PRELIM 03 - Pharmacodynamics Flashcards by Juan Carlos Cornelio

Refers to the cellular macromolecule or macromolecular complex with which the drug interacts to elicit a cellular or systemic response

Receptor/Drug targets

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Refers to the ability to bind to receptors

Affinity

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Refers to the ability to activate receptors and generate a response

Efficacy/Intrinsic activity

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Refers to the amount of drug needed to produce an effect; affected by both affinity and efficacy

Potency

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Refers to the ability to distinguish between receptors

Specificity

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Tissue response is proportional to number of receptors occupied; by Clark and Gadum (Theories of drug receptor interaction)

Occupancy theory

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Retains the assumption that tissue response is proportional to number of receptors occupied; by Ariens and Stephenson (Theories of drug receptor interaction)

Modified occupancy theory

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Drug receptor interaction effect is proportional to the rate of drug receptor combination; by Croxatto and Paton (Theories of drug receptor interaction)

Rate theory

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According to the rate theory, __________ has a high rate of association and dissociation

Agonist

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According to the rate theory, __________ has a high rate of association and low rate of dissociation

Antagonist

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Combination of ligand and receptor produces a change in conformation of the receptor; by Koshland (Theories of drug receptor interaction)

Induced fit theory

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Interaction of small molecules (drug) with macromolecule (receptor) results in SCP and NSCP; by Belleau (Theories of drug receptor interaction)

Macromolecular perturbation theory

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According to the macromolecular perturbation theory, the _________ has an agonist effect

Specific conformational perturbation (SCP)

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According to the macromolecular perturbation theory, the __________ has an antagonist effect

Nonspecific conformational perturbation (NSCP)

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Proposes that when a ligand binds, this results in a change in receptor stage from inactive to active; by Black and Leff (Theories of drug receptor interaction)

Two-state receptor theory

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Uses equilibrium dissociation constants for the interactions between the receptor and each ligand; by De lean et al. (Theories of drug receptor interaction)

Ternary complex model

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According to the ternary complex model, the __________ factor denotes the mutual effect of the two ligands on each other’s affinity for the receptor

Cooperativity

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__________ activity indicates the production of physiologic effect without the drug

Constitutive

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2 receptor states (AI)

Active (Ra), Inactive (Ri)

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Intrinsic activity is 1; Maximal shift to Ra (Characteristic of drug effect)

Agonist

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Intrinsic activity is >0 and <1; Partial shift to Ra (Characteristic of drug effect)

Partial agonist

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Intrinsic activity is 0; No effect on equilibrium (Characteristic of drug effect)

Antagonist

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Intrinsic activity is <0; Shift to Ri (Characteristic of drug effect)

Inverse agonist

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Prevents activation of receptor by agonist; may be competitive or noncompetitive (Types of antagonist)

Receptor antagonist

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Opposes effects of agonist through a different receptor (Types of antagonist)

Physiologic antagonist

Renders a substance inactive by binding to it (Types of antagonist)

Chemical antagonist

Structurally similar to agonist, binds reversibly to the same site of agonist; can be overcome by increasing agonist concentration (Types of receptor antagonist)

Competitive antagonist

Cannot be overcome by increasing agonist concentration (Types of receptor antagonist)

Noncompetitive antagonist

Binds irreversibly (covalently) to the same site of agonist (Types of noncompetitive antagonist)

Irreversible antagonist

Binds to a different site (allosteric site) from the site of the agonist (Types of noncompetitive antagonist)

Allosteric inhibitor

Refers to the conversion of a signal carried by a chemical messenger into an intracellular response

Signal transduction

Channels that allow passive diffusion of ions down electrochemical gradients across the cell membrane

Ion channels

Action potential across the cell membrane causes conformational change in the channel that opens or closes the gate (Types of ion channels)

Voltage-gated channels

Binding of a chemical substance (a ligand) with the channel causes conformational in the channel that opens or closes the gate (Types of ion channels)

Ligand-gated channels

3 components of G protein-coupled receptor (GEH)

