3 Absorption and Distribution

Question 1

What two factors affect area under the curve?

Answer 1

bioavailability of the drug

clearance rate of the person

Question 2

Clearance is inversely related to what?

Answer 2

area under the curve

Question 3

What is drug absorption?

Answer 3

process by which drugs move from their site of administration to the plasma

Question 4

What factors affect drug absorption?

Answer 4

1. chemical composition and delivery of drug
2. regional differences in blood flow
3. transport mechanisms
4. permeability characteristics (lipid solubility)
5. ion-trapping
6. nonspecific binding
7. surface area

Question 5

What is aqueous diffusion?

Answer 5

small molecules

Question 6

What is lipid diffusion?

Answer 6

• passive process
• driven by concentration gradient
• rate of absorption increases with increasing drug concentration
• the more lipid soluble the faster the rate of transport
• if too lipid soluble may not be soluble in aqueous gut fluid and this limits absorption

Question 7

When acids or bases are protonated are they charged? Is the ionized form more soluble or less lipid soluble?

Answer 7

acids protonated= uncharged (acidic env good)
bases protonated= charged
(basic env good)

ionized=less lipid soluble

Question 8

Degree of ionization depends on what?

Answer 8

difference between pH and pKa

Question 9

Where is the main site of drug absorption?

Answer 9

stomach

Question 10

What type of metabolism is oral administration? How is this affected by enterohepatic circulation?

Answer 10

first pass: pass through liver, only a fraction of drug reaches system circulation (bioavailability, F)
Enterohepatic circulation: drugs may be secreted into the bile and reabsorbed via instentine-can delay delivery to systemic circulation and reduce bioavailability

Question 11

What is the salt factor?

Answer 11

the fraction of total drug that will be delivered as active drug to the systemic circulation ( like bioavailability)

Question 12

What are the advantages to sublingual(similar to buccal)?

Answer 12

• bypass portal circulation and avoid first pass metabolism

- higher pH may be beneficial for absorption of more basic drugs

Question 13

What are the advantages to rectal?

Answer 13

50-60% of absorbed drug by-passes portal circulation and therefore avoids first pass metabolism
-useful in cases of nausea and vomiting

Question 14

How are inhaled drugs absorbed?

Answer 14

passive diffusion and is facilitated by large surface area

Question 15

How are transdermal drugs absorbed? WHat are the benefits? COns?

Answer 15

passive diffusion across skin driven by concentration gradient
Pros
-controlled release of drug-steady blood-level profile
-user friendly
-bypass GI

Con
-skin barrier limits the number of drugs that can be delivered

Question 16

How does blood flow affect IV drug administration? What are the pros of parterenteral?

Answer 16

• blood flow to the area maintains the concentration gradient
• drug absorption is faster in highly vascularized tissue such as skeletal muscle

Pro

• greater degree of reliability and precision
• fewer problems with absorption

Question 17

WHat are disadvantages of parenteral?

Answer 17

• tissue damage and irritation
• drug must be in solution
• limited volume

Question 18

What are the factors that affect distribution?

Answer 18

1. regional differences in blood flow
2. tissue mass
3. transport mechanics
4. permeability characteristics
5. ion trapping
6. protein binding

Question 19

What does albumin bind to?

Answer 19

acidic drugs

Question 20

What does alpha 1 acid glycoprotein bind to?

Answer 20

basic drugs

Question 21

What is one compartment distribution?

Answer 21

rapid equilibrium is achieved between plasma and tissue distribution following drug administration
-plasma concentration-time profile declines mono-exponentially

Question 22

What is two compartment distribution?

Answer 22

rapid distribution to a central compartment(plasma) is followed by slow distribution to other tissues/binding sites.
-bi-exponential plasma concentration-time profile

Question 23

What is volume of distribution?

Answer 23

how evenly distributed a drug is in the body

Question 24

What is Vd?

Answer 24

theoretical volume of fluid into which the total drug administered would have to be diluted to produce the concentration in the plasma

Question 25

What can serve as drug reservoirs?

Answer 25

fat and muscle and plasma proteins (sulfonamides compete)