Pharmacokinetics

Question 1

What are the mechanisms of drug permeation?

Answer 1

Aqueous diffusion (par acellular pathway), lipid diffusion (transcellular pathway), special carrier, endo/exocytosis

Question 2

Absorption

Answer 2

transfer of a drug from its site of administration to the blood stream

Question 3

What is the level of absorption for IV drugs?

Answer 3

Complete, 100%, because the entire dose reaches the systemic circulation

Question 4

Oral Route

Answer 4

Maximum convenience, but absorption may be slower and less complete than with other routes

Question 5

First Pass Effect

Answer 5

Effect where ingested drugs are fractionally metabolized in the gut all and liver before reaching circulation

Question 6

Sublingual

Answer 6

The drug enters systemic circulation directly from under the tongue. Drug bypasses the first pass effect. Enteral route

Question 7

Rectal

Answer 7

There is a partial avoidance of the first pass effect. Enteral route

Question 8

Parental Routes

Answer 8

IV, intramuscular, subcutaneous (below skin) and intradermal (in skin)

Question 9

What is the solubility of nonionized molecules?

Answer 9

Liposoluble and can diffuse through the cell membrane

Question 10

What is the solubility of ionized molecules?

Answer 10

Low liposolubility and have difficulty passing through the membrane

Question 11

For weak acids, which form will permeate through the membranes?

Answer 11

The uncharged (protonated) form (HA)

Question 12

What is permeating for weak bases?

Answer 12

The uncharged form (unprotanted) will permeate while the charges form will not

Question 13

Conceptually, what does the Henderson Hasselbach Equation tell you?

Answer 13

Tells you that the ratio between unprotonated and protonated forms is based on pH and PK

Question 14

Weak acids are excreted better in_________, weak bases are excreted faster in ___________.

Answer 14

Alkaline urine, acidic urine

Question 15

According to the HH equation, when pH=PK

Answer 15

Unprotonated concentration=protonated concentration

Question 16

For each unit of pH above the pK…

Answer 16

The unprotonated concentration will be ten time the protonated concentration

Question 17

For each unit of pH below the PK….

Answer 17

The protonated concentration will be ten time the unprotonated concentration

Question 18

Why does most drug absorption occur in the small intestine?

Answer 18

Because of its large surface area. Any factor that accelerated gastric emptying will increase the rate of drug absorption

Question 19

How does blood flow affect absorption?

Answer 19

Increased blood flow will increase absorption

Question 20

P-glycoprotein (MDR1)

Answer 20

Transporter protein responsible for transporting several drugs across cell membranes. Reduced drug absorption.

Question 21

Bioavailability

Answer 21

Fraction of administered dose of a drug that reaches the systemic circulation

Question 22

How do you determine bioavailability?

Answer 22

Compare the area under the curve of a particular route with the AUC after IV infection (should be 100%)

Question 23

what factors can affect bioavailability?

Answer 23

Drug formulation, chemical instability, food and drug interactions, first pass metabolism, drug solubility, P-glycoprotein

Question 24

Pharmaceutically Equivalent

Answer 24

Contain the same active ingredient and are identical in concentration, dosage form, and route of administration

Question 25

Bio equivalent

Answer 25

When two pharmaceutically equivalent drugs have nearly superimposable concentration time plots

Question 26

What is the point of looking at bioequivalence?

Answer 26

If two drugs are bioequivalent, one can safely replace the other

Question 27

Drug Distribution

Answer 27

Process by which a drug leave the blood stream and enters the extracellular fluid or the cells of the tissues

Question 28

What determined drug distribution?

Answer 28

Blood flow, capillary permeability, tissue volume, drug binding, drug hydrophobicity

Question 29

Which parts of the body receive the drugs first/get most of the drugs?

Answer 29

Vessel rich groups that get lots of blood (brain, liver, kidney...) then it foes to the muscles

Question 30

What do acidic drugs bind to?

Answer 30

Plasma albumin

Question 31

What do basic drugs bind to?

