Test 1 Part IV

Question 1

saying the clearance of a drug is 2mg/min would be an example of __________________

Answer 1

zero order kinetics

Question 2

define half life

Answer 2

the time it takes for the total amount of drug in the body to be reduced by 1/2

Question 3

_________ half lives must elapse before the full effect of a dosing regiment can be seen

Answer 3

4

Question 4

a drugs half life is dependent on what two factors

Answer 4

Vd and clearance

Question 5

define bioavailability

Answer 5

the fraction of unchanged drug reaching systemic circulation following administration

Question 6

what is the bioavailability of any drug administered IV assumed to be?

Answer 6

100%

Question 7

what decreases the bioavailability of drugs administered PO?

Answer 7

poor absorption across the GI tract
first pass elimination

Question 8

what are the two main organs that affect the bioavailability of drugs administered PO

Answer 8

liver and GI tract

Question 9

when is a loading dose utilized

Answer 9

when drugs have long half lives

Question 10

what is the goal with the loading dose?

Answer 10

to promptly raise blood concentration levels

Question 11

what is the most important influencing factor with dosing a loading dose?

Answer 11

volume of distribution (Vd)

Question 12

what is the most important influencing factor with dosing a maintenance dose

Answer 12

clearance

Question 13

what is the purpose of the mainteance dose?

Answer 13

to keep a steady state of drug in the body. just enough is given to replace what was eliminated since the preceding dose

Question 14

T/F: rate of administration may be crucial with a loading dose

Answer 14

true

Question 15

what can be an adverse effect of a loading dose

Answer 15

transient, potentially severe toxicity

Question 16

what is biotransformation

Answer 16

a process of drug metabolism that alters the chemical structure of a lipid soluble drug to make it water soluble for elimination

Question 17

only ______________ substances can be excreted in the kidneys

Answer 17

water soluble

Question 18

byproduct metabolites formed from biotransformation are often _____________ pharmacologically active than the parent drug, but they could also be _____________, _____________, or _______________

Answer 18

less; inactive; more enhanced activity; toxic activity

Question 19

what is the principle organ of drug metabolism and thus also of biotransformation

Answer 19

liver

Question 20

what are other areas of drug metabolism besides the liver

Answer 20

GI tract, Lungs, skin, kidneys, brain

Question 21

the _________________ harbors a lot of micro-organisms that are capable of many biotransformation reactions

Answer 21

lower gut

Question 22

if there is compromise of the liver, primary site of metabolism for drug A, what can be the result?

Answer 22

significant elevations of plasma levels, which is clinically relevant in drug-drug interactions

Question 23

drug metabolizing enzymes are found specifically in the ________________ of the liver

Answer 23

endoplasmic reticulum

Question 24

what are the phases of biotransformation

Answer 24

phase I - oxidative reduction
phase II - conjugation

Question 25

in phase I of biotransformation, oxidation =

Answer 25

P450 + P450 reductase + NADPH + O2

Question 26

the oxidation process of phase I biotransformation will consume one molecule of ___________ (reduced) and produce ______________ + _____________

Answer 26

O2; a metabolite; H2O

Question 27

which phase of biotransformation changes the polarity of the drug

Answer 27

phase I - oxidation

Question 28

if a metabolite produced from a phase I reaction is sufficiently polar it will be ______________; if not then it will ________________

Answer 28

excreted; undergo phase II reaction

Question 29

what are the 2 key enzymes involved in the phase I (oxidative reduction) of biotransformation

Answer 29

NADPH-cytochrome P450 oxidoreductase (flavoprotein) and Cytochrome P450

Question 30

what would increase the availability of P450s

Answer 30

repeated administration of or exposure to exogenous chemicals

Question 31

what does CYP (P450) "induced" mean

Answer 31

there is an enhanced rate of synthesis or reduced rate of degradation

Question 32

what are the results/consequences of being CYP (p450) "induced"

Answer 32

1. results in accelerated metabolism and usually in a decrease in the pharmacologic action of the inducer and co-administered drugs 2. may exacerbate metabolite mediated toxicity

Question 33

what environmental/occupational factors have been found to be capable of inducing P450 enzymes

Answer 33

1. smoking 2. industrial workers 3. those that work with insecticides

Question 34

what drugs have been found to be P450 inducers

Answer 34

1. antipsychotics 2. various sedative-hypnotics 3. anticonvulsants 4. rifampin

Question 35

in general, if a drug is a p450 inducer or inhibitor it is safe to assume what?

Answer 35

all drugs within that class have same action on P450

Question 36

if something is a P450 inhibitor, what is the result

Answer 36

decreased metabolism

Question 37

what is the mechanism at which a drug is a P450 inhibitor?

Answer 37

tells the apo protein responsible for making the P450 not to make it --> decreases metabolism

Question 38

_____________ is responsible for metabolizing over 50% of prescription drugs metabolized in the liver

Answer 38

CYP3A4

Question 39

P450 is an enzyme, and is specifically a ________________

Answer 39

hemoprotein

Question 40

if an enzyme is described as microsomal, you know that means what?

Answer 40

they are a part of the Smooth ER and Rough ER

Question 41

what are the microsomal reactions of a phase I biotransformation reaction

Answer 41

Cytochrome P450 oxidation

Question 42

what are the non-microsomal reactions of a phase I biotransformation reaction

Answer 42

oxidation and hydrolysis

Question 43

phase II of biotransformation is called ___________________

Answer 43

conjugation

Question 44

define what happens in the Phase II (conjugation) biotransformation reaction

Answer 44

metabolic byproducts (not sufficiently polar) of phase I are further conjugated into highly polar molecules by an endogenous substrate

Question 45

phase II of biotransformation forms drug conjugates, what is the purpose of this?

Answer 45

makes the drug metabolites highly polar, which makes them readily excreted and often inactivated

Question 46

what endogenous substrates are commonly used in a phase II biotransformation reaction

Answer 46

glucuronic acid, sulfuronic acid, acetic acid, amino acid

Question 47

where do endogenous substrates for phase II biotransformation reaction come from

Answer 47

diet and often affected by nutrition status

Question 48

2 drugs may compete for the same endogenous substrate during a phase II biotransformation reaction, what could be the result of this

Answer 48

the faster drug may deplete substrate reserves and impair the metabolism of the slower reacting drug. if the slower reacting drug has a narrow therapeutic index --> toxicity/death

Question 49

what is required for a phase II biotransformation reaction to occur

Answer 49

1. endogenous substrate 2. energy 3. transferase

Question 50

what is the most dominant transferase enzyme found in the cytoplasm for phase II biotransformation reaction

Answer 50

uridine 5'-diphosphate-flucuronosyl transferases (UGTs)