DEPRESSANTS

• The history of depressant drug use,
• Commonalities among depressant drugs,
• Methods of administering depressants,
• Effects of specific depressant drugs,
• Benefits and risks of depressant drug use.

Depressant drugs reduce the action of the central nervous system and can produce physical dependence, psychological dependence and tolerance. All depressant drugs share some basic similarities of action. They are all commonly used to improve mood and diminish inhibitions. All depressant drugs affect coordination, judgment and anxiety at low doses and trigger sedation at medium doses. At higher doses they can produce a pattern of decreasing respiration and convulsions that can potentially lead to death. In addition there are enough differences between depressant drugs to create subcategories which include alcohol, opiates, barbiturates and tranquilizers.

Alcohol

History. Alcohol, or ethanol, is a colorless liquid solvent that has an unpleasant taste and odor. It has been ingrained in the cultures of the world to socialize, honor people, relax, and to escape from the stressors of life. It was traded as a commercial product as far back as 2,000 B.C. and it was commonly used in the ancient civilizations of Mesopotamia, Egypt, Greece, and Rome. The U.S. federal government placed an excise tax on alcohol in 1791. Alcohol production in America was a natural outgrowth of farming. Almost every home had a still or fermentation crock to make beer, wine, and whiskey. One-third or more of the daily caloric intake of the hard working early American settlers came from alcohol. Presently this trend is being repeated by farmers in the hills of Tibet who also consume alcohol to supplement to their daily caloric needs.

Alcohol use starts early in life and has become heavily infused into our culture. Today nearly five percent of high school seniors use alcohol on a daily basis. By grade twelve 95% of boys and 92% of girls have indulged in alcohol. 13 Other than tobacco, alcohol is one of the first drugs a person in our society experiments with.

Methods of Administration. Alcohol is ingested as a liquid or as an ingredient added to another substance.

Effects. Alcohol is a depressant and a sedative-hypnotic that affects the brain's reticular activating system, freeing it from the cortex and releasing inhibitions, reducing attention and judgment and prolonging reaction time. This causes a person in the early phases of intoxication to appear euphoric, hyperactive, mentally alert and if intoxication progresses to feel depressed, sluggish, react with inappropriate behavioral and emotional responses and even loose consciousness. Alcohol consumption lowers body temperature through heat loss and sweating and secretions of stomach acids and urine production are increased. Short-term tolerance develops in which a person appears less intoxicated after many hours than they would after a few hours. On the positive side alcohol does increase the good fat (HDL) and decrease the bad fat (LDL) circulating in the blood.17 Even though low to medium doses of alcohol have clear physical and behavioral actions there is also a strong influence exerted by the set and setting in which alcohol is consumed. These factors can have a profound effect on whether alcohol use results in decreasing or increasing anxiety.13

Alcohol is available as methyl, isopropyl and ethyl products. Methyl or wood alcohol gets its name because it is derived from wood products. Consuming small amounts affects the retina of the eye and causes blindness and larger amounts can be fatal. Isopropyl or rubbing alcohol is also poisonous. Ethyl alcohol is present in alcoholic beverages. Ethyl alcohol is the main ingredient in beer, wines, cordials, liqueurs, and distilled spirits. The concentration of ethyl alcohol is approximately four percent by volume in domestic beer, 10 to 12% in table wines, 17 to 20% in cocktails, and 40 to 50% in distilled liquors. The amount of alcohol present in a drink is expressed as proof which is the percentage of alcohol by volume. The percentage by volume is one-half the proof number. If, for example, whiskey is one hundred proof it has a 50% alcohol content. Ethyl alcohol contains other chemical ingredients called congeners that come from the grapes, fruits, flavorings and colorings.

Ethyl alcohol has twice as many calories per gram as does sugar. It contains no vitamins, minerals, protein or fat. It is, however, an ideal energy source in that it is more rapidly metabolized by the body than sugars and is preferred over sugar as the body's first source of energy. It is composed of a carbohydrate that is not used by most body cells until it is metabolized by a special liver enzyme called hydrogenase. Heavy drinking increases enzyme activity and metabolizes alcohol more rapidly than light drinking. Because alcohol does provide calories it satisfies the appetite to a point that the individual may not eat properly.

