Pharmacokinetics, Metabolism, Absorption, Distribution, and Excretion Flashcards

Comprehensive vocabulary flashcards covering key pharmacokinetic principles including ADME, compartment models, metabolic pathways, enzyme types, and elimination mechanics.

Pharmacokinetics

The study of what the body does to a drug, encompassing the processes of absorption, distribution, metabolism, and excretion (ADME).

Pharmacodynamics

The study of what a drug does to the body, focusing on its biochemical, physiological, and therapeutic effects.

Bioavailability ($F$)

The percentage or fraction of an administered drug dose that reaches systemic circulation in a chemically unchanged form.

Area Under the Curve (AUC)

A pharmacokinetic parameter representing total integrated drug exposure in plasma over time, commonly calculated using the trapezoidal rule.

Volume of Distribution ($V_d$)

The theoretical volume required to contain all of the drug in the body at a concentration equal to that in plasma, calculated as $V_d = \frac{\text{Dose}}{\text{Concentration}}$.

First-Order Kinetics

An elimination process where the rate of drug elimination is directly proportional to plasma concentration, removing a constant fraction of drug per unit time.

Zero-Order Kinetics

An elimination process where a constant amount of drug is removed per unit time, regardless of the plasma drug concentration.

Elimination Half-Life ($t_{1/2}$)

The time required for the plasma concentration of a drug to decline to $50\%$ of its original value, calculated as $t_{1/2} = \frac{0.693}{k}$.

Elimination Rate Constant ($k$)

The fraction of drug in the body removed per unit time during the elimination phase, defined as $k = \frac{\text{CL}}{V_d}$.

Steady-State Concentration

The equilibrium condition achieved when the rate of drug administration equals the rate of drug elimination, which takes approximately $5$ half-lives under first-order kinetics.

One-Compartment Open Model

A pharmacokinetic model that treats the body as a single homogeneous compartment where drug distribution occurs instantaneously after administration.

Two-Compartment Open Model

A pharmacokinetic model where drug distribution occurs reversibly between a well-perfused central compartment and a slower-equilibrating peripheral compartment.

Biotransformation

The chemical conversion of lipophilic, non-polar drugs into hydrophilic, polar compounds to facilitate excretion from the body.

Microsomal Enzymes

Enzymes located on the smooth endoplasmic reticulum that catalyze glucuronide conjugation, most oxidations, and some reductions, and are inducible by drugs and diet.

Non-Microsomal Enzymes

Enzymes located primarily in the cytoplasm and mitochondria that catalyze non-glucuronide conjugations, hydrolyses, and some oxidations, and are non-inducible.

Phase I Metabolism

Biotransformation reactions (oxidation, reduction, and hydrolysis) that introduce or unmask polar functional groups on a drug molecule.

Phase II Metabolism

Conjugation reactions where a drug or its Phase I metabolite combines with an endogenous substrate (such as UDP-glucuronic acid or glutathione) to form a highly polar conjugate.

N-Dealkylation

A Phase I oxidative reaction where an alkyl group is removed from a nitrogen atom, exemplified by the biotransformation of imipramine, diazepam, codeine, and caffeine.

O-Dealkylation

A Phase I oxidative reaction where an alkyl group is removed from an oxygen atom, exemplified by the biotransformation of codeine, indomethacin, and dextromethorphan.

pKa

The negative base-10 logarithm of the acid dissociation constant ($K_a$), representing the pH at which a drug is $50\%$ ionized and $50\%$ unionized.

Ion Trapping

The accumulation of a weak acid or weak base across a biological membrane into a compartment with a pH that causes the drug to become ionized and unable to diffuse back.

First-Pass Metabolism

The initial biotransformation of an orally administered drug in the intestinal wall or liver prior to reaching systemic circulation, which reduces its bioavailability.

P-glycoprotein

An ATP-dependent membrane efflux transporter encoded by the MDR1 (ABCB1) gene that actively pumps xenobiotics out of cells and across biological barriers.

MDR1 Gene Mutation

A genetic mutation in ABCB1 commonly seen in Collies and Shepherds that impairs P-glycoprotein functionality at the blood-brain barrier, resulting in neurotoxicity from drugs like ivermectin and loperamide.

Plasma Protein Binding

The reversible association of a drug with blood proteins like albumin, where only the unbound (free) fraction is pharmacologically active and able to diffuse into tissues.

Glomerular Filtration

A passive renal elimination process in which free, unbound drugs with molecular weights below the filtration threshold pass from capillary blood into the nephron lumen.

Tubular Secretion

An active transport mechanism occurring in the proximal convoluted tubules of the nephron that moves drug molecules from blood capillaries into the tubular lumen.

Tubular Reabsorption

The passive diffusion of unionized, lipophilic drugs back from the renal tubular fluid into systemic capillary circulation.

Urine Alkalinization

The therapeutic process of raising urine pH (e.g., using sodium bicarbonate) to increase the ionization and renal excretion of weak acid drugs like barbiturates by preventing tubular reabsorption.