/ther'euh pyooh"tiks/, n. (used with a sing. v.)
the branch of medicine concerned with the remedial treatment of disease.
[1665-75; see THERAPEUTIC, -ICS]

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Treatment and care to combat disease or alleviate pain or injury.

Its tools include drugs, surgery, radiation therapy, mechanical devices, diet, and psychiatry. Treatment may be active, to cure a disease (requiring no further treatment after recovery), treat it long-term, or heal a wound; symptomatic, to relieve symptoms until the immune system heals the body; supportive, to keep body functions going until the disease clears; or palliative, to minimize discomfort for patients with no chance of recovery. It almost always includes prevention, usually tertiary (see preventive medicine). Therapeutic measures can be chosen, combined, and tailored based on accurate diagnosis to fit each patient. See also alternative medicine; chemotherapy; holistic medicine; hydrotherapy; nuclear medicine; occupational therapy; physical medicine and rehabilitation; psychotherapy; respiratory therapy.

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      treatment and care of a patient for the purpose of both preventing and combating disease or alleviating pain or injury. The term comes from the Greek therapeutikos, which means “inclined to serve.”

      In a broad sense therapeutics means serving and caring for the patient in a comprehensive manner, preventing disease as well as managing specific problems. Exercise, diet, and mental factors are therefore integral to the prevention, as well as the management, of disease processes. More specific measures that are employed to treat specific symptoms include the use of drugs to relieve pain or treat infection, surgery to remove diseased tissue or replace poorly functioning or nonfunctioning organs with fully operating ones, and counseling or psychotherapy to relieve emotional distress. Confidence in the physician and in the method selected enhances effectiveness.

      The rationale for preventive medicine is to identify risk factors in each individual and reduce or eliminate those risks in an attempt to prevent disease. Primary prevention is the preemptive behavior that seeks to avert disease before it develops—for example, vaccinating children against diseases. Secondary prevention is the early detection of disease or its precursors before symptoms appear, with the aim of preventing or curing it. Examples include regular cervical Papanicolaou test screening and mammography. Tertiary prevention is an attempt to stop or limit the spread of disease that is already present. Clearly, primary prevention is the most cost-effective method of controlling disease.

      The five leading causes of death in the United States are cardiovascular disease, cancer, cerebrovascular disease, accidental injuries, and chronic lung disease. The single most preventable cause of death in the United States is cigarette smoking, which is linked to cardiovascular disease (heart attack), cancer (lung, larynx, bladder, pancreas, and so on), cerebrovascular disease (stroke), and chronic lung disease (emphysema, chronic bronchitis).

      Following earlier work by the Canadian Task Force on the Periodic Health Examination, the U.S. Preventive Services Task Force was established to evaluate the effectiveness of various screening tests, immunizations, and prophylactic regimens based on a critical review of the scientific literature. Its report, Guide to Clinical Preventive Services, lists the recommendations for the 60 target conditions evaluated by the panel.

       immunization is the best method for preventing infectious diseases. Standard immunizations of infants and children include those for diphtheria, tetanus, and pertussis (DTP); polio (OPV); measles, mumps, and rubella (MMR); Haemophilus influenzae type b (HbCV); and hepatitis B (HBV). A yearly vaccine against the influenza virus should be administered to adults who are older than (old age) 65 years of age, to those at risk because of chronic cardiopulmonary disease, and to those in chronic care facilities. Adults also should be immunized once at age 65 years against pneumococcal pneumonia with a vaccine containing 23 of the most common strains of Streptococcus pneumoniae (Table 4).

      Acquired immunodeficiency syndrome ( AIDS), caused by the human immunodeficiency virus (HIV), is also a major infectious disease problem. Although a vaccine is expected, obstacles to its development are great. The only primary preventive measures currently available are either to abstain from sexual contact or to use condoms and, among intravenous drug users, to avoid sharing needles. Almost 25 percent of adult AIDS cases in the United States are related to infection from needles used to administer illegal drugs.

      The risk factors for coronary artery disease (coronary heart disease) that can be modified to prevent myocardial infarction are cigarette smoking, hypertension, an elevated serum cholesterol level, a sedentary lifestyle, obesity, stress, and excessive alcohol consumption. In addition to an elevated total serum cholesterol level, an elevated low-density lipoprotein (LDL) level and a decreased high-density lipoprotein (HDL) level are significant risk factors. The total cholesterol level and elevated LDL level can be reduced by appropriate diet, whereas a low HDL can be raised by stopping smoking and increasing activity. If these measures do not provide adequate control, a variety of drugs capable of lowering the cholesterol level are available.

      The major risk factor for stroke is hypertension, with cigarette smoking and diabetes mellitus significantly increasing the risk. Transient ischemic attacks (TIAs) occur before stroke in 20 percent of patients and consist of sudden onset of one or more of the following symptoms: temporary loss of vision in one eye, unilateral numbness, temporary loss of speech or slurred speech, and localized weakness of an arm or leg. Attacks last less than 24 hours and resolve without permanent damage until the stroke occurs.

      The most important preventive behaviour in averting cancer is the avoidance of cigarette smoke. Smoking accounts for 30 percent of all cancer deaths, and there is increasing recognition of the danger of environmental or sidestream smoke to the nonsmoker. Primary prevention of skin cancer includes restricting exposure to ultraviolet light by using sunscreens or protective clothing. Secondary preventive measures include mammography, clinical breast examinations, and breast self-examinations for breast cancer; pelvic examinations and Papanicolaou tests for cervical and ovarian cancer; and sigmoidoscopy, digital rectal examinations, and stool tests for occult blood for colorectal cancer.

      Demineralization of bone and a reduction in bone mass ( osteoporosis) occur most often in men and women age 70 or older and may result in fractures, low back pain, and loss of stature. Osteoporosis in postmenopausal women that is caused by estrogen deficiency is the most common manifestation. The most effective method for preventing loss of bone mass after menopause is estrogen replacement therapy and increased calcium intake. Primary preventive measures include increasing physical activity and avoiding cigarettes and heavy alcohol consumption.

      Alcohol abuse (alcoholism) is the primary reason that accidents are the fourth leading cause of death in the United States. Other factors are failure to wear seat belts or motorcycle helmets, sleep deprivation, and guns in the home. Taking reasonable precautions and being aware of the potential dangers of alcohol and firearms can help reduce the number of deaths due to accidents.

