Question 1

What four factors determine the rate of passive drug diffusion across cell membranes?

Accepted Answer

Passive diffusion rate depends on membrane surface area, the drug's lipid-water partition coefficient, the concentration gradient between compartments, and membrane thickness. These factors work together to control how quickly small lipophilic drugs cross cell membranes. Higher partition coefficients and steeper concentration gradients accelerate diffusion, while thicker membranes slow it.

Question 2

Why do orally administered drugs absorb more rapidly in the small intestine?

Accepted Answer

The small intestine provides optimal conditions for rapid drug absorption through duodenal microvilli, which dramatically increase the membrane surface area available for diffusion. Additionally, oral administration creates a substantial concentration gradient between the gastrointestinal lumen and the bloodstream, facilitating quick diffusion into blood vessels. This anatomical advantage makes the small intestine highly efficient for drug uptake.

Question 3

How does lipid solubility affect a drug's ability to cross membranes?

Accepted Answer

Highly lipid-soluble drugs with elevated partition coefficients diffuse readily across cell membranes because they dissolve in the lipid bilayer. The nonionized form of weak acids or bases is lipid-soluble and easily diffusible, while the ionized form is lipid-insoluble and poorly diffusible. This property is fundamental to passive diffusion efficiency.

Question 4

Why is drug diffusion into the brain restricted compared to other tissues?

Accepted Answer

The blood-brain barrier is a thick, highly selective membrane lined by glial cells that severely limits drug diffusion into brain tissue. This restrictive structure protects the central nervous system but prevents many drugs from reaching therapeutic concentrations in the brain. Only small, highly lipophilic molecules can effectively cross this barrier through passive diffusion.

Question 5

How do pH changes influence the diffusion of weak acid and base drugs?

Accepted Answer

Weak acids and bases exist in both nonionized and ionized forms depending on pH. Alterations in pH levels shift the equilibrium between these forms, affecting diffusion rates since only the nonionized, lipid-soluble form crosses membranes efficiently. Changes in gastrointestinal or bodily fluid pH therefore directly impact drug absorption and bioavailability.

Question 6

What is the relationship between drug concentration and passive diffusion rate?

Accepted Answer

During passive diffusion, the drug absorption rate increases linearly with concentration increase. This direct proportional relationship means that doubling the drug concentration doubles the diffusion rate, as long as the concentration gradient remains the driving force. This linear kinetics distinguishes passive diffusion from other transport mechanisms.

Question 7

How do capillary membranes compare to the blood-brain barrier in drug diffusion?

Accepted Answer

Thin, permeable capillary membranes efficiently diffuse drugs into blood vessels throughout the body, enabling rapid systemic drug distribution. In contrast, the thick blood-brain barrier lined by glial cells severely restricts drug passage into the brain. This structural difference explains why most drugs achieve high systemic concentrations but low brain concentrations.

Passive Diffusion: Overview and Kinetics

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