ADME

Question 1

A scientific discipline that aims to quantitatively characterize the effect of the body on the drug

Answer 1

Pharmacokinetics (PK)

Question 2

ADME

Answer 2

Absorption: drug transfer from its site of administration to the general circulation

Distribution: Drug molecules carried by blood to site of action

Metabolism: Transformation from one drug product to another

Excretion: Removal of the drug product (or metabolite) from the body

Question 3

The drug to travel form its site of administration to its target site at desirable concentrations and at desirable time frame

Answer 3

The overall goal in drug therapy

Question 4

The site of action is localized around the site of administration

Answer 4

Local drug administration

Question 5

The site of action is far from the site of administration and must be transported via the bloodstream

Answer 5

Systemic drug administration

Question 6

A common route of drug administration

Answer 6

Extravascular route

Question 7

Before the drug is absorbed through the GI walls,

Answer 7

It should be available as molecules solubilized in the interstitial fluids

Question 8

Solid must under go ______ and liquid must under go _____

Answer 8

Solids must undergo disintegration and dissolution, liquids much undergo dissolution

Question 9

For most drugs, the optimum site for drug absorption after oral administration is

Answer 9

The upper portion of the small intestine or duodenum region

Question 10

The anatomy of the duodenum provide:

Answer 10

• large surface area for the drug to passively diffuse

- high perfusion through a large network of capillaries

Question 11

Large particles are delayed for ______ by the presence of food in the stomach

Answer 11

3-6 hours

Question 12

Gastric emptying of solids v. Liquids

Answer 12

About 50% of liquids empty in 20 minutes

About 50% of solids remain after 2 hours

Question 13

Small intestine pH gradient and what it means

Answer 13

(6.5-7)
Retention time is about 3-4 hours
Independent of solid particle size or fed status
Gradient bacterial content duodenum (sterile) to ileum (confluent)

Question 14

Large intestine pH and what it means

Answer 14

(7)
Avg, takes 53 hours from ingestion to excretion
Unabsorbed molecules spend ~90% of time in large intestine and rectum (minimum absorption)
Highest bacterial content (anaerobic)

Question 15

The rate and extent to which an active drug ingredient or therapeutic moiety is absorbed from a drug product and becomes available at the site of action

Answer 15

Bioavailability

Question 16

Fraction of the administered dose which reaches the systemic circulation relative to an intravenous dose (F)

Answer 16

Absolute bioavailability

Question 17

Bioavailability data are used to determine:

Answer 17

• amount of drug absorbed from dosage form
• rate at which the drug was absorbed
• duration of the drug’s presence in the biologic fluid or tissue
• relationship between drug blood levels and clinical efficacy and toxicity

Question 18

FDA requires bioavailability data for

Answer 18

NDA, Abbreviated NDA, supplemental applications (for changes in manufacturing, new indications, and new/additional doses)

Question 19

The rates of absorption and elimination are equal

Answer 19

Peak height concentration (Cmax)

Question 20

MEC

Answer 20

Minimum effective concentration, must be achieved for the patient to exhibit adequate response

Question 21

MTC

Answer 21

Minimum toxic concentration

Question 22

Relationship between dose and Cmax

Answer 22

Cmax (and AUC) increase with increased dose

Question 23

Reflects the rate of absorption from a formulation, which determines the time needed for the MEC to be reached and to maintain it

Answer 23

Time of Peak (Tmax)

Question 24

Changes in the rate of drug absorption change the

Answer 24

Cmax and Tmax

Question 25

When the rate of abortion is decreased

Answer 25

Cmax is lowered and Tmax occurs at a later time

Question 26

The serum blood concentration over time; measure of the total amount of drug absorbed into the circulation following the administration of a single dose

Answer 26

AUC (area under curve)

Question 27

If equivalent doses of a drug in different formulations provide different AUC values =

Answer 27

Differences in the extent of absorption (Graph on Slide 23) | —-Formulation A Delivers much greater amt of drug to circulatory system than other two formulations

Question 28

Oral dosage strengths are based on considerations of the proportion of the dose

Answer 28

That is expected to be aborbed

Question 29

The absolute bioavailability following oral dosing is compared to

Answer 29

IV dosing

Question 30

When F is less than 1, oral doses

Answer 30

Must be larger than IV doses to provide the same concentration of drug in the plasma

Question 31

As bioavailability worsens,

Answer 31

The variability from patient to patient tends to increase

Question 32

What enzyme in the liver is responsible for a lot of drug metabolism?

