This document discusses key concepts in pharmacology including: - Pharmacodynamics is the study of what drugs do to the body, how they act on receptors and their downstream effects. Pharmacokinetics describes how the body affects drugs through absorption, distribution, metabolism and excretion. - Dose-response curves can be graded, showing the change in effect with increasing dose on a linear scale, or quantal, showing the percentage of a population exhibiting an effect. - The therapeutic window is the difference between the effective dose (ED50) and the toxic (TD50) or lethal dose (LD50). Understanding dose-response helps optimize drug safety and efficacy.

1. Pharmacology; the study of drug and their action on the body.
Toxicology; Study of adverse effects of chemicals or physical agents on living organisms.
Pharmacokinetics; describes the effects of the body on drugs, eg, absorption, metabolism, excretion, etc.
Pharmacodynamics; is the study of what a drug does to the body.
Drug receptors : The molecular components of the body with which drugs interact to bring about their
effects
Distribution; Drug movement from the site of administration into the tissues.
Elimination : The phase of drug inactivation or removal from the body by metabolism or excretion
Endocytosis : Absorption of material across a cell membrane
Exocytosis : Expulsion of material from the cell into the extracellular space
Transporter; A specialized molecule (usually protein) that carries a drug across a membrane.
Placebo;
THE NATURE OF DRUGS
Drugs in common use include inorganic ions, nonpeptide organic molecules, small peptides and proteins,
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nucleic acids, lipids, and carbohydrates.
PRINCIPLES OF PHARMACODYNAMICS
regulate the effects of drugs on the human body and to have a maximal effect
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two dose-response relationships (curve);
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1. Graded; Emax (maximum effective dose)
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Graded dose-response and dose-binding graphs. (In isolated tissue preparations, concentration is usually used as
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the measure of dose.)
A. Relation between drug dose or concentration (abscissa) and drug effect (ordinate). When the dose axis is
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linear, a hyperbolic curve is commonly obtained.
B. Same data, logarithmic dose axis. The dose or concentration at which effect is half-maximal is denoted
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EC50, whereas the maximal effect is Emax.
C. If the percentage of receptors that bind drug is plotted against drug concentration, a similar curve is
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obtained, and the concentration at which 50% of the receptors are bound is denoted Kd, and the maximal
number of receptors bound is termed Bmax.
EC50; is used only for graded dose-response curve
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2. Quantal; population of individuals
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Quantal dose- response curves.
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demonstrate the average effect of a drug, as a function of its concentration, in a population of individuals
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Individuals are typically observed for the presence or absence of a response (for example, sleep or no sleep)
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useful for predicting the effects of a drug when it is administered to a population of individuals and for
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determining population-based toxic doses and lethal doses.
ED50 (dose at which 50% of subjects exhibit a therapeutic response to a drug), TD50 (dose at which 50% of
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subjects experience a toxic response), and LD50 (dose at which 50% of subjects die).
Note that ED50 is the dose at which 50% of subjects respond to a drug, whereas EC50 is the dose at which a
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drug elicits a half-maximal effect in an individual subject.
ED50 – Dose that causes therapeutic effect in 5% of the patients
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TD50 – Toxic effect in 50%
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LD50 – Lethal outcome in 50%
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The difference between ED50 and TD50/LD50 is called therapeutic window.
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2. Effectors; Molecules that translate the drug-receptor interaction into a change in cellular activity
Example; adenylyl cyclase
Efficacy (maximum effect of the drug); Maximum effect produced from the given drug. (For example
Morphine has far greater pain reducing effect than Aspirin)
Potency; acting on same receptor - amount of drug needed to produce response a little dose of one produces
the effect that more of another drug would = more potent
Agonist;Activator; binds to and activates the receptor
Antagonist; Inhibitor so Molecule that prevents/inhibits the action of an agonist but has no effect in the
absence of the agonist
Full agonist: medication that causes full activation of the system
Partial agonist; causes partial activation of the system
Compettitive (reversible) antagonist; antagonist binds to same receptor site as agonist and
competes for binding - have affinity but no efficacy.
Non-competitive (irreversible) antagonist; İt İs where antagonist binds at site other than
agonist binding site
Effects of antagonists on dose-response curves
1.Competitive
Binds and prevents agonist action but can be overcome with increased agonist concentration.
Causes parallel shift to right of the agonist-response curve
2.Irreversible
Binds and forms irreversible covalent bonds with receptor
Causes parallel shift to right of the agonist-response curve and reduced maximal asymptote.
3.Non-competitive
Signal transduction rather than receptor effects
Downstream responses are blocked (e.g. Ca2+ influx)
Reduces slope and maximum of dose response curve
Compare the antagonistss
1) Competitive:
Molecule similar to agonist.
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Binds active site
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Maximum effect unchanged
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Km (affinity) is lowered.
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2) Non-competitive :
Molecule different from agonist.
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Does NOT bind active site
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Maximum effect lowered
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Km is unchanged. (as maximum effect and the half effect are unchanged)
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Spare receptors
Exist when max response to a drug can be achieved with less than all the receptors bound by drug, EC50 < Kd
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Increases sensitivity of system to agonist
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lineweaver–burk plot; determine the equilibrium constant for an enzymatic reaction