L8, L9 Pharmacokinetics

Question 1

What makes up pharmacokinetics?

Answer 1

drug absorption
drug distribution
drug metabolism
drug excretion

Question 2

drug in circulation will be at ______ with tissue reservoirs?

Answer 2

equilbrium

Question 3

only a fraction of drug that binds to specific receptors will have a ____

Answer 3

pharmacological effect

Question 4

how does the drug get to the site of action?

Answer 4

• crosses membrane
• gets into systemic circulation or lymph system
• needs to workout how best to get the drug into circulation

Question 5

what is the first barrier to oral administration of drugs?

Answer 5

GI epithelium

Question 6

what is membrane diffusion favored by?

Answer 6

concentration gradient - high

+ change on drug (inside of cell is -)

Question 7

what does the pKa represent?

Answer 7

pH value when 1/2 of the drug in protonated and half deprotonated

Question 8

what is pH trapping

Answer 8

for weakly acidic drugs, the protonated, electrically neutral drug is predom. in the highly acidic environment of the stomach. the uncharged drug can pass through lipid bilayers of GI mucosa. the weakly acidic drug is then trapped as it is deprotonated to its electrically charged form in the more basic environment of the plasma.

Question 9

what is the version of Henderson Hasselablch equation that I will use?

Answer 9

Pka - pH = log [HA]/[A-]

HA protonated form
A- deprotonated form

Question 10

a weakly acidic drug in an acidic enviromment will ne ?

Answer 10

protonated - neutral

Question 11

a weakly acidic drug in an basic or neutral environment will be?

Answer 11

deprotonated - charged

Question 12

what is pKa

Answer 12

acid dissociation constant

Question 13

if the pH < pKa -

Answer 13

protonated form favored (HA, BH+)

Question 14

if pH > pKa -

Answer 14

unprotonated form favored ( A-, B)

Question 15

define absorption

Answer 15

getting drug into circulation

bioavailability

Question 16

what is bioavilability

Answer 16

drug reaching circulation / drug administered

Question 17

what are routes of administration?

Answer 17

enteral - oral, by mouth
parenteral - directly to circulation, CSF etc. using SC, IM, IV, IA, IT (intrathecal)
mucous membrane - sublingual, nasal, rectal etc.
transdermal - nicotine patch, androgel etc.

Question 18

what are the advantages of enteral drug administration?

Answer 18

simple
cheap
self-administer
low infection rate

Question 19

what are the disadvantages of the enteral administration drug route?

Answer 19

passes through GIT
first pass metabolism
relatively slow delivery

Question 20

which drugs pass through the cell membrane more efficiently?

Answer 20

hydrophobic and neutral drugs

Question 21

what is first pass metabolism?

Answer 21

after drugs pass GI epithelium they are carried by the portal system to the liver before entering systemic circulation. With this process, liver enzymes may inactivate a fraction of the ingested drug

Question 22

what are the advantages of parenteral drug administration?

Answer 22

rapid onset

high bioavailability

Question 23

what are the disadvantages of parenteral drug administration?

Answer 23

infection
need skilled personal for delivery
hurts
irreversible effect

Question 24

what is the fastest way to get a drug to target organ?

Answer 24

IV, IA or intrathecal

Question 25

for drugs that are soluble in oil-based solutions what parenteral route should I use?

Answer 25

IM

Question 26

what are advantages of mucous membrane drug administration?

