Pharmakokinetics

Question 1

Definition of Pharmacokinetics

Answer 1

what the body does to the drug

Question 2

Definition of pharmacodynamics

Answer 2

what the drug does to the body

Question 3

PK/PD definition

Answer 3

relation between pharmacokinetic and pharmacodynamic

Question 4

what are the 2 primary measures

Answer 4

1. CLEARANCE
2. VOLUME OF DISTRIBUTION

Question 5

clearance is the only parameter that determines what?

Answer 5

Clearance (Cl) is the only parameter that determines maintenance dose rate required to achieve a target plasma concentration (and therefore effect) at stetheady state

Question 6

what is volume of distribution

Answer 6

Volume of distribution (Vd) is an essential determinant of drug half-life, as t1/2 = 0.693 * Vd/Cl.

What this means is that for 2 drugs with the same clearance, but different voluymes of distribution, the bigger volume with have a longer half-life.

Question 7

what is bioavailability

Answer 7

Fraction of unchanged drug reaching the systemic circulation (F).

Question 8

what does systemic circulation (F) depend on in intravenous dosing?

Answer 8

f = 100%

Question 9

what does systemic circulation (F) depend on in oral dosing?

Answer 9

F depends on Absorption and Clearance

Question 10

what are 2 types of in vivo PK experiments

Answer 10

IV bolus dose
oral dose

Question 11

where is an intravenous bolus administered

Answer 11

plasma compartment

Question 12

where is oral dosing administered

Answer 12

Dosed into the gastro-intestinal tract

Question 13

what is Absorption

Answer 13

The Process by which a drug moves from the site of administration to the site of action

Question 14

what is absorption quantified by

Answer 14

Quantified by the Absorption rate constant (A First Order Process)

Question 15

what 3 unique properties does oral absorption require

Answer 15

Water Soluble in the gut

Lipophilic for membrane permeation

Water soluble in plasma

Question 16

what is distribution

Answer 16

is the process by which a drug moves from the bloodstream into the peripheral tissues

Question 17

what is distribution driven by

Answer 17

Driven by the relative affinity of binding for blood and tissue compartments

Question 18

what is distribution quantified by

Answer 18

Quantified by the Volume of Distribution (Vd)

“The ratio between the amount of drug in the body and the amount in the plasma”

Question 19

what 2 ways can calculate volume of distribution

Answer 19

Question 20

metabolism definition

Answer 20

Metabolism is the irreversible chemical alteration of a drug by a biological system

Question 21

Drug Metabolism can happen in most organs and is covered by 2 Phases:

what are the 3 phase 1 reactions and what is its aim

Answer 21

Introduces a new chemical group via:
Oxidation Reactions
Reduction Reactions
Hydrolysis Reactions

Aim: To produce Inactive metabolites

Question 22

Drug Metabolism can happen in most organs and is covered by 2 Phases:

what are the 3 phase 2 reactions and what is its aim

Answer 22

Conjugates the molecule with charged chemical species via:
Glucouronidation
Acylation
Sulfation

Aim: To decrease lipophilicity and increase solubility for enhanced excretion

Question 23

what is excretion

Answer 23

Excretion is the irreversible elimination of a drug from the systemic circulation and Clearance can be used to define excretion

Question 24

what are the 2 routes that make up drug excretion

Answer 24

Renal Excretion – Into the Urine

Hepatic Excretion – Into the Bile (Faeces)

Question 25

what are 3 other excretion routes

Answer 25

Sweat Milk Saliva

Question 26

what is half life

Answer 26

Half life (t1/2): This is the time taken for the plasma concentration of a drug to decline by 50%

Question 27

what are the two phases of metabolism?

Answer 27

Phase 1 → drug is inactivated Phase 2 → making drug more susceptible for elimination

Question 27

what must we do to out curve before calculating the elimination rate constant (k)?

Answer 27

what must we do to out curve before calculating the elimination rate constant (k)?

Question 28

how do we calculate the half life of a drug?

Answer 28

On a first order monoexponential decline curve, the half-life can be estimated anywhere on the curve

Question 29

the slope of the line in a galf life graph is equal to what

Answer 29

Slope of the line = Elimination rate constant (k)

Question 30

what 2 ways lets you calculate the slope of the line

Answer 30

Question 31

what is the most important primary measure of PK

Answer 31

Clearance is the most Important Primary Measure of PK

Question 32

what effect does low clearance have on the theraputic effect

Answer 32

Question 33

Why is Clearance important?

Answer 33

Clearance is the ONLY parameter that determines the maintenance dose rate required to achieve a target plasma concentration (and therefore effect) at steady state

Question 34

what are 2 ways of calculating total clearance

Answer 34

Question 35

what is the main organ for drug clearance

Answer 35

liver

Question 36

What affects the hepatic clearance?

Answer 36

Enzymatic activity in the liver Hepatic blood flow (Rate Limiting Step

Question 37

what is maximum hepatic clearance equal to?

Answer 37

Maximum hepatic clearance is equal to liver blood flow (Q) Therefore, if the total blood clearance is greater than liver blood flow (Q), there must be extra-hepatic clearance

Question 38

how do we calculate hepatic clearance?

Answer 38

Hepatic clearance = liver blood flow X Extraction ratio

Question 39

what 2 things determines the clearance by each organ

Answer 39

Extraction ratio and Blood flow for each organ determines the clearance by each organ

Question 40

what is whole body clearance

Answer 40

Whole body clearance is the sum of all organ clearances

Question 41

What is the bioavailability of a drug?

Answer 41

fraction of unchanged drug that reaches the systemic circulation

Question 42

for IV dosing, f must equal what

Answer 42

F must always equal 1 (100%)

Question 43

For Oral Dosing, Bioavailability depends on what 2 things:

Answer 43

Absorption from the Gut Clearance

Question 44

Bioavailability is calculated using dose-adjusted AUCs of oral and iv dosing by:

Answer 44

Question 45

Why can a drug be 100% absorbed but still have zero bioavailability?

Answer 45

first pass effect

Question 46

*key equation to remember Relationship between half-life (t1/2) in hours and the elimination rate constant (k) (hours-1)

Answer 46

t1/2 = 0.693 / k

Question 47

*key equation to remember Volume of distribution (Vd, Units: mL, L)

Answer 47

𝑉𝑑=𝐷𝑜𝑠𝑒 𝐴/𝐴0

Question 48

*key equation to remember Whole Body Clearance (Cl, Units: mL.min-1, L.h-1)

Answer 48

𝐶𝐿=𝑘 ∗𝑉𝑑 𝐶𝑙=𝑑𝑜𝑠𝑒 ∗𝐹 /𝐴𝑈𝐶

Question 49

*key equation to remember Oral Bioavailability (F, Units: %)

Answer 49

Question 50

describe where the following would be on a pharmacokinetics graph: safety window toxicity level minimum effective concentration theraputic window

Answer 50