BIOL 103: BIOLOGY OF ADDICTION  -- Lecture Notes
Stan Eisen
Biology Department
Christian Brothers University
650 East Parkway South
Memphis, TN 38104

Mail To:
seisen@cbu.edu
(901) 321-3447

(Updated January 6, 2006)

Some Useful Web Addresses:

The National Institute on Alcohol Abuse and Alcoholism -

http://www.niaaa.nih.gov/

Lecture Topics

Addiction Defined
Diffusion
Modes of Entry I. Oral administration
Minicourse 1: The digestive system
Inhalation
Minicourse 2: Respiratory system
Modes of Entry III. Injection
Minicourse 3: The circulatory system
Modes of Entry IV. Miscellaneous
Minicourse 4: The excretory system
Termination of Drug Action
Minicourse 5: Structure of the nervous system
Structure of neurons
How Neurotransmitters work
Types of Neurotransmitters
Principles of Pharmacokinetics and Pharmacodynamics
On the Use of Depressants
Mode of action, metabolism & toxicity of alcohol
Alcoholic cirrhosis and liver transplant surgery
Fetal Alcohol Syndrome
Treatment of alcoholics & drug addicts
Acupuncture as a detox treatment modality
Minicourse 6: Principles of Genetics
The genetics of alcoholism
From Test Tube to Pharmacy Shelf: Regulation of Drug Development
Inhalants
NS depressants
Barbiturates
Benzodiazepines and "Second Generation" Anxiolytics
Psychostimulants I: Cocaine
Psychostimulants II: Amphetamines
Caffeine
Nicotine
Antidepressants
Opioids
Marijuana
Psychedelics
Anabolic-Androgenic Steroids
Schedule of controlled substances

Addiction defined

          Perhaps the easiest way to define addiction is that it constitutes whatever it takes to follow the following downwards spiral:

 

A DEFINITION OF ADDICTION, WITH ALCOHOL AS THE MODEL

Complete Defeat admitted

          This downwards spiral is due to three phenomena:

1.     Tolerance, in which there is an increased need for greater amounts and more frequent doses in order to acquire the same effect. This is caused by an increase of catabolic enzymes which metabolize the drug faster, thereby decreasing blood concentrations faster. An example of such an enzyme is alcohol dehydrogenase;

2.     Physical dependence, in which there are physical symptoms associated with withdrawal, or the cessation of taking the drug. These symptoms can be life-threatening, as in alcohol, or they can be inconvenient but not life-threatening, as in heroin or morphine;

3.     Psychological dependence, in which brain chemistry and circuitry are altered by the continued presence of the drug. The number of receptors for a particular neurotransmitter may decrease or increase, and this leads to the increasing amounts of the drug in order "just to feel normal."

 Diffusion:

          Diffusion is defined as the "movement of molecules from a region of higher to lower concentration; it requires no energy and tends to lead to an equal distribution" (Mader, 1998).

          In the context of living cells, the definition of diffusion is modified to the "movement of molecules through a plasma membrane from a region of higher to lower concentration."

          Our present model for the structure of plasma membranes was introduced by S. Singer and G. Nicolson in 1972. According to the fluid-mosaic model of membrane structure, plasma membranes have two components, phospholipids and proteins. The phospholipids arrange themselves spontaneously into a bilayer, in which the (hydrophobic) fatty acid chains are oriented in the interior of the bilayer, while the (hydrophilic) phosphate groups are oriented towards the exterior. The proteins are scattered throughout the membrane in an irregular pattern, and may have several functions:

1.     Channel proteins allow a particular molecule or ion to cross the plasma membrane freely. For example, water can diffuse into or out of cells very quickly;

2.     Carrier proteins interact with specific molecules or ions, such as sodium (Na+) or potassium (K+), so that they can cross the plasma membrane. These proteins are particularly important in understanding the function of neurons;

3.     Cell Recognition proteins serve as the basis of our immune system. Certain white blood cells, such as lymphocytes, are capable of recognizing foreign cells or tissues by the types of cell recognition proteins on the plasma membrane;

4.     Receptor proteins are sites on plasma membranes to which compounds will bind, and thereby cause a change in the function of that cell. Neurotransmitter molecules and drug molecules exert their effects on neurons by binding to receptor proteins  For more information regarding receptors, visit http://receptome.stanford.edu/HPMR ;

5.     Enzymatic proteins have a catalytic function, in which they will catalyze a specific reaction. The binding of a neurotransmitter molecule to a receptor protein may, in turn, activate an enzymatic protein which will catalyze a reaction inside the cell.

