Pharmacokinetics: Drug absorption, Distribution, and Elimination

Question 1

Involves absorption of the drug from aqueous solution in the stomach or intestinal lumen across GI epithelial membranes into the plasma

Answer 1

The oral route (enteric drug absorption)

Question 2

What are the two types of drug absorption across GI membranes?

Answer 2

Active transport and Passive transport

Question 3

Drugs bind to a protein carrier in the membrane with a high degree of structural specificity in

Answer 3

Active Transport

Question 4

Transport system is commonly linked to ATP consumption and can thus transport against a concentration gradient

Answer 4

Active Transport

Question 5

The active transport system is readily

-Limits the amount of drug that can be transported

Answer 5

Saturated

Question 6

More common than active transport, since the system is less selective with regard to what drugs can be transported

Answer 6

Passive transport

Question 7

The passive transport system is not readily saturatable because it does not depend on a

Answer 7

Protein carrier

Question 8

In passive transport, drugs will only move

Answer 8

Down a concentration gradient

Question 9

“Water loving” drugs that form hydrogen bonds with aqueous solvents.

❖ Usually possess a net charge that makes it difficult to pass through a lipid membrane

Answer 9

Hydrophilic Drugs

Question 10

The only hydrophilic drugs that can pass through protein pores and be passively transported across biological membranes are those that are

Answer 10

Small (MW less than 100)

Question 11

Have no net charge at physiological pH and can therefore pass through biological membranes more easily than hydrophilic drugs

Answer 11

Hydrophobic (Lipophilic) Drugs

Question 12

Best predictor of drug entry into the body

Answer 12

Lipid-To-Water Partition Coefficient (P)

Question 13

Will pass more readily through the GI epithelial membranes

Answer 13

Drug with higher P value

Question 14

Only uncharged drugs can move passively across

-Why the distinction between weak acids and bases is so important

Answer 14

GI membranes

Question 15

The distribution of unprotonated to protonated drug can be determined from the

Answer 15

pKa and ambient pH

Question 16

A very important predictor of drug absorption when we know the pH at the site of absorption

Answer 16

pKa

Question 17

At equilibrium, the total drug concentration (uncharged + charged) will be higher in the compartment with the greater degree of

Answer 17

pH-dependent ionization

Question 18

Are not absorbed into the plasma from the stomach, but instead must wait until they enter the intestine where the pH is elevated

Answer 18

Weak Bases

Question 19

What is the pH of the intestines?

Answer 19

5.3-5.4

Question 20

The more blood flow at a site, the more efficiently drug absorption occurs at that

Answer 20

Site

Question 21

Present a 500-times greater surface area for absorption than that of the stomach

Answer 21

Intestinal Vili

Question 22

As a result of this large surface area and a high rate of blood flow, is considered to be the most efficient area of drug absorption

Answer 22

Intestine

Question 23

Defined as the fraction (often given as a %) of orally administered drug that gains access to the systemic circulation in a chemically unaltered form

Answer 23

Oral Bioavailability (%F)

Question 24

What are 4 factors that decrease oral bioavailability?

Answer 24

First-pass hepatic transformation, hydrophilicity, metabolic and pH instability, and Physical properties of the drug preparation

Question 25

When a drug is absorbed along the intestine, the portal circulation brings it to the liver before it reaches the systemic circulation. Many drugs are chemically altered (i.e., metabolized) in this hepatic pass, thereby inactivating a significant fraction of the drug

Answer 25

First-Pass hepatic metabolism

Question 26

Most important factor unrelated to drug formulation itself

Answer 26

First-pass metabolism

Question 27

If a drug is too hydrophilic, it will never gain access to the body and will thus have a low

Answer 27

Bioavailability

Question 28

When two drug preparations differ to the point that their bioavailabilities also differ, they are said to be

Answer 28

Bioinequivalent

Question 29

Most common in hydrophobic drugs that are poorly water soluble (e.g., steroids)

Answer 29

Bioinequivalence

Question 30

Arises when the bioinequivalence of two drug preparations leads to a difference in therapeutic outcome

