7-12

Pharmacodynamics

What the drug does to the body, including drug effects (physiologic/biochemical changes) and drug action (mechanism of effect)

Ligand

A drug, hormone, neurotransmitter, or chemical that binds to a receptor

Receptor

A cellular protein target that binds a ligand and triggers a biological response

Drug

A substance that produces a physiological effect in the body, used to treat, cure, mitigate, prevent, or diagnose disease

Functional modifiers

Drugs that alter body functions without replacing substances or killing organisms, e.g., atropine, xylazine, furosemide

Replenishers

Drugs that replace deficient substances in the body, e.g., calcium, iron, vitamins, electrolytes

Diagnostics

Agents used to detect disease or evaluate body function, e.g., tuberculin, fluorescein, contrast media

Chemotherapeutics

Drugs that act against infectious organisms or abnormal cells, including antibacterials, antivirals, antiparasitics, antifungals, anticancer drugs

Receptor (mechanism)

Protein that binds a ligand and undergoes conformational change to activate signal transduction pathways

Type 1 receptors

Ligand-gated ion channels that act in milliseconds, e.g., GABA-A, nicotinic ACh receptors

Type 2 receptors

G-protein-coupled receptors (GPCRs) acting in seconds to minutes, e.g., α₂, β₂, opioid receptors

Type 3 receptors

Enzyme-linked (kinase-linked) receptors acting in minutes to hours, e.g., insulin and growth factor receptors

Type 4 receptors

Intracellular/nuclear receptors acting in hours to days, regulating gene transcription

Ligand-gated ion channels

Membrane receptors that open when a ligand binds, allowing ion flow (Na⁺, Cl⁻) and producing very fast responses

GABA-A receptor

A ligand-gated channel causing Cl⁻ influx → hyperpolarization, leading to sedation, hypnosis, muscle relaxation, anticonvulsant effects

Nicotinic acetylcholine receptor

Ligand-gated channel causing Na⁺ influx → depolarization, important in neuromuscular transmission

GPCR (G-protein-coupled receptor)

Large receptor family that activates G proteins and second messengers after ligand binding

Adenylyl cyclase

Enzyme activated/inhibited by G proteins that produces cAMP, regulating heart rate and smooth muscle tone

cAMP (cyclic AMP)

Second messenger that increases heart rate, bronchodilation, vasodilation when elevated

Phospholipase C pathway

GPCR pathway producing DAG and IP₃, increasing intracellular Ca²⁺ signaling

Gαs

G protein subunit that stimulates adenylyl cyclase, increasing cAMP

Gαi

G protein subunit that inhibits adenylyl cyclase, decreasing cAMP

Gαq

G protein subunit that activates phospholipase C → DAG + IP₃

α₁ receptor

Adrenergic receptor coupled to Gαq, causes vasoconstriction via IP₃/DAG pathway

α₂ receptor

Adrenergic receptor coupled to Gαi, decreases cAMP and sympathetic output

β₁ receptor

Adrenergic receptor coupled to Gαs, increases cAMP, increases cardiac activity

β₂ receptor

Adrenergic receptor coupled to Gαs, increases cAMP, causes bronchodilation and vasodilation

Enzyme-linked receptors

Receptors with intrinsic or associated enzyme activity, often involving phosphorylation cascades

Insulin receptor

Tyrosine kinase receptor that increases glucose uptake via phosphorylation signaling

Atrial natriuretic factor receptor

Guanylyl cyclase receptor increasing cGMP, promoting natriuresis

Nuclear receptors

Intracellular receptors that bind lipophilic drugs and regulate gene transcription

Steroid receptors

Nuclear receptors for glucocorticoids, sex hormones, mineralocorticoids

Non-steroid nuclear receptors

Receptors for vitamin A and vitamin D derivatives

Affinity

Strength of drug binding to receptor, determines potency, duration, and reversibility

Intrinsic activity

Ability of a drug to activate a receptor after binding, determines agonist vs antagonist behavior

Agonist

Drug with high affinity and intrinsic activity, fully activates receptor response

Partial agonist

Drug with affinity but reduced intrinsic activity, produces submaximal response

Antagonist

Drug with affinity but no intrinsic activity, blocks receptor activation

Covalent bond (drug-receptor)

Very strong irreversible bond, leads to long-lasting effects until receptor is replaced

Ionic bond

Electrostatic attraction between oppositely charged drug and receptor, strong and reversible