Since the plasma membrane consists of protein and phospholipids, lipid-soluble drug molecules can diffuse easily through them, but water-soluble molecules cannot. As you will see, an understanding of diffusion is critical to understanding the passage of drugs from the stomach and the intestine into the bloodstream, from the fluid bathing cells (interstitial fluid) into the interior of cells (cytoplasm), and from the interior of cells into the interstitial fluid, and from the kidneys back into the bloodstream.

Within 1 minute of entering the bloodstream, drug molecules will become distributed fairly evenly throughout the blood volume. By that time, drug molecules which travel back & forth between blood capillaries and tissues.

Capillaries have pores which allow the passage of larger molecules between blood and tissues. As long as molecules can pass through these pores, transport of drug molecules out of blood capillaries and into tissues, and back into blood is independent of lipid solubility, since pores are large enough for even fat-insoluble molecules to penetrate.

The blood-brain barrier is a system of capillaries in the brain which lack pores. Instead they have extensions of astrocytes to form a fatty barrier called the glial sheath. Only fat-soluble molecules can cross the blood-brain barrier.

The placental barrier separates 2 separate living entities. In addition to allowing the free exchange of normal nutrient and waste molecules, the placental barrier allows the movement of drug molecules, including alcohol, cigarettes, and cocaine (Julien, 1998).

          Julien, R. M. 1998. A Primer of Drug Action. W. H. Freeman, edition 8.

          Mader, S. 1998. Biology. WCB MCGraw-Hill, edition 6.

Modes of Entry I. Oral administration

For oral administration to occur, the drug must be soluble, stable in stomach fluid, and capable of penetrating the lining of the intestine. As mentioned earlier, all psychoactive drugs are lipid-soluble and readily cross cell membranes.

The disadvantages of oral administration include the following:

1.     The drug can cause vomiting and stomach distress;

2.     Actual dosage is variable;

3.     Some drugs cannot be administered by mouth, e.g. insulin;

4.     It is relatively slow -- requiring sufficient time to reach the small intestine, which can be 20-40 minutes.

Minicourse 1: Structure of the digestive system

          The following is a description of the pathway of food through the digestive system:

          Food is typically chewed in the mouth, where it is mixed with saliva secreted by the salivary glands. Saliva is a slightly alkaline solution which contains salivary amylase, an enzyme which initiates the chemical breakdown of starch. Saliva lubricates food to facilitate its movement from the mouth through the esophagus into the stomach.

          When food enters the stomach, it is exposed to gastric juices, which contain pepsin in a solution of hydrochloric acid. The pH of gastric juice is 2. There is also a small amount of gastric alcohol dehydrogenase, which initiates the breakdown of alcohol. Females tend to have a lower concentration of gastric alcohol dehydrogenase in their gastric juice, so a greater amount of alcohol enters their bloodstream. This may account for the tendency for females to be affected by a lesser amount of alcohol than males.

          Food will then enter the small intestine, which is lined with small, fingerlike extensions called villi, whose function is to increase the surface area of the small intestine. Inside each villus, there is a capillary system and a lymphatic vessel called a lacteal.

          Sugars and amino acids enter villi cells and are absorbed into the capillaries of the villus. Fats are first broken down into glycerol and fatty acid molecules, which diffuse into the lacteals, where they are reassembled into fat molecules.

          Drug molecules will diffuse into the capillaries of the villi, and will then be distributed throughout the body via the circulatory system.

Modes of Entry II. Inhalation

          Inhalation avoids the unpredictability of the gastrointestinal tract. It is also very rapid. It is so rapid, in fact, that the amount of time required for a bolus of nicotine from a puff of smoke to reach the brain is approximately 7 seconds. Drugs which are inhaled, such as halothane tend to be very small and highly lipid-soluble.

Minicourse 2: The respiratory system

          The human respiratory system includes a series of structures which conduct air to and from the lungs. Air enters the respiratory system typically via the nose. Air is filtered, warmed and moistened as it passes through the nasal cavities towards the pharynx, or throat. Some drugs, such as cocaine, can be absorbed through the mucous membranes of the upper respiratory tract.