Treatment of symptoms

      Pain is the most common of all symptoms and often requires treatment before its specific cause is known. Pain is both an emotional and a physical experience and is difficult to compare from one person to another. One patient may have a high pain threshold and complain only after the disease process has progressed beyond its early stage, while another with a low pain threshold may complain about pain that would be ignored or tolerated by most people. Pain from any cause can be increased by anxiety, fear, depression, loneliness, and frustration or anger.

      Acute pain serves a useful function as a protective mechanism that leads to the removal of the source of the pain, whether it be localized injury or infection. Chronic pain serves a less useful function and is often more difficult to treat. Although acute pain requires immediate attention, its cause is usually easily found, whereas chronic pain complaints may be more vague and difficult to isolate.

      The ideal method for treating pain is to eliminate the cause, such as to surgically remove an inflamed structure, to apply hot compresses to a muscle spasm, or to set a fractured bone in a cast. Alternatives to drug therapy, such as physical therapy, should be relied on whenever possible. The analgesic drugs most often used to alleviate mild and moderate pain are the nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, acetaminophen, or indomethacin. If these are ineffective, a weak opiate (narcotic) such as codeine, hydrocodone, or oxycodone would be the next choice. Severe pain not controlled by these agents requires a strong opiate such as morphine or meperidine. Because opiates are addictive, their use is controlled by the Controlled Substances Act, and individuals prescribing or dispensing these drugs must register annually with the Drug Enforcement Administration. Each drug is assigned to one of five groups, from schedule I, which includes drugs that have the highest potential for abuse, to schedule V, which includes drugs with a limited dependence-causing potential.

      Nausea and vomiting are common symptoms that may arise from diseases of the gastrointestinal tract, including gastroenteritis or bowel obstruction, from medications, such as analgesics or digoxin, or from nervous system disturbances such as migraine headaches or motion sickness. Vomiting is controlled by a vomiting centre located in the medulla oblongata of the brain stem.

      Identifying and treating the cause is important, especially if the condition responds well to treatment and is serious if not addressed. A bowel obstruction can occur as a result of adhesions from previous abdominal surgery. Obstruction or decreased bowel motility also can occur with constipation and fecal impaction. Such important and treatable causes must be ruled out before resorting to antiemetic (serving to prevent or cure vomiting) drugs. The most frequently used antiemetic agents are the phenothiazines, the most popular being prochlorperazine (Compazine [trademark]). Antihistamines may be useful in motion sickness, but newer and more powerful drugs are needed to control the vomiting associated with cancer chemotherapy. Ondansetron is given to patients undergoing cancer chemotherapy, surgery, or radiation therapy with agents that cause severe nausea and vomiting. This drug is very effective in these patients.

      Nausea and vomiting are experienced by more than 50 percent of pregnant (pregnancy) women during the first trimester. These symptoms are referred to as morning sickness, although they can occur at any time of the day. They may be distressing, but they cause no adverse effect on the fetus. Drug therapy is not only unnecessary; it should be avoided unless proved safe for the fetus. Treatment involves rest and intake of frequent small meals and pyridoxine (vitamin B6).

      Acute diarrhea can result from food poisoning, laxatives, alcohol, and some antacids but usually is caused by an acute infection with bacteria such as Escherichia coli, Salmonella, and Staphylococcus aureus. In infants, acute diarrhea is usually self-limiting, and treatment consists primarily of preventing dehydration. Traveler's diarrhea affects up to half of those traveling to developing areas of the world. Preventive measures include chewing two tablets of bismuth subsalicylate (Pepto-Bismol [trademark]) four times a day, drinking only bottled water or other bottled or canned beverages, and eating only fruits that may be peeled, canned products, and restaurant food that is piping hot. Avoiding dairy products, raw seafood and vegetables, and food served at room temperature also limits exposure. Severe cases require antibiotic therapy.

      Coughing is a normal reflex that helps clear the respiratory tract of secretions and foreign material. It also can result from irritation of the airway or from stimulation of receptors in the lung, diaphragm, ear (tympanic membrane), and stomach. The most common cause of acute cough is the common cold. Chronic cough is most often caused by irritation and excessive mucus production that results from cigarette smoking or from postnasal drainage associated with an allergic reaction.

      Treatment includes humidification of the air to loosen secretions and to counteract the drying effect of coughing and inflammation. Moist air from a vaporizer or a hot shower helps, as do hot drinks and soups. Antihistamines (antihistamine) are often used to treat acute cough, but their value is questionable if an allergy is not present. They may also cause additional drying of the respiratory mucosa. Guaifenesin is widely used in cough preparations to help liquefy secretions and aid expectoration. Decongestants (decongestant) reduce secretions by causing vasoconstriction of the nasopharyngeal mucosa. The most common decongestants found in many cough preparations are pseudoephedrine, phenylephrine, and phenylpropanolamine. They may cause high blood pressure, restlessness, and urinary retention and should be used with caution in anyone being treated for hypertension. Narcotics are powerful cough suppressants, codeine being the most frequently used. Several safer nonnarcotic antitussive (cough-preventing) agents are available such as dextromethorphan, which has almost equal effectiveness but fewer side effects. Most cough preparations containing dextromethorphan also contain a decongestant and an expectorant. Because coughing is an important defense mechanism in clearing secretions from blocked airways, a productive cough (one that produces secretions) should not be suppressed.

      Insomnia is a difficulty in falling asleep or the feeling that sleep is not refreshing. Transient insomnia occurs when there are stressful life events or schedule changes, as shift workers or those who travel across multiple time zones experience. A disturbed sleep can also be related to the intake of stimulating drugs, anxiety, depression, or medical conditions associated with pain. Anxiety usually causes difficulty in falling asleep, whereas depression is associated with early morning awakening. The elderly spend less time sleeping, and their sleep is lighter and marked by more frequent awakenings. This situation is exacerbated by afternoon napping.

      The treatment of insomnia involves establishing good sleep hygiene: maintaining a consistent schedule of when to retire and awaken, setting a comfortable room temperature, and minimizing such disruptive stimuli as noise and light. Daily exercise is beneficial but should be avoided immediately before bedtime. Stimulants should be avoided, including nicotine and caffeine. Alcohol (alcohol consumption) disrupts the normal sleep pattern and should also be avoided. Drinkers sleep more lightly and frequently awaken unknowingly, which leaves them feeling unrefreshed the next day.