The blood alcohol level that is produced will depend on the presence of food in the stomach, the consumption rate of alcohol, the strength of the alcohol, and the drinker's body composition. Food and other substances in the stomach can vary the absorption rate of alcohol from a half-hour to two to six hours. The greater the muscle mass the lower will be the alcoholic concentration in the blood. The following chart illustrates how the concumption of alcohol effects of blood alcohol level:

As the person progresses from a state of relaxation to hypnosis confidence in their performance increases but motor skills and the ability to solve complicated mental problems is reduced. Impaired performance in activities requiring skill decreases more as the blood alcohol rises. The level of alcohol needed to cause severe effects is drastically reduced when other sedative-hypnotics such as barbiturates, tranquilizers and opiates are combined with alcohol.4

The transport of alcohol takes place as follows:

1. When alcohol is swallowed it moves from the esophagus to the stomach.
   
   
2. Alcohol absorption begins in the stomach. 20% will pass through the stomach wall into the veins. If food is present in the stomach the passage of the remaining alcohol into the small intestine will be delayed.
   
   
3. 80% of the alcohol is absorbed into the veins from the small intestine. The venous system transports alcohol to the liver where it is oxidized.
   
   
4. The liver is capable of oxidizing approximately one-half of an ounce of alcohol per hour. Any surplus alcohol is circulated throughout the body raising the blood alcohol concentration. 98% of ingested alcohol is metabolized by liver enzymes.
   
   
5. Changes in the functioning of the brain occur as the alcohol reaches the brain.

Carbon dioxide found in mixed drinks causes an early opening of the stomach's pyloric valve which allows alcohol to pass into the small intestine and to be absorbed more rapidly. The liver breaks ethyl alcohol into acetaldehyde and finally into acetate. The acetate enters the energy producing pathways of the body and is eventually eliminated as carbon dioxide and water. Two to five percent of the alcohol is eliminated form the body in sweat, urine, and as tears but the majority of the alcohol must be oxidized by the enzymes in the liver. The liver slows down its normal functioning to metabolize alcohol. All body cells produce the alcohol methanol which is converted into formaldehyde, carbon dioxide and water by the liver enzyme dehydrogenase. When ethyl alcohol is consumed it is converted to acetaldehyde which competes with the cell's methanol for the same liver enzymes to complete its metabolism. This results in a build-up of formaldehyde in the body cells and contributes to the side effect called a hangover. Women produce lower levels of alcohol dehydrogenase resulting in approximately 30% more alcohol in their bloodstream than do men.27 Therefore, in women alcohol reaches the brain and other organs more quickly and produces a more rapid intoxication than it does in men. Hormone levels also play a role in alcohol metabolism. The menstrual cycle and oral contraceptives decreases the elimination of alcohol from the body. Alcohol consumption in women has also been associated with increased chances of breast cancer and osteoporosis. In the latter case alcohol seems to block the absorption of nutrients including calcium.

Drinking coffee, taking a cold shower, or exercising will not speed up the sobering process because alcohol is metabolized at a constant rate per hour. The initial alcohol effect generally lasts from two to three hours and the rebound effect may last up to twelve hours. The rebound effect is characterized by a rise in a person's energy level that produces headaches, tension, dehydration, and behavioral characteristics involving argumentative and aggressive behavior.
Chronic Use. Low to moderate drinking does little permanent harm to an individual but chronic use results in physical and psychological dependence and tolerance. Malnutrition can result from continuous drinking and is due to deficiencies of vitamins B, C, and E.26 Long term alcohol use may also lead to liver hepatitis and eventual cirrhosis because the metabolism of alcohol takes priority over the liver's normal metabolic functions. Alcohol is involved in approximately 50% of the cases of liver cirrhosis which is a diffuse scarring of the liver.6 There are three phases in the development of cirrhosis. The first phase is the fatty liver phase in which fatty deposits form in the liver. This phase does not interfere with normal liver function, has no negative clinical consequences and is reversible when ethanol intake is stopped. The second phase is called the destructive phase. In this phase the liver becomes inflamed, fat cells form and a necrosis begins which is characterized by diminishing liver cells, decreased liver functioning and an increase in fibrous cell formation. The last phase is called the destructive phase. In this phase a narrowing of the veins supporting the liver causes hypertension, an enlarged spleen and increased blood flow to the esophagus. The reduced liver functioning and increased pressure in the esophagus often results in bleeding in the esophagus, jaundice and the eventual inability of the liver cells to perform their normal metabolic functions. The end result of this phase can be liver failure. Among heavy drinkers 100% will develop the fatty liver phase, 30% will enter the destructive phase and 10% will develop cirrhosis.7

Years of heavy drinking can result in mental disorders. Korsakoff's syndrome- is a an alcohol induced psychotic condition induced by thiamine deficiency which produces confusion, loss of balance, impaired memory and permanent damage to the central nervous system. It may require extended custodial care. Wernicke's syndrome is associated with the loss of contact with realty and meaningless speech patterns. Polyneuritis- is an inflammation of the central nervous system that causes a burning and prickling sensation in the hands and feet. Heavy drinkers also experience lowered resistance to infectious diseases like pneumonia.



