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

Pharmacology

study of substances that interact with living systems thru chemical processes

Pharmacology

term that works by →

by binding to regulatory molecules & act/inhib. normal body activities used to treat, prevent or diagnose disease

Toxicology

undesirable effects of chemicals on living systems

Pharmacogenomic

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 f/x

Knockin

Overexpression of a gene

Small interfering RNAs

interfere with protein synthesis w/ extreme selectivity

Antisense oligonucleotide

Complementary RNA or DNA can interfere

w/ transcription of RNA

Agonist

Act.: effector molecules

or

inhib.: 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 &

prevents constitutive activity

Allosteric agents

Bind to receptor → enhance or inhibit receptor f/x

but do NOT prevent binding of the agonist

Xenobiotic

Molecules NOT synthesized w/in body

Toxin

Poison of biological origin

Chirality

Molecule that has non-superposable mirror image, often b/c of a asymmetric Carbon atom

Racemic mix

Both S & 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 absence of ligand

Pharmacokinetic

What the body does to the drug

Absorption

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

Distribution

Transport drug to the site of action

Permeation

Passage of a drug through various Physical Barriers

Elimination

Metabolic inactivation

&

excretion from the body

Receptor

initiates a chain of biochemical events leading to a drug's effect

&

Component of a cell or organism that interacts w/ a drug

Affinity

Strength of drug-receptor coupling

affinity

determines CC lvls of drug required to form a signif. number of drug/receptor complexes that p→ effect.

EC50

cc lvl of agonist resulting in half-maximal response

KD

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

Bmax

Total # 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

B→ receptors in a reversible manner

&

progressively inhibits agonist response

Irreversible Antagonist

Affinity is so high that receptor is unavailable to bind agonist.

Irreversible Antagonist

Duration of action independent of rate of elimination

&

more dependent on rate of turnover of receptor molecules

Partial Agonist

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 maximum effect

Efficacy

Ability of a drug to reach Receptors & produce a maximum effect (productivity)

Lethal dose (LD50)

Dose required to kill 50% of animals tested

Median effect dose (ED50)

Dose required to p→ desired effect (quantal effect) in 50% of indiv.

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