      When medication is required, physicians usually prescribe one of the sleep-inducing benzodiazepines. They may have long-, intermediate-, or ultrashort-acting effects. None should be used regularly for long periods. Various nonbenzodiazepine hypnotics and sedatives are also available, and their usefulness varies according to individual preference.

Designing a therapeutic regimen
      Once the physician makes a diagnosis or identifies the most likely cause of the symptoms and decides on the appropriate treatment, an entirely new set of conditions becomes operative. One of the first conditions to be considered is the patient's reason for seeking medical advice and the patient's expectations. The patient's visit may have been precipitated by the discovery that a friend's minor symptom, similar in nature to one the patient has been experiencing, proved to be something serious. If tests can rule out this possibility, reassurance may serve as a therapeutic action. When possible, physicians work to cure a disease and thereby relieve the symptoms, but many times the disease is unknown or chronic and incurable. In either case, relief from or improvement of symptoms or restoration of normal functioning is the goal. When neither a cure nor complete relief of symptoms is possible, an explanation of the disease and knowledge of the cause and what to expect may provide significant relief. Patients often want to know the name of the disease, what caused it, how long it will last, what additional symptoms may occur, and what they can do to assist the physician's treatment to hasten recovery. Providing information about the disease can help to alleviate anxiety and fears that could otherwise impede the patient's progress.

      An essential ingredient of any successful therapeutic regimen is the positive attitude of the patient toward the physician. A relationship of trust and respect for the physician based on reputation or years of supportive care is one of the physician's most powerful therapeutic tools.

      When selecting a management plan, the physician usually has several options, and the outcomes or consequences of each will vary. Often, the best choice is one made together with the patient, who may have definite preferences for a trial of therapy over further testing or for oral medication rather than an injection, even if the latter would provide more rapid relief. The possible side effects of the medicine or treatment may well influence therapeutic choice, such as if a person would prefer dizziness to nausea. Once a course of therapy is selected, a new decision tree arises that leads to new options, depending on the response. Further testing, increasing the dose of medication, or changing to a new drug may be required. Almost every treatment has some degree of risk, from either unwanted side effects or unexpected complications. The physician describes these risks in terms of probability, expecting the patient to accept or reject the treatment based on these odds and his or her willingness to suffer the side effects or to risk the complications to achieve relief.

      Another factor affecting therapeutic success is patient compliance—the degree to which patients adhere to the regimen recommended by their physician. Therapeutic regimens that require significant changes in lifestyle, such as recommendations to follow a special diet, begin an exercise program, or discontinue harmful habits like smoking cigarettes, are likely to result in poor compliance. Also, the greater the number of drugs prescribed and the more complicated the regimen, the poorer is the compliance. A patient is much more likely to successfully follow a regimen of taking a single dose of medication daily than one prescribed four times daily. Patients also may not fully realize the need to continue taking the medication after their symptoms have subsided, despite a physician's instruction to finish the medicine. Patient compliance may be most difficult to achieve in chronic but generally asymptomatic illnesses such as hypertension. Patients who experience no symptoms may need to be convinced of the necessity of taking their medication daily to prevent the occurrence of an untoward event (in hypertension, a stroke or other cardiovascular problems). Similarly, patients with depression or anxiety may want to discontinue medication once their symptoms abate. Until a relapse occurs, they may not recognize the need to continue taking the medication until instructed to taper the dosage slowly.

      In deciding which therapeutic regimen is likely to be most effective, the physician must depend on scientific studies that compare one drug or treatment regimen with others that have been proved effective. The most dependable study is one that is truly objective and removes the possibility of bias on the part of the patient who wants the drug to work and the bias of the physician who may expect a certain outcome and subtly influence the interpretation. Such a study is “double-blind”: it controls for both possible tendencies by comparing an active drug with an inactive “look-alike” drug. Neither the patient nor the physician knows which drug the patient is taking, so that neither one's bias can influence the result. Although this is the best way to demonstrate the effectiveness of a drug, it is sometimes very difficult to control for all the variables that could influence the outcome, such as varying degrees of stress one group or another may be under. Physicians will use the results of a wide variety of studies similar to this study to decide whether a regimen or drug is likely to work in a given patient; however, they will depend most heavily on their past experience with drugs or other techniques that have worked under similar circumstances. It is knowledge based on experience and on understanding of the patient that leads to the greatest therapeutic success.


Prophylactic measures of nutrition (nutrition, human)
General requirements
      Adequate nutritional intake is required to maintain health and prevent disease. Certain nutrients are essential; without them a deficiency disease will result. Required nutrients that cannot be synthesized by the body and therefore must be taken regularly are essential amino acids, water-soluble and fat-soluble vitamins, minerals, and essential fatty acids. The U.S. Recommended Dietary Allowances (RDAs), one of many sets of recommendations put out by various countries and organizations, have been established for these essential nutrients by the Food and Nutrition Board of the National Academy of Sciences (Table 5). These RDAs are guidelines and not absolute minimums. Intake of less than the RDA for a given nutrient increases the risk of inadequate intake and a deficiency disorder. Nutritional requirements are greater during the periods of rapid growth (infancy, childhood, and adolescence) and during pregnancy and lactation. Requirements vary with physical activity, aging, infections, medications, metabolic disorders (e.g., hyperthyroidism), and other medical situations. RDAs do not address all circumstances and are designed only for the average healthy person.

       protein, needed to maintain body function and structure, consists of nine essential amino acids that must be provided from different foods (food) in a mixed diet. Ten to 15 percent of calories should come from protein. The oxidation of 1 gram (0.036 ounce) of protein provides 4 kilocalories of energy. The same is true for carbohydrate, but fat yields 9 kilocalories.

      Carbohydrate provides about 45 percent of calories in the American diet, in the form of sugars, starches (complex carbohydrates), and dietary fibre (indigestible carbohydrates). Fibre is not digestible but increases the bulk of the stool and facilitates faster intestinal transit, which some believe reduces the risk of colon cancer by diminishing the time that cancer-producing substances in the diet remain in contact with the bowel wall. Increasing bulk also decreases the concentration of these substances. Dietary fibre can be insoluble (wheat bran) or soluble (oat bran and psyllium). Only the soluble fibres found in oats, fruit, and legumes lower blood cholesterol and benefit individuals with diabetes by delaying the absorption of glucose.

