Introduction To Pharmacology

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 costeffectiveness 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

Drug

Shape and Properties of

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  finished

preparations

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     



High Degree of Automation 

 



chemists chemical engineers packaging engineers production specialists to make production economic, safe, etc. Separation of isomers (Thalidomide) 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)