constant

Question 70

which meds cross membranes easier? protein bound or free/unbound form?

Answer 70

free/unbound

Question 71

CYP enzymes are

Answer 71

hepatic enzymes responsible for drug metabolism of many meds

Question 72

measuring the clearance of a med gives insight on

Answer 72

how well an organ is functioning

Question 73

equation for volume of distribution

Answer 73

Vd = amount in body at equlib OVER conc in plasma

Question 74

Cmax

Answer 74

dose concentration that dose achieves

Question 75

Tmax

Answer 75

time is takes to reach Cmax