      The most concentrated source of energy is fat, the source of fat-soluble vitamins and essential fatty acids. Thirty-seven percent of calories in the American diet come from fat, but the ideal is closer to 30 percent. The average American diet also contains 450 milligrams daily of cholesterol, but less than 300 milligrams is recommended.

      The recommended daily diet as determined by the U.S. Department of Agriculture is called the Food Guide Pyramid and consists of 6 to 11 servings of bread, cereal, rice, or pasta; 3 to 5 servings of vegetables; 2 to 4 servings of fruit; 2 to 3 servings of fish, meat, poultry, dry beans, eggs, or nuts; and 2 to 3 servings of milk, yogurt, or cheese.

Requirements in infancy
      Nutritional needs are greatest during the first year of life. Meeting the energy demands during this period of rapid growth requires 100 to 120 kilocalories per kilogram per day. Breast milk, the ideal food, is not only readily available at the proper temperature, it also contains antibodies from the mother that help protect against disease. Infant formulas closely approximate the contents of breast milk, and both contain about 50 percent of calories from carbohydrate, 40 percent from fat, and 10 percent from protein.

      Breast milk or commercial formula is recommended for the first six months of life and may be continued through the first year. Solid foods are introduced at four to six months of age starting with rice cereal and then introducing a new vegetable, fruit, or meat each week. Cow's milk should not be given to infants younger than six months of age, and low-fat milk should be avoided throughout infancy because it does not contain adequate calories and polyunsaturated fats required for development. Additional iron and vitamins should be given, especially to infants at high risk of iron deficiency, such as those with a low birth weight.

      Toddlers are usually picky eaters, but attempts should be made to include the following four basic food groups in their diet: meat, fish, poultry, or eggs; dairy products such as milk or cheese; fruits and vegetables; and cereals, rice, or potatoes. Mealtime presents an excellent opportunity for social interaction and strengthening of the family unit. This starts with the bonding between mother and child during breast-feeding and continues as a source of family interaction throughout childhood.

Requirements in adolescence
      Nutritional needs during adolescence vary according to activity levels, with some athletes requiring an extremely high-calorie diet. Other adolescents, however, who are relatively sedentary consume calories in excess of their energy needs and become obese. Peer pressure and the desire for social acceptance can profoundly affect the quality of nutrition of the adolescent as food intake may shift from the home to fast-food establishments.

       pregnancy during adolescence can present special hazards if the pregnancy occurs before the adolescent has finished growing and if she has established poor eating habits. Pregnancy increases the already high requirements for calcium, iron, and vitamins in these teenagers.

      Eating disorders such as anorexia nervosa and bulimia arise predominantly in young women as a result of biological, psychological, and social factors. An excessive concern with body image and a fear of becoming fat are hallmarks of these conditions. The patient with anorexia nervosa has a distorted body image and an inordinate fear of gaining weight; consequently she reduces her nutritional intake below the amount needed to maintain a normal minimal weight. Severe electrolyte disturbances and death can result. Bulimia (bulimia nervosa) is a behavioral disorder marked by binge eating followed by acts of purging (e.g., self-induced vomiting, ingestion of laxatives or diuretics, or vigorous exercising) to avoid weight gain.

Requirements of the elderly (old age)
      The elderly often have decreased intestinal motility and decreased gastric acid secretion that can lead to nutritional deficiencies. The problem can be accentuated by poorly fitting dentures, poor appetite, and a decreased sense of taste and smell. Although lower levels of activity reduce the need for calories, older persons may feel something is wrong if they do not have the appetite of their younger years, even if caloric intake is adequate to maintain weight. The reduction in gastric acid secretion can lead to decreased absorption of vitamins and other nutrients. Nutritional deficiencies can reduce the level of cognitive functioning. Vitamin supplementation, especially with cobalamin (vitamin B12), may be particularly valuable in the elderly.

      The diet of the geriatric population is often deficient in calcium and iron, with the average woman ingesting only half the amount of calcium needed daily. Decreased intake of vegetables can also contribute to various nutritional deficiencies.

       constipation, which is common in the elderly, results from decreased intestinal motility and immobility and is worsened by reduced fluid and fibre intake. The multiple medications that the elderly are likely to be taking may contribute to constipation and prevent the absorption of certain nutrients. Some drugs, such as the phenothiazines, may interfere with temperature regulation and lead to problems during hot weather, especially if fluid intake is inadequate.

Requirements in pregnancy
      The growing fetus depends on the mother for all nutrition and increases the mother's usual demand for certain substances such as iron, folic acid, and calcium, which should be added as supplements to a balanced diet that contains most of the other required nutrients. The diet of adolescent girls, however, is often deficient in calcium, iron, and vitamins. If poor nutritional habits have been established previously and are maintained during pregnancy, the pregnant adolescent and her fetus are at increased risk.

      In addition to avoiding junk foods, the pregnant woman should abstain from alcohol, smoking, and illicit drugs because these all have a detrimental effect on the fetus. Caution should be used in taking all over-the-counter medicines during pregnancy, including vitamin and mineral supplements. Although the average recommended weight gain during pregnancy is approximately 11.3 kilograms (25 pounds), the pregnant woman should be less concerned with a maximum weight gain than she is with meeting the nutritional requirements of pregnancy. Low weight gain (less than 9.1 kilograms) has been associated with intrauterine growth retardation and prematurity in the United States.

      Women who are breast-feeding should continue taking vitamin supplements and increasing their intake of calcium and protein to provide adequate breast milk. This regimen will not interfere with the mother's ability to slowly lose the weight gained during pregnancy.

Therapeutic measures of nutrition
      Changes in diet can have a therapeutic effect on obesity, diabetes mellitus, hypertension, peptic ulcer, and osteoporosis.

      About one-fourth of the American population meets the definition of obesity (20 percent above ideal body weight). Obesity occurs when the number of calories consumed exceeds the number that is metabolized, the remainder being stored as adipose (fat) tissue. Many theories address the causes of obesity, but no single cause is apparent. Multiple factors influence weight, including genetic factors, endocrine levels, activity levels, metabolic rates, eating patterns, and stress.

