Topic 7 - Drug Absorption and Distribution

Question 1

ADME

Answer 1

Absorption
Distribution
Metabolism
Excretion

Question 2

Absorption

Answer 2

Movement of drug from where it was administered into the bloodstream

Question 3

Enteral

Answer 3

Administration that passes through the intestines
Passes through liver

Question 4

What routes are Enteral

Answer 4

Oral (PO), Rectal (PR)

Question 5

Parenteral

Answer 5

Route that bypasses the intestine
Avoids the liver

Question 6

Parenteral Routes

Answer 6

Intravenous (IV)
Intramuscular (IM) Subcutaneous (SC)
Topical
Sublingual (SL)

Question 7

What routes bypass the liver

Answer 7

Parenteral

Question 8

Rectal Route (Overdose)

Answer 8

If drug is not pushed in deep enough then drug is absorbed by rectal walls –> Drug goes directly into blood vessels while avoiding the liver

Question 9

How does polar impact lipid solubility

Answer 9

The more polar a drug is the less likely it can cross the lipid bilayer

Question 10

The more N and O molecules in a drug the more?

Answer 10

The more polar it is meaning the less lipid soluble it is

Question 11

Higher logP means?

Answer 11

The drug is very hydrophobic

Question 12

Low Polar Surface Area means?

Answer 12

The drug is more lipid soluble

Question 13

Fick’s Law of Diffusion

Answer 13

Drugs flow from high concentration to low concentration

The larger the gradient the higher the rate of flow

Question 14

Why is Lipid Solubility important in crossing the membrane?

Answer 14

A very lipid soluble drug will partition into the bilayer quite easily

Forms a larger gradient within the bilayer which drives the rate of flow

There is way more drugs to move within the bilayer

Question 15

Ionization effects on Absorption

Answer 15

Charged drugs do not diffuse across membranes as they are water soluble

Question 16

Ionization effects on Absorption (pH and pKa)

Answer 16

An acid in an acidic environment will be less ionized and will favour more of the lipid soluble form

Question 17

Route that a drug takes when taken orally

Answer 17

Stomach –> Intestine –> Portal Vein –> Liver –> Systemic Circulation

Question 18

First Pass Metabolism

Answer 18

Drugs taken orally have to pass through the Liver before they enter the systemic circulation

Question 19

On average how many times will a drug past the liver

Answer 19

About once every four circuits will the drug pass through the portal vein and the liver again

Question 20

What is oral bioavailability

Answer 20

The intact drug, a fraction of an oral dose that reaches the systemic circulation

Question 21

Fraction Escaping Gut (Fg)

Answer 21

Amount of drug that enters the portal vein and leaves the intestines

drug in portal vein / drug dose

Question 22

Fraction Escaping Liver (fH)

Answer 22

Amount of drug that is left over after being metabolized by liver

drug in systemic circulation / drug in portal vein

Question 23

Hepatic Extraction Ratio (EH)

Answer 23

1-fH
1 - drug in systemic circulation
Amount of drug that is removed by liver

Question 24

Oral Bioavailability (F)

Answer 24

fg x fh
Fraction of drug that escaped the intestines x Fraction of drug that escaped the liver

or

Amount of drug escaping liver / dose of drug taken

Question 25

Thoracic Duct

Answer 25

Chylomicron carries lipophilic drugs through the thoracic duct to enter the systemic circulation

Question 26

Apparent Volume of Distribution AVd

Answer 26

A theoretical volume of plasma that contains all of the drug in the plasma Creates a concentration equal to the plasmas

Question 27

Calculating AVd

Answer 27

1) Check concentration of drug in plasma (10mg/L) 2) Check original dose given (100mg) 3) Determine volume of distribution 100mg/X = 10mg/L X = 10L

Question 28

Why do we use AVd instead of concentration of drug in systemic circulation

Answer 28

Amount of dose impacts the systemic circulation concentration, meaning it is not consistent A change in dose will change concentration and thus, changes AVd, makes it a better value for comparison

Question 29

Systemic Circulation and Distribution Relationship

Answer 29

High distribution means there is less concentration of drug in systemic circulation

Question 30

What determines AVd (Tissue Factors)

Answer 30

Lipophilic unbound drugs will be partitioned in fat and will not be free for binding

Question 31

What determines AVd (Blood Factors)

Answer 31

Plasma Protein Binding, Drugs bound to plasma proteins are unavailable for binding

Question 32

AVd Formula

Answer 32

Plasma Volume + Volume of Tissue x (fu/fuT) fu = fraction of unbound drug in blood fuT = fraction of unbound drug in tissue

Question 33

What happens where their is less plasma proteins

Answer 33

More unbound drug

Question 34

fu/fuT ratio greater than 1 means that?

Answer 34

Low Tissue Unbound, lots of drugs bound and partitioned in fat Very Lipophilic Fraction of unbound drugs in blood is greater than the fraction of unbound drugs in tissue

Question 35

fu/fuT ratio less than 1 means that?

Answer 35

Low plasma drug unbound --> Lots of drug is bound to plasma --> Drug is hydrophilic

Question 36

Lipophilicity and Drugs Bound

Answer 36

Low amount of unbound drugs in plasma = Hydrophilic drug (Drugs are all bound to plasma proteins) Low amount of unbound drugs in tissue = Lipophilic drug (Drugs are all bound to fat)

Question 37

Competition for Plasma Binding Proteins

Answer 37

A competing drug can bind to plasma proteins and displace the initial drug Leads to an increase in drugs in plasma = increase of drug in tissue = Larger response

Question 38

Distribution Compartments

Answer 38

A model that helps us to understand drug behaviour and distribution Not physically real

Question 39

Central Compartment

Answer 39

Blood and other highly vascularized tissues (Brain) that distribute any incoming drug instantly Drugs leave via Liver etc. Is in equilibrium with tissue compartmentes

Question 40

Shallow Tissue Compartment

Answer 40

Tissues and organs that rapidly distribute a given drug

Question 41

Deep Tissue Compartment

Answer 41

Tissue and Organs that slowly distribute a given drug (Fat)