Pharmacology: Pharmacokinetics Absorbtion

Question 1

What determines if a drug can get into its target site through passive diffusion?

Answer 1

The partition coefficient. (Drug size, ability to dissolve through lipids, and drug ionization)

Question 2

What determines if molecules can pass to target site through filtration?

Answer 2

Size

Question 3

What four ways can drugs get to their target site?

Answer 3

Passive diffusion, filtration, active transport and endocytosis

Question 4

How does blood help maintain a gradient so drug can continually cross the gut membrane?

Answer 4

Blood whisks away drug so the gradient is constantly lower on the vessel side.

Question 5

How does plasma affect drug movement from gut to vessel?

Answer 5

If drug binds to plasma proteins, it is no longer included in the equilibrium of free drug and shifts equilibrium to inside of gut.

Question 6

For weak acids, which species is lipid soluble and which is charged?

Answer 6

The acid is lipid soluble and the base is charged.

Question 7

For weak bases, which species is lipid soluble and which is charged?

Answer 7

The acid is charged and the base is lipid soluble.

Question 8

How do you know how much of your drug will pass through lipid membranes?

Answer 8

Henderson-Hasselbach: pH=pK + log(base/acid)

Question 9

Why is morphine not absorbed from the stomach as well as aspirin?

Answer 9

It is a weak base, is charged at the stomach pH and cannot pass through the membrane. Aspirin is not ionized at stomach pH and gets across the membrane more easily.

Question 10

How could you excrete barbiturates more quickly?

Answer 10

Increase urine acidity. Barbituates are noncharged weak bases. The higher plasma pH (7.5) will drive the drug into the urine.

Question 11

What type of drug will enter the CNS the quickest?

Answer 11

Nonionized and hydrophobic molecules. The blood-brain barrier is a thick lipid membrane.

Question 12

2 families of active transport mechanisms

Answer 12

ABC and SLC

Question 13

How do ABC family transporters function?

Answer 13

They cleave ATP and use the energy to force the drug out against the concentration gradient.

Question 14

How do SLC family transporters function?

Answer 14

The transporter uses the concentration gradient of a different ion. When the other drug comes in the drug of concern goes out against its gradient.

Question 15

Why is it difficult to get anti-tumor drugs into tumor cells?

Answer 15

They have high expression of ABC family transporters. Drugs enter by diffusion, but are picked up by the ATP transporter and are transported out of the cell. Specifically MDR1/ABCB1/P-glycoprotein.

Question 16

Where does the anti-depressant drug Prozac act?

Answer 16

SLC family transporter. It is a serotonin uptake transporter that inhibits uptake so serotonin stays in the blood longer.

Question 17

How does drug movement happen in the liver?

Answer 17

Hepatocytes metabolize drugs and have ABC transporters that lead to the blood vessels or bile. SLC transporters carry the drugs either way.

Question 18

How does drug movement occur in the kidney?

Answer 18

ABC transporters pump drugs out of endothelial cells and into tubules for secretion. SLC transporters work in both directions.

Question 19

How does drug movement occur in the small intestine?

Answer 19

Both ABC and SLC transporters work in both directions (lumen and blood stream)

Question 20

How does drug movement occur in the brain?

Answer 20

ABC transporters keep things out of the brain and SLCs work in both directions.

Question 21

Where is the major site of enteral drug absorption?

Answer 21

Small intestine

Question 22

What is the major mode of parenteral drug absorption?

Answer 22

I.V.

Question 23

Where do many lipophilic drugs bind?

Answer 23

Albumin in plasma. Although plasma proteins have low affinity for drugs, there are many more of them than the actual target receptors.

Question 24

How could you release more drug into the body after it has been administered hours ago?

Answer 24

Give a drug with a higher affinity for plasma protein.

Question 25

How can you get a high volume of distribution in a fat ass?

Answer 25

Lipid soluble molecules get sucked into the fat depot.

Question 26

What are the protected compartments?

Answer 26

CNS, eye, joints and fetus

Question 27

Through what do drugs need to pass to get to the brain?

Answer 27

Blood-brain barrier which is closed off by tight junctions. Drugs must pass through astrocytes if they want to get to the capillaries.

Question 28

Blood-brain barrier characteristics

Answer 28

Few pores, lipid solubility facilitates penetration, ABC transporters in and out

Question 29

What transporter acts as the brain’s gate keepers?

Answer 29

MDR1 (P-glycoprotein) expressed on endothelial cells and in choroid plexus. Specifically pumps HIV proteases, anti-cancer drugs, morphine)

Question 30

Why does transport occur so slowly to the placenta?

Answer 30

Blood volume is low in the placenta

Question 31

How does the kidney get rid of metabolites?

Answer 31

Filtration

Question 32

How do you figure adult creatine clearance in the kidney?

Answer 32

Schwartz Equation

Question 33

How are organic cations transported in tubular secretion?

Answer 33

OCT1 and OCT2 present on the blood side of the proximal tubule transport cations from the blood into the cells. MDR1 and OCT3 are present on the urine side of the cell and transport molecules into the urine.

Question 34

How are organic anions transported in tubular secretion?

Answer 34

OATs transport ions into the epithelial cells from the blood and MDRs transport them into the urine