Absorption/Distribution

Question 1

What is drug absorption?

Answer 1

Mass transfer process that involves movement of unchanged drug molecules from the site of absorption to the bloodstream

Question 2

What is the rate limiting step for drug absorption?

Answer 2

Crossing the epithelia or endothelia

Question 3

What is the rate of absorption related to?

Answer 3

Time

Question 4

What is the rate of absorption measured by?

Answer 4

Time parameters (ka, tmax)

Question 5

What is ka?

Answer 5

Absorption rate constant

Question 6

What is tmax?

Answer 6

time for the drug concentration to reach maximum in the plasm

Question 7

What is absorption t1/2?

Answer 7

The time for 50% of the administrated dose is absorbed

Question 8

What is the extent of absorption related to?

Answer 8

Magnitude or amount of the drug reaching to systemic circulation

Question 9

How is the extent of absorption measured?

Answer 9

Bioavailability (F) of the drug

Question 10

What are the 4 factors influencing drug absorption from oral admin?

Answer 10

Type of dosage form
Physico-chemical properties of the drug
Physio-anatomic condition of the host patient
Pathologic conditions of the host patient

Question 11

What are the two main factors of physico-chemical properties of the drug

Answer 11

Aqueous solubility and permeability (log p)

Question 12

What is the preferred route of administration?

Answer 12

oral

Question 13

What do lipids and proteins in the blood do for circulating concentration of the drug?

Answer 13

Serve to increase the circulating drug concentration for certain aqueous insoluble drugs

Question 14

What is permeability also dependent on?

Answer 14

pH (ionization)

Question 15

What affects aqueous solubility and permeability?

Answer 15

Molecular weight
Ionization constant (pKa)
Solid state form
Particle size

Question 16

What are charged species restricted to during absorption?

Answer 16

Paracellular pathway

Question 17

What can drug release from the dosage form be affected by?

Answer 17

Excipients and manufacturing processes

Question 18

For absorption to occur, drug molecules need to be in ____ at the absorption site

Answer 18

Solution

Question 19

Rank the rate of drug absorption from the oral dosage forms

Answer 19

Solutions
Emulsions
Suspensions
Capsules
Tablets
Coated Tablets
Enteric coated tablets
Sustained release tablets

Question 20

Drugs administered in ____ usually produce the most available drug product

Answer 20

Solution

Question 21

What is the most important physicochemical parameter for absorption of the drug

Answer 21

Solubility

Question 22

Low aqueous solubility results in ____ oral absorption

Answer 22

poor

Question 23

Solubility of weak acids and bases in aqueous medium is dependent on __

Answer 23

pH

Question 24

What happens when you decrease the particle size of a hydrophobic particle?

Answer 24

Surface area decreases
Need a surface active agent to increase effective surface area

Question 25

What is the rate of absorption of an ionizable drug predicted by?

Answer 25

The pKa of the drug and the pH of the absorption environment

Question 26

What must high lipid soluble drugs be accompanied by?

Answer 26

adequate water solubility

Question 27

Equation for permeability

Answer 27

Permeability = ((𝐷𝑖𝑓𝑓𝑢𝑠𝑖𝑜𝑛 𝑐𝑜𝑒𝑓𝑓𝑖𝑐𝑖𝑒𝑛𝑡) (𝑃𝑎𝑟𝑡𝑖𝑡𝑖𝑜𝑛 𝑐𝑜𝑒𝑓𝑓𝑖𝑐𝑖𝑒𝑛𝑡))/(𝑀𝑒𝑚𝑏𝑟𝑎𝑛𝑒 𝑡ℎ𝑖𝑐𝑘𝑛𝑒𝑠𝑠))

Question 28

What is stomach emptying?

Answer 28

It is the normal physiological process of the progression of the gastric contents toward the duodenum

Question 29

What can the rate of drug absorption be influenced by when talking about gastric emptying?

Answer 29

The rate at which the drug arrives at the small intestine

Question 30

What can gastric emptying rate be modified by?

Answer 30

Light physical activity - faster Vigorous exercise delays it Type, volume, viscosity, temperature of the ingested food (liquids eave the stomach faster than semisolids) Concurrent drug therapy with cholinergic drugs increase the rate of gastric emptying

Question 31

What can limit the availability of drug molecules for absorption in the gut wall?

Answer 31

Enterocytes in the upper segment of the small intestine that express cytochrome P450 (CYP3A4)

Question 32

How can oxidation reactions mediated by CYP affect absorption?

Answer 32

Reactions involving the removal of various groups that make it less soluble

Question 33

Biliary salts example

Answer 33

They can interact with drugs such as neomycin and kanamycin to form insoluble and non-absorbable complexes

Question 34

What happens during drug secretion by efflux transporters in the GI?

Answer 34

after a drug penetrates the intestinal membrane and is in the cytoplasm of the enterocyte it may be subjected to secretion process mediated by a transporter which moves the drug back to the intestinal lumen

Question 35

What are the active carrier mediated efflux transporter proteins?

Answer 35

P-glycoprotein or multi drug resistance 1

Question 36

What does p-glycoprotein do?

Answer 36

limits drug absorption

Question 37

Where is p-glycoprotein expressed?

Answer 37

in the luminal membrane of the small intestine enterocytes

Question 38

How does drug degradation occur in the GI?

Answer 38

Gastric acid or several enzymes through enzyme mediated metabolism

Question 39

Examples of enzymes that degrade drugs?

Answer 39

lyases hydrolases proteases glycosidases sulfatases

Question 40

What is found more which decreases pH?

Answer 40

more bacteria

Question 41

Where in the GI tract are bacteria low in numbers?

Answer 41

The proximal part of the small intestine

Question 42

What pathologic conditions can change stomach emptying and GI permeability?

Answer 42

Celiac disease constipation diarrhea vomiting

Question 43

What alterations of the GI causes changes in drug absorption?

Answer 43

Population of intestinal drug metabolizing enzymes pH of the intestine Normal GI flora (antibiotics) Secretion of digestive enzymes Intestinal blood flow (CV diseases) Hepatic diseases ( liver cirrhosis)