test 3

Question 1

rate of elimination

Answer 1

mass removed per unit time (mg/hr)

Question 2

which order is the clearance

Answer 2

first order drugs

Question 3

concentration

Answer 3

mass per volume (mg/L)

Question 4

clearance

Answer 4

volume per unit time (L/hr) , Q X E, flow rate times extraction ratio, clearance is a consitant and based on pt liver, kidney, and blood flow to different organs.

Question 5

the resevior represents

Answer 5

vd

Question 6

the extractor represents

Answer 6

organ eliminating drug

Question 7

amount represents

Answer 7

mass of drug in the body “dose”

Question 8

volume represents

Answer 8

vd

Question 9

Q represents

Answer 9

blood to/from organ

Question 10

C and Cout represents

Answer 10

drug going in / out of organ (extractor)

Question 11

E represents

Answer 11

Extraction ratio, Rate of Elimination divided by Rate of presentation

Question 12

high E vs low E

Answer 12

high means the liver chews it up, low means there is a slower process in the liver “how effective is the body at removing the drug”

Question 13

rate of presentation

Answer 13

how much drug is being presented/unit time, Q X Cin - flow to the extractor and multiplying by the concentration of the drug that is entering

Question 14

Rate of elimination

Answer 14

flow rate into and out of the extractor, Q, and multiplying by the difference between the concentration coming in and coming out OR Rate of presentation X Q X E. Concentration dependent. ROE x Cl volume cancles. ROE = Conc x CL

Question 15

extraction ratio

Answer 15

rate of elimination divided by the rate of presentation (C in-C out)/ C in

Question 16

what variables could we manipulate in order to change the rate of drug elimination

Answer 16

blood flow to make Q lower than normal - liver is more confined. Q and E can affect the liver to remove the drug

Question 17

Cl / vd

Answer 17

clearance

Question 18

as k becomes small

Answer 18

half life longer, clearance small, vd large

Question 19

if Cl is big

Answer 19

K is big (hr -1)

Question 20

fractional RoE

Answer 20

RoE / Ao (dose)

Question 21

can you change the extraction ratio?

Answer 21

yes! drug inhibitor of an enzyme, enzyme inducer- cl changes and goes up, give more drug

Question 22

enzyme inducer

Answer 22

clearance will change and go up! excreting the drug faster. half life will decrease and give more drug because of eliminating more frequent!

Question 23

why does k stay the same

Answer 23

cl and vd are dependent on body weight. as cl increases the vd will also increae. the half life will also stay the same. if a drug is fat soluble then the k may change

Question 24

other ways to say drug metabolism

Answer 24

xenobiotic metabolism, drug metabolism, drug biotransformation

Question 25

in general drug metabolism

Answer 25

converts a lipophillic substance, chemical to a metabolite (product) that is more hydrophilic than the parent drug in order to facilitate elimination - filtered more easily - the drug is usually catalyzed by enzymes

Question 26

in drug metabolism it is usually catalyzed by enzymes

Answer 26

1. multiple enzymes and paths are possible for a single drug | 2. multiple metabolites with varying properties are possible - metabolite can be more active than the parent drug

Question 27

routes of elimination for top 200 drugs by percentage

Answer 27

75% metabolism 20% kidneys 15% bile (does not chemically alter the drug or else it would be metabolism - hepatocyte takes from blood and puts it in the bile!)

Question 28

consequences of drug metabolism

Answer 28

usually inactivation, the pharmacological activity (therapeutic or toxic) may be changed, resulting metabolites can be classified as active or inactive

Question 29

inactive metabolites

Answer 29

devoid of pharmacological activity, metabolic changes result in the termination of drug action, chemical properties of the drug are changed, affecting how a drug interacts with target or changes the distribution of the drug EX: blocks alpha1 receptors and then blocks Beta1 receptors when metabolized

Question 30

active meatabolites

Answer 30

have pharmacological activity, similar to the desired activity, unexpected/new activity not observed with parent drug

Question 31

what effect can a quinone do

Answer 31

causes harm in the body - deplete glutathione which can result in no liver activity afterwards

Question 32

nor/des

Answer 32

without a methyl group

Question 33

drug bioactivation

Answer 33

``` parent drug (prodrug) has no pharmacological activity to attain pharmacological activity the prodrug must undergo metabolism - more lipophilic will cross the membrane and enhance absorption, when it overcomes activation it is now more polar ```

Question 34

where is the highest concentration of drug metabolizing enzymes

Answer 34

liver

Question 35

phase one reactions

Answer 35

oxidation, hydrolysis, reduction, add or reveal a polar functional group, inc water solubility and facilitate excretion, does not always terminate drug action, metabolite may undergo phase 2 reactions. can go through several phase one reactions, small functional group

Question 36

phase two reactions

Answer 36

conjugation, add biomolecules to a functional group on drug or phase one metabolite. increases water solubility and facilitates elimination, increases molecular weight (sulfate or glutathione) and requires a high energy cofactor, usually terminates drug action, phase 2 conjugates may undergo phase 1 metabolism

Question 37

oxidation

Answer 37

most common phase 1 reaction, largely catalyzed by the cytochrome 450 enzymes, responsible for metabolism of 85% of drugs, several isoforms of CYP450, broad substrate specificity, looks for lipophilic and tries to make it more hydrophilic

Question 38

about CYP450

Answer 38

contains heme molecules bound to iron (Fe), absorbs light at or near 450 nm when Fe is bound to carbon monoxide, embedded in the endoplasmic reticulum of cells, requires a NADPH and molecular oxygen - something has to be reduced,

Question 39

major CYP reactions

Answer 39

``` aromatic, aliphatic, acyclic hydroxylation alkene oxidation o and n dealkylation deamination N oxidation ```

Question 40

hydroxylation

Answer 40

adding a hydroxyl group, at places with little steric hindrance, para and ortho are the most reactive by p450

Question 41

alkene oxidation

Answer 41

converts it to an epoxide by a p450, very reactive molecule

Question 42

epoxide hydrolase

Answer 42

converts epoxide to two alcohols with addition of H2O, no p450 added, makes the molecule much less reactive

Question 43

O and N dealkylation

Answer 43

CYP2D6, remove methyl groups (alkyl groups)

Question 44

deamination vs dealkylation

Answer 44

deamination removes entire amine group, dealkylation just removes the methyl and makes the amine group primary

Question 45

N and S oxidation

Answer 45

adds an OH group. CYP. also catalyzed by flavin-containing monooxygenases (FMOs), FMOs and CYPs share a substrate