Overdose. A glass of beer or wine and a shot of distilled alcohol all contain approximately one-half ounce of alcohol. One drink will raise the blood alcohol level of a person by approximately .02 percent. If the blood alcohol level reaches .30 the person can pass out and if it reaches .35 alcohol acts like a surgical anesthetic. A blood alcohol level of .40 or above will induce coma or death. If death occurs it usually occurs by direct depression of respiration or regurgitation of vomit. The rapid absorption of alcohol reduces the effectiveness of stomach pumping in alleviating an overdose. Administering stimulants as an anecdote to overdose results in significantly higher rates of death.35 It appears that continuous monitoring of the patient's heart rate, blood chemistry and lung activity is presently the best way to treat alcohol overdose.18

Side Effects. The breakdown of alcohol causes a number of changes in the liver. The lactate produced in the breakdown of alcohol can change the acid-base balance of the blood increasing fatty acids in the liver, uric acid in the blood and the loss of essential ions such as calcium, magnesium and zinc through excessive urination. The rapid metabolism of alcohol causes low blood sugar levels that result in fatigue, irritability, headaches, nausea, dizziness and tremors.13 The dehydration also takes place in brain cells. When they rehydrate after drinking they swell and create pain as they swell back to their normal size.27 We commonly associate these symptoms with a hangover. There are many theories as to what causes a hangover. It is believed that a hangover is caused by the accumulation of acetaldehyde, dehydration, depletion of important enzymes which causes a build-up of formaldehyde and inert toxic substances called congeners. Fluid intake and time for the body to metabolize and stabilize itself are the only cures for a hangover.

A cross dependence exists with tranquilizers and barbiturates that can potentiate the effects of alcohol. Early studies with alcohol reinforced it reputation to enhance sexual desire and performance. However, most recently studies have determined that alcohol decrease sexual performance in both sexes.

Alcohol freely passes through the placenta. Drinking " mothers to be" have a high probability of giving birth to children suffering from Fetal Alcohol Effects (FAE) or Fetal Alcohol Syndrome (FAS). FAS is among the three leading causes of birth defects and is only one that is preventable. The fetal blood alcohol level can reach ten times that of the drinking mother due to the fetuses inability to metabolize the alcohol and its small body mass.3 Alcohol also has a negative effect on the development of the fetal brain. Children born with FAS show a pattern of facial deformities (small head with wide eyes), growth deficiencies, and mental retardation. The severity of FAS is related to the amount of alcohol consumed by the expectant mother.

Withdrawal. Alcohol withdrawal produces flu-like symptoms including gastric problems, diarrhea and delirium tremens involving muscle spasms, low blood pressure and sweaty skin.33 Weakness, rapid heartbeat and vomiting may also occur. Behavioral symptoms include depressed mood, anxiety and irritability. The symptoms typically disappear in five to seven days unless alcohol delirium develops.

The delirium is much less common that simple withdrawal and usually develops after five to 15 years of heavy drinking.39 The first symptoms of alcohol tremens appear within the second or third day of alcohol cessation and is marked with hyperactivity, vivid hallucinations, muscle tremor, delusions and agitated behavior. The syndrome runs its course within two to three days.2

Unique Aspects. Illnesses associated with anxiety and insomnia used to be treated with alcohol. It was one of our original tranquilizers. Alcohol aids digestion by increasing gastric secretions during meals. Another unique aspect of alcohol is that its rate of metabolism is not affected by increasing the drug's dosage. It takes approximately three hours to metabolize one ounce of alcohol and increasing the dose does not increase or decrease its metabolism. There are few remaining medical uses of alcohol. Alcohol has been used as an effective disinfectant, antiseptic, as a means for cooling the skin in the case of fever, and for the prevention of bed sores.

Narcotic Analgesics (Opiates)

History . Opium has its origin of use in Southeast Asia and parts of the Middle East. Opiates are naturally occurring substances which come from the poppy plant and include opium, codeine, morphine, and heroin. Opium resin has been an item of trade for thousands of years. Opium was used as an alternative for alcohol by the Arabs and the Romans to induce relaxation and euphoria. It was used in many of the patented medicines available in the United States in the 1800s including a mixture of opium and alcohol called laudanum. The eating of opium changed to the smoking of it in China in the late 18th century.

Methods of Administration. Opiates can be injected, smoked, and inhaled as a vapor.

Effects. When opiates are administered the person becomes less active and finds it difficult to concentrate, feels drowsy and may lapse into sleep. When taken orally over half of the opiate is broken down by the liver immediately before it can produce a physical effect making injection, snorting and inhalation the preferred route of administration to experience the drug effects. A very pleasant high also occurs with its use although this is often accompanied by nausea in the less experienced opiate user. Approximately 90% of the drug is excreted within 24 hours.20 Like most depressant drugs opiates decrease body temperature and reduce blood pressure and respiration. They further dilate the blood vessels near the skin causing a warm flushed sensation around the face and neck. In large doses breathing may stop.