          Air will then pass through the glottis, an opening into the larynx. The vocal cords are located here. The vocal cords consist of flexible bands of connective tissue imbedded in mucous membranes. Air will continue past the larynx through the trachea, a hollow tube consisting of cartilage.

          The trachea is lined with tissue endowed with cilia, whose function is to trap particulate matter such as dust, pollen and soot. These particles are mixed with mucus and then pushed up the trachea via the beating of the cilia. When this small plug of mucus with particulate matter reaches the back of the throat, it induces a gag reflex so that the plug is swallowed. This is the manner in which the respiratory system cleanses itself. (One of the components of cigarette smoke anesthetizes the ciliated cells which push these pollutants out of the respiratory system. The short-term effect is that the particles of cigarette tar then persist in the lungs, causing local irritation. The long-term effect is that harmful chemicals, particularly carcinogens, have a longer period of time to leach out of the particles to affect the tissues of the lungs.)

          The trachea divides into two primary bronchi which enter the right and left lungs. The bronchi branch further into progressively finer bronchioles, which finally terminate in an elongated structure containing air pockets or sacs, called alveoli. It is here, in the alveoli, where gas exchange actually takes place.

          Alveoli are endowed with numerous capillary beds, which facilitate the diffusion of oxygen into the bloodstream and carbon dioxide out of the bloodstream.

          Ventilation is accomplished by inspiration, the inhalation of air into the respiratory system, and expiration, the exhalation out of the respiratory system out of the respiratory system.

          Inspiration is primarily caused by the contraction of the diaphragm, a dome-shaped muscle that forms the floor of the thoracic cavity. When the diaphragm contracts, thus causing negative pressure which forces air into the lungs. The entry of air into the lungs causes the alveoli to inflate. During forced inhalation, the external intercostal muscles contract as well. The external intercostal muscles pull the chest cavity outwards and upwards, thereby increasing the amount of space available for the lungs to expand.

          Expiration occurs when the diaphragm relaxes. The recoil of the diaphragm pushes air out of the lungs, thereby partially deflating the alveoli in the lungs. During exercise or forced expiration, the internal intercostal muscles contract to pull the chest cavity downwards and inwards.

          The quantity of respired air can be measured with a spirometer. The amount of air moved into and out of the lungs with each normal breath is called the tidal volume. Tidal volume averages 500 ml. The extra volume of air which can be inhaled is called the inspiratory reserve, and it averages 3000 ml in males and 2100 ml in females. The extra volume of air which can be exhaled is called the expiratory reserve, and it averages 1200 ml in males and 800 ml in females. The sum of these volumes, tidal volume + inspiratory reserve + expiratory reserve is called the vital capacity.

          Even when a person has exhaled as much air as possible, there is still air in the respiratory system. This volume of air is called the residual, and it averages 1200 ml for males and 1000 ml for females. The sum of vital capacity + residual is total capacity.

 

Average lung capacities for normal 20-year old males and females

Measured in milliliters

 

Parameter

Males

Females

Tidal volume (TV)

500

500

Inspiratory Reserve (IR)

3000

2100

Expiratory Reserve (ER)

1200

800

Vital Capacity (VC=TV+IR+ ER)

4700

3400

Residual (RE)

1200

1000

Total Capacity (TC=VC + RE)

5900

4400

As mentioned earlier, gas exchange occurs in the alveoli. Oxygen molecules pass from the air space of an alveoli into its capillary bed via simple diffusion -- oxygen concentration in the air is greater than it is in the bloodstream. At the same time, carbon dioxide molecules passes out of the capillary bed of an alveolus into its air space by simple diffusion. The amount of surface area required for these processes of diffusion is quite large -- the surface area of the alveoli in an average human lung is roughly equal to the surface area of a tennis court.

          Once oxygen molecules have entered the bloodstream, they will then diffuse into red blood cells, where they will bind with hemoglobin. Each hemoglobin molecule can carry up to four oxygen molecules. With hemoglobin, the oxygen-carrying capacity of whole blood is 20 ml of oxygen per 100 ml. Without hemoglobin, the oxygen-carrying capacity drops to a mere 0.25 ml per 100 ml.