Hydrogen bond

Weak to moderate interaction involving H bonded to O or N, reversible

Van der Waals forces

Weak interactions from temporary electron shifts, require close proximity

Hydrophobic interaction

Association of nonpolar drug regions with nonpolar receptor areas

Lock and key theory

Model stating receptor is rigid and perfectly matches a specific drug

Induced fit theory

Model where receptor changes shape upon drug binding to improve interaction

Occupancy theory

Drug effect proportional to fraction of receptors occupied

Spare receptors

Situation where max effect occurs without full receptor occupancy

Rate theory

Drug effect depends on frequency of drug-receptor interactions

Macromolecular perturbation theory

Combines induced fit and rate concepts for receptor activation

Activation-aggregation theory

Receptors exist in equilibrium between inactive (Ri) and active (Ra) states

Two-state receptor model

Receptors exist in active and inactive conformations, ligands shift equilibrium between them

Inverse agonist

Drug that binds receptor and reduces constitutive (basal) activity

Constitutive activity

Baseline receptor activity without ligand binding

Full agonist (two-state model)

Drug that binds preferentially to active receptor state (Ra)

Antagonist (two-state model)

Drug with equal affinity for active and inactive receptor states, no effect on baseline activity

Agonist

Drug that mimics endogenous compounds, has affinity and intrinsic activity, produces a biological response

Endogenous ligand

Naturally occurring body substance that binds receptors, e.g., endorphins (morphine-like peptides)

Antagonist

Drug that blocks agonist effects, has affinity but no intrinsic activity, used as receptor blocker or antidote

Full agonist

Drug producing 100% maximal receptor response, fully activates effector system

Partial agonist

Drug producing submaximal response (

Inverse agonist

Drug producing the opposite effect of agonist, decreases constitutive receptor activity (negative intrinsic activity)

Morphine

Full μ-opioid receptor agonist, produces analgesia via endorphin-like action

Buprenorphine

Partial μ-opioid agonist, produces ceiling effect with reduced adverse effects

Diazepam (paradox concept context)

Drug acting on GABA-A receptor, produces sedation and anticonvulsant effects via agonism

Beta-carbolines

Compounds acting on GABA-A receptor producing anxiety, agitation, seizures, opposite of benzodiazepines

Flumazenil

Benzodiazepine receptor antagonist, reverses effects of benzodiazepines without producing opposite effects

Pharmacologic antagonism

Antagonism where drugs act on the same receptor system

Competitive antagonist

Antagonist binding to the same receptor site as agonist, effect depends on concentration

Reversible competitive antagonist

Competitive antagonist that is surmountable by increasing agonist concentration

Irreversible competitive antagonist

Competitive antagonist forming covalent bond, non-surmountable, reduces receptor availability

Non-competitive antagonist

Antagonist binding to allosteric site or different site, reduces max response

Allosteric antagonist

Drug binding to non-active site, alters receptor shape and reduces agonist effect

Physiologic antagonism

Drugs acting on different receptors producing opposite physiological effects

Epinephrine (anaphylaxis example)

Drug counteracting histamine effects via α₁ (vasoconstriction) and β₂ (bronchodilation) receptors

Chemical antagonism

Direct chemical interaction where drugs neutralize or bind each other, preventing receptor interaction

Chelation

Process where drugs bind metals (e.g., lead + Ca-EDTA) forming excretable complexes

Drug addition

Combination where two drugs produce sum of individual effects (1 + 1 = 2)

Potentiation

One drug enhances effect of another with little/no effect alone (0 + 1 > 1)

Synergism

Combined drug effect greater than sum of effects (1 + 1 > 2)

Antagonism (drug interaction)

One drug reduces or blocks effect of another (2 + 0 < 2)

Meloxicam

NSAID used in analgesia and anti-inflammatory therapy, example of additive interaction

Paracetamol

Analgesic used in pain and fever control, often combined with NSAIDs

Clavulanic acid

β-lactamase inhibitor that enhances amoxicillin activity (potentiation)

Amoxicillin

β-lactam antibiotic acting on bacterial cell wall synthesis

Sulfonamide

Antibacterial inhibiting folate synthesis

Trimethoprim

Antibacterial inhibiting dihydrofolate reductase

Dose-response curve

Graph showing relationship between drug dose and biological effect

Graded dose-response curve

Dose-response in single subject, continuous measurement of effect intensity

Potency

Amount of drug required to produce 50% of maximal effect (EC50-related concept)

Efficacy

Maximum effect a drug can produce, reflects intrinsic ability to activate receptor

Ceiling dose

Dose beyond which no further therapeutic effect increases

Right shift (dose-response)

Indicates decreased potency, requires higher dose for same effect

Left shift (dose-response)

Indicates increased potency, lower dose produces same effect

Competitive antagonist effect on curve

Causes decreased potency but unchanged efficacy

Non-competitive antagonist effect on curve

Causes decreased potency and decreased efficacy

Partial agonist effect with full agonist

Reduces overall response, acting as functional antagonist

Quantal dose-response curve

Population-based curve showing all-or-none responses

ED50

Dose effective in 50% of population, measure of drug effectiveness

Therapeutic index (TI)

Safety measure: LD50 or TD50 divided by ED50

LD50

Dose lethal to 50% of population, used in toxicity measurement