Chapter 5: The Action of Drugs

Many drugs come directly from plants or are chemically derived from plant substances that may have evolved to protect the plant from being eaten.  The use of plants by medicine men and women of primitive cultures has grown into today's multi-billion dollar pharmaceutical industry.

Commercially available drugs are currently known by three different types of names—the chemical name, the generic name, and the brand name.  The chemical name is the complete chemical description of the drug molecule.  The generic name is the official, legal name of the drug and is often a simpler version of the chemical name.  A brand name specifies a particular formulation and manufacturer and is copyrighted.

Drugs can be categorized by their major effects.  Stimulants produce wakefulness and a sense of energy.  Depressants, on the other hand, slow the activity of parts of the nervous system.  Opioids, also called narcotics, reduce pain.  Hallucinogens produce altered perceptions.  Psychotherapeutic drugs control mental disorders.  Some drugs, including marijuana and nicotine, are difficult to classify because they have effects typical of more than one category.  Drugs can be identified by the appearance of commercial tablets or capsules, by the packaging or appearance of illicit drugs, or by a variety of chemical tests.

Drugs have both specific effects, those related to the concentration of a particular chemical, and nonspecific effects, those influenced by expectations, experience, and setting.  Nonspecific effects are also called placebo effects, those produced by an inactive chemical that the user believes to be a drug.  In medical testing, a double-blind procedure is used to help separate specific and nonspecific effects; in such procedures, neither the test subjects nor the evaluators know whether a subject is receiving a placebo or an active drug until after the trial is over.

A dose-response relationship means there is a correlation between a response and the quantity of drug administered; such a relationship is a strong demonstration of a specific drug effect.  Because each drug can produce many effects, many dose-effect relationships can be studied for a given drug. Researchers measure effective and lethal doses in animal tests, and determine a margin or range of safety for a drug in humans.  The safety margin is the difference between the dose that produces the desired therapeutic effect in most patients and the lowest dose producing an unacceptable toxic reaction.  A drug that is potent produces an effect at a very low dose.  The time course of a drug is an additional consideration because drugs vary in the timing of the onset, duration, and termination of their effects.  If doses aren't spaced appropriately, the drug's concentration in the body may be too high or low to be effective or safe.

In order for a drug to have an effect on the brain, it must enter the body and move through the bloodstream.  There are four major routes of drug administration: oral ingestion, injection, inhalation, and topical application.  In oral ingestion, drug chemicals must withstand the digestive process, get through the cells lining the GI tract, and then pass through the liver without being metabolized before they enter the general circulation.  Injection, the second major route, can occur in several different ways. In intravenous injection, the drug is delivered directly into the bloodstream, so high concentrations of a drug can be administered, and effects occur rapidly.  Drugs can also be injected into a muscle or under the skin.  The third major route is inhalation, in which a drug moves into the bloodstream through capillary walls in the lungs.  Effects are rapid following inhalation because blood moves fairly quickly from the lungs to the brain.  The final major route, topical application, tends to be a slower process, although absorption through the mucous membranes occurs more rapidly than absorption through the skin.

Once a drug enters the bloodstream, some drug molecules attach to proteins in the blood and become inactive, while other molecules travel freely in the blood and move to sites of action.  Some drugs can pass through the blood-brain barrier and act directly on cells in the brain, usually by affecting a particular neurotransmitter system.  Drugs may alter the concentration of a neurotransmitter or interact with its receptors.

A drug ceases to have an effect when it is excreted unchanged from the body or is chemically changed.  The liver is an importation site for drug deactivation.  Certain liver enzymes can change the chemical structure of a drug, and the resulting metabolite is excreted by the kidneys.  In a few cases, metabolites are active, and the effects of a drug are prolonged.  Over time, the body can detect the presence of a foreign drug molecule and trigger production of more of the specific drug-metabolizing enzymes, a process known as enzyme induction.

Tolerance to a drug can occur in several ways.  Drug disposition, or pharmacokinetic, tolerance occurs when use of a drug increases the rate of its metabolism or excretion.  Behavioral tolerance occurs when individuals learn to compensate for nervous system impairment caused by a drug, so the drug may have the same biochemical effect but a reduced behavioral effect.  Finally, pharmacodynamic tolerance occurs when neuron sensitivity to a drug changes, possibly through a change in the production of neurotransmitters or in the number of receptors.  Pharmacodynamic tolerance can result in withdrawal reactions if drug use ceases.