T2 - Drug Distribution and Metabolism E2

Question 1

What is the purpose of drug disposition?

Answer 1

Lowers its concentration in the plasma

Question 2

Describe drug disposition

Answer 2

1. Drug distribution
2. Drug elimination → Drug metabolism and drug excretion

Question 3

What is drug distribution?

Answer 3

The reversible mass transfer process of a drug from one location to another within the body

Question 4

Where are drug mass transferred?

Answer 4

Drugs moves from vascular to the extravascular space that occurs through the endothelial lining of blood capillaries

Question 5

What factor does the rate of drug distribution strongly depend on?

Answer 5

The features of the capillary bed under consideration

Question 6

What are steps of drug distribution?

Answer 6

1. The transport of drug by blood to different tissues
2. The transport of the drug from blood into the tissue across the cell membrane

Question 7

How is the rate of blood flow compensate for its irregularity in the body?

Answer 7

Blood flow to a particular tissues determines the rate and extent of drug distribution to the particular tissue

Question 8

What are the mechanisms of drug transfer in comparison to drug absorption?

Answer 8

Similar movements across endothelia and cell membranes such as passive diffusion and carrier mediated active transport

Question 9

What influences drug distribution?

Answer 9

Reversible binding to:

Plasma proteins and tissue elements

Question 10

What is the difference between plasma protein and tissue element reversible binding events?

Answer 10

Plasma proteins limit drug distribution outside the vascular system

Tissue elements promote drug distribution outside the vascular system

Question 11

What is the key concept of drug distribution?

Answer 11

Only free, unbound drug molecules can efficiently cross endothelia and thus engage in the pseudo-equilibrium of distribution

Question 12

Depict the image of drugs progression in the body

Answer 12

Question 13

Depict the factors that influence drug distribution

Answer 13

Question 14

Depict the movement of unionized and ionized drugs throughout the body

Answer 14

Question 15

What is volume of distribution (Vd)?

Answer 15

The theoretical body fluid volume required to dissolve the amount of drug in the body (A) to give the observed (measured) drug concentration in plasma

Question 16

What is the quantitative definition of Vd?

Answer 16

Vd = amount of drug in body (A)/ measured concentration of the drug in plasma (C)

Question 17

What is the volume distribution of a drug from an IV bolus?

Answer 17

The amount of drug in body is equal to the injected dose, then [plasma] can be calculated of the drug during this time

Question 18

What is the irreversible loss of the drug in the body?

Answer 18

Drug elimination

Question 19

What processes of ADME lead to drug elimination?

Answer 19

Drug metabolism and excretion

Question 20

What is drug metabolism?

Answer 20

The enzymatic conversion of one chemical form into another

Question 21

What is the pro and con of lipid solubility?

Answer 21

Lipid solubility is effective for absorption, however, reduces drug excretion

Question 22

Compare how water-soluble and and lipid soluble drugs are eliminated?

Answer 22

W: undergo excretion

L: undergo renal tubule reabsorption

Question 23

What are the drug metabolism pathways?

Answer 23

Phase 1 and 2

Question 24

What are the reactions of Phase 1 metabolism?

Answer 24

1. Oxidation (CYPs, Alcohol dehydrase)
2. Hydrolysis (esterases)
3. Reduction

Question 25

What are the reactions of Phase 2 metabolism?

Answer 25

1. Conjugation (Glucouronic acid UGT)
2. Acetylation (NAT)
3. Methylation (TPMP)
4. Sulfate

Question 26

What are the drug metabolizing organs?

Answer 26

1. Hepatic
2. Extrahepatic

Question 27

What are the extrahepatic organs that metabolize drug?

Answer 27

1. Intestine
2. Kidneys
3. Biliary
4. Lung
5. Placenta
6. Skin

Question 28

What are the outcomes of drug metabolism?

Answer 28

1. Renders pharmacologically active drug to inactive metabolites
2. Occasionally yields pharmacologically active metabolites
3. Rarely leads to toxic metabolites
4. Pharmacologically inactive (prodrugs) are rendered active

Question 29

What are examples of drug metabolisms yielding pharmacologically active metabolites?

Answer 29

1. Amitryptyline to Nortriptyline
2. Imipramine to Desipramine
3. Codeine to Morphine

Question 30

What are examples of drug metabolisms that can lead to toxic metabolites?

Answer 30

Paracetamol to N-acetyl-p-benzoquinone imine (NAPQI)

Question 31

What are examples of drug metabolisms that activates prodrugs?

Answer 31

1. Pivampicillin to Ampicillin
2. Enalapril to Enalaprilat
3. Phenacetin to Paracetamol

Question 32

What are the factors that affect drug metabolism?

Answer 32

1. Drug-drug interactions (enzyme induction and inhibition)
2. Physiologic and pathologic factors (Age, sex, enzyme genetics, liver disease, diet, pregnancy)

Question 33

Describe the mechanism of the inhibitor and how it slows down metabolism?

Answer 33

Inhibitor → Rapid direct inhibition of CYP450 isoenzymes → Decrease metabolism of target drug and increase in toxicity

Question 34

Describe the mechanism of the inducers and how it increases metabolism?

Answer 34

Inducer → slow synthesis or degradation of CYP450 isoenzymes → Increased metabolism of target drug and increased excretion