G protein, Effector enzyme, Heptahelical receptor

The largest and most diverse group of receptors

G protein-coupled receptor (GPCR)

Meaning of G protein

Guanosine-nucleotide binding protein

3 subunits of G protein (ABG)

Alpha (α), Beta (β), Gamma (γ)

cAMP, DAG, IP3, and Ca2+ are all examples of __________

2° messengers

Are enzymes that phosphorylates proteins

Receptor protein kinases

Are enzymes that binds kinases which can phosphorylate proteins

Receptor bind protein kinases

An example of receptor protein kinase that has intrinsic tyrosine kinase activity

Receptor tyrosine kinase

Signal transducer protein of receptor tyrosine kinase

Grb2

__________ is a guanine nucleotide exchange factor (GEF) for Ras

Son of sevenless (SOS)

SOS is a GEF for __________, a monomeric G protein located in the plasma membrane

Ras

__________ is a serine protein kinase that is also called MAPKKK (Mitogen activated protein kinase kinase kinase)

Raf

_________ is a factor that allows exchange of GDP for GTP; involved in activation

Guanine nucleotide exchange factor (GEF)

________ are proteins that increase GTPase activity of G proteins or Ras; involved in inactivation

GTPase activating proteins (GAP)

An example of receptor protein kinase that has intrinsic serine/threonine kinase activity

Receptor serine/threonine kinase

Signal transducer protein of receptor serine/threonine kinase

Smad

An example of receptor bind protein kinase that binds with JAK (Janus kinase), an example of tyrosine kinase

Cytokine receptor/JAK-STAT receptor

Signal transducer protein of cytokine receptor/JAK-STAT receptor

Signal transducer and activator of transcription (STAT)

A receptor enzyme that has intrinsic guanylyl cyclase activity

Receptor guanylyl cylase

2 kinds of receptor guanylyl cyclase (MS)

Membrane-bound, Soluble

2° messenger of receptor guanylyl cyclase

cGMP

Signal cascade of receptor guanylyl cyclase

PKG

__________ receptors are used for hydrophobic drugs

Intracellular

2 kinds of intracellular receptors (CN)

Cytosolic, Nuclear

Signal cascade of intracellular receptors

Response element

Refers to the ability of receptors to amplify signal duration and intensity

Signal amplification

Response may be __________ or __________ (NG)

Non-genomic, Genomic

E.g. ion influx/efflux, alteration of protein activity; is usually immediate and brief (Types of response)

Non-genomic

E.g. gene expression; usually delayed and prolonged (Types of response)

Genomic

Refers to a decrease in response to a drug due to continued stimulation of receptors with agonists

Desensitization

Refers to a rapid desensitization

Tachyphylaxis

Happens due to endocytosis of receptors and sequestration inside cells

Downregulation

A plot of the degree of a given response against the plasma concentration/dose of the drug

Graded-dose response curve

A measure of the amount of drug necessary to produce an effect

Potency

A measure of the ability of the drug to elicit a response when it interacts with a receptor; involves a drug's maximum effect

Efficacy

A plot of the proportion of the population that produces a response against the dose of the drug

Quantal-dose response curve

__________ effect is also known as either-or effect

Quantal

The dose at which 50% of individuals exhibit the specified quantal therapeutic effect

Median effective dose (ED50)

The dose at which 50% of individuals exhibit the specified quantal toxic effect

Median toxic dose (TD50)

The dose at which 50% of individuals exhibit the specified quantal lethal effect

Median lethal dose (LD50)

Refers to the range between the minimum therapeutic dose and the minimum toxic dose

Therapeutic window

Refers to the ratio of the dose that produces toxic effect in half the population (TD50) to the dose that produces therapeutic effect (ED50) in half the population

Therapeutic index

Refers to the ratio of the dose that produces toxic effect in 1% of the population (TD1) to the dose that produces therapeutic effect (ED99) in 99% of the population

Margin of safety

__________ is an example of a drug that has a small therapeutic index

Warfarin

__________ is an example of a drug that has a large therapeutic index

Penicillin