L31 - Absorption: Physiological Factors Affecting Drug Absorption 2

Question 1

What does bile facilitate?

Answer 1

Excretion of a number of endogenous and exogenous compounds and aids digestion of fat and fat-soluble vitamins

Question 2

What are the parts in enterohepatic recycling? (3)

Answer 2

• bile facilitates digestion of fat
• some drugs are eliminated in part by biliary secretion
• drugs eliminated into SI, may be absorbed again and reach systemic circulation

Question 3

What if F?

Answer 3

Fraction of parent drug reaching systemin circulation after oral administration
F=1 all drug absorbed
F=0 no drug absorbed

Question 4

What does the amount of drug absorbed depend on? (3)

Answer 4

• its release from dosage form
• stomach, intestinal and hepatic (first pass) metabolism
• its permeation through GI mebrane

Question 5

What are the ways of transportation of drug across the GI membranes? (4)

Answer 5

• paracellular transport
• diffusion
• facilitated diffusion
• drug transporters

Question 6

What is the removal rate of drug from inside cell far more efficient than sometimes?

Answer 6

Rate of entry
= good protective mechanism for cells
- prevents toxic compounds from accumulating intracellularly

Question 7

Why are some tumor cells resistant to anticancer drugs?

Answer 7

Drugs transported into cell are removed so efficiently that conc never gets high enough to be effective

Question 8

What does specific transport protein equal?

Answer 8

Specific transport protein = multidrug resistance protein

Question 9

What are efflux pumps?

Answer 9

Celullar proteins that can prevent intracellular acuumulation of drugs by pumping drug that enters cell right back out

Question 10

What are examples of efflux pump?

Answer 10

P-Glycoprotein (PGP)
- present in dif tissues (intestine, placental membrane, blood-brain barrier)

Question 11

What is PGP responsible for? (3)

Answer 11

• Poor bioavailability
• Low CNS concentration of numerous drugs
• Prevent oral delivery of many anti-cancer drugs

Question 12

What do PGP inhibitors do?

Answer 12

Prevent drug efflux from endothelial cells and increase oral bioavailability

Question 13

What do 1st and 2nd gen PGP inhibitors also inhibit?

Answer 13

CYP3A4 = reduced drug clearance

Question 14

What are 3rd gen PGP inhibitors specific for?

Answer 14

Transporter
- clinically effective
E.g/ administration of topotecan with PGP inhibitor elacridar
= inc oral bioavailability from 40 to 97%

Question 15

What is the role of dosage form? (5)

Answer 15

• accurate dosing
• Protect the drug (storage and after administration)
• Conceal bad taste/odour
• Easy delivery for certain routes/specific patient groups (suspensions, liquids, syrups, suppositories)
• Optimize delivery and release - fast release, controlled (extended) release

Question 16

What are the categories of oral dosage forms? (4)

Answer 16

• rapid release (solutions, effervescent tablets)
• delayed release (enteric-coated)
• slow release (0 order kinetics)
• slow release (1st order kinetics)

Question 17

What may 2 pharmaceutical dosage forms have… but…?

Answer 17

• same rate os absorption
• identical Cmax calues at dif Tmax
  (Due to signficant lagtime

Question 18

What is an examples if delayed absorption? (2)

Answer 18

Gastro-resistant/enteric-coated tablets
- time bomb
- retard used to describe these dosage forms

Question 19

What may some disage forms have different? Eg/

Answer 19

1st order absorption rates
- most drugs taken orally, the rate of absorption is greater than the rate of elimination

Question 20

What is 1st order like in terms of absorption? (2)

Answer 20

• amount absorbed per unit time depends on quantity of drug at site of absorption
• greater amoubnt to be absorbed = faster rate

Question 21

What is 0 order like in absorption?

Answer 21

Amount released per unit time is constant over period of absorption

Question 22

How does food influence drug absorption? (2)

Answer 22

• GI absorption sometimes modified by food
• eating habits vary in different cultures

Question 23

What is an example of drug modified by presence of food? (2)

Answer 23

Lapatinib - breast cancer drug
- food = inc bioavailability by 167%
- fatty meal = inc bioavailability by 325%

Question 24

Why should tetracyclines be paid attention to? (3)

Answer 24

• taken under fasting conditions to maximise bioavailability
• GI absorption dec by presence of Al, Ca, Mg and Fe
• milk products are contra-indicted

Question 25

How taking of sodium fluoride pose a problem?

Answer 25

Treats osteoporosis
- if Ca supplement also prescribes

Question 26

What should be avoided when taking antacids?

Answer 26

Milk products

Question 27

What may delayed/slowed release dosage form be sensitive to?

Answer 27

Presence of food in digestive system
- change of GI transit time

Question 28

What may the amount of drug reaching systemin circulation be in presence of food? (3)

Answer 28

• increased
• decreased
• unaffected