Lecture 4: pharmacokinetics

Question 1

whats is the acronyms for pharmacokinetics

Answer 1

“ADME”
absorption
distribution
metabolism 
excretion

Question 2

Factors Affecting Drug Absorption

Answer 2

• rate of dissolution (e.g., of tablet)
• surface area
• blood flow
• lipid solubility
• pH partitioning

Question 3

what kind of transport do most drugs use?

Answer 3

simple diffusion- non protein mediated transport

Question 4

what is a major transporter of drugs OUT of cells?

Answer 4

P-glycoprotein (active transport)

Question 5

why is aspirin better absorbed in the stomach?

Answer 5

is a weak acid

becomes trapped in basic compartments (looses H+ and becomes charged)

Question 6

why is amphetamine no absorbed in the stomach?

Answer 6

weak base

becomes trapped in acidic compartments because can’t lose extra H+

Question 7

what factors effect drug distribution?

Answer 7

• ability of drugs to enter the cells
(= same considerations as for absorption above)
• blood flow to tissues
• ability of drugs to exit the vascular
system (next)

Question 8

what kind bind drugs in vasculature?

Answer 8

protein (albumin)

-drug is not bioactive

Question 9

what type of drugs does the blood brain barrier let through?

Answer 9

lipid soluble

ionized or polar ONLY IF HAVE TRANSPORTER

Question 10

what are sites of peripheral drug concentration?

Answer 10

1) Fat
2) tissue (muscle, liver)
3) bone (tetracyline)
4) transcellular reservoirs (GI tract)

Question 11

what is the primary site of biotransformation or metabolism?

Answer 11

liver

Question 12

what does the liver do with drugs?

Answer 12

1) may activate a prodrug

2) crucial for renal elimination of lipophilic drugs (makes them more polar so trapped)

Question 13

what are secondary areas of drug metabolism?

Answer 13

– kidney proximal tubules
– lungs (type II cells)
– intestines
– testes (Sertoli cells)
– skin epithelial cells
– brain
– plasma

Question 14

what are the two phases of drug metabolism (biotransformation)?

Answer 14

phase 1: oxidation, reduction, hydrolysis

phase 2: conjugation

Question 15

what enzymes do oxidative process use?

Answer 15

those found on smoother ER (cytochrome P 450)

Question 16

phase II biotransformation: conjugation

Answer 16

makes drugs more water soluble and more excretable (molecule added= very polar)

Question 17

Glucuronidation

Answer 17

–major route of metabolism for drugs and
endogenous compounds (steroids, bilirubin)
–occurs in the endoplasmic reticulum
–inducible

Question 18

sulfation

Answer 18

–another major route of drug metabolsim

–occurs in the cytoplasm

Question 19

– acetylation and methylation

Answer 19

• typically makes drugs less water soluble
• addition of these groups by transferases tends to reduce drug activity;
i.e., inactivates drug

Question 20

what decreases bioavailability of orally administered drugs?

Answer 20

first pass metabolism

-goes into portal vein to liver and doesn’t get into bloodstream

Question 21

what is the major route of drug excretion?

Answer 21

renal

Question 22

what are nonrenal routes of drug excretion?

Answer 22

• bile
• sweat
• breath
• breast milk

Question 23

what are the steps in renal drug excretion

Answer 23

1) glomerular filtration
- small molecules filter
- proteins dont
2) passive tubular reabsorption
- lipid soluble drugs
- unionized weak acids and bases
3) active tubular secretion
- protein bound drugs

Question 24

Factors that Modify

Renal Drug Excretion

Answer 24

• pH-dependent ionization
(shown above under absorption)
• competition for active tubular
transport
• age... GFR falls in all as we age

Question 25

Excretion rate:

Answer 25

the mass eliminated per unit time
3⁄4 with first order kinetics, this increases as the plasma
concentration increases

Question 26

Clearance:

Answer 26

the plasma volume from which all of the
solute is removed per unit time (i.e., ml/min = a flow rate)
3⁄4 with first order kinetics, this remains constant as plasma
concentrations change

Question 27

Zero order kinetics

Answer 27

• constant amount eliminated per unit
• the drug elimination process is
saturated
• consequently, the amount of drug
eliminated is independent of the drug
concentration

Question 28

First order kinetics

Answer 28

constant fraction is eliminated per unit
time
drug elimination process is not saturated
the mass of drug eliminated is
directly related to the drug concentration

Question 29

Capacity-Limited Reactions

Answer 29

• displays zero order kinetics initially
• displays first order kinetics as the drug
concentration falls

Question 30

loading dose

Answer 30

initial large dose followed by maintenance dose for drugs with a long half life
ex= digoxin

Question 31

in the clinic after how many 1/2 lives does steady state need to be approached

Answer 31

4 is minimal acceptable time