Drug Action and Receptors

Flashcards about how drugs act, drug-receptor interactions, agonists, antagonists, and receptor types.

Pharmacodynamics

The study of the biochemical, cellular, and physiological effects of drugs and their mechanisms of action (drug on the body).

Drug Receptor (or Drug Target)

The cellular macromolecule or macromolecular complex with which a drug interacts to elicit a cellular or systemic response.

Agonist

A drug that produces an observable change in the state of a physiological system.

Antagonist

A drug that may not produce a direct effect but can interfere with the production of a cellular response to an agonist.

Affinity

The tendency of a drug to bind to receptors, described by the equilibrium dissociation constant (Kd).

Equilibrium Dissociation Constant (Kd)

Kd = ([D] [R])/ [DR]. The smaller the Kd, the higher the affinity between the ligand and the receptor.

Potency

The amount (dose/concentration) of drug needed to produce a defined response or effect; often represented by EC50 or ED50.

Efficacy

A drug’s capacity to produce an effect; defines the tendency of a drug to activate the receptor once bound; also defined as intrinsic activity.

EC50/ED50

Concentration or dose of a drug needed to produce 50% of the maximal response/effect.

Emax

The maximal response that a drug can produce.

Spare Receptor

Receptors that remain unbound when an agonist is producing its maximal biological response, amount of agonist needed to elicit 50% of the response is often lower than the amount of agonist needed to occupy 50% of the receptors.

Full Agonist

A drug that produces a maximal response equal to the maximal capability of the system to report a cellular response.

Partial Agonist

A drug that produces a maximal response that is below the maximal capability of the system.

Inverse Agonist

A drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist.

Allosteric Regulatory Site

A site on a receptor, different from the active site, where a molecule (allosteric modulator) binds to change the protein's activity.

Allosteric Modulation

The process resulting from the binding of allosteric modulators at a regulatory site, causing a conformational change in a receptor molecule, which results in a change in the binding affinity of the ligand.

Competitive Antagonist

An antagonist that, in the presence of a competitive antagonist, the agonist occupancy at a given agonist concentration is reduced, because the receptor can accommodate only one molecule at a time.

Irreversible Competitive Antagonist

The antagonist binds to the same site on the receptor as the agonist but dissociates very slowly, or not at all, from the receptors, with the result that no change in the antagonist occupancy takes place when the agonist is applied.

Chemical Antagonist

Two substances combine in solution neutralizing the effect of the active drug is lost

Pharmacokinetic Antagonism

The antagonist effectively reduces the concentration of the active drug at its site of action.

Physiological Antagonists

Interaction of two drugs whose opposing actions in the body tend to cancel each other.

Receptor-Response Blockers

Non-competitive antagonism describes the situation where the antagonist blocks at some point downstream from the agonist binding site on the receptor and interrupts the chain of events that leads to the production of a response by the agonist.

Primary Agonist

If the drug binds to the same recognition site as the endogenous agonist.

Allosteric (or allotopic) Agonists

Drugs which bind to a different region on the receptor, referred to as an allosteric or allotopic site.

Desensitization (Tachyphylaxis)

The effect of a drug gradually diminishes, developing in the course of a few minutes, when it is given continuously or repeatedly.

Tolerance

The effect of a drug gradually diminishes, developing more gradually, taking hours, days, or weeks, when it is given continuously or repeatedly.

Drug Target

A generally protein (or in some cases DNA, like for antimicrobial, antitumor drugs, and so on) to which a drug binds to elicit whatever pharmacologic effect it will produce.

Ligand-Gated Ion Channels (Ionotropic Receptors)

A type of receptor involved mainly in fast synaptic transmission, consisting of heteromeric assemblies of four or five subunits with transmembrane helices arranged around a central aqueous channel.

G Protein-Coupled Receptors (GPCRs) (Metabotropic Receptors or 7-Transmembrane or Heptahelical Receptors)

A type of receptor with structures comprising seven membrane-spanning α-helices, often linked as dimeric structures, the third intracellular loop interacts with the G protein - Examples include muscarinic acetylcholine receptors, adrenoceptors, neuropeptide and chemokine receptors, and protease-activated receptors.

Kinase-Linked Receptors

Receptors for various growth factors incorporate tyrosine kinase in their intracellular domain - Cytokine receptors have an intracellular domain that binds and activates cytosolic kinases when the receptor is occupied.

Nuclear Receptors

A family of 48 soluble receptors that sense lipid and hormonal signals and modulate gene transcription.

Biased Agonism

The different conformations that receptors can adopt may be preferentially stabilized by different ligands and may produce different functional effects by activating different signal transduction pathways.