Pharmacokinetics

Question 1

what are the 4 main pharmacokinetic processes

Answer 1

1) absorption
2) distribution
3) metabolism
4) excretion

Question 2

what is absorption

Answer 2

movement of the drug into systemic circulation

Question 3

what is bioavailability

Answer 3

fraction of administered drug that reaches the systemic circulation unchanged

Question 4

what route is associated with the highest and the lowest bioavailability

Answer 4

highest: IV (100%)
lowest: oral

Question 5

If 70% of buprenorphine is metabolized by the liver in one pass, what is the oral bioavailability?

Answer 5

30%

Question 6

the most rapid absorption is associated with what route

Answer 6

IV (essentially instantaneous)

Question 7

faster absorption is associated with ___________ effect and _________ duration, whereas slower absorption is associated with _______________ effect and _________ duration

Answer 7

faster absorption is associated with stronger effect and shorter duration

slower absorption is associated with smaller effect and longer duration

Question 8

what is the risk if absorption is too slow

Answer 8

may not reach MEC for desired effect (drug is being eliminated as it is being absorbed)

Question 9

what are the two classifications of administration and what is the difference

Answer 9

enteral (goes through liver before entering systemic circulation) and parenteral (does not pass through liver before entering systemic circulation)

Question 10

classify oral, IM, IV, and SQ as either parenteral or enteral

Answer 10

Enteral: oral
Parenteral: IV, IM, SQ

Question 11

what is always a concern with oral drugs

Answer 11

emesis and GI irritation possible, so the drug may never reach the MEC due to vomiting

Question 12

is sublingual route enteral or parenteral

Answer 12

parenteral (it is absorbed across the oral mucosa into the systemic circulation)

Question 13

what type of drugs is SQ good for

Answer 13

insoluble, oily, or solid pellets (note: should not be chemically irritating)

Question 14

how could you slow the absorption of an IM drug

Answer 14

form an oily suspension

Question 15

what type of administration is suitable for large volumes of drugs

Answer 15

IV bolus injection

Question 16

what is a major drawback of IV administration

Answer 16

need to administer slowly to prevent cardiac toxicity

Question 17

what is the safest route of administration of irritating drugs

Answer 17

IV CRI

Question 18

if you needed to deliver a drug to a specific site (ex. the testes) in high concentrations, what route of administration would you choose

Answer 18

topical

Question 19

what is the difference between topical and transdermal

Answer 19

transdermal is absorbed into the systemic circulation from the skin to have actions elsewhere in the body; topical is meant to be absorbed and act on the site of administration

Question 20

in what form is a drug more easily absorbed and what would this form be for a weak acid and weak base

Answer 20

more easily absorbed in unionized form (lipid soluble form); AH or B

Question 21

in what form is a drug more easily excreted and what would this form be for a weak acid and weak base

Answer 21

ionized form (water soluble form); A- or BH+

Question 22

Will a weakly acidic drug with a pKa of 4.4 be better absorbed from the stomach (pH = 1.4) or small intestine (pH = 6.4)?

Answer 22

stomach (because it will be in its unionized form, AH)

Question 23

A weakly basic drug with a pKa of 8.4 is administered orally. Will it be better absorbed from the stomach (pH = 2.4) or small intestine (pH = 6.4)

Answer 23

small intestine (because more will be in its unionized form, B)

Question 24

Assuming you want to maximize absorption, would most oral drugs be weak acids or weak bases?

Answer 24

weak acids

Question 25

Do drugs accumulate on the side of the membrane where ionization is highest or lowest?

Answer 25

highest (aka BH+ or A-)

Question 26

Will a base accumulate in an environment that is more acidic or more basic?

Answer 26

It will accumulate where it is BH+ therefore acidic

Question 27

Will an acid accumulate in an environment that is more acidic or more basic?

Answer 27

It will accumulate where it is A- therefore basic

Question 28

What is distribution

Answer 28

movement of the drug from systemic circulation into other tissues

Question 29

what is the distribution pathway

Answer 29

blood plasma -> extracellular fluid -> cells

Question 30

T/F only a small fraction of each dose reaches the target receptor sites

Answer 30

true (the rest accumulates where it isn't needed or is excreted before it reaches target receptors)

Question 31

what 4 factors influence drug distribution

Answer 31

1) physiochemical properties of the drug 2) anatomy and physiology of the animal 3) plasma protein binding 4) tissue drug binding

Question 32

once a drug enters blood, how long does it take to distribute to the entire blood volume

Answer 32

1-2 minutes

Question 33

in the short term, tissues that ____________ receive more drug; in the long term, tissues that _______________ receive drug as equilibrium between occurs

Answer 33

have higher blood flow; are larger but less well-perfused

Question 34

what types of drugs enter the BBB well

Answer 34

highly lipid soluble and low protein-binding

Question 35

T/F protein bound drug will not be distributed to tissues to produce the effect and instead will be excreted

Answer 35

F; they will not be able to enter tissues to produce a desired effect, but they will also not be excreted

Question 36

what is the consequence of plasma protein binding on half-life and drug intensity

Answer 36

increases half-life but decreases intensity of effect

Question 37

T/F protein/drug binding is a nonlinear, saturable process

Answer 37

T

Question 38

The local anesthetic lidocaine is a weak base. It must diffuse into neurons to reach its target receptors. If infected tissue is more acidic than healthy tissue, would you expect lidocaine to be more or less effective in infected tissue.