      The treatment of obesity requires reducing calorie intake while increasing calorie expenditure ( exercise). Because obesity is a chronic illness, it requires long-term lifestyle changes unless surgery is performed to effect permanent changes in the digestion of food. Thus fad diets, no matter how effective they are in the short term, remain inadequate for long-term weight control. A reduction in calorie intake of 500 kilocalories per day should lead to a loss of 0.45 kilogram (1 pound) per week. This reduction can be increased by greater calorie reduction or an accompanying exercise program. With exercise, the weight loss will be primarily fat, whereas without it, muscle is lost as well. Exercise also leads to a “positive” addiction that makes it easier to sustain regular exercising for long periods. It reduces the risk of heart disease and can improve self-esteem.

      Weight-reduction diets for the obese individual should be similar to those used by nonobese persons but with fewer calories—namely, a low-fat diet that avoids high-calorie foods. One of the most popular and successful of these diets is the very-low-calorie diet (VLCD) that results in rapid fat loss while minimizing the loss of lean muscle tissue. These diets require supplementation with potassium and a vitamin-mineral complex. Fad diets that eliminate one foodstuff, such as carbohydrate or protein, may give short-term results but fail in the long term to maintain the weight loss. Furthermore, these diets can lead to medically significant problems, such as ketosis (a buildup of ketones in the body).

      Appetite-suppressing drugs have limited short-term and no long-term effectiveness. surgery can provide long-term benefits but it is an option only to those at least 45.3 kilograms heavier than their ideal body weight who are willing to suffer the common complications. The most frequently performed procedures are vertical banded gastroplasty and gastric bypass, both of which effectively reduce the size of the stomach.

      Diet is the cornerstone of diabetic treatment whether or not insulin is prescribed. The goal is to regulate the patient's blood glucose level to as close to normal as possible and for the patient to achieve and maintain an ideal weight. Refined and simple sugars are avoided, and saturated fat is reduced by focusing the diet on poultry and fish rather than meat as a major source of protein. Soluble fibre such as that found in beans and oatmeal is recommended in contrast to the insoluble fibre found in wheat and bran. Artificial sweeteners are effective low-calorie replacements for simple sugar. The American Diabetes Association's recommendations are similar to those of the American Heart Association—that is, adhering to a balanced diet with restricted saturated fat intake while maintaining normal weight. Three or four meals of equal caloric content are spaced throughout the day, especially when supplemental insulin is needed.

      Many patients with hypertension benefit from a low-sodium diet (reduced sodium chloride [table salt] intake) and physicians often recommend this as part of the initial therapy for hypertension. If alterations in diet fail to counteract the hypertension, drugs such as diuretics may be prescribed along with potassium supplements (because most diuretics may deplete potassium). Other dietary measures are directed toward achieving an ideal body weight because obesity contributes to hypertension and increases the risk of cardiovascular disease. An adequate low-sodium diet can be achieved with a no-added-salt diet—that is, no salt is added to food after preparation, and foods with a high-sodium content such as cured meats are avoided. Low-sodium diets should be combined with increased potassium, which can be obtained by eating fruits, especially bananas, and vegetables, or using salt substitutes.

      In the past a bland diet and frequent ingestion of milk and cream were the mainstays of ulcer treatment. Today the only dietary regimen is the avoidance of such irritating foods as spicy and highly seasoned foods and coffee. The newer drug therapies decrease gastric acidity much more than antacids and other dietary measures do. The infection of the stomach by Helicobacter pylori is now recognized as a major factor in chronic gastritis and recurrent peptic ulcer in many patients. This bacterial infection requires a treatment regimen consisting of antibiotics and a bismuth-containing compound, which is different from the treatment of an ulcer that is not caused by H. pylori.

      Although little can be done to treat osteoporosis once it is established, a great deal can be accomplished to prevent it, as has been discussed above (see above Preventive medicine (therapeutics)). Osteoporosis, the loss of bone density, occurs in men and women older than (old age) 70 years of age and is manifested primarily in hip and vertebral fractures. It is most noticeable in postmenopausal women who have not taken estrogen. Estrogen replacement therapy, which should be combined with supplemental calcium, is most effective in decreasing bone resorption when begun during menopause, although it will provide some benefit if started later. In women who have an intact uterus, estrogen must be taken with progesterone to reduce the risk of endometrial cancer.

Biological therapy

blood and blood cells
      Blood transfusions (blood transfusion) were not clinically useful until about 1900 when the blood types (blood typing) A, B, and O were identified and cross-matching of the donor's blood against that of the recipient to prove compatibility became possible. When blood with the A antigen (type A or AB) is given to someone with anti-A antibodies (type B or O blood), lysis of the red blood cells (erythrocyte) occurs, which can be fatal. Persons with blood type O are universal red cell donors because this blood type does not contain antigen A or B; however, because type O blood contains antibodies against both A and B, patients with this blood type can receive only type O blood. Fortunately, type O is the most common blood type, occurring in 40 to 60 percent of people, depending on the selected population (e.g., 40 percent of the white population has blood type O, while 60 percent of Native Americans have it). Conversely, persons with type AB blood are universal recipients of red blood cells. Having no antibodies against A or B, they can receive type O, A, or B red blood cells.

      Most individuals are Rh-positive, which means they have the D antigen of the complex Rh system; approximately 15 percent of the population lack this antigen and are described as Rh-negative. Although anti-D antibodies are not naturally present, the antigen is so highly immunogenic (able to provoke an immune response) that anti-D antibodies will usually develop if an Rh-negative person is transfused with Rh-positive blood. Severe lysis of Rh-positive red blood cells will occur at any subsequent transfusion. The condition erythroblastosis fetalis, or hemolytic disease of the newborn, occurs when Rh-positive babies are born to Rh-negative mothers who have developed anti-D antibodies either from a previous transfusion or by maternal-fetal exchange during a previous pregnancy. The maternal antibodies cross the placenta and cause distress of the red blood cells of the fetus, often leading to severe hemolytic anemia and brain damage, heart failure, or death of the fetus. If an Rh-negative mother has not developed anti-D antibodies, she may be treated with Rho (D) immune globulin in the 28th week of pregnancy, when the therapy is most effective. Rho (D) immune globulin prevents the mother's immune system from recognizing the fetal Rh-positive blood cells. However, if the mother develops antibodies, the fetus and the mother must be closely monitored. If delivery occurs at the normal time following a full-length pregnancy, the infant may receive a blood transfusion to replace damaged or diseased red blood cells with healthy blood cells. Early delivery, however, is often necessary, and in severe cases, blood transfusion in the womb is performed.