          Breathing is regulated by respiratory centers of the brain, located in the medulla. Neurons in the dorsal region of the medulla regulate the basic rhythm of breathing by sending a burst of impulses to the diaphragm and external intercostal muscles, causing them to contract. When the neurons become inactive, the muscles relax, so expiration occurs. Respiratory centers in the pons help regulate the transition from inspiration to expiration. These respiratory centers are sensitive to certain central nervous system depressants, e.g. alcohol.

Modes of Entry III. Injection

Injection can be intravenous (directly into vein), intramuscular (directly into muscle), subcutaneous (just under skin.)

In general, the advantages of injection are that absorption is faster and more accurate, since the unpredictable digestive system is bypassed. The disadvantages are the following:

1.     Rapid rate of absorption allows little time for response to overdose;

2.     Sterile techniques must be used. The risk of infection, particularly by AIDS and hepatitis C are much higher by injection than by ingestion;

3.     Administration cannot be recalled, so that lethal overdoses are possible.

Intravenous injections, in which the drug is injected directly into a vein, can be administered slowly or stopped, and they can be very precise. Irritating drugs can be diluted into physiological saline. At the same time, however, administration may be too fast and allergic reactions may be too vigorous to be controlled. Drugs that are not soluble in blood or those that are dissolved in oily liquids cannot be administered intravenously because of danger of blood clots. Intravenous injections also run the risk of transmitting pathogens.

The onset of effects with an intramuscular injection are faster than oral administration but slower than intravenous injection. Subcutaneous injection in which the drug as administered just underneath the surface of the skin allows for rapid absorption. Irritating drugs should not be given subcutaneously.

Minicourse 3: The circulatory system

According to Solomon et al. (1999), the human circulatory system performs the following functions:
1. Transports nutrients from the digestive system and from storage depots to each cell of the body;

1.     Transports oxygen from the lungs to the cells of the body;

2.     Transports metabolic wastes from each cell to organs that excrete them;

3.     Transports hormones from endocrine glands to target tissues;

4.     Helps maintain fluid balance;

5.     Defends the body against invading microorganisms

6.     Helps distribute metabolic heat within the body, which helps maintain a constant body temperature;

7.     Helps maintain appropriate pH

Blood consists of plasma, blood cells and platelets. Plasma is the fluid component of blood. Approximately 92% of the volume of plasma is water, and 7% is protein. The remaining 1% includes the materials being transported in the plasma, including dissolved gases, nutrients, waste molecules, and hormones.

There are 3 classes of plasma proteins:

          Fibrinogen

          Globulins (including alpha, beta and gamma)

          Albumin

          When clotting proteins are removed from plasma, the remaining fluid is called serum.

          Plasma proteins help regulate the distribution of fluid between plasma and interstitial fluid. They are too large to pass through the walls of blood vessels, so they help regulate osmotic pressure as well. Plasma proteins also function in regulating blood pH to within a very narrow range, 7.35 to 7.45.

          Blood cells:

          Red blood cells, or erythrocytes function to transport oxygen and carbon dioxide. By the time a red blood cell is released into the bloodstream from the marrow where it was produced, the cell is enucleated (without a nucleus). Each red blood cell is 7 to 8 microns in diameter. The biconcave shape of the cell allows for a high surface-area-to-volume ratio. Red blood cells are flexible enough to allow the cell to bend and twist as it passes through capillaries.

          White blood cells or leukocytes are an internal defense to pathogens. A typical stained blood smear will show a variety of leukocytes, each with a specific function:

 

Characteristics and Functions of Leukocytes

 

Type

Percentage

Function

Neutrophils

70%

Principal phagocytic cells in the blood -- they detect and ingest bacteria.

Eosinophils

1-3%

Detoxify foreign proteins and other substances --numbers increase during allergic reactions and in response to certain parasitic infections

Lymphocytes

25-35%

Produce antibodies and destroy foreign or cancerous cells -- specific immunity

Monocytes

6%

Leave the bloodstream to differentiate into macrophages which attack pathogens

          Platelets assist in the clotting process. When a blood vessel is damaged, platelets will be sticky and will adhere to the edges of the wound. Activated platelets will then release substances which will initiate the clotting process, eventually producing a fibrous plug consisting of fibrin. The process of clot formation involves a cascade of at least 12 different reactions.

