Katzung Chapter 1: Nature of Drugs and Chapter 2: Drug Receptors and Pharmocodynamics

Pharmacology

The study of substances that interact with living systems through chemical processes by binding to regulatory molecules and activating or inhibiting normal body activities used to treat, prevent or diagnose disease

Toxicology

The undesirable effects of chemicals on living systems

Pharmacogenomics

The relation of the individual's genetic makeup to his or her response to specific drugs

Knocked out

Mutated gene product is absent or nonfunctional.

Knockdown

Limited suppression of a gene's function

Knockin

Overexpression of a gene

Small interfering RNAs

Small segments of RNA can interfere with protein synthesis with extreme selectivity

Antisense oligonucleotides

Complementary RNA or DNA can interfere with the transcription of RNA

Agonist

Activate effector molecules or inhibit molecules responsible for terminating the action of endogenous agonists

Antagonist

Blocks binding of other molecules to a receptor

Partial agonist

Partially activate effector molecules

Inverse agonist

Stabilizes the receptor in the inactive form and prevents constitutive activity

Allosteric agents

Bind to the receptor and enhance or inhibit receptor function but do not prevent binding of the agonist

Xenobiotics

Molecules not synthesized within the body

Toxins

Poison of biological origin

Chirality

Molecule that has non-superposable mirror image, often because of a asymmetric carbon atom

Racemic mix

Both S and R forms

Dissociation constant

Propensity of a larger object (ligand/receptor complex) to separate reversibly into two smaller objects (ligand and receptor)

Desensitization

After repeated or sustained activation of a receptor by a ligand the response is diminished or abolished

Constitutive activity

Receptor activity in the absence of ligand

Pharmacokinetics

What the body does to the drug

Absorption

Transport of a drug into the blood from the site of administration

Distribution

Transport of the drug to the site of action

Permeation

Passage of a drug through various physical barriers

Elimination

Metabolic inactivation and excretion from the body

Receptor

Component of a cell or organism that interacts with a drug and initiates a chain of biochemical events leading to a drug's effect

Affinity

Strength of drug-receptor coupling determines the concentration of drug required to form a significant number of drug/receptor complexes that will produce an effect.

EC50

Concentration of agonist resulting in half-maximal response

KD

Concentration of free drug at which half-maximal binding to receptor is observed

Bmax

Total number of receptor sites

Spare receptors

Maximum response of an agonist when less than 100% of receptors are bound by drug, excess of receptors

Competitive antagonist

Binds to receptors in a reversible manner and progressively inhibits agonist response

Irreversible Antagonist

Affinity is so high that receptor is unavailable to bind agonist. Duration of action independent of rate of elimination and more dependent on rate of turnover of receptor molecules

Partial Agonists

Produces a lower response at full receptor occupancy (decreased ability to activate the receptor)

Chemical Antagonist

Binds to and inactivates another drug

Physiological Antagonist

Physiological function controlled by opposing regulatory pathways

Desensitization

Diminished response after repetitive or continuous exposure to ligand

Downregulation

Receptor internalization and/or degradation

Phosphodiesterases

Breaksdown (degrades) cyclic nucleotides

Potency

Concentration (EC5O) or dose (ED50) of a drug required to produce 50% of the maximum effect

Efficacy

Ability of a drug to reach receptors and produce a maximum effect

Lethal dose (LD50)

Dose required to kill 50% of animals tested

Median effect dose (ED50)

Dose required to produce desired effect (quantal effect) in 50% of the individuals

Median toxic dose (TD50)

Dose required to produce toxic effect in 50% of animals tested

Therapeutic index

Ratio of TD50 to the ED50

Idiosyncratic

Unusual response to a drug

Hyporeactive

Diminished effect of a drug

Hyperactive

Increased effect of a drug

Tolerance

Response to a drug decreases after continued administration

Tachyphylaxis

Response to a drug decreases rapidly