Opiates are very effective pain killers. Their pain killing affect is the most powerful of all drugs. Pain involves two components; the sensation of pain and the reaction to pain. Opiates relieve both but are particularly effective at reducing the reaction to pain. Opiates bind to receptor cites in the central nervous system, mimic the body's pain relieving endorphins and produce a dreamlike state. Opiates work by inhibiting the release of the neurotransmitters dopamine and norepinephrine thus reducing pain, hunger and aggression. Constipation occurs, and the pleasure centers of the brain are stimulated causing euphoria. When injected, heroin is more psychologically depending than morphine due to the intense euphoria it produces.

Heroin is a white powder that has a bitter taste. Of the more than one dozen opiate compounds that have been developed heroin represents a semisynthetic form of morphine that has been altered to increase its absorption. It crosses the blood-brain barrier more easily than morphine and produces a depressant effect three to four times more potent than morphine. Heroin, however, is first metabolized by reducing it to morphine. It is usually diluted with lactose (mild sugar). Heroin enters the country at about 95% purity. It is diluted for sale on the street to approximately three to five percent purity. A Mexican version of opiate known as black tar approaches 60 to 90% purity. Many addicts begin their habit by sniffing the powder or injecting it. When heroin is injected into a vein it scars and can eventually collapse.

The effects of heroin are often unpleasant. It is common to experience nausea, and vomiting after injecting the substance. Mannitol, a laxative, is often added to heroin to counteract its constipating effect. Heroin use usually progresses through two stages. In the first stage pleasure or euphoria is experienced. This is followed by a second stage in which the user is addicted and must continue the drug to prevent withdrawal symptoms.14

We possess natural opiate like substances in our brain. These are called enkephalins and endorphins. They are released in response to pain and pleasure related activities. They are naturally released by such activities as exercise, eating, and sexual activity. Smoking, alcohol and opiate use can also release the same response and artificially induce pleasurable sensations similar to those produced by these naturally occurring neurotransmitters.

Methadone is a synthetic from of heroin and is equal in strength to morphine when injected. When it is taken in a high enough concentration it blocks the euphoria produced by heroin. The oral ingestion of methadone suppresses the physical symptoms of morphine and heroin withdrawal and has the advantage of not inducing euphoria. Injection of methadone, however, can induce euphoria similar to heroin. For this reason methadone is formulated with inert ingredients to limit its abuse. Methadone takes approximately 24 hours to metabolize compared to eight for heroin. Experimental use with a drug called LAAM (levo-ampha-actylmethadol), which is longer lasting has made it easier for addicts to function in their jobs and gives them more independence than methadone maintenance programs.16

Chronic Use. Chronic intake of opiates such as morphine or heroin leads to tolerance, physical and psychological dependence. There is a clear lack of any brain or organ damage from opiate use in contrast to chronic alcohol abuse. The deaths that do occur are often associated with robbery, suicide, infections and poor quality control over the drug.37 A significant danger from chronic morphine and heroin use occurs with people who administer the drug intravenously. The increased number of deaths associated with intravenous use is often related to infected needle sharing.

Overdose. Morphine and related opiate overdose results in severe respiratory depression. The use of the drugs naloxone and naltrexone are often administered as antagonists and counteract the overdose effect of opiates.

Side Effects. All depressant drugs interact with one another to produce significant sedation and respiratory depression. The sedative and pain reducing effects of opiates are intensified by the use of amphetamines. Opiate use can affect the metabolism of a wide variety of drugs because the opiate drugs require the same liver enzymes for their metabolism resulting in the accumulation of a significant amount of the other drugs for the liver to breakdown.

Withdrawal. It is very unlikely that opiate withdrawal will result in circulatory collapse or death as it does in alcohol and barbiturate withdrawal.11 The heroin withdrawal symptoms start within 6 hours of the last dose and within 24 hours for morphine. They produce anxiety, relentlessness, irritability and craving for the drug. Later a runny nose, tears, and minor stomach cramps, vomiting, joint pains, weakness, goose bumps and insomnia appear.30 In general the more rapid the beginning of withdrawal (as with heroin verses morphine) the more severe are the symptoms and the quicker they subside. Within twelve to 48 hours all appetite is lost. Vomiting may occur, the person may feel chills and cramps, and develop goose pumps over the body. Within two to four days the bones and muscles still ache and muscle spasms continue. The worst is over in approximately five days. If death occurs from heroin use it is usually associated with the combined use of alcohol or barbiturates. Withdrawal is often reported as painful. Antagonist drugs given in the withdrawal process increase painful symptoms because the severity of the withdrawal depends on how rapid the number of opiate receptors are reduced and they reduce the number quickly.

