Pharmacodynamics, Pharmacokinetics, and Personalized Drug Therapy Flashcards

Flashcards for reviewing pharmacodynamics, pharmacokinetics, and personalized drug therapy.

Ligand synthesis

Signaling molecules produced by signaling cells.

Ligand release and transport

Ligands are released into the extracellular space and transported to target cells.

Receptor binding

Ligands bind specifically to receptors on or within recipient cells.

Signal transduction

The ligand-receptor complex transforms the extracellular signal into an intracellular message.

Biological response

The cell responds by altering gene expression, enzyme activity, or other cellular functions.

Ligand removal

Ligands are degraded or detached to terminate the signal.

Ion-channel receptors

Open or close ion channels directly upon ligand binding, leading to rapid responses.

G protein-coupled receptors (GPCRs)

The largest receptor family, characterized by extracellular ligand-binding domains and intracellular G proteins.

Protein kinase receptors

Enzymatic receptors that activate intracellular kinase domains upon ligand binding, leading to phosphorylation cascades.

Intracellular receptors

Lipophilic ligands diffuse into cells and bind to nuclear receptors, regulating gene transcription directly.

Agonists

Activate receptor activity.

Antagonists

Block receptor activity.

Inverse agonists

Suppress receptor activity.

Enzyme inhibitors

Alter metabolic pathways.

Affinity

The strength of the binding between a drug and its receptor, often quantified by the dissociation constant (KD).

Potency

The amount of drug required to produce a specific effect; a more potent drug achieves the effect at lower concentrations.

Efficacy

The maximum effect a drug can produce once bound to the receptor (Emax).

Full agonists

Bind receptors with high efficacy (α=1), producing maximal responses.

Partial agonists

Have less than maximal efficacy (α<1), eliciting submaximal responses even at full receptor occupancy.

Antagonists

Bind without activating the receptor (α=0), blocking agonist effects.

Graded dose-response curves

Show continuous changes in effect with increasing drug dose or concentration for individual subjects.

Quantal dose-response curves

Depict the proportion of a population responding to a given dose, illustrating all-or-none effects.

ED50

Dose producing 50% of maximum effect.

LD50

Dose lethal to 50% of subjects.

Therapeutic Index (TI)

Ratio of LD50 or TD50 to ED50, indicating safety margin.

Selectivity

The ability of a drug to preferentially bind to certain receptor subtypes.

Specificity

The likelihood that a drug affects only its intended target, minimizing off-target effects.

Competitive antagonists

Bind reversibly to the same site as the agonist, shifting dose-response curves rightward without affecting maximal response.

Non-competitive antagonists

Bind irreversibly or at allosteric sites, reducing maximal response regardless of agonist concentration.

Allosteric antagonists

Bind to separate sites, inducing conformational changes that prevent receptor activation.

Chemical antagonists

Modify ligands structurally, preventing receptor binding.

ED50

Effective dose in 50% of subjects.

TD50

Toxic dose in 50% of subjects.

Pharmacokinetics (PK)

Describes what the body does to the drug—absorption, distribution, metabolism, and excretion.

Pharmacodynamics (PD)

Describes what the drug does to the body—mechanism of action, effect, and response.

First order kinetics

A constant fraction of drug is eliminated per unit time; elimination rate is proportional to drug concentration.

Zero order kinetics

A constant amount of drug is eliminated per unit time; occurs when elimination pathways are saturated.

One-compartment model

Assumes instantaneous distribution throughout the body.

Two-compartment model

Differentiates between plasma and peripheral tissues.

Cmax

Peak plasma concentration.

Tmax

Time to reach Cmax.

AUC

Area under the plasma concentration-time curve, representing total drug exposure.

Bioavailability (F)

Fraction of administered dose reaching systemic circulation.

Volume of Distribution (Vd)

Theoretical volume in which the drug distributes; influences dose calculation.

Clearance (CL)

Volume of plasma cleared of drug per unit time; determines maintenance dose.

Elimination rate constant (Kel)

Fraction of drug eliminated per unit time.

Half-life (T1/2)

Time for plasma concentration to reduce by half; guides dosing intervals.

Loading dose (DL)

Achieves therapeutic levels rapidly.

Maintenance dose (MD)

Maintains steady-state levels.

Pharmacokinetic variability

Changes in drug absorption, distribution, metabolism, or elimination affecting drug levels.

Pharmacodynamic variability

Differences in receptor sensitivity, signaling pathways, or downstream effects causing variable responses despite similar drug levels.

Intrinsic resistance

Naturally low permeability, efflux pumps, or target modifications.

Acquired resistance

Genetic mutations alter drug targets or increase drug efflux.

Cross-resistance

Resistance to one drug confers resistance to similar drugs.

Additive

Effects sum.

Synergistic

Effects greater than sum.

Potentiation

One drug enhances the effect of another without effect alone.

Antagonistic

One drug diminishes or blocks the effect of another.

Mutations

Rare, often harmful, affecting protein structure/function.

Polymorphisms

Common variants (≥1%) affecting enzyme activity or receptor function.

Pharmacogenetics

Focuses on individual gene variants affecting drug response.

Pharmacogenomics

Examines multiple gene interactions across the genome influencing drug response.

Personalized (Precision) Medicine

Tailors therapy based on individual genetic and molecular profiles.