          The heart is a muscular pump which provides the force for moving blood through the circulatory system. The human heart consists of 4 chambers. The right atrium receives blood from the superior vena cava (draining the head and neck) and from the inferior vena cava (from the torso, arms and legs). When it contracts, blood passes through the tricuspid valve to the right ventricle.     When the right ventricle contracts, blood passes through the pulmonary valve to the pulmonary artery. The pulmonary artery brings blood to the lungs, where it is oxygenated. Blood will return to the heart via the pulmonary veins into the left atrium. When the left atrium contracts, blood passes through the mitral valve into the left ventricle. When the left ventricle contracts, blood passes through the aortic semilunar valve into the systemic circulation via the aorta.

          Cardiac muscle cells which comprise the heart are unusual because they can contract spontaneously. The means by which the contractions of all cardiac muscles are coordinated to allow for the efficient pumping of the heart is by means of a pacemaker, the sinoatrial node. The sinoatrial node is the location where the nerve stimuli to contract originate. The sinoatrial node, in turn, is connected to the cardiac centers of the medulla. The electrochemical impulses which regulate the beating of the heart can be recorded in the form of an electrocardiogram.

          Cardiac output is the volume of blood pumped by the left ventricle into the aorta in one minute, and is equal to the produce of stroke volume x heart rate. Stroke volume is equal to the amount of blood which can be pumped during each contraction of the left ventricle. The average stroke volume is 70 ml. At rest, when the heart is pumping approximately 72 times/minute, the cardiac output is therefore approximately 5 Liters/minute. During exercise, the cardiac output can increase 4- or 5-fold.

          The allocation of blood during rest and exercise periods will also change:

 

Comparison of Cardiac Output at Rest and During Exercise (All numbers are in ml/minute)

 

 

At rest

During exercise

Cardiac output

5,400

17,500

Blood flow to:

Brain

Abdomen

Kidney

Muscle

Skin

Heart

 

750

1400

1100

850

450

250

 

750

600

600

12,500 (!)

1,900

750

          The heart pumps the body's total volume of blood in 1 minute. Therefore, once a drug is absorbed, distribution is within 1 minute.

          Blood pressure is the force exerted by the blood against the inner walls of the blood vessels. It is proportional to cardiac output, blood volume, and resistance to blood flow. In a clinical setting, blood pressure is measured with a stethoscope and a sphygmomanometer at the brachial artery, and is indicated by two numbers. The first number indicates the systolic pressure, i.e. the pressure of blood when the heart is contracting. The second number indicates the diastolic pressure, i.e. the pressure of blood when the heart is at rest.

          The "plumbing" that is associated with the heart in circulating blood includes arteries, which carry blood away from a heart chamber, veins, which transport blood back to the heart, and capillaries, where exchange occurs between the bloodstream and internal tissues.

          The capillary system is extensive. No single functioning cell of the body is more than 20 to 30 microns away from a capillary. In comparison, the average RBC is 7 microns in diameter.)

Drugs quite quickly become evenly distributed throughout bloodstream, diluted not only by blood but also by total amount of water contained in the body. Most drugs are not confined to the bloodstream. Capillaries have pores between cells that allow passage of molecules between blood and body tissues. Most drugs travel freely from blood through pores in capillary membrane, passing along concentration gradient until equilibrium is established.

          Transport of drug molecules out of blood capillaries and into tissues, and back into blood is independent of lipid solubility, since pores are large enough for even fat-insoluble molecules to penetrate.

Some drugs can be bound to proteins. Protein-bound drugs are essentially trapped in bloodstream. However, protein-bound drugs exist in equilibrium with unbound drugs.

Capillaries comprising the blood-brain barrier and the placental barrier have unusual properties, and thereby affect the diffusion of materials across those membranes.

          The term blood-brain barrier refers to those capillaries found in the brain. These capillaries lack pores. Instead, they have extensions of astrocytes to form a fatty barrier called a glial sheath. This glial sheath allows only fat-soluble molecules to diffuse out of the bloodstream and into brain tissue.

