Question 1

What are the main types of physiological barriers that restrict drug distribution?

Accepted Answer

Physiological barriers are semi-permeable structures that control drug movement into tissues and cells. The six primary barriers are the blood endothelial barrier, cell membrane, blood-brain barrier, blood-cerebrospinal fluid barrier, blood-placental barrier, and blood-testis barrier. Each barrier has distinct permeability properties that determine which drugs can cross based on size, lipophilicity, and transport mechanisms.

Question 2

How does the blood-brain barrier differ from the vascular endothelium?

Accepted Answer

The vascular endothelium is highly permeable to most drugs, including ionized, un-ionized, and lipophilic molecules smaller than 600 Daltons. In contrast, the blood-brain barrier consists of brain capillaries with tight junctions between endothelial cells, making it impervious to non-lipophilic drugs. Only lipophilic molecules and drugs transported actively by carrier proteins can cross the blood-brain barrier.

Question 3

What mechanisms allow drugs to cross the cell membrane?

Accepted Answer

Drugs cross cell membranes through three primary mechanisms. Lipophilic drugs and small molecules permeate easily through passive diffusion across the lipid bilayer. Larger or hydrophilic molecules require active transport via carrier proteins. The specific mechanism depends on drug size, chemical properties, and the availability of transport proteins in the cell membrane.

Question 4

Why is the blood-placental barrier less restrictive than the blood-brain barrier?

Accepted Answer

The blood-placental barrier consists of multiple layers of trophoblast cells that are less tightly joined than brain capillaries. It allows lipophilic molecules smaller than 1000 Daltons to pass into fetal circulation by passive diffusion, including barbiturates, anesthetics, antibiotics, and steroids. This reduced barrier function exposes the fetus to potential teratogens, requiring drug restriction during pregnancy.

Question 5

How do tight junctions affect drug permeability across physiological barriers?

Accepted Answer

Tight junctions are continuous connections between endothelial cells that prevent drug diffusion between cells. The blood-brain barrier and blood-cerebrospinal fluid barrier both feature tight junctions that block most hydrophilic substances from passing. These junctions force drugs to cross through cells rather than between them, creating a highly selective barrier that only permits lipophilic drugs or those actively transported by specific carrier proteins.

Question 6

What size limitations apply to drugs crossing the vascular endothelium?

Accepted Answer

The vascular endothelium freely permits most drugs smaller than 600 Daltons to cross into extracellular fluid, regardless of whether they are ionized, un-ionized, or lipophilic. Larger complexes, such as drugs bound to plasma proteins, are excluded from crossing the endothelial barrier. This size cutoff allows rapid distribution of most therapeutic drugs from capillaries into tissues.

Question 7

What is the role of the blood-testis barrier in drug distribution?

Accepted Answer

The blood-testis barrier is formed by neighboring Sertoli cells joined by tight junctions that restrict drug diffusion from capillaries into the testis. This barrier protects spermatids from drug exposure by preventing most molecules from entering the testicular tissue. Like the blood-brain barrier, it creates a specialized microenvironment with limited drug accessibility.

생리적 장벽

Browse More Videos