      Whole blood, which contains red blood cells, plasma, platelets, and coagulation factors, is almost never used for transfusions because most transfusions only require specific blood components. It can be used only up to 35 days after it has been drawn and is not always available, because most units of collected blood are used for obtaining components.

      Packed red blood cells are what remains of whole blood after the plasma and platelets have been removed. A 450-millilitre unit of whole blood is reduced to a 220-millilitre volume. Packed red blood cells are used most often to raise a low hemoglobin or hematocrit level in patients with chronic anemia or mild hemorrhage.

      Leukocyte-poor red blood cells are obtained by employing a filter to remove white blood cells (leukocytes (leukocyte)) from a unit of packed red blood cells. This type of transfusion is used to prevent febrile (fever) reactions in patients who have had multiple febrile transfusion reactions in the past, presumably to white blood cell antigens. Removal of leukocytes from blood components is referred to as leukocyte reduction, or leukoreduction. In addition to lowering the risk of febrile transfusion reactions, leukoreduced blood components may have a decreased chance of transmitting cytomegalovirus, a member of the herpesvirus family, as well as other strictly cell-associated viruses. Transfusion using leukoreduced blood components also reduces the risk of immunization to white cells and to platelet antigens and perhaps reduces the risk of the immunosuppressive effects of transfusion.

      Platelet transfusions are used to prevent bleeding in patients with very low platelet counts, usually less than 20,000 cells per microlitre, and in those undergoing surgery or other invasive procedures whose counts are less than 50,000 cells per microlitre.

      Autologous transfusion is the reinfusion of one's own blood. The blood is obtained before surgery and its use avoids transfusion reactions and transfusion-transmitted diseases. Donation can begin one month before surgery and be repeated weekly, depending on the number of units likely to be needed. Intraoperative blood salvage is another form of autologous transfusion. The intraoperative blood salvage device recovers the shed blood, which is then anticoagulated, centrifuged to concentrate the red blood cells, and washed in a sterile centrifuge bowl. This salvaged blood (primarily washed red cells) can be rapidly infused into the patient during surgical procedures.

      Plasma, the liquid portion of the blood, is more than 90 percent water. It contains all the noncellular components of whole blood including the coagulation factors, immunoglobulins and other proteins, and electrolytes. When frozen, the coagulation factors remain stable for up to one year but are usually transfused within 24 hours after thawing. However, some of the clotting factors, such as factor VIII (or antihemophilic factor, AHF) and factor V, are very labile even after the plasma is frozen and require the addition of stabilizing substances (e.g., glycine) or the use of special freezing procedures. Fresh frozen plasma is used in patients with multiple clotting factor deficiencies, such as in those with severe liver disease or massive hemorrhage.

      Cryoprecipitate is prepared from fresh frozen plasma and contains about half the original amount of coagulation factors, although these factors are highly concentrated in a volume of 15–20 millilitres. Cryoprecipitate is used to treat patients with deficiencies of factor VIII, von Willebrand factor, factor XIII, and fibrinogen because it is rich in these factors.

      Specific clotting factor concentrates are prepared from pooled plasma or pooled cryoprecipitate. Factor VIII concentrate, the antihemophilic factor, is the preferred treatment for hemophilia A. A monoclonal antibody–purified human factor VIII is also available. Factor IX complex, the prothrombin complex, is also available for treating hemophilia B (factor IX deficiency).

Immunoglobulins (antibody)
      Immune serum globulin (ISG), obtained from the plasma of a pool of healthy donors, contains a mixture of immunoglobulins, mainly IgG, with lesser amounts of IgM and IgA. It is used to provide passive immunity to a variety of diseases such as measles, hepatitis A, and hypogammaglobulinemia. Intravenous immunoglobulins (IVIGs) provide immediate antibody levels and avoid the need for painful intramuscular injections.

      Hyperimmune serum globulin is prepared in the same way as the nonspecific immunoglobulin above but from patients who are selected because of their high titres of specific antibodies. Rh-immune globulin is given to pregnant Rh-negative women to prevent hemolytic disease of the newborn. Other hyperimmune serum globulins are used to prevent hepatitis B, tetanus, rabies, and varicella-zoster in exposed individuals.

Bone marrow transplantation (bone marrow transplant)
      Bone marrow transplantation does not involve the transfer of a discrete anatomic organ as occurs in other forms of transplantation, but it entails the same risk of rejection by the recipient, which is called graft-versus-host disease (GVHD). The main indications for bone marrow transplantation are leukemia, aplastic anemia, and congenital immunologic defects.

      Immunosuppressive drugs and irradiation are usually used to prepare the recipient. Close matching of tissue between donor and recipient is also essential to minimize GVHD, with autologous transplantation being the best method to avoid the disease (the patients donate their own marrow at times of remission to be used later). Allogeneic (homologous) bone marrow transplants by a matched donor (preferably a sibling) are the most common.

      Bone marrow transplantation initially was not recommended for patients older than 50 years of age, because of the higher mortality and morbidity that results and because the incidence of GVHD increases in those over age 30. However, in the United States many transplant centres have performed successful bone marrow transplantations in patients well beyond age 50. People who donate bone marrow incur no risk, because they generate new marrow to replace that which has been removed. General anesthesia is required, however, to aspirate the bone marrow from the iliac crests, which is then infused into the recipient.

Hematopoietic growth factors
      The hematopoietic growth factors are potent regulators of blood cell proliferation and development in the bone marrow. They are able to augment hematopoiesis when bone marrow dysfunction exists. Recombinant DNA technology has made it possible to clone the genes responsible for many of these factors. Some are commercially available and can be used to stimulate white blood cell (leukocyte) development in patients with neutropenia (a decrease in the number of neutrophilic leukocytes) associated with cancer chemotherapy.

