Pharmacology and Pharmacokinetics: ADME, Drug Targets, and Response Factors

A comprehensive vocabulary flashcard set covering foundational principles of pharmacology, pharmacodynamics, pharmacokinetics (ADME), membrane transport, drug metabolism phases, and physiological response factors based on lecture notes.

Pharmacology

The study of the properties of drugs and their interactions with living systems.

Pharmacodynamics

The study of the relationship between drug concentration and biological effects (physiological or biochemical) over time, operationally summarized as what the drug does to the body.

Pharmacokinetics

The quantitative assessment of the absorption, distribution, metabolism, and excretion (ADME) of drugs from the body over time, operationally summarized as what the body does to the drug.

Induced Fit Hypothesis

The theory stating that a drug induces a unique conformational change in its target structure that is distinct from the conformation induced by the physiologic ligand.

Type I Kinase Inhibitors

Small molecule molecularly targeted drugs that act as competitive inhibitors for the ATP-binding site of a kinase.

Type II Kinase Inhibitors

Small molecule kinase inhibitors that target and recognize the inactive conformation of a kinase.

Agonist Affinity

The tenacity with which a drug binds to its receptor, defined as the probability that a drug molecule will bind to an available receptor at any given time.

Agonist Efficacy

An intrinsic property of a drug determining its ability to produce a biological effect once bound to its receptor.

Reverse Agonist

A drug that produces an opposite biological response compared to receptor stimulation by conventional agonists, typically by decreasing basal intrinsic receptor activity.

Physiological Antagonism

A mechanism wherein a drug antagonizes a biological effect by activating an opposing compensatory physiological response via a distinct receptor pathway.

Chemical Antagonism

A mechanism of drug antagonism where a drug directly reduces active agonist concentration by reacting with it to form a chemical complex.

Pharmacokinetic Antagonism

Antagonism occurring when one drug accelerates the metabolism or elimination of another drug, thereby reducing its active concentration.

Rule of 6's

A 6-step dosing calculation method used to set up standardized pediatric IV drug infusions when premixed bags are unavailable.

Child-Pugh Classification

A clinical scoring system evaluating liver disease severity using five measures: total bilirubin, serum albumin, PT INR, ascites, and hepatic encephalopathy.

Chronopharmacology

The study of how drug responses, absorption, and metabolism fluctuate in coordination with biological and circadian rhythms.

CagA Protein

A virulence factor produced by Helicobacter pylori that recruits the phosphatase SHP-2 to alter host cell migration and adhesion.

Dissolution

The process by which a solid dosage form enters solution, frequently serving as the rate-limiting or rate-controlling step in the absorption of drugs with low solubility.

Amorphism

The non-crystalline state of a solid drug having no internal crystal structure, representing the highest energy state with greater aqueous solubility and dissolution rate than crystalline forms.

Fick's Law of Passive Diffusion

A mathematical principle $\frac{dQ}{dt} = \frac{D \times A \times \Delta C}{h}$ stating that the rate of diffusion is directly proportional to surface area ($A$) and concentration gradient ($\Delta C$), and inversely proportional to membrane thickness ($h$).

Sink Conditions

A state during passive diffusion where the drug is immediately cleared or diluted on the receiving side, maintaining a constant maximum concentration gradient.

Henderson-Hasselbalch Equation

The mathematical equation $\text{pH} = \text{pKa} + \log\left(\frac{[\text{nonprotonated species}]}{[\text{protonated species}]}\right)$ used to calculate the ratio of uncharged to charged drug species in a solution of known pH.

P-glycoprotein (P-gp / MDR1)

An ATP-binding cassette (ABC) efflux transporter encoded by ABCB1 that actively pumps drugs out of enterocytes back into the gut lumen, limiting oral bioavailability.

PEPT1

A high-capacity, proton-coupled influx cotransporter located in the gut that transports peptide-like drugs such as $\beta$-lactam antibiotics, ACE inhibitors, and valacyclovir.

OATP1B1

An organic anion transporting polypeptide uptake transporter encoded by SLCO1B1 on hepatocytes that mediates hepatic uptake of statins.

Apparent Volume of Distribution ($V_d$)

A mathematical proportionality factor correlating the total amount of drug in the body to its plasma concentration $V_d = \frac{\text{Dose}}{C_0}$.

Biotransformation

The enzymatic or transporter-mediated structural conversion of endogenous or exogenous (xenobiotic) compounds within a biological system.

Phase I Biotransformation

Metabolic processes (oxidation, reduction, hydrolysis) that introduce or expose functional groups ($\text{-OH}$, $\text{-NH}_2$, $\text{-SH}$, or $\text{-COOH}$) on a drug molecule.

Phase II Biotransformation

Synthetic conjugation reactions in which an endogenous donor moiety (e.g., glucuronic acid, sulfate, acetyl, methyl, or glutathione) is attached to a substrate.

Phase III Biotransformation

Membrane-transport disposition processes that move drugs or metabolites across cellular membranes without altering their chemical structures.

Carboxylesterases (CES)

Phase I hydrolytic enzymes (such as CES1 and CES2) that catalyze the cleavage and transesterification of ester and amide bonds.

Cytochrome P450 (CYP)

A superfamily of heme-containing Phase I monooxygenase enzymes responsible for mediating approximately 90% of oxidative drug biotransformation.

Single Nucleotide Polymorphism (SNP)

A single nucleotide DNA sequence variation occurring at a frequency of greater than 1% in a given population.

Enterohepatic Circulation

The recycling process in which a drug excreted in bile into the intestine is deconjugated (e.g., by microbial $\beta$-glucuronidase) and reabsorbed into the portal circulation.

Area Under the Curve (AUC)

A key pharmacokinetic parameter derived from a plasma concentration-time curve that measures the total systemic exposure of a drug.

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

The time required for the plasma concentration of a drug to decrease by 50%, calculated as $t_{1/2} = \frac{0.693}{K_{el}}$.

Systemic Drug Clearance ($CL_s$)

The quantitative measure of the volume of plasma completely cleared of a drug per unit time, expressed as $CL_s = K_{el} \times V_d$.

Bioavailability ($F$)

The fraction or percentage of an administered drug dose that reaches the systemic circulation intact, calculated as $F = \frac{\text{AUC}_{\text{oral}}}{\text{AUC}_{\text{injected}}} \times 100$.

Lead Optimization

The phase in drug discovery where a hit/lead compound is chemically refined to simultaneously optimize efficacy, safety, solubility, absorption, and metabolic stability.

Therapeutic Window

The range of plasma drug concentrations spanning between the minimum concentration necessary to produce a desired therapeutic effect and the concentration threshold causing adverse side effects.