Answer 38

Less effective. Rationale: 1) to diffuse into tissues, lidocaine needs to be in its unionized form (aka B) 2) in an acidic environment, lidocaine will be in the BH+ form, which is ionized

Question 39

Explain: Mepivacaine is a weak base used for equine nerve blocks that diffuses better in tissues than other local anesthetics because it has a lower pKa

Answer 39

pH is greater than pKa - favours the B form, which makes it easier to diffuse into tissues

Question 40

From a pharmacokinetic point of view, what are the two compartments of the body

Answer 40

1) vascular compartment 2) everything else

Question 41

a higher Vd indicates

Answer 41

more drug has left the bloodstream and entered tissues

Question 42

if some drug has been distributed to other tissues, Vd will be ____________ than blood volume

Answer 42

greater

Question 43

how do we express Vd

Answer 43

L/kg BW or mL/kg BW

Question 44

drugs with a small Vd may require _________ doses to be effective

Answer 44

larger

Question 45

drugs with a large Vd may take _______ time to excrete

Answer 45

longer (the drug needs to be in the blood to be delivered to an organ of elimination)

Question 46

You would expect a water-soluble (ionized) drug to have a ________ Vd, whereas you would expect a lipid-soluble (unionized) drug to have a ___________ Vd

Answer 46

small to intermediate; high

Question 47

What would be more readily excreted in the urine, a drug with a pKa of 7.4 that is a weak acid or a weak base? Assume blood pH = 7.4 and urine pH = 5.4

Answer 47

weak base; want it to be in its ionized form in the urine (BH+ vs AH)

Question 48

What is another word for metabolism

Answer 48

biotransformation

Question 49

define metabolism

Answer 49

any chemical change made to a drug from the body

Question 50

what are the two goals of metabolism and what is the exception?

Answer 50

1) make drug more water soluble 2) make drug inactivated Exception: pro-drugs that must be metabolized into their active form

Question 51

what is the main location of drug metabolism

Answer 51

liver

Question 52

what are phase I reactions? what are phase II reactions?

Answer 52

phase 1: non-synthetic "functionalization" phase 2: biosynthetic "conjugation"

Question 53

phase I reactions inactivate drugs mainly by what mechanism

Answer 53

oxidation

Question 54

in comparison to the parent molecule, phase 1 metabolites are usually more (2)

Answer 54

water-soluble and chemically reactive

Question 55

phase II metabolites are usually (3)

Answer 55

polar, inactive and readily excreted

Question 56

what dietary component of phase II metabolism are cats deficient in

Answer 56

glucuronic acid

Question 57

cats are deficient in many transferases for phase II metabolism, which has what consequence

Answer 57

they have difficulty metabolizing many drugs and they therefore reach higher concentrations and have longer duration of action

Question 58

what is the normal process of acetaminophen metabolism and how does this differ in the case of toxicity

Answer 58

normally: undergoes phase II metabolism by conjugation to glucuronic acid or sulphate overdose: conjugation pathways overwhelmed -> metabolized via phase I metabolism by P450 enzymes into highly reactive NAPQI -> liver failure

Question 59

you have a cat present with acetaminophen toxicity - what is your first step?

Answer 59

administer a source of glutathione -> get the phase II conjugation pathways working again

Question 60

what are 6 factors that impact the rate of drug metabolism

Answer 60

1) enzyme induction and inhibition 2) multidrug therapy 3) distribution 4) age 5) genetics 6) disease

Question 61

A food/drug constituent increases the activity of a hepatic enzyme. What effect will this have on drug action and rate of drug metabolism?

Answer 61

decreases the drug action by increasing the rate of drug metabolism

Question 62

what are the organs involved in elimination

Answer 62

kidney, liver, lungs, intestinal tract, other (sweat, milk, tears)

Question 63

T/F glomerular filtration is a non-saturable and non-selective process

Answer 63

T

Question 64

a constant ________ of drug in the body is eliminated per unit tme

Answer 64

fraction

Question 65

after how many half-lives have we essentially eliminated all of the drug

Answer 65

4-5

Question 66

what is steady state

Answer 66

when plasma concentration of drug varies between two set levels without any accumulation

Question 67

steady state is achieved within how many half-lives for any regular dosing regimen

Answer 67

5

Question 68

why is a steady state reached and the plasma concentration doesn't continually go up

Answer 68

kidneys filter a constant fraction of drug per time; a situation is reached within the dosing regimen where the amount administered per dose is equal to the amount cleared by the kidneys, so the values stabilize

Question 69

how do we minimize fluctuations in drug concentration

Answer 69

giving small doses frequently (ex. a CRI)

Question 70

if rate of drug administration is doubled, what happens to the steady state drug concentration, Css

Answer 70

doubles

Question 71

how can you reach Css instantly

Answer 71

give a loading dose, wait 1 half-life and then give normal dose

Question 72

In the case of renal failure, what happens to drug half life and why

Answer 72

increases, because the rate of excretion decreases

Question 73

how are some drugs excreted by the liver

Answer 73

undergoing phase II metabolism followed by active excretion into bile -> into gut -> eliminated in feces

Question 74

T/F enterohepatic recycling depends on route of administration

Answer 74

F; just depends on secretion of the drug into the bile

Question 75

what is drug response proportional to

Answer 75

concentration of free drug at the target organ

Question 76

how do we express clearance

Answer 76

volume (because it will not change based on the concentration of drug)