Principles of Pharmacology

Definitions

Pharmacology

Is defined as the study of the effects of chemical substances

(Drugs) on the function of living systems.

Drug

Is any biologically active substance that alters biological system

(cell structure or function) chemically.

Drugs:

CH3(CH2)14COOH

Pharmacodynamics

Mechanism of action

Pharmacological effects

Side effects

Pharmacokinetics

What the drug does to the body

What the body does to the drug

Absorption

Distribution

Elimination ( Biotransformation , excretion)

Drug Action
1

interaction of drug molecule with biological tissue.

Mechanism of action
specific drug action e.g. morphine binding to opioid

receptors.

Drug effect
behavioral effects

No Magic Bullets!

Drug delivered into biological system

Effects all cells that have receptors

Desired effect

All other effects = Side effects

All drugs have multiple effects

= Therapeutic effect

Drug Names
At least three names

Chemical name
Describes molecular structure

Generic name (non proprietary )

Official legal name

Trade name (proprietary)

Brand name

Street name

Example: Amphetamine
2

chemical

Generic

trade

street

dl-2 amino-1
phenylpropan
e

dlampheta
mine

Benzedri
ne

speed,
bennies,

Drug Equivalence

Chemical equivalence
Identical chemical compounds

Biological equivalence
Affect the same systems in the same way

Clinical equivalence
Same behavioral effect
Different molecules affecting different systems

Pharmacodynamics:
The action of a drug on the body, includes:
1- Receptor interactions.
2- Dose-response phenomena.
3- Mechanisms of therapeutic and toxic action.

Drug Receptor
3

A macromolecular component of a cell with which a drug

interacts to produce a response.

Usually it is a protein.

Types of Protein Receptors

1- Regulatory change the activity of cellular enzymes
2- Enzymes may be inhibited or activated.
3- Transport e.g. Na+ /K+ ATPase .
4- Structural Skeleton of the cells

Drug-receptor interaction

At

equilibrium:
[D] x [R] x k1 =
[DR] x k-1
Agonist Drugs
so that:
[DR]

Drugs that interact with and activate receptors; they possess

both affinity and efficacy

Two types

k1
=
Full an agonist with maximal efficacy

Partial an agonist with less then maximal efficacy

[D] [R]

k-1
4

-1

dissociation
constant (kd)

Antagonist Drug
Antagonists interact with the receptor but do NOT change the receptor

they have affinity but NO efficacy

two types

Competitive

Noncompetitive

Competitive Antagonist

Competes with agonist for receptor

Surmountable with increasing agonist concentration

Displaces agonist dose response curve to the right (dextral shift)

Reduces the apparent affinity of the agonist .

Non competitive Antagonist

Drug binds to receptor and stays bounded irreversibly does not leave
receptor

Produces slight dextral shift in the agonist DR curve in the low concentration
range this looks like competitive antagonist

But, as more and more receptors are bound (and essentially destroyed), the
agonist drug becomes incapable of eliciting a maximal effect

Drug Receptor Curve

Graded

response
measured on a
continuous
scale Gradual
( dose ->
Quantification of drug safety
small response
ED50
change)
Percent
Responding
Quantal
response is an
either/or event
Steep ( dose ->
large response
change )
relates dose
Effectiveness, toxicity, lethality

ED50 - Effective Dose 50; the dose at which 50 % of the population or sample
manifests a given effect; used with quantal drug receptor curves.

LD50 lethal Dose 50 - dose which kills 50 % of the subjects

The therapeutic index

The higher the TI the better the drug.

TI vary from :

1.0 (some cancer drugs)

to:

>1000 (penicillin)

Drugs acting on the same receptor or enzyme system often have the same TI: (eg 50
mg of hydrochlorothiazide about the same as 2.5 mg of indapamide)

4.

frequency
of response
nuclear
in a(gene) linked
(long lasting)
population
of
individuals

Ionchannel

receptors

Structure:Proteinporesinthe
plasmamembrane

Second Messengers

Small, non protein, water-soluble molecules or ions

Readily spread throughout the cell by diffusion

Two most widely used second messengers are:

1.

Cycle AMP

2.

Calcium ions Ca2+

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