Introduction to Pharmacology

1
Introduction to Pharmacology

• CHEM 4000
• Chemistry Seminar
• April 30, 2004 May 3, 2004
• Robin B. Reed

2
Overview of Presentation

• Definitions
• Drug Studies
• Drug Manufacture

3
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

4

• 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

5

• 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

6
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

7

• 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

8

• Pharmacodynamics
• study the mechanisms by which drugs work
• also study endogenous agents

9
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

10
Model of Drug/Receptor Binding
11

• Binding Studies
• Association to receptor
• Dissociation from receptor
• Forces of binding
• Covalent
• Electrostatic
• Hydrophobic
• Clearance
• adsorption
• t1/2

12
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

13
Pharmaceutical Industries
14
Researching Institutes

• St. Jude GMP Facility
• Gene-based molecules
• Drugs
• Vaccines
• Proteins

15
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

16

• 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.

17
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

18
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/clo
  ning.jsp?idns99992658)