Unique Aspects. Opiates are the most effective drugs for relieving pain even at low doses and do not significantly affect the ability to feel, see or experience other stimuli. This makes morphine and heroin unique in comparison to alcohol and barbiturates which relieve pain but at doses that impair performance, emotional control and the ability to think. In some cases opiates have been used to relieve the pain of people suffering from terminal illnesses such as cancer. Opiates can cause potentially lethal alterations in heartbeat, depressed respiration, coma, and death due to respiratory failure. They also constrict the pupils and suppress the cough reflex. Opiates appear to release histamine which causes itching and inflammation at the injection sites and significantly decrease stomach acids and intestinal contractions that result in significant constipation. Opiates have also been used to alleviate the symptoms of diarrhea.

Barbiturates

History. Barbiturates are sedative-hypnotics. They were first introduced in 1903 and their numbers expanded to over 2500 different variations. They have a wide variety of effects that range from mild sedation to sleep and coma. Their sedative effect decreases physical and mental activity and reduces excitement. The hypnotic effect causes drowsiness and sleep from which the person can be easily aroused.18 The general depression of central nervous system makes them useful in treating epilepsy. They are divided into short (lasting two to three hours), intermediate (five to six hours) and long acting (six to ten hours) substances. Short-acting barbiturates are represented by the drugs Amytal and Seconal and Luminal represents the long-acting barbiturates.

Methods of Administration. Barbiturates are generally taken in tablet form or can be injected.



Effects. The effects barbiturates produce depend on how rapidly they are absorbed, metabolized. They are usually taken orally because they are rapidly absorbed and intramuscular injection causes irritation at the site of injection. The duration of the drug effects can vary between eight and 120 hours. The slow metabolism of most barbiturates motivates the user limit its use to once a night because there is a carryover of the drug effects to the next day.24

In low doses heart rate, blood pressure and respiration are reduced and anxiety gives way to a calm feeling. They are also taken to alleviate insomnia and the effects of epilepsy. Barbiturates, however, interfere with REM (rapid eye movement) sleep by decreasing the time spent in REM, the number of cycles and the quality of REM activity. This phase of sleep accounts for about one-quarter of a person's total sleep time. When we are deprived of REM sleep we become irritable and anxious. As rapid tolerance develops to barbiturates the total sleep time may be reduced by half within a two week period thus requiring more time to fall asleep and shortening the total sleep time. The person may become anxious as a result of not getting enough sleep and returns to taking barbiturates to solve the problem.

The rate of barbiturate elimination from the body depends upon how quickly the drug is metabolized by the liver. Barbiturates may cause liver damage and hormone imbalances as they interact with liver enzymes. Even the short acting barbiturates are not completely removed from the body by the next day which allows them to cause a hangover effect involving mood changes, decreased motor skills, hyperactivity, nausea and vomiting. The longer acting barbiturates pose a greater chance of hangover effect because they are metabolized more slowly. Continued barbiturate use has a cumulative effect on the central nervous system that is more life threatening than the opiates. It is believed that barbiturates cause their effects by stimulating the same receptors as tranquilizers. This also means that barbiturates will have cross tolerance and cross dependency with the tranquilizers. If taken in large doses or in combination with alcohol or other depressant drugs effects are potentiated and can result in death. They further affect the nervous system by depriving the neurons of glucose (the neuron's most usable source of energy) resulting in calmness, drowsiness, or sleep.

Chronic Effects. One of the effects of chronic barbiturate use is a reduction in short and long-term memory. If barbiturate use is stopped there is a good chance of recovery from these diminished memory effects.36 The slow metabolism and rapid tolerance to barbiturates helps produce tolerance, psychological and physical dependence. There is also a reduction in the reinforcing effect due to the rapid development of tolerance. The sleep inducing effects of barbiturates can be reduced as much as 50% within a two week period.1 Physical dependence, psychological dependence, and tolerance can develop with prolonged barbiturate use.

Overdose. Barbiturate overdose represents a life-threatening situation. There is no specific anecdote for barbiturate overdose and the use of stimulants to counteract the effects results in the possibility of higher death rates. The shorter acting barbiturates have greater potential for overdose because they are rapidly absorbed and eliminated. In severe intoxication the person appears comatose (semi- conscious)with reduced reactions, slow, rapid and shallow breathing and has a high likelihood of collapse of their circulatory system.29

Side Effects. Consuming low to moderate levels of barbiturates cause effects similar to equal amounts of alcohol but with less potential for aggressiveness and violence. In contrast with alcohol there is no dilation of blood vessels in the extremities, no increase of stomach secretions and therefore less negative effects on vitamin absorption, less chance of the development of ulcers and no increase in urine production. Although the drowsiness symptoms may last only a few hours the residual depression similar to a hangover continues into the next day. This residual effect should alert machine operators about deteriorated mental performance which may occur the day after barbiturate use.