      The first to be developed was erythropoietin, which stimulates red blood cell production. It is used to treat the anemia associated with chronic renal failure and that related to therapy with zidovudine (AZT) in patients infected with HIV. It may also be useful in reversing anemia in cancer patients receiving chemotherapy. Filgrastim (granulocyte colony-stimulating factor [G-CSF]) is used to stimulate the production of white blood cells, which prevents infection in patients whose white blood cells are diminished because of the effects of anticancer drugs. G-CSF also mobilizes progenitor, or stem, cells into the peripheral blood circulation. These cells can be harvested and used for bone marrow rescue. Another is sargramostim (granulocyte-macrophage colony-stimulating factor [GM-CSF]), which is used to increase the white blood cell count in patients with Hodgkin's disease or acute lymphoblastic leukemia who are undergoing autologous bone marrow transplantation.

Biological response modifiers
      Biological response modifiers, used to treat cancer, exert their antitumour effects by improving host defense mechanisms against the tumour. They have a direct antiproliferative effect on tumour cells and also enhance the ability of the host to tolerate damage by toxic chemicals that may be used to destroy the cancer.

      Biological response modifiers include monoclonal antibodies, immunomodulating agents such as the bacille Calmette-Guérin (BCG) vaccine used against tuberculosis, lymphokines and cytokines such as interleukin-2, and the interferons (interferon).

      The three major classes of interferons are interferon-α, produced by white blood cells; interferon-β, produced by fibroblasts; and interferon-γ, produced by lymphocytes. The interferons are proteins produced by these cells in response to viral infections or other stimuli; they have antiviral, antiproliferative, and immunomodulatory properties that make them useful in treating some viral infections and cancers. They do not act directly on the viruses but rather indirectly, increasing the resistance of cells to viral infections. This can be particularly useful in patients who have an impaired immune system and a diminished ability to fight viral infections, especially those with AIDS.

      Interferon-α is produced by a recombinant DNA (recombinant DNA technology) process using genetically engineered Escherichia coli. Recombinant interferon-α appears to be most effective against hairy-cell leukemia and chronic myelogenous leukemia, lymphoma, multiple myeloma, AIDS-associated Kaposi's sarcoma, and chronic type C hepatitis. It is moderately effective in treating melanoma, renal cell carcinoma, and carcinoid. It also can enhance the effectiveness of chemotherapy in some cancers. Unfortunately, treatment with this drug can be quite toxic.

      Interferon-γ may prove useful in treating a different set of diseases—for example, chronic conditions such as rheumatoid arthritis.

Hormones (hormone)
      The term hormone is derived from the Greek hormaein, meaning “to set in motion.” It refers to a chemical substance that has a regulatory effect on a certain organ or organs. There are sex hormones such as estrogen and progesterone, thyroid hormones, insulin, adrenal cortical and pituitary hormones, and growth hormones.

      Estrogens (estradiol, estone, and estriol) promote the growth and development of the female reproductive system—the vagina, uterus, fallopian tubes—and breasts. They are responsible for the development of secondary sex characteristics—growth of pubic and axillary hair, pigmentation of the nipples and genitals—and contribute to bone formation. The decrease in estrogen after menopause contributes to bone demineralization and osteoporosis, and hormone replacement therapy is often recommended to counteract this occurrence (see above Preventive medicine (therapeutics)). Postmenopausal estrogen also prevents atrophic vaginitis, in which the vaginal mucosa becomes thin and friable. Estrogens can be administered orally, through the skin (transdermally), vaginally, and intramuscularly.

      Progestins combined with estrogens comprise the oral contraceptives that inhibit ovulation by affecting the hypothalamus and pituitary. Progestin-only pills and injections are also effective contraceptives that work by forming a thick cervical mucus that is relatively impenetrable to sperm. Although the mortality associated with all forms of birth control is less than that associated with childbirth, this is not true for women older than the age of 35 years who smoke cigarettes. Their risk of stroke, heart attacks, and other cardiovascular problems is greatly increased, and the use of oral contraceptives is contraindicated. Levonorgestrel is a synthetic progestin that is implanted beneath the skin of the upper arm in six Silastic (trademark) capsules and provides birth control for five years.

      Androgens (androgen) consist of testosterone and its derivatives, the anabolic steroids. Testosterone is produced in the testes in males, and small amounts are produced by the ovary and adrenal cortex in females. Testosterone is used to stimulate sexual organ development in androgen-deficient males and to initiate puberty in selected boys with delayed growth. The anabolic steroids (anabolic steroid) are testosterone derivatives that provide anabolic activity with less stimulation of growth of the sexual organs. The use of anabolic steroids to increase muscle strength and endurance has been universally deplored by the medical community. This practice may have serious long-term effects such as the development of atherosclerotic disease because of effects on the blood lipids, especially the lowering of high-density lipoproteins. Their use in juvenile athletes can cause premature epiphyseal closure (early ossification of the growth zone of bones), compromising the attainment of their full adult height.

      Human chorionic gonadotropin (HCG) is a hormone produced by cells of the placenta that can be extracted from the urine of pregnant women days after fertilization and thus is used in the early detection of pregnancy. It is also used to stimulate descent of the testicles in boys with prepubertal cryptorchidism and to treat infertility in men with underdeveloped testicles. Because it can stimulate the thyroid, it was inappropriately thought to be useful in treating obesity; there is no clinical proof of its effectiveness in this application.

       growth hormone, produced by the pituitary gland, stimulates linear growth and regulates metabolic functions. Inadequate secretion of this hormone by the pituitary will impair growth in children (childhood disease and disorder), which is evidenced by their poor rate of growth and delayed bone age (i.e., slowed bone development). A synthetic preparation of the hormone is used to treat children who have a congenital deficiency of growth hormone.