Answer 26

``` DIRECT ACTION rapid absorption low infection incidence convenient no harsh GI environment + first pass metabolism ```

Question 27

mucous membranes are highly vascular and drugs enter ____ into the systemic circulation

Answer 27

directly

Question 28

what is atropine?

Answer 28

from Atropa belladonna - Deadly nightshade counters "rest and digest" form PNS competitive antagonist of muscarinic receptor it dilates pupil, increase heart rate, reduces salivation

Question 29

in order for a drug to pass transdermally, what should the drug be?

Answer 29

highly lipophilic - nicotine or estrogen patches

Question 30

what is transdermal administration ideal for?

Answer 30

drugs that must be slowly and continuously administered over extended periods of time

Question 31

what are the benefits of transdermal drug administration?

Answer 31

- no infection risk - simple - convenient

Question 32

what is the rate of absorption affected by?

Answer 32

local, regional and systemic factors

Question 33

what has the greatest effect on absorption?

Answer 33

regional blood flow

Question 34

the rate of absorption affects what?

Answer 34

- local concentration of the drug | - duration of action

Question 35

what primarily achieves drug distribution? what plays a minor role in drug distribution?

Answer 35

circulatory system | lymphatic system

Question 36

once the drug hits systemic circulation, it is able to go where?

Answer 36

to any target organ - except brain and testes...

Question 37

what is used to define and monitor therapeutic drug levels?

Answer 37

concentration of drug in plasma

Question 38

what is the volume of distribution?

Answer 38

extent to which the drug partitions between the plasma and the tissue compartments its the fluid volume that would be required to contain the total amount of absorbed drug in the body at a concentration equivalent to that in the plasma at steady state

Question 39

what is the equation for volume of distribution?

Answer 39

Vd = Dose / [Drug]plasma

Question 40

when are Vd low?

Answer 40

drugs that are retained within vascular compartment

Question 41

when are Vd high?

Answer 41

drugs that are highly distributed into muscle, adipose and nonvascular compartments

Question 42

a drug that is highly distributed, gives a ____ plasma concentration for a set dose

Answer 42

lower

Question 43

what is the most abundant plasma protein?

Answer 43

albumin

Question 44

drugs with high affinity for plasma proteins keep Vd ____ and free drug ___

Answer 44

low | low

Question 45

what happens to the drug concentration in the distribution phase?

Answer 45

results in sharp decrease in the plasma drug concentration shortly after intravenous administration of a drug bolus - because of the drug elimination from the body

Question 46

what happens to the drug concentration during the elimination phase?

Answer 46

the plasma drug concentration decreases more slowly during the elimination phase due to the " reservoir" of drug in tissues that can diffuse back into blood to replace the drug that has been eliminated

Question 47

*The half time for drug________ is longer than the | half time for drug _____

Answer 47

elimination | distribution

Question 48

what is the first extracellular compartment where drug concentration increases?

Answer 48

vessel rich group

Question 49

which groups have a higher capacity for taking up drug than vessel rich?

Answer 49

muscle rich and adipose rich

Question 50

what group accumulates the greatest amount of drug at the slowest rate?

Answer 50

adipose rich group

Question 51

what drug character can enter liver cells?

Answer 51

hydrophobic drugs

Question 52

what can the liver do to drugs?

Answer 52

- may make them more active | - usually become inactive and ready for excretion (biotransformation - red/ox conj/hyd)

Question 53

where are most drugs broken down?

Answer 53

liver

Question 54

where are most drugs excreted?

Answer 54

by the kidney some in bile some oral drugs not fully absorbed - feces

Question 55

what determines the kinetics of drug elimination by the kidney?

Answer 55

balance of filtration, secretion, and reabsorption

Question 56

what factors influence renal excretion?

Answer 56

increased urine flow | pH trapping

Question 57

how do drugs get from liver to intestines?

Answer 57

ABC transporters (ATP binding cassette)

Question 58

define clearance?

Answer 58

the amount of active drug cleared relative to the amount in plasma

Question 59

what is the equation for clearance?

Answer 59

clearance = metabolism + excretion / [drug in plasma] clearance = clearance (by kidney + liver + anywhere else)

Question 60

what happens to the rate of drug elimination when plasma drug concentration is increased?

Answer 60

increases *amount of drug excreted is proportional to the concentration in the plasma E = (Vmax X C) / (Km + C)

Question 61

what happens if you saturate the mechanisms involved in clearance?

Answer 61

you no longer see first order kinetics

Question 62

what is half life?

Answer 62

the amount of time over which the drug concentration in the plasma decreases to one-half of its original value follows first order kinetics - what I will be dealing with

Question 63

what factors increase half life?

Answer 63

decreasing clearance - liver, kidney, cardiac failure - inhibition of CY P450 increasing Vd (plasma concentration LOW) - major = drug properties - solubility, binding to plasma proteins, binding within compartments - minor = obesity, edema/ascities

Question 64

what is the therapeutic range?

Answer 64

steady state when what goes in = whats going out

Question 65

where do we want the steady state concentration to lie?

Answer 65

within the therapeutic range

Question 66

what is the loading dose?

Answer 66

allows you to get to therapeutic range quicker takes Vd into account huge dose one time

Question 67

what is maintenance dose?

Answer 67

dose required to maintain the drug concentration within the therapeutic range

Question 68

how many half-lifes does it take to reach a steady state concentration in the plasma?

Answer 68

4 half lives

Question 69

what happens when drug delivery beats the rate of breakdown?

Answer 69

saturation leads to zero order elimination