Withdrawal. Barbiturate withdrawal is very similar to alcohol withdrawal. The withdrawal can be associated with seizures thus withdrawal should only be attempted under medical supervision. The severity of the withdrawal symptoms are directly related to the speed at which drug is removed from the body. The withdrawal often leaves the person feeling sick and having sensations of feeling hot and cold.

Unique Aspects. Most prescriptions for barbiturates are made for people suffering from anxiety and insomnia. They are also used as a general anesthetic. They have valuable medical use in preventing convulsions caused by epileptic seizures and convulsions arising from cocaine use, tetanus, and cerebral hemorrhages. The release of inhibitions produced by the drug may result in extreme antisocial behavior. Their effect can be lethal when combined with alcohol.

Methaqualone is a non-barbiturate sedative-hypnotic. It was synthesized in India as an anti-malaria drug but proved to be a better sedative and gained popularity as a non-barbiturate sleeping pill. When it was first prescribed in the United States in 1965 it had already developed a reputation in Europe as a euphoriant and aphrodisiac and was called the love drug . It gave a heroin-like high without drowsiness. Quaaludes and Sopors are examples of popular brands of methaqualone. In 1973 it was rated a schedule II drug and presently has been removed from the market. It is still widely abused. It produces an effect that lasts between 20-40 hours. Methaqualone has the benefit over barbiturates of having a less dramatic effect on REM sleep and creates a euphoria without the drowsiness associated with barbiturates. Illicit dosage ranges from 75 mg to 2 grams a day. It has a very quick and rapid absorption with over 90% of it absorbed within two hours.22 Its effects last approximately one hour. Common side effects of methaqualone use includes fatigue, dizziness, dryness of the mouth, nausea and vomiting, anorexia, sweating and a hangover-like effect. They are often taken with alcohol to increase their sedative effect although severe central nervous system depression results from this drug combination.

Minor Tranquilizers

History. Tranquilizers were first synthesized in the 1930s and were first used to tame animals when it was learned that they had muscle relaxant and sedative properties. They were marketed in the United States in the 1950s and 1960s. At this time the major sedative-hypnotics that were available included barbiturates, alcohol and meprobamate; all which posed problems such as excessive sedation, intoxication and physical dependence.38 Barbiturates especially showed negative side effects in the elderly, the population most frequently needing such medication. Since that time several analogues including valium, librium and xanax have been introduced. They have been marketed as the drug of choice in the management of anxiety, to induce sleep, insomnia, and stress related conditions. More tranquilizers are sold in the United States than barbiturates, amphetamines, and opiates combined.

Methods of administration. Tranquilizers can be ingested in tablet form or injected intramuscularly.

Effects. Minor tranquilizers are prescribed to produce the selective effect by relieving anxiety, tension, mental excitement, muscle tension, convulsions, and insomnia without producing significant side effects. Euphoria results from the administration of 100-150 mg. a day. They have a sedative effect but also have a wider range of safety than do the barbiturates. The drug is distributed slowly and takes about four to eight hours to reach peak levels. Two milligrams a day can effectively treat anxiety while 40 mg a day may be necessary to treat alcohol withdrawal. Approximately four months is the typical cut off point for treatment with many minor tranquilizers.9 These drugs affect the part of the brain that controls emotions. The brain has specific receptors for Valium and Librium even though no natural neurotransmitter is excreted by the body for these receptor sites. They are very lipid soluble which allows rapid penetration into the brain. Because these drugs are most often prescribed for lengthy periods their long term effects are important. They seem to work by enhancing the effect of GABA (gamma-aminobutyric acid) which raises the threshold needed for excitation thus inducing muscle relaxation. GABA impedes the firing of neurons in many parts of the central nervous system, especially in the cerebral cortex.34 Minor tranquilizers also cause an anticonvulsant effect and lower stress reactions. It is thought that the selective effect on GABA helps explain their wide range of safety and presumably nonlethal safety from overdose.23 Tranquilizers potentiate the effect of alcohol markedly.

In higher doses the minor tranquilizers resemble barbiturates in their ability to impair higher mental functions and skill related activities such as operating machinery. Intravenous injection has been shown to cause memory loss.

Chronic Effects. Psychological dependence, physical dependence and tolerance all develop to the use of these drugs. The psychological dependence may be mild in many cases and the craving and related drug seeking behavior is less pronounced than with the barbiturates. Since these drugs remain in the body for at least a day cumulative effects can commonly occur if they are taken in daily doses.

