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Flashcards in Pharmacokinetics Deck (60):
1

What are the mechanisms of drug permeation?

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

2

Absorption

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

3

What is the level of absorption for IV drugs?

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

4

Oral Route

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

5

First Pass Effect

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

6

Sublingual

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

7

Rectal

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

8

Parental Routes

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

9

What is the solubility of nonionized molecules?

Liposoluble and can diffuse through the cell membrane

10

What is the solubility of ionized molecules?

Low liposolubility and have difficulty passing through the membrane

11

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

The uncharged (protonated) form (HA)

12

What is permeating for weak bases?

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

13

Conceptually, what does the Henderson Hasselbach Equation tell you?

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

14

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

Alkaline urine, acidic urine

15

According to the HH equation, when pH=PK

Unprotonated concentration=protonated concentration

16

For each unit of pH above the pK...

The unprotonated concentration will be ten time the protonated concentration

17

For each unit of pH below the PK....

The protonated concentration will be ten time the unprotonated concentration

18

Why does most drug absorption occur in the small intestine?

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

19

How does blood flow affect absorption?

Increased blood flow will increase absorption

20

P-glycoprotein (MDR1)

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

21

Bioavailability

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

22

How do you determine bioavailability?

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

23

what factors can affect bioavailability?

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

24

Pharmaceutically Equivalent

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

25

Bio equivalent

When two pharmaceutically equivalent drugs have nearly superimposable concentration time plots

26

What is the point of looking at bioequivalence?

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

27

Drug Distribution

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

28

What determined drug distribution?

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

29

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

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

30

What do acidic drugs bind to?

Plasma albumin

31

What do basic drugs bind to?

Alpha1-acid glycoprotein

32

What increases the risk of bilirubin encephalopathy?

Displacement of unconjugated bilirubin from albumin by sulfonamide drugs

33

Warfarin and plasma protein concerns

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

34

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

Lipid soluble due to tight binding of zonula occludens

35

Metabolism of Drugs

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

36

What reactions are involved in drug metabolism?

Phase I and phase II reactions

37

Phase I reactions:

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

38

Prodrugs

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

39

Cyclophosphamide

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

40

How are Prodrugs usually converted into active metabolites?

Through hydrolysis of an ester or amide linkage

41

Phase II Reactions

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

42

What is the main site of drug metabolism?

The liver

43

Where are the enzyme systems for phase I reactions located?

The ER

44

Where are the enzyme systems for phase II reactions located?

Cytosol

45

What system catalyzes most phase I reactions?

CytochromeP450 system

46

What are the three main xenobiotic receptors?

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

47

Enzyme Induction

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

48

What are the clinical consequences of enzyme induction?

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

49

What drugs inhibit cytochromes P450?

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

50

Macrolide Antibiotics

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

51

What else can transcriptionally regulate P-glycoprotein?

PXR

52

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

There is a genetic variation in enzymes that catalyze drug metabolism

53

What does grapefruit juice inhibit?

CYP3A4 and P-glycoprotein in the small intestine

54

What is the most common mechanism of drug excretion?

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

55

Volume of distribution

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

56

Clearance

Measure of the body's ability to eliminate the drug

57

Bioavailability

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

58

Volume of distribution formula

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

59

Maintenance Dose

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

60

Loading Dose

Quick way to achieve a target plasma level