Drug Distribution, Metabolism, and Elimination

This set of vocabulary flashcards covers principles of drug bioavailability, compartmental distribution, plasma protein binding, metabolism phases, and renal and biliary excretion mechanisms based on the lecture notes.

Bioavailability

The fraction of drug ($F$) that reaches systemic circulation; it is equal to $1$ ($100\%$) for intravenous administration and is typically less than $1$ for oral administration.

First Pass Effect

The pre-systemic metabolism of a drug (such as Morphine) within the small intestine or liver after oral administration, which can significantly reduce bioavailability.

Body Compartment Fluids

Fluids such as Extracellular fluid ($4.5\%$), Interstitial fluid ($16\%$), Lymph ($1.2\%$), Intracellular fluid ($30-40\%$), and Transcellular fluid ($2.5\%$).

ADME

A pharmacokinetics acronym representing the four stages of drug disposition: Absorption, Distribution, Metabolism, and Excretion.

Plasma Protein Binding (Albumin)

The binding of drugs to the most important plasma protein, which mainly binds acidic drugs and is saturable.

B-Globulin & acid glycoprotein

Plasma proteins primarily responsible for binding basic drugs.

Thiopental

A lipid-soluble drug that binds to fat and is utilized for induction rather than maintenance of anesthesia.

Chloroquine

An anti-malarial drug that exhibits binding to melanin in tissues.

Volume of Distribution (Vd)

A parameter relating the total amount of drug in the body to its plasma concentration, calculated as $\frac{\text{Amount of drug in body (mg)}}{\text{Plasma concentration of drug (mg/L)}}$.

Hypoalbuminaemia

A condition resulting in decreased plasma protein binding, which can affect drugs like Warfarin.

Phase I Reactions

Catabolic reactions including Oxidation, Reduction, and Hydrolysis that typically result in chemically active products.

Phase II Reactions

Anabolic (synthetic) reactions involving conjugation (e.g., Glucuronidation) that result in chemically inactive products.

CYP450 enzymes

Haem proteins (microsomal enzymes) involved in Phase I oxidation; drugs can serve as substrates, inducers, or inhibitors for these enzymes, such as EtOH for $CYP2E1$.

Glomerular Filtration

A renal excretion process where drugs with a molecular weight less than $20,000\,Da$ cross the barrier freely, while protein-bound drugs do not.

Active Tubular Secretion

An efficient active transport mechanism for acids (e.g., Penicillin) and bases (e.g., Pethidine) into the renal tubule.

Ion Trapping

A process where basic drugs ionize in acidic urine, preventing their reabsorption across the renal tubule and favoring excretion.

Biliary Excretion

The secretion of polar, high molecular weight drugs/metabolites (greater than $250,000\,Da$) from hepatocytes into the bile for elimination in faeces.

Enterohepatic cycling

The process where hydrophilic drugs (like Morphine conjugates) are hydrolyzed to active drugs and reabsorbed, creating a reservoir that prolongs drug action.