L5

Question 1

What are the 4 ways that small molecules cross cell membranes?

Answer 1

1. Diffusion through lipid membranes
2. Diffusion through aqueous pores
3. Transmembrane carrier proteins
4. Pinocytosis

Question 2

What 2 mechanisms are important for drug movement?

Answer 2

1. Lipid-mediated transport
2. Carrier-mediated transport

Question 3

Lipid solubility is crucial for what 3 factors?

Answer 3

1. drug absorption
2. Penetration into the brain and other tissues
3. elimination

Question 4

Weak acids and bases exist in what two forms depending on pH? (2)

Answer 4

1. Ionized (charged)
2. Unionized (uncharged)

Question 5

What happens in pH partitioning with weak acids and weak bases? (2)

Answer 5

1. Weak acids accumulate in regions of high pH (alkaline).
2. Weak bases accumulate in regions of low pH (acidic).

Question 6

What does pH partitioning affect?

Answer 6

Drug distribution across different body regions.

Question 7

What is carrier-mediated transport and where is it important? (2)

Answer 7

• Involves binding to a transmembrane protein that changes conformation to transport molecules.
  -Important in the renal tubule, biliary tract, blood-brain barrier, and gastrointestinal tract.

Question 8

What is the role of plasma proteins in drug activity?

Answer 8

Drugs bound to plasma proteins are pharmacologically inactive

Question 9

What plasma protein primarily binds drugs, especially acidic ones?

Answer 9

Albumin.

Question 10

What does extensive plasma protein binding affect?

Answer 10

It slows drug elimination (metabolism and/or excretion).

Question 11

How is drug distribution measured?

Answer 11

Volume of Distribution (Vd) = Dose/[Drug]plasma.

Question 12

If a drug has a high Volume of Distribution (Vd), where does it tend to accumulate?

Answer 12

In tissues such as muscle and fat.

Question 13

How do most drugs leave the body?

Answer 13

Via urine, either unchanged or as polar metabolites.

Question 14

What organ plays a key role in drug metabolism?

Answer 14

The liver.

Question 15

Which enzyme family is primarily responsible for drug metabolism?

Answer 15

Cytochrome P450.

Question 16

What happens in Phase I and Phase II of drug metabolism?

Answer 16

Phase I: P450 introduces reactive groups (e.g., hydroxyl).

Phase II: Glucuronide is attached, forming an inactive, excretable product.

Question 17

What is the role of the P450 enzyme family?

Answer 17

1. They metabolize drugs, making them more polar and aiding in their elimination.

Question 18

What are some common substrates for CYP1A2 and CYP3A4/5 enzymes? (2)

Answer 18

1. CYP1A2: Caffeine, paracetamol.
2. CYP3A4/5: Ciclosporin, nifedipine.

Question 19

What can influence variations in P450 activity?

Answer 19

1. Genetic polymorphisms
2. Environmental factors (e.g., grapefruit juice, cigarette smoke)

Question 20

What is the effect of metabolism on prodrugs?

Answer 20

Metabolism can convert inactive prodrugs into active drugs or toxins.

Question 21

What percentage of drugs are passively reabsorbed by diffusion in the kidney?

Answer 21

Lipid-soluble drugs are passively reabsorbed unless converted to polar metabolites.

Question 22

How does urine pH affect drug elimination?

Answer 22

1. Alkaline urine enhances elimination of acidic drugs.
2. Acidic urine enhances elimination of basic drugs.

Question 23

What does the half-life of a drug refer to?

Answer 23

The time it takes for 50% of the drug to be eliminated from the body.

Question 24

What is toxicokinetics?

Answer 24

The study of how poisons are absorbed, distributed, metabolized, and eliminated in the body.

Question 25

What are two common tissues where toxicants accumulate?

Answer 25

1. Fat (e.g., DDT)
2. Liver and kidney (for heavy metals)