          The capillaries of the placental barrier separate 2 living entities. The growing fetus is completely dependent on the maternal circulation for the delivery of nutrients and oxygen and for the removal of waste molecules and carbon dioxide. Psychoactive drugs can also pass through the placental barrier. The effects of maternal ingestion of alcohol, nicotine and cocaine are well documented.

          References:

Solomon, E. P.; Berg, L. R.; Martin, D. W. 1999. Biology. Saunders College Publishing, edition 5.

Modes of Entry IV. Miscellaneous

Drugs can be administered through a variety of mucous membranes. For example, heart patients take nitroglycerine as a tablet under the tongue, absorption directly through the mouth. Cocaine, when sniffed, adheres to the membranes on inside of nose and is absorbed directly into bloodstream.

Other examples include nicotine in snuff or chewing gum, nasal decongestants which are administered via a nasal spray, and Fentanyl, a narcotic pain-killer given to children post-surgery as a lollipop.

Some drugs can be administration through the skin. With this method, the active ingredient is slowly absorbed through the skin into bloodstream. For example, people trying to discontinue smoking will self-administer nicotine with a patch. Estrogen is given in the same manner to postmenopausal women. The drug is slowly released from the patch and is absorbed into the systemic circulation over a period of days so that blood levels remain relatively constant.

Minicourse 4: The excretory system

          The functions of the excretory system include osmotic regulation, excretion of nitrogenous and other waste products, and the regulation of a constant blood pH.

          In the course of a single day, the kidneys will process 180 liters of blood, and will produce 1.5 liters of urine. The functional unit of kidneys is the nephron. As blood passes through a glomerulus, some fluid, which has dissolved nutrient, waste and salt molecules in it, will diffuse into the glomerular capsule. This fluid, called the filtrate, will become progressively more urine-like as it progresses through the nephron. All of the nutrient molecules, and most of the water will be reabsorbed and returned to the bloodstream. By the time this filtrate has reached the collecting duct, it will have become urine. The following chart shows the concentrations of selected materials in blood, the filtrate as it first enters the glomerular capsule and the collecting duct:

 

CONCENTRATIONS, IN MG/ML OF SELECTED MATERIALS

 

 

Molecule

Efferent arteriole (blood)

Glomerular capsule (filtrate)

Collecting duct (urine)

Urea

30

30

2000

Uric acid

4

4

50

Inorganic salts

720

720

1500

Proteins

8000

0

0

Amino acids

50

50

0

Glucose

100

100

0

         

          While amino acids, glucose molecules and water are reabsorbed into the blood, some materials are secreted across the tubule epithelium in a direction opposite to that of reabsorption. Potassium, hydrogen, and ammonium ions are secreted into the filtrate. The secretion of hydrogen ions is important in the regulation of blood pH.

          The amount of water that is released is regulated by antidiuretic hormone, (ADH or vasopression), a hormone secreted by the posterior pituitary gland. ADH makes the collecting ducts more permeable to water so that more water is reabsorbed and a smaller volume of concentrated urine is produced. Alcohol inhibits the activity of ADH, thus causing people to produce more urine per unit time.

          As urine is produced, it flows from the collecting ducts into the renal pelvis, a funnel-shaped structure inside the kidney. Urine then flows into one of two ureters, which are tubular muscles. By peristaltic movement, the ureters bring urine to the urinary bladder, where it is stored. The urinary bladder can retain up to 100 ml of urine. Urine exits the body via the urethra. The process of voiding the bladder involves the voluntary relaxation of the outer sphincter muscle, which is composed of (voluntary) striated muscle fibers. The change in pressure bearing on the inner sphincter muscle, which is composed of (involuntary) smooth muscle fibers, causes a reflex in which the inner sphincter muscle relaxes, thus allowing the flow of urine. Muscles in the wall of the urinary bladder then push urine out of the bladder.

Termination of Drug Action

          Drug action can be terminated by two processes. First, the active molecule can be metabolized into an inactive form. Because psychoactive drugs are small and lipid-soluble, they will follow concentration gradient back into bloodstream. From there, drug molecules are converted into metabolites which are more water-soluble, bulkier, and less biologically active. The enzymes which catalyze these metabolic processes in liver cells are collectively called P450 enzymes. Drug-metabolizing enzymes in liver cells have low specificity, therefore cross-tolerance will occur. The factors affecting drug metabolism can be genetic, environmental, or physiological. Most metabolites exit via the urine, so they form the basis for urine testing.

