Lecture 2 barriers to drug deliver

Question 1

Describe bioavailability in drug delivery.

Answer 1

Bioavailability is the rate and extent to which an active agent is absorbed and becomes available at the site of action to elicit a therapeutic response.

Question 2

what influences bioavailability in drug delivery

Answer 2

It is influenced by absorption, distribution, metabolism, and elimination processes.

Question 3

What is the concept of relative bioavailability?

Answer 3

Relative bioavailability compares the rate and extent of absorption of two drug formulations (test vs. standard) administered via the same route.

Question 4

Define absolute bioavailability in pharmacokinetics.

Answer 4

Absolute bioavailability compares the bioavailability of a drug via a specific route of administration with its bioavailability after intravenous (IV) administration.

Question 5

How is absolute bioavailability calulated

Answer 5

It is calculated as the ratio of the AUC of the route of interest to the AUC after IV administration, always less than 1 if not administered intravenously

Question 6

How can 100% bioavailability for oral drugs be achieved?

Answer 6

Drug must be completely released into solution in gastrointestinal fluid, remain stable in the solution, pass through the epithelium of the gastrointestinal tract without undergoing first-pass metabolism in the gut wall or liver.

Question 7

List the barriers to drug delivery.

Answer 7

Barriers to drug delivery include biological (physical) barriers, physicochemical barriers, drug metabolism and elimination processes, patient compliance issues, and immunological barriers.

Question 8

Explain the physical barriers to drug delivery.

Answer 8

Physical barriers include cell membrane barriers, epithelial barriers with mucus layers and biochemical obstacles like degradative enzymes, hydrophobic membranes with poor absorption of charged molecules, and efflux systems that pump out substances through specific pumps.

Question 9

Describe passive diffusion in drug delivery.

Answer 9

Passive diffusion involves the movement of drugs down a concentration gradient according to Fick’s law.

Question 10

What is paracellular drug delivery?

Answer 10

Paracellular drug delivery involves drug molecules moving between adjacent epithelial cells, limited to small hydrophilic molecules.

Question 11

Define transcellular drug delivery.

Answer 11

Transcellular drug delivery involves drugs moving across epithelial cells, commonly seen with low molecular weight and hydrophobic molecules.

Question 12

How does carrier-mediated transport work in drug delivery?

Answer 12

Carrier-mediated transport in drug delivery involves active absorption or facilitated diffusion using specialized membrane proteins with specificity for a set of substrates.

Question 13

Describe facilitated transport in drug delivery.

Answer 13

Facilitated transport in drug delivery works with the concentration gradient passively, such as glucose transporters.

Question 14

What is endocytosis in drug delivery?

Answer 14

Endocytosis in drug delivery involves the internalization of plasma membrane with the engulfment of extracellular material, including receptor-mediated and adsorptive endocytosis.

Question 15

Describe the endocytic process in drug delivery.

Answer 15

1) Target molecules bind to receptors in the plasma membrane.

2) Areas coated with ligands form deep pockets in the plasma membrane surface.

3) Pockets pinch off, forming endosomes (coated vesicles).

4) Endosomes fuse with primary lysosomes to form secondary lysosomes.

5) Ligands may be removed and absorbed into the cytoplasm or degraded in acidic lysosomal conditions.

6) The lysosomal and endosomal membranes separate.

7) Endosomes fuse with the plasma membrane, making receptors available for ligand binding again.

Question 16

Explain the structure and function of the blood-brain barrier.

Answer 16

The blood-brain barrier consists of endothelial cells surrounded by pericyte and astrocyte endfeet. It is a highly specialized barrier designed to protect the brain from harmful molecules. Tight junctions composed of complex and diverse proteins, including transmembrane proteins, restrict the passage of most molecules into the brain.

Question 17

What is the role of tight junctions in the blood-brain barrier?

Answer 17

Tight junctions in the blood-brain barrier restrict the passage of most molecules into the brain, allowing only specific substances like O2, CO2, and water to freely cross.

Question 18

How do small drug molecules interact with the blood-brain barrier?

Answer 18

Less than 2% of small drug molecules can bypass the blood-brain barrier. Most molecules cannot freely cross the barrier, except for lipophilic molecules and nutrients.

Question 19

Define endocytosis in the context of drug delivery.

Answer 19

Endocytosis is the process by which cells absorb molecules by engulfing them. In drug delivery, endocytosis plays a crucial role in the internalization of target molecules bound to receptors on the cell membrane.