The Drug Scene and Chemical Concepts

You can find them almost anywhere.

They are tranquilizers and sedatives, psychedelic stimulants and psychedelic anesthetics.

Sally Squires, in the Washington Post on January 12, 2000, wrote about drugs and the brain.  She catalogued the impact of more than a dozen drug substances on the way that our brains work.  A drug almost always "lights up reward or pleasure circuits".  They affect neurotransmitters, they cause cells to fire - or not fire.  They stimulate natural pathways.

So where is the problem?

The problem is chemistry.  Our brains and bodies operate within narrow ranges based on the evolutionary development of dose and response.  Natural messenger chemicals, present at concentrations that have developed within narrow limits act to cause cellular response - the basis of the mechanics of what we think, feel and do.

Our bodies are fooled by the chemistry of the drug molecules.  Receptors on cells react to these artificial neurotransmitters and bring us the highs and the lows and the other stimulation we seek.

But these neurotransmitters aren't quite right.  The receptors are like locks and these chemical keys don't quite fit.   Force them and you can open the door, but then the lock is broken, isn't it? 

And they may flood our brains.  We have no way to control the concentrations of these moleculaes at the receptor.  Rate is concentration dependent.  We can reach the highest of highs, the lowest of lows, but we cannot predict or prevent the overdosing that we might also encounter.

"Some of these changes may well be benign, says Dr. Alan Lesher, Director of the National Institute on Drug Abuse (NIDA).  "Some are not.  But if you use a drug, you have changed your brain in big or little ways".

Drugs and Chemical Concepts.

That pill or white powder is a chemical substance, or more likely a mixture of substances. 

And you don't know its properties!  You don't know its pK_a, you don't know its fat solubility and how quickly it will pass across the tissue in your duodenum into your blood.  You don't know if it will precipitate to deposit a solid in your blood when it gets there and you don't know how quickly it will cross the blood-brain barrier to get at your receptors.  And you don't know if the concentration will be so high as to destroy those cell receptors forever.

It might be a mixture and even though you have had good experience with silimilar substances, this one may behave differently.   It might have a compound in it that speeds to your brain and kills you with an innocent and unexpected overdose.

Why we test Drugs

One hundred years ago, men swallowed chemical compounds to see how their bodies behaved.  Some of them died.  

Now the FDA requires careful testing of all substances we might use as drugs.  Even before we look at whether the drug is effective we look at its safety.  And  chemistry is important.  How a drug gets absorbed and what factors can affect that absorption are some of the early criteria we must seek.  The fundamental importance of basic chemical principles rules the safety of the chemical compounds we ingest.

Work in groups as assigned by your instructor.  Answer the two application questions, then consider the evaluation exercise:

Application 1:

We showed how drugs like phenobarbitol and penicillin had concentrations of unionized and ionized (disassociated) forms depending on the pH and their pK_a.  We also indicated that the unionized form would be likely to pass through the walls of the duodenum into the system:

Refer to the table below:

The Henderson Hasselbach Equation can give us a clue to the extent of ionization at any pH.  At the pH of the duodenum (pH=6), which one of the drug pairs below is more likely to be in the most unionized, fat soluble state thus more likely to pass through the walls of the duodenum:

Henderson-Hasselbach Equation

Application 2:

The history of the barbiturates shows that early workers found barbituric acid was inactive.  But they designed a series of chemical derivatives of barbituric acid in which different fat-like C and H containing (hydrocarbon chains) were attached to the barbituric acid molecule. These compounds were sedatives - some acted with lightning speed and went away quickly.  Others were slow to act but the sedative effects lingered on.  All of them had about the same pK_a.

Can you suggest, in terms of chemical concepts, a reason why those with large hydrocarbon groups attached worked quickly and went away quickly whereas the materials with small hydrocarbon groups attached fell in the slow acting, lingering effect group?  Is your answer cosistent with the inactivity of barbituric acid?

Evaluative Case Study:

Designer Drugs
Certain legitimate drugs can be abused by overuse.  But that isn't enough for some people.  Chemists are clever people and some chemists have synthesized chemical compounds that are like legitimate drugs but that have an enhanced effect.

These are illicit activities, of course.   They are illicit and dangerous, too since the preparation of analogues runs many risks.

Case: Develop a Designer Drug Brochure:
With a background now in the chemical principles affecting delivery of drugs, and with knowledge of the factors that can cause damage to brain receptors:

Compose and publish on the class web page a two-page brochure that you would distribute to students in University science classes that alerts them to the scientific, social and personal risks of designer drugs:

Consider, but do not limit to:

• Neural pathways and neorotransmitters

• Chemical kinetics

• rate of transfer across tissue

• acid/base properties

• possibility of addiction

• possibility of legal consequences

Drug Addiction is an Illness
Dr. Matt Hermes, Editor

This ChemCases.com case study is aimed at those of you who might respond to rational thinking in your understanding of man and drugs. We suspect that those who are or who might become addicted will not be capable now of finding answers here.

Drug addiction is an illness. Some of us find that after periods of drug use, we crave drugs in the face of the most dire consequences. We can face loss of health, family, money, job, self-respect and even our lives and yet we will continue a pattern of compulsive and destructive drug use.

For those who are addicted, there is little effective advice in the practical terms of the scientist. Recovery depends on a peculiar combination of medical assistance, the counsel of peers and a substantial dependence on a higher power to assist in the daily quest for complete abstinence.

For those wonderful people we hope for a future awakening and a passage of denial.

Some Resources:

• Clubdrugs.org

• Alcoholism and Alcohol Abuse

• National Council on Alcoholism and Drug Dependence

• National Institute on Drug Abuse

• Science of Drug AddictionTreatment

• Peer Support:
  Narcotics Anonymous
  Alcoholics Anonymous

Principal Investigator
Laurence I. Peterson, Dean
College of Science and Mathematics
Kennesaw State University
1000 Chastain Rd.
Kennesaw, GA 30144-5591
770-423-6160
FAX 770-423-6530
email lpeterso@kennesaw.edu

Program Director
Matthew E. Hermes, 
76 Meridian Rd.
Beaufort, SC 29907
843-322-0486

email hayden@islc.net