Answer 30

Therapeutic inequivalence

Question 31

The most important determinant of whether bioinequivalence leads to therapeutic inequivalence is the

Answer 31

Therapeutic index

Question 32

One major reason for use of the intravenous (IV) route is increased

Answer 32

Speed of action (Ex: anti-arrythmics)

Question 33

Trapped in the plasma because their large size precludes entry into other water compartments, like the IF

Answer 33

High molecular weight drugs

Question 34

Smaller size permits entry into the IF, but the drugs cannot passively cross cell membranes to enter the ICF

Answer 34

Hydrophilic Low Molecular Weight (LMW) Drugs

Question 35

Can enter all three compartments (plasma, IF, and ICF) and thus swim in the biggest pool

Answer 35

Hydrophobic LMW Drugs

Question 36

Distribute only in the plasma because the drug-protein complexes cannot enter the IF or ICF

Answer 36

Drugs that bind to plasma proteins

Question 37

Most drugs that bind to plasma proteins bind to

Answer 37

Albumin

Question 38

Drug molecules that bind to albumin are inert, since only the free form of the drug is

Answer 38

Pharmacologically active

Question 39

Bind strongly to albumin

Answer 39

Anionic Hydrophobic Drugs

Question 40

Do not bind strongly to albumin

Answer 40

Hydrophilic drugs

Question 41

Premised on the fact that: 1. The body is a single compartment into which drug distributes uniformly. 2. The drug concentration in that compartment is the same as the plasma concentration

Answer 41

Vd

Question 42

A dilution space normalized to body size and also indicative of a drugs tendency to distribute beyond the vascular space into tissues

Answer 42

Vd

Question 43

If the Vd is greater than 42L (total body water volume) than the drug must be

Answer 43

Tissue bound

Question 44

Body lipid content can impact distribution (e.g., a lipophilic drug will have a higher Vd in an

Answer 44

Obese person

Question 45

Drugs are eliminated from the body in which two primary ways?

Answer 45

1. ) Drug metabolism | 2. ) Renal elimination

Question 46

For renal elimination, what are the three partitioning events?

Answer 46

1. ) Glomerular filtration 2. ) Tubular secretion 3. ) Tubular reabsorption

Question 47

How much filtrate is there from each 600 mL/min of renal plasma flow in a healthy adult?

Answer 47

125 mL/min (GFR = 125 mL/min)

Question 48

A non-saturatable process

Answer 48

Glomerular filtration

Question 49

In glomerular filtration, only free (non-protein-bound) drug can be filtered, with drug pKa and lipophilicity having

Answer 49

No effect

Question 50

Drug moves from the blood to the lumen of the proximal nephron tubule by an active transport mechanism in

Answer 50

Tubular secretion

Question 51

Tubular secretion has two separate carrier-mediated systems for

Answer 51

Acids and bases

Question 52

Characterized by saturable protein carriers with little specificity for drug structure

Answer 52

Tubular secretion

Question 53

What kinds of drugs can be secreted by tubular secretion?

Answer 53

Drugs that were free or protein-bound

Question 54

By the time the drug reaches the lumen of the distal nephron tubule, its concentration is

Answer 54

Very high

Question 55

The drug then diffuses passively back out of the nephron lumen into the blood. This is called

Answer 55

Tubular reabsorption

Question 56

The only drugs that can undergo tubular reabsorption are

Answer 56

Free and unionized drugs

Question 57

In other words, pH partitioning occurs during

Answer 57

Tubular reabsorption

Question 58

Alkalinizes the urine and increases anionic (acidic) clearance

Answer 58

Bicarbonate

Question 59

Acidifies the urine and increases cationic (basic) clearance

Answer 59

Ammonium Chloride (NH4Cl)

Question 60

Refers to the volume of some biological fluid (e.g., plasma) from which, over a specified interval of time, all drug present is removed

Answer 60

Clearance

Question 61

Clearance mechanisms typically follow

Answer 61

First order kinetics

Question 62

The time it takes for the plasma concentration or the amount of drug in the body to be reduced by one-half (50%)

Answer 62

Half-life (t 1/2)