Overdose. In larger doses the sedative effect changes to a hypnotic (sleep inducing) effect causing tiredness, drowsiness, and a feeling of detachment that is very similar to sleep walking. Headaches, dizziness, ataxia (sensation of the body swaying), confusion and disorientation occur and profoundly affect the elderly.8 Due to the fact that these drugs are so widely prescribed they are also frequently associated with suicide attempts. However, adults who attempt suicide do not usually die unless the drug is taken in conjunction with other depressants such as alcohol.

Side Effects. Side effects from taking minor tranquilizers include drowsiness, feeling sluggish, skin rashes, diminished sex drive, and an increase in the sensitivity to alcohol. The weight gain is often due to stimulation of the appetite. Valium and Librium do not interfere with REM sleep to the extent that barbiturates do. However, prolonged use can cause exaggerated periods of extended REM sleep and insomnia. Although less common, weight gain and menstrual irregularities may occur. Patients who begin a course of treatment may experience initial hostility with children and women especially prone to this reaction. Children who use these drugs for situational anxiety such as the fear of going to school may experience intellectual impairment which may outweigh the emotional benefit obtained from their use. The side effects that occur increase with age, the length of use and the presence of liver disease.

Withdrawal. Very high doses in the range of 60 mg per day are necessary before withdrawal marked by convulsions or psychosis occur. Since these drugs have such a long duration of action withdrawal may not occur until three to six days.32 Abrupt withdrawal can typically result in anxiety, agitation, insomnia, tension and restlessness and may not become apparent for several hours.25 Perceptual disturbances consisting of an oversensitivity to loud sounds or bright lights and strange smells also occur.
Unique Aspects. Minor tranquilizers are very effective muscle relaxants and are often used to treat muscle spasms. Like barbiturates tranquilizers play an important role in the treatment of spasticity, epilepsy, tetanus and rabies to relieve muscle tenseness. They are also used in the control of withdrawal symptoms of alcohol, opiates, and barbiturates. They help ease discomfort during the withdrawal period and reduces the agitation and irritability experienced in the alcohol withdrawal. Because cross tolerance exists with alcohol large doses are often needed by the chronic alcoholic to suppress withdrawal symptoms. Tranquilizers can be substituted for alcohol in the alcoholic, especially those that drink to dampen their anxiety. These drugs are commonly used to relieve anxiety but do not relieve the underlying problem that causes it.

Major Tranquilizers

History. Prior to the introduction of major tranquilizers the treatment of mental patients ranged from imprisonment, death, physically binding them, dunking them in ice water, injecting them with insulin until they went into coma, lobotomizing and dosing them with a variety of prescription medications. It was a time when knives and forks could not be provided at meals. There were the seclusion rooms where nothing but a mattress and a single light bulb illuminated a creature, nude or in rags, paced like a caged animal. There was also the insulin suite and the lobotomy ward.5 One of the major problems of dealing with mental patients was violence that often involved beat- up patients and staff, rooms torn apart, windows broken and excrement thrown around.

The major tranquilizers are called antipsychotics or neuroleptics. They have been called the true tranquilizers because they produce a tranquil state without sedation or euphoria in people suffering from mental disorders. However, they are seldom abused by normal individuals because of their pronounced side effects.10

Some of the common major tranquilizers used today include Thorazine, Prolixin, Stelazine and Mellaril. Thorazine was marketed in 1955. Before this drug was introduced schizophrenia treatment of the mentally ill meant permanent hospitalization. Under Thorazine therapy withdrawn patients became active and hallucinations were diminished enough to allow hospital release. The use of major tranquilizers has dramatically affected the treatment of psychotic patients and dramatically decreased their length of hospitalization.

Methods of Administration. These drugs are taken in tablet form or intramuscularly when agitated patients need to be quickly tranquilized.

Effects. Major tranquilizers are used in the treatment of severe mental disorders such as schizophrenia, paranoia and depression because they induce reduced agitation, hyperactivity and clearer thinking. Hyperactivity diminishes rapidly and may be induced by a dopamine blocking action. In normal people this effect would induce sedation but in schizophrenic's it reduces hallucinations, confused thinking impulsiveness and disinterest in the surrounding environment with little agitation, aggression or anxiety.12 Intellect and insight remain unaltered.

Adequate dosage is imperative with these drugs. They are often misprescribed with an inadequate dose compromising its effectiveness and an overdose causing side effects. When the individual's symptoms stabilize the dosage is typically reduced to the lowest possible level to produce the desired effects. It may take three weeks or more for the individual to show a positive effect and up to six months of treatment for the drug to reach its full effectiveness in treating mental disorders. Absorption of the drug is fast, usually taking 10 to 30 minutes with the psychotic symptoms diminishing within several days or weeks.24 If the drug is discontinued the psychotic effects may not return for up to three months due to the long drug action. The action of these drugs are similar and the preference of a drug of choice is often dependent upon the degree of side effects they produce.

