Pharmacokinetics

Question 1

Absorption

Answer 1

Movement of drug from site of administration to bloodstream

Question 2

Factors affecting Absorption

Answer 2

Concentration gradient, size (<1 kDA), lipid solubility/membrane permeability

Question 3

Charged drug

Answer 3

Hydrophilic and cannot diffuse

Question 4

Uncharged drug

Answer 4

hydrophobic, passive diffusion

Question 5

Which route of administration is not absorption?

Answer 5

Intravenous (IV)

Question 6

Distribution

Answer 6

Reversible movement of drug from bloodstream to tissues

Question 7

Factors affecting distribution

Answer 7

Concentration gradient, size (<1 kDA), lipid solubility/membrane permeability
Blood flow, protein binding

Question 8

Blood flow and order (high –> low conc.)

Answer 8

Drug is delivered to tissues in relation to perfusion:
heart, liver, kidneys, brain –>muscles, skin, –> fat

Question 9

Protein binding and example

Answer 9

Drugs bind reversibly to plasma proteins
Ex. albumin

Question 10

What is the effect of protein binding?

Answer 10

Sequester (trap) drug in blood –> can’t distribute to target receptors, becomes pharmacologically inactive
decrease [free drug] = decrease therapeutic effect

Question 11

Volume of distribution (Vd)

Answer 11

Relates amount of drug in body to its concentration in the blood

Question 12

What does a large Vd mean (>42L)

Answer 12

drug distributes outside blood and body fluids into tissues/fat

Question 13

What does a small Vd mean (<42 L)

Answer 13

drug has limited distribution, typically restricted to blood or physiological fluid components

Question 14

Volume of Intracellular fluid (ICF)

Answer 14

28L

Question 15

Volume of Extracellular fluid (ECF)

Answer 15

14L

Question 16

Volume of Interstitial fluid

Answer 16

11L

Question 17

Volume of Plasma

Answer 17

3L

Question 18

Metabolism and its objective

Answer 18

Conversion of parent drug to metabolite(s), prepare drug for excetion

Question 19

How and where does metabolism occur?

Answer 19

primarily in liver via 2 enzyme-catalyzed processes

Question 20

Phase 1 of metabolism

Answer 20

Oxidation/reduction/hydrolysis
P450 enzymes add new or uncover existing polar group = increase H2O solubility

Question 21

P450 enzyme inducers

Answer 21

increase enzyme activity = metabolism speeds up

Question 22

What effect does a drug + inducer have?

Answer 22

Increase P450 = increase metabolic rate
subtherapeutic response

Question 23

P450 enzyme inhibitors

Answer 23

decrease enzyme activity = metabolism slows down

Question 24

What effect does a drug + inhibitor have?

Answer 24

Decrease enzyme activity = decrease metabolism
toxicity (drug accumulates in body)

Question 25

Phase 2 metabolism

Answer 25

Non-P450 enzymes covalently add large, polar, endogenous molecules to Phase 1 metabolite or parent drug

Question 26

What effect does Phase 2 have?

Answer 26

Change in structure + large = can’t fit into receptor
Polar = hydrophillic, prone to excretion

Question 27

Prodrugs

Answer 27

Inactive drugs that become pharmacologically active after metabolism

Question 28

Kidney excretion results in?

Answer 28

Irreversible loss of drug from body

Question 29

What are the 2 primary routes of drug excretion?

Answer 29

1. Passive glomerular filtration
2. Active tubular secretion

Question 30

Passive glomerular filtration

Answer 30

Small drugs passively diffuse from blood to kidney

Question 31

Active tubular secretion

Answer 31

Large drugs actively transported by protein carriers from blood to kidney

Question 32

Passive tubular reabsorption

Answer 32

Small/hydrophobic drugs with high concentration reabsorbed from kidney to blood, depends on urine pH

Question 33

Excretion with bile

Answer 33

Drugs actively secreted from liver to intestine via common bile duct

Question 34

What does it mean for bile excretion to be an active process?

Answer 34

Carrier mediated, not limited by size, protein binding, or ionization

Question 35

Why are some areas of the lines of different routes of administration on a C vs T graph parallel?

Answer 35

Same drug = same distribution, metabolism, and excretion.
Only difference is absorption

Question 36

How can you tell which line represents oral and IV administration on a C v.s. T graph?

Answer 36

IV: Cmax is at t=0 because it is instantaneous

Question 37

MEC

Answer 37

Minimum effective concentration of a drug

Question 38

Therapeutic Range

Answer 38

Concentration range between MEC and MTC, range where drug is considered effective and safe

Question 39

MTC

Answer 39

Minimum toxic concentration of a drug. If [drug]>MTC -> toxic effects

Question 40

Elimination Half-life (t1/2)

Answer 40

Time required for drug concentration to decrease by one half (50%)

Question 41

Drug washout

Answer 41

Time required for a drug to be completely eliminated from the body (approximately 5 half-lives)

Question 42

Repeat dosing

Answer 42

Administration of multiple doses of a drug over time

Question 43

Peak and trough

Answer 43

Maximum and minimum drug concentrations in the body

Question 44

Steady state

Answer 44

Rate of drug elimination equals rate of drug administration

Question 45

Passive approach

Answer 45

Reaching steady state by giving repeated doses over 5 half-lives

Question 46

Active approach

Answer 46

Reaching steady state by giving a loading dose

Question 47

Loading Dose (LD)

Answer 47

Single large dose to quickly raise plasma drug concentration to therapeutic level

Question 48

Maintenance Dose (MD)

Answer 48

Smaller doses given at intervals to maintain steady state

Question 49

Vd

Answer 49

Volume of distribution of a drug

Question 50

How do we calculate LD for IV administration?

Answer 50

Same equation except F=1 (bioavailability = 100%)