Introduction to

Pharmacology

CHEM 4000
Chemistry Seminar
April 30, 2004 & May 3, 2004
Robin B. Reed
 Overview of Presentation
 Definitions
 Drug Studies
 Drug Manufacture
 What is Pharmacology?
From the Greek pharmakon (drug),
legein (to speak)
 Broadly
defined as the study of how
chemical agents affect living
processes.
Hormones
Neurotransmitters
Growth factors
local Autocrine factors
Drugs (Pharmaceuticals)
Toxic agents in the environment
 the medicinal/ organic chemist may create
the candidate compound (sometimes
referred to as a new chemical entity, NCE),
it is the pharmacologist who is responsible
for testing it for pharmacological activity.

 ultimately will lead to the discovery of

novel drug targets for therapeutic
intervention in diseases where distal steps
in signal transduction have gone awry
 Pharmacology studies the effects of drugs
and how they exert their effects.
 acetylsalicylic acid (ASA) can reduce
inflammation, pain and fever
inhibit the action of a human cell
membrane enzyme known as
cyclooxygenase, which is responsible for
the synthesis of a number of inflammatory
mediators
 penicillin cures certain bacterial infections
disrupt the synthesis of cell walls in
susceptible bacterial strains by inhibiting a
key enzyme
 Some Pharmacology Definitions
and Areas of Study
 Pharmacotherapeutics - use of drugs to
treat disorders; the emphasis is on clinical
management
 Pharmacoepidemiology - study of the
effect of drugs on populations; questions
dealing with the influence of genetics are
particularly important
 Pharmacoeconomics - study of the cost-
effectiveness of drug treatments; the cost
of medications is of worldwide concern,
particularly among certain groups such as
the elderly and AIDS patients
 Pharmacokinetics
study the fate of drugs once ingested
and the variability of drug response in
varying patient populations
how the body absorbs, distributes,
metabolizes, and excretes drugs
calculation of various rates brings a
quantitative component to assessing
drug action
 Pharmacodynamics
study the mechanisms by which drugs
work
also study endogenous agents
 Basics of Pharmacology
 Chemical Shape and Properties of
Drug
Complimentary to receptor binding site
Very important in determining if drug
will be an agonist or antagonist
Paradigm is requirement of at least
three points of contact for specific
interaction of drug to receptor
Chiral vs. non-chiral
Flexibility and rotation of internal bonds
Model of Drug/Receptor
Binding
 Binding Studies
Association to receptor
Dissociation from receptor
Forces of binding
Covalent
Electrostatic
Hydrophobic

 Clearance
adsorption
t1/2
 Types of Pharmaceutical
Manufacturers
 pharmaceutical preparations
 finished drugs
 biological products, such as serums
and vaccines
 bulk chemicals and botanicals used
in making finished drugs
 diagnostic substances such as
pregnancy and blood glucose kits
Pharmaceutical Industries
 Researching Institutes
St. Jude GMP Facility
 Gene-based
molecules
 Drugs
 Vaccines
 Proteins
 Steps in Manufacture of
Drugs
 Scientific
Research to discover/synthesize
new compounds, or improve existing
compounds
(R & D)
 Computer simulation
 Combinatorial chemistry
 Develop safe and effective applications of
promising compounds
 Screen compounds in bacterial cultures or
animal subjects
 Clinical trials on humans
 Clinical Trials
 Kidneys and liver are two most important organs

 In Phase I trials, researchers test a new drug or

treatment in a small group of people (20-80) for the first
time to evaluate its safety, determine a safe dosage
range, and identify side effects.

 In Phase II trials, the study drug or treatment is given to

a larger group of people (100-300) to see if it is effective
and to further evaluate its safety.

 In Phase III trials, the study drug or treatment is given to

large groups of people (1,000-3,000) to confirm its
effectiveness, monitor side effects, compare it to
commonly used treatments, and collect information that
will allow the drug or treatment to be used safely.

 In Phase IV trials, post marketing studies delineate

additional information including the drug's risks,
benefits, and optimal use.
 Production
 Scale-up of Production
 chemists
 chemical engineers
 packaging engineers
 production specialists to make production economic,
safe, etc.
 Separation of isomers (Thalidomide)
 High Degree of Automation
 Milling and micronizing machines pulverize substances
into extremely fine particles, reduce bulk chemicals to
the required size
 finished chemicals are combined and processed further
in mixing machines
 mixed ingredients are mechanically capsulated, pressed
into tablets, or made into solutions
 Quality Control/Quality Assurance
 Alternative Production
Methods
 Bacteria
 Microorganisms to produce
simple chemicals for manufacture
process
 Microorganisms to produce full
length polypeptides
 Bacteria produce human insulin
 “Pharm Animals”
 Transgenic Sheep carry gene for
human Factor IX (Science, vol. 278,
1997)
 Cows that produce human
antibodies (http://
www.newscientist.com/hottopics/cloning/cloning.jsp?id
=ns99992658)