Pharmacokinetics

Question 1

What is more important to biological action? Free drug or protein bound drug?

Answer 1

Free drug!

Question 2

Absorption

Answer 2

Movement from a site of administration to the systemic circulation

Question 3

Distribution

Answer 3

Movement of drug from the systemic circulation to perfused tissue and between tissue compartments

Question 4

Metabolism

Answer 4

Biotransformation of the administered drug. Mainly hepatic, but other tissues metabolize also.

Question 5

Excretion

Answer 5

Removal of drugs and their metabolites from the body, mainly in bile or urine.

Question 6

Only route of administration that bypasses the absorption process?

Answer 6

Intravenous

Question 7

How does absorption occur?

Answer 7

Diffusion through membranes by small, nonpolar, uncharged molecules. Diffusion through aqueous intracellular spaces (capillary fenestrations). Less importantly: permeation through membrane channels and active transport using pumps.

Question 8

C of a drug

Answer 8

Plasma concentration

Question 9

Graphical difference between C in intravenous and extravascular administration

Answer 9

Intravenous = C is max at time of injection, decays afterwards.
Extravascular = Absorption time, C increases to a peak, then decays.

Question 10

Bioavailability

Answer 10

The fraction of an oral dose that reaches the systemic circulation. Can range from 0-1.

Question 11

Factors that limit bioavailability

Answer 11

Incomplete absorption in the GI tract.

First pass metabolism by the liver (which can largely be evaded by routes of administration that aren’t oral).

Question 12

How to determine bioavailability from a graph?

Answer 12

Bioavailability can be determined by measuring the area under the curve(AUC) following a single dose, then comparing it to the AUC following the same dose administered IV.

Question 13

Where in the GI tract are drugs absorbed?

Answer 13

Can happen anywhere, but the duodenum and the small intestine are the major site for absorption. Large surface area, longer transit time, pH in a range that leaves weak acids and bases largely non-polarized so it can pass through membranes.

Question 14

Factors that influence drug distribution

Answer 14

Binding to plasma proteins (generally 95-99%). Vascularity of the tissue (drugs distribute most rapidly to highly perfused tissues.

Question 15

Most important proteins for drug binding?

Answer 15

Albumin and alpha1-acid glycoprotein.

Question 16

Distribution and redistribution

Answer 16

Drug leaves blood enters vessel rich group. Then will exit, enter blood, and enter other groups (muscle, adipose tissue).

Question 17

Vd, why it’s important

Answer 17

Volume of distribution. Important because a measurement of plasma concentration in the body underestimates the total amount that actually exists in the body. Drug has already migrated into tissues. Its a measure of the plasma volume that would need to exist if all of the drug was in the plasma.

Question 18

Significance of Vd

Answer 18

High Vd means drug has accumulated in tissues. Low Vd means most of drug is in plasma.

Question 19

Equation for Vd

Answer 19

Vd = A/C

A=total amount in body.

Question 20

Does excretion of drug metabolites count as elimination?

Answer 20

NO! Elimination through excretion must occur to actual drug.

Question 21

Rate of elimination

Answer 21

Mostly a first order process, that is related directly to plasma drug concentration. The higher the concentration, the higher the rate of elimination.

Question 22

Clearance

Answer 22

A constant that relates rate of elimination to plasma concentration.

Question 23

Clearance equation

Answer 23

Cl= rate of elimination/C in plasma.

Question 24

What is maximum clearance for any organ?

Answer 24

Related to maximum perfusion. 1600 ml/min

900 hepatic, 720 renal.

Question 25

Extraction Ratio

Answer 25

Index of an organ’s efficiency in eliminating a given drug. The fraction of the plasma that is cleared of the drug during each pass through the organ

Question 26

Extraction Ratio Equation

Answer 26

E= (Cin-Cout)/Cin. Can range from 0-1

Question 27

Clearance of a drug by an organ is based on…

Answer 27

Plasma flow to the organ and its extraction ratio.

Question 28

Clearance of a drug by an organ equation.

Answer 28

Cl=Q *C

Question 29

High extraction drug?

Answer 29

E>=0.7 Clearance is limited by perfusion, so “Flow limited.”

Question 30

Low extraction drug?

Answer 30

E =<0.3 These are capacity limited. Reduced perfusion rate actually helps the extraction ratio.

Question 31

Total clearance?

Answer 31

Cl total = Cl hepatic + Cl renal + Cl other

Question 32

Phase I reactions

Answer 32

Oxidation and reduction reactions that create a polar molecule. These reactions reduce activity of the parent drug, and increase likelihood of renal excretion.

Question 33

Phase II reactions

Answer 33

Occur after phase I reactions, not catalyzed by CYP450s. Mostly take place in the cytoplasm and ER of hepatocytes. Add acetylene or glucuronate, acetate. Mostly all inactive, except with notable exceptions (morphine glucuronate).

Question 34

What enzymes catalyze phase I reactions?

Answer 34

CYP450’s located on hepatocytes, very important in the liver. Gi tract CYPs prevent absorption. A few are responsible for metabolizing most drugs.

Question 35

Hepatobiliary excretion

Answer 35

Mainly high MW drugs and metabolites. Can be recycled to the liver through enterohepatic circulation.

Question 36

Renal Excretion

Answer 36

Via glomerular filtration. Only unbound drug gets excreted and clearance is limited to GFR. Via secretion, which occurs in the proximal tubule.

Question 37

FEU

Answer 37

Fraction excreted Unchanged

Question 38

Renal Clearance of a drug excluding renal metabolism

Answer 38

Cl Renal = FEU * Clearance total

Question 39

Henderson Hasselbalch equation

Answer 39

pH=pKa log [a/HA]