Drug Absorption Continued

Comprehensive flashcards covering drug absorption mechanisms, equations, physiological factors, and pharmacokinetic principles from the lecture notes.

Henderson-Hasselbach Equation (Weak Acid)

$$pH = pKa + \log \frac{[A^-]}{[HA]}$$

Henderson-Hasselbach Equation (Weak Base)

$pH = pKa + \log \frac{[RNH_2]}{[RNH_3^+]}$ OR $pH = pKa + \log \frac{[Base]}{[Salt]}$

Extent of ionization factors

The pka of the drug and the pH of the medium.

pH-Partition Hypothesis

The principle that drug ionizes at different degrees on either side of a membrane, leading to unequal total drug concentrations where the compartment with greater ionization contains the greater concentration.

Drug Affinity

The attraction of a drug for a particular tissue component which can influence and prevent the drug's movement across the membrane.

Factors Affecting Bioavailability

First pass hepatic metabolism, solubility of the drug, and the nature of the drug formulation.

Physical factors influencing absorption

Blood flow to the site, surface area of the site, and contact time at the absorption surface.

Enterocytes

Simple columnar epithelial cells that line intestinal walls, containing drug transporters, tight junctions, and drug metabolizing enzymes.

Tight junctions

Structural components of enterocytes including Claudin and Occludin that regulate the paracellular space.

Active Transport

A carrier-mediated trans-membrane process that requires energy to move drugs against a concentration gradient; it is saturable and subject to competition between drugs of similar structure.

P-gp (MDR1)

An energy-dependent, membrane-bound efflux transporter that acts as a defense mechanism to prevent drug accumulation.

Facilitated Diffusion

A carrier-mediated transport that moves along a concentration gradient (high to low) without energy; it is structurally selective and saturable but plays a minimal role in drug absorption.

PEPT1 (SLC15A1)

A proton/peptide co-transporter that serves as an uptake transporter in the solute carrier (SLC) genetic superfamily.

Pinocytosis

A vesicular transport process involving the engulfment of small solutes or fluids by the cell.

Phagocytosis

A vesicular transport process involving the engulfment of larger particles or macromolecules by the cell.

Pore (Convective) Transport

The crossing of very small molecules like urea or water through cell membranes via transport proteins that form open channels.

Ion-Pair Formation

The process where a highly ionized drug joins with an opposite charge ion to form a neutral complex that diffuses easily across membranes.

Grapefruit substance interaction

Flavonoids (naringin and bergamottin) in grapefruit juice inhibit P-gp and CYP3A, increasing the bioavailability of drugs like dextromethorphan.

Total transit time

The time it takes for residues to exit the body via feces, typically ranging from $0.4$ to $5$ days.

Ptyalin

A salivary amylase found in the oral cavity (saliva pH = 7).

Mucin

A glycoprotein that lubricates food and is used for buccal absorption of lipid-soluble drugs.

Parietal cells

Stomach cells that secrete acid when stimulated by gastrin and histamine.

Antral milling

The process in the antral part of the stomach of breaking down large particles.

Duodenum Enzymes

Trypsin, chymotrypsin, and carboxypeptidase (hydrolysis of proteins); Amylase (digestion of CHOs); Pancreatic lipase (hydrolyzes fats).

Rectum absorption

Absorption that avoids the hepatic first-pass effect via the superior, middle, and inferior hemorrhoidal veins.

Splanchnic circulation

A network that receives $28\%$ of the cardiac output and maintains the concentration gradient for drug absorption.

Lymphatic System Absorption

A pathway for lipophilic drugs via lacteals that bypasses the liver/first-pass effect, draining into the vena cava.

Absolute oral Bioavailability (F) formula

$F = F_a \times F_g \times F_h$ where $F_a$ is fraction absorbed, $F_g$ is intestinal escape, and $F_h$ is hepatic escape.

Rule of Five

Predicts poor absorption if H-bond donors > 5, H-bond acceptors > 10, MW > $500\,Da$, or ClogP > 5.