Answer 32

Cytochrome C

Question 33

What does this equation and the components mean? F = Fa X Fi X Fh

Answer 33

``` F= bioavailability Fa= the fraction of the administered dose that is not destroyed in the gut or lost in feces Fi= the fraction of the dose that escapes metabolism in the intestinal wall Fh= the fraction of the dose that escapes metabolism on first-pass through the liver ```

Question 34

Transport without external energy and molecules diffuse randomly in all directions

Answer 34

Passive Transport

Question 35

The rate of transfer of diffusion

Answer 35

Flux (measured in mass per unit area)

Question 36

Molecules diffuse from a region of high concentration to a region of low concentration

Answer 36

Fick’s law of diffusion

Question 37

The location, extent, and degree of distribution are dependent on

Answer 37

The drug’s properties and individual patient characteristics

Question 38

Drugs can distribute into these fluids

Answer 38

1. Plasma (3 L) 2. Intracellular water (27 L) 3. Interstitial water (12 L) Where the drug dissolves affects concentration

Question 39

Drugs are present in the body in two states

Answer 39

Bound (to protein) | Free (plasma, interstitial fluid and lymph, tissues)

Question 40

What drugs diffuse across the membrane the easiest?

Answer 40

Hydrophobic, small, not bound to plasma protein

Question 40

The pressure gradient between the arterial end of the capillaries entering the tissue and the venous capillaries leaving the tissue

Answer 40

Hydrostatic pressure

Question 40

The difference between the capillary hydrostatic pressure and the blood osmotic pressure

Answer 40

Net Filtration pressure (NFP)

Question 40

As the blood newly enters the capillary (arterial end) the pressure of the capillary blood is slightly higher than that of tissue causing

Answer 40

Fluid to leave the capillary bed and enter the tissues Also known as: hydrostatic or filtration pressure

Question 40

Venues have lower pressure than tissue fluids allowing the filtered fluid to

Answer 40

Return to the venous capillary Also known as absorptive pressure

Question 41

Partitioning and accumulation of a drug in the tissue or organ

Answer 41

Drug affinity

Question 42

The time for the drug distribution is generally measured by the time for 50% distribution

Answer 42

Distribution half life

Question 43

Relation to the blood flow to the organ, the volume of the organ, and the partitioning of the drug into the organ tissues

Answer 43

Distribution Constant

Question 44

An estimated value used because the true volume a drug is absorbed into (distributed) is not known

Answer 44

Volume of Distribution It is not a physiological volume, it is hypothetical

Question 45

Determined by the same physiological and drug-related factors that control drug distribution

Answer 45

Volume of Drug distribution

Question 46

The decline from peak plasma concentrations after drug administration results from drug elimination or removal by the body

Answer 46

Metabolism

Question 47

Elimination of most drugs from the body involves both

Answer 47

Metabolism (bio transformation) and renal excretion

Question 48

The principle site of metabolism is

Answer 48

The liver

Question 49

The enzymes responsible for oxidation and reduction of drugs and certain metabolites are monoxygenase enzymes know as

Answer 49

Mixed-Function Oxidases Constitute ETC enzymes

Question 50

The terminal component of the electron transport chain in the ER and acts as both an oxygen and substrate binding locus for drugs and endogenous substrates

Answer 50

Cytochrome P-450

Question 51

Responsible for metabolism >70% of drugs

Answer 51

Cytochrome-P450 Families (numbers) and subfamilies (letters) CYP2c(, 2C19, and 3A4 >50% of oral drugs

Question 52

Inactive and must be biotransformed in the body to metabolites that have pharmacological activity, intentionally designed to improve drug stability, increase systemic absorption, or prolong activity

Answer 52

Pro drugs

Question 53

What are the two major groups of reactions for pathways of drug biotransformation

Answer 53

``` Phase I (asymmetric): oxidation, reduction, hydrolysis Phase II (synthetic): conjugation ```

Question 54

Phase I biotransformation reactions usually occur

Answer 54

First and introduce or expose a functional group on the drug molecule

Question 55

Once a polar constituent is recreated or placed into the molecule

Answer 55

A phase II reaction may occur

Question 56

Derived from biochemical compounds involved in carbohydrate, fate, and protein metabolism

Answer 56

Conjugating reagents

Question 57

Refers to the irreversible removal of drug from the body by all routes of elmination

Answer 57

Drug elimination

Question 58

Drug elimination is usually divided into two components

Answer 58

Excretion and Biotransformation

Question 59

The removal of the intact drug

Answer 59

Drug excretion

Question 60

The process by which the drug is chemically converted in the body to a metabolite

Answer 60

Biotransformation or drug metabolism

Question 61

The main excretory organ for the removal of metabolic waste products and plays a major role in maintaining the normal fluid volume and electrolyte composition

Answer 61

Kidney

Question 62

To maintain salt and water balance, the kidney

Answer 62

Excretes excess electrolytes, water, and waste products while conserving solutes necessary for proper body function

Question 63

The two endocrine functions of the kidneys

Answer 63

1. Secretion of renin to regulate BP | 2. Secretion of erythropoietin, which stimulates RBC

Question 64

Briefly describe the anatomy of renal filtration

Answer 64

- Kidney is supplied blood via the renal artery - Each arterial carries blood into nephrons to Bowman’s capsule to filter the blood in the glomerulus - Blood flows out into a second capillary network that surrounds the tubules including the Loop of Henle

Question 65

The volume of blood flowing through the renal vasculature per unit time

Answer 65

Renal Blood Flow (RBF) 1.2 L/min or 1700 L/d

Question 66

The renal blood flow minus the volume of RBCs present, important factor in the rate of drug filtration at the glomerulus

Answer 66

Renal plasma flow (RPF)

Question 67

About 120 mL/min or 180L/d

Answer 67

Glomerular filtration rate (GFR) about 20% of the RPF

Question 68

Ratio of GFR/RPF

Answer 68

Filtration fraction

Question 69

The process by which a drug is excreted via the kidneys may include

Answer 69

Glomerular filtration, active tubular secretion, and tubular reabsorption

Question 70

The ratio of the sum of the glomerular filtration and active secretion rates less the reabsorption rate divided by the plasma drug concentration

Answer 70

Renal clearance

Question 71

May give an indication for the mechanism of renal excretion of the drug

Answer 71

Clearance ratio <1 — drug is partially reabsorbed =1 — drug is filtered only >1 — drug is actively secreted