Chronic Use. Since they produce no euphoria they produce little or no psychological dependence. Tolerance develops very slowly to these drugs so when they are prescribed accurately they are used with a wide range of safety for long periods of time to treat mental disorders. Because of their long term use particular attention should be paid to the side effects.21

Overdose. Generally the safety margin between a therapeutic dose and an overdose is wide. If overdose occurs the effects include lowered blood pressure, temperature irregularities, seizures, sleepiness and respiratory depression.

Side Effects. Minor side effects include a photosensitivity in which the person can easily sunburn, a halt in the menstrual cycle, weight gain, gynecomastia (development of breasts) and galactorrhea of the production of breast milk. The accumulation of the drug in the eyes can cause a change in eye color and diminish vision.15 Persistent dry mouth, low blood pressure, weight gain and constipation are common. One of the chief side effects of these drugs is a condition similar to parkinson's disease which produces muscle rigidity and tremor, difficulty in walking often characterized by short shuffling steps and a facial expression that is fixed and shows no emotional response. Other side effects include a condition known as akathisia which is a restless desire to move and is associated with tapping their feet and rocking back and for. These symptoms are often mistaken for anxiety. Another condition that can occur is called tardive dyskinesia. This condition is permanent and includes symptoms such as quivering upper lips, lip smacking and puckering and flailing of the limbs. Often these antipsychotic drugs will be discontinued to prevent or reduce the effects of tardive dyskinesia.19

Withdrawal. Withdrawal is unlikely because of the extended presence of the drug that may last up to a year. This significantly diminishes the possibility of physical dependence. Muscle discomfort and difficulty in sleeping have been reported if the drug is abruptly discontinued.

Unique Aspects. The drugs have a unique benefit in delaying ejaculation which is beneficial to individuals who suffer from premature ejaculation, in relieving severe itching, nausea, vomiting, severe hiccups and the symptoms of acute alcoholism. It should be emphasized that these drugs do not cure these conditions. The best treatment may be a combination of drug therapies, psychological help and a supportive environment that helps shape healthy behaviors. The most common cause of relapse in the schizophrenic patient in outpatient care is their failure to take their medication.


SUMMARY

Depressant drugs produce tolerance, physical dependence and psychological dependence and slow the functioning of the central nervous system. Alcohol is a sedative hypnotic whose effects range from mild relaxation and release of inhibitions to drowsiness and sleep. Ethyl alcohol is metabolized by special liver enzymes. This short term advantage is negated by the fact that the active liver cells transform to a fatty cell that can no longer perform it functions. Alcohol is the most immediate source of energy available to the body. Alcohol's affects on the brain include its detrimental affect on memory, reasoning, self-control, judgment, senses, coordination and the vital brain centers (breathing and respiration). Blood alcohol of .35 will have an effect equal to that of a surgical anesthetic. A Blood alcohol level of .40 will induce coma or death.

The naturally occurring opiates include opium, codeine, morphine, and heroin. The substance produces euphoria, and relaxation. They produce effects very similar to our body's own endorphins which are released when we experience pain and pleasure. Endorphins are naturally released by such activities as exercise, eating, and sexual activity. Smoking, alcohol use and opiate use artificially induce pleasurable sensations similar to those produced by the endorphins. Withdrawal from opiates is very severe. Methadone is a synthetic form of heroin. It suppresses the euphoric effects of heroin and is metabolized in 24 hours compared to eight hours for heroin.

Barbiturates have a wide variety of effects that range from relieving tension and anxiety to causing mild sedation and inducing sleep. Their use does interfere with REM sleep, the number of cycles and the quality of cycle. Chronic use results in temporary loss of short and long-term memory. Overdose can be life threatening. For this reason methaqualone was introduced to induce the same basic benefits of barbiturates but at the same time have a significantly less dramatic negative effect on REM sleep. But due to its abuse potential methaqualone was removed from the market.

Minor tranquilizers were developed in the 1950s to relieve anxiety, tension, convulsions, and insomnia without producing significant side effects. They affect the part of the brain that triggers emotions. They are able to produce a tranquil state without euphoria or sedation. Valium, Librium and Xanax are three of the most commonly known tranquilizers.

Major tranquilizers are neuroleptics or antipsychotics. They are used in the treatment of severe mental disorders such as schizophrenia. They help alleviate the symptoms of mental problems and facilitate therapy. They began a revolution in the treatment of schizophrenia, paranoia and psychotic patients.


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