Second, the active drug molecule may be secreted via several routes. Highly volatile or gaseous agents, such as anesthetics or alcohol can exit via the lungs. Other routes of drug elimination include the lungs, bile, sweat, saliva, breast milk. For example, measurable amounts of nicotine can be detected in mother's milk, and antibiotics given to cows may end up in milk served to babies.

Mode of Admini-stration

Time of onset of effects

Persis-tence of effects

Precision of blood concentra- tions & dosage

Likelihood of reversing effects of an overdose

Suscepti-lity to blood-borne diseases, e.g. AIDS

Oral

Slow (20-40 minutes)

Long

Least predictable

Possible - in hospital setting, it is possible to pump the stomach contents

Virtually nil

Inhalation

Fairly rapid (< 1 minute)

Relatively long

More reliable

Less likely

Very unlikely

Intravenous injection

Very rapid (<< 1 minute)

Relatively short

Most precise

Least likely

High susceptibi-lity

 

Minicourse 5: Structure of the nervous system

The nervous system can be divided into 2 parts, the central nervous system (CNS), and the peripheral nervous system (PNS). The central nervous system consists of nerves that are in the brain and spinal cord, while the peripheral nervous system consists of nerves that lie outside the brain and spinal cord. These nerves are both sensory (afferent) and "motor" to (efferent) all muscles and organs.

The Central Nervous System:

There are an estimated 100 billion neurons in the brain and spinal cord. The spinal cord extends from the lower end of the medulla to the sacrum and consists of neurons involved in the following:

a.      Carrying sensory information from skin, muscles, joints, and internal body organs to the brain;

b.     Organizing and modulating the motor outflow to the muscles (to produce coordinated muscle responses.);

c.      Modulating sensory input (including pain - impulse input);

d.     Providing autonomic (involuntary) control of vital body functions.

The lower part of the brain, the brain stem, includes the medulla, pons, and midbrain. All impulses that are conducted between the spinal cord and brain pass through brain stem. The three parts of the brain stem collectively regulate vital body functions, such as respiration, blood pressure, heart rate, GI functioning, and stages of sleep and wakefulness. They are also involved in behavioral alerting, attention, and arousal responses.

Behind the brain stem is the cerebellum. It is a highly convoluted structure connected to brain stem by large fiber tracts and is necessary for proper integration of movement and posture. Alcohol & barbiturates depress cerebellar function.

Above the brain stem is the diencephalon, which includes the hypothalamus, pituitary gland, various fiber tracts, subthalamus, and thalamus.

The subthalamus lies underneath the thalamus in the midbrain. Together with basal ganglia, it constitutes one of our motor systems, the extrapyramidal system. In Parkinson’s disease, there is a deficiency of dopamine which originate from cell bodies in the substantia nigra, one of the subthalamic structures.

The hypothalamus is the principal center of integration for the entire autonomic (involuntary or vegetative) nervous system. It controls eating, drinking, sleeping, regulation of body temperature, sexual behavior, blood pressure, emotion & water balance. It also controls hormonal output of the pituitary gland, by secreting releasing factors and is the site of action for primary and side effects of drugs.

The limbic system is closely associated with the hypothalamus. Its major components are the amygdala and hippocampus. These structures exert primitive types of behavioral control. They integrate emotion, reward, and behavior with motor and autonomic function. Because the limbic system and hypothalamus interact to regulate emotion and emotional expression, these structures are targets of psychoactive drugs.

The hypothalamus and limbic areas contain structures important in psychopharmacology, including dopamine-rich reward centers such as the ventral tegmental area, median forebrain bundle, and nucleus accumbens. Activity of dopaminergic neurons in these areas is affected by opioid, GABA-ergic, and other neuronal influences. As a result, drugs subject to compulsive abuse act here.

          The cerebrum is the largest portion of brain and is separated into 2 distinct hemispheres divided by function. Interpretation of sensory input and of motor activity are controlled by different areas of the brain:

         

 

Functional areas of the cerebrum (adapted from Mader, 1998)

 

Structure

Function

Frontal lobe

Motor functions

Parietal lobe

Receives information from receptors in the skin

Occipital lobe

Interprets visual input