Answer 31

Alpha1-acid glycoprotein

Question 32

What increases the risk of bilirubin encephalopathy?

Answer 32

Displacement of unconjugated bilirubin from albumin by sulfonamide drugs

Question 33

Warfarin and plasma protein concerns

Answer 33

Warfarin is highly bound to albumin and only a small fraction is free. Sulfonamide so will displace warfarin causing a significant increase in the plasma level of free warfarin--->increase bleeding

Question 34

What are the only drugs that can cross the blood-brain barrier?

Answer 34

Lipid soluble due to tight binding of zonula occludens

Question 35

Metabolism of Drugs

Answer 35

Most lipid soluble drugs are not easily excreted because they can be reabsorbed easily. They must undergo a biotransformation that will make them more polar and inactive metabolites which can be easily excreted

Question 36

What reactions are involved in drug metabolism?

Answer 36

Phase I and phase II reactions

Question 37

Phase I reactions:

Answer 37

Oxidations, reduction, decarboxylations, deamination, hydrolytic reactions. Usually result in polar, inactive metabolites

Question 38

Prodrugs

Answer 38

Pharmacologically inactive compounds that are designed to maximize the amount of active species that reaches the site of action

Question 39

Cyclophosphamide

Answer 39

Drug that is bio activated by metabolism to an active anticancer metabolite

Question 40

How are Prodrugs usually converted into active metabolites?

Answer 40

Through hydrolysis of an ester or amide linkage

Question 41

Phase II Reactions

Answer 41

Conjugation reactions that form a covalent bond between the drug molecule and something else (amino acid, sulfate, etc...)

Question 42

What is the main site of drug metabolism?

Answer 42

The liver

Question 43

Where are the enzyme systems for phase I reactions located?

Answer 43

The ER

Question 44

Where are the enzyme systems for phase II reactions located?

Answer 44

Cytosol

Question 45

What system catalyzes most phase I reactions?

Answer 45

CytochromeP450 system

Question 46

What are the three main xenobiotic receptors?

Answer 46

Aryl hydrocarbon receptor (AhR) Pregnane X receptor (PXR) Constitutive lay active receptor (CAR)

Question 47

Enzyme Induction

Answer 47

Drugs will bind to xenobiotic receptors which activates the receptor, allowing it to translocation to the nucleus and bind to the promotes of various enzymes

Question 48

What are the clinical consequences of enzyme induction?

Answer 48

A drug can increase its own metabolism, a drug can increase the metabolism of a coadministered drug (can reduce plasma concentrations below therapeutic levels)

Question 49

What drugs inhibit cytochromes P450?

Answer 49

Amidodarone, cimetidine, ketoconazole,erythromycin, chloramphenicol, grapefruit juice

Question 50

Macrolide Antibiotics

Answer 50

Inhibit P-glycoproteins which can lead to increased serum levels of drugs (e.g., digoxin) that are excreted by P-glycoprotein

Question 51

What else can transcriptionally regulate P-glycoprotein?

Answer 51

PXR

Question 52

What is the most common factor responsible for variations drug responses?

Answer 52

There is a genetic variation in enzymes that catalyze drug metabolism

Question 53

What does grapefruit juice inhibit?

Answer 53

CYP3A4 and P-glycoprotein in the small intestine

Question 54

What is the most common mechanism of drug excretion?

Answer 54

Renal excretion (a small number are excreted in the bile)

Question 55

Volume of distribution

Answer 55

A measure of the apparent space in the body available to contain the drug

Question 56

Clearance

Answer 56

Measure of the body's ability to eliminate the drug

Question 57

Bioavailability

Answer 57

The fraction of the drug that is absorbed into the systemic circulation

Question 58

Volume of distribution formula

Answer 58

Vd=amount of drug in body/plasma drug concentration. Theoretical with no real life application.

Question 59

Maintenance Dose

Answer 59

Schedule of drug administration to maintain specific range of drug plasma concentration over a long period of time

Question 60

Loading Dose

Answer 60

Quick way to achieve a target plasma level