      Adrenal corticosteroids (corticoid) are any of the steroid hormones produced by the adrenal cortex except for the sex hormones. These include the mineralocorticoids (aldosterone) and glucocorticoids (cortisol), the secretion of which is regulated by the adrenocorticotrophic hormone (ACTH (adrenocorticotropic hormone)) produced in the anterior pituitary. Overproduction of ACTH by the pituitary gland leads to excessive secretion of glucocorticoids from the adrenal gland, resulting in Cushing's syndrome. This syndrome also can result from an increased concentration of corticosteroids secreted by benign and malignant tumours of the adrenal gland; conversely, the production of an insufficient amount of adrenal corticosteroids results in primary adrenocortical insufficiency (Addison disease) (Addison's disease). The glucocorticoids are used primarily for their potent anti-inflammatory effects in rheumatic disorders, collagen diseases, dermatologic diseases, allergic disorders, and respiratory diseases and for the palliative management of leukemia and lymphoma. Cortisone and hydrocortisone are less potent than prednisone and triamcinolone, but dexamethasone and betamethasone have the greatest anti-inflammatory potency. Disadvantages of corticosteroid use include the masking of signs of infection, an increase in the risk of peptic ulcer, the development of edema and muscle weakness, loss of bone substance (osteoporosis), and glucose intolerance resembling diabetes mellitus.

       insulin, secreted by the pancreas, is the principal hormone governing glucose metabolism. Insulin preparations were extracted from beef or pork pancreas until recombinant DNA (recombinant DNA technology) technology made it possible to manufacture human insulin. Three preparations are available: rapid-acting (Regular, Semilente [trademark]), intermediate-acting (NPH, Lente [trademark]), and long-acting (PZI, Ultralente [trademark]). Other antidiabetic agents are available for treating non-insulin-dependent diabetes mellitus (NIDDM), also referred to as adult-onset diabetes, or type II diabetes. The sulfonylureas are oral hypoglycemic agents used as adjuncts to diet and exercise in the treatment of NIDDM.

      Thyroid hormones include thyroxine and triiodothyronine, which regulate tissue metabolism. Natural desiccated thyroid produced from beef and pork and the synthetic derivatives levothyroxine and liothyronine are used in replacement therapy to treat hypothyroidism that results from any cause.

Drug therapy

General features
Principles of drug uptake and distribution
      Study of the factors that influence the movement of drugs throughout the body is called pharmacokinetics, which includes the absorption, distribution, localization in tissues, biotransformation, and excretion of drugs. The study of the actions of the drugs and their effects is called pharmacodynamics. Before a drug can be effective, it must be absorbed and distributed throughout the body. Drugs taken orally may be absorbed by the intestines at different rates, some being absorbed rapidly, some more slowly. Even rapidly absorbed drugs can be prepared in ways that slow the degree of absorption and permit them to remain effective for 12 hours or longer. Drugs administered either intravenously or intramuscularly bypass problems of absorption, but dosage calculation is more critical.

      Individuals respond differently to the same drug. Elderly (old age) persons, because of reduced kidney and liver function, may metabolize and excrete drugs more slowly. Because of this and other factors, the elderly usually require lower doses of medication than do younger people.

      Other factors that affect the individual's response to drugs are the presence of disease, degree of nutrition or malnutrition, genetics, and the presence of other drugs in the system. Furthermore, just as the pain threshold varies among individuals, so does the response to drugs. Some people need higher-than-average doses; some, being very sensitive to drugs, cannot tolerate even average doses, and they experience side effects when others do not.

      Infants and children may have different rates of absorption than adults because bowel motility is irregular or gastric acidity is decreased. Drug distribution may be different in some people, such as premature infants who have little fatty tissue and a greater proportion of body water. Metabolic rates, which affect pharmacokinetics, are much higher during childhood, as anyone with a two-year-old can attest. The dosages of drugs for children are usually calculated on the basis of weight (milligrams per kilogram) or on the basis of body surface area (milligrams per square metre). If a drug has a wide margin of safety, it may be given as a fraction of the adult dose based on age, but the great variation in size among children of the same age complicates this computation. Children are not small adults, and drug dosages may be quite different than they are for adults.

      The elderly are particularly susceptible to adverse drug effects because they often have multiple illnesses that require their taking various medications, some of which may be incompatible with others. In addition to decreased renal and hepatic function, gastric acid secretion decreases with age, and arteriosclerosis narrows the arteries, decreasing blood flow to the intestines and other organs. The precautions followed in prescribing medication for the elderly are an excellent example of the principle that should govern all drug therapy—drugs should be used in the lowest effective dose, especially because side effects increase with concentration. Because of illness or frailty, elderly people often have less reserve and may not be able to tolerate minor side effects that younger adults might not even notice.

      When drugs are given in repeated doses, a steady state is achieved: the amount being administered equals the amount being excreted or metabolized. With some drugs, however, it may be difficult to determine the proper dose because of individual variations. In these cases, determining the plasma level of the drug may be useful, especially if the therapeutic window (i.e., the concentration above which the drug is toxic and below which it is ineffective) is relatively small. Plasma levels of phenytoin, used to control epilepsy; digitalis, prescribed to combat heart failure; and lithium, used to moderate bipolar disorder (traditionally called manic-depressive disorder), should be monitored.

Indications for use
      The purpose of using drugs is to relieve symptoms, treat infection, reduce the risk of future disease, and destroy selected cells such as in the chemotherapeutic treatment of cancer. The best treatment, however, may not require a drug at all. Recognizing that no effective medication exists is just as important as knowing which one to select. When more than one drug is useful, physicians should select the one that is most effective, least hazardous, and least expensive. A recently developed drug may promise better results, yet it will be less predictable and possibly more expensive. Every drug has multiple actions: it will affect organs and systems beyond those to which it is specifically targeted. Some patients may also experience idiosyncratic effects (abnormal reactions peculiar to that individual) as well as allergic reactions to certain drugs—additional reasons to select drugs carefully and avoid their use altogether when simpler measures will work just as well. A case in point is the belief that penicillin or other antibiotics (antibiotic) will cure viral infections—they will not. While new antiviral drugs are under development, using antibiotics unnecessarily is unwise and potentially dangerous. The number of drug-resistant organisms is growing and must be counteracted by the judicious prescribing of these chemicals.

      Unnecessary drug use also increases the possibility of drug interactions that may interfere with drug effectiveness. Interaction can occur in the stomach or intestinal tract where the presence of one drug may interfere with the absorption of another. Antacids, for example, reduce the absorption of the popular antibiotic tetracycline by forming insoluble complexes. Of greater importance is the interference of one drug with another. Some drugs can inhibit metabolism, which allows the amount of the drug to accumulate in the system, leading to potential toxicity if the dose is not decreased. Cimetidine, a drug used to treat peptic ulcers, causes few side effects by itself, but it does inhibit drug-metabolizing microsomal enzymes in the liver, increasing concentrations of many drugs that depend on these enzymes to be metabolized. This inhibition can be serious if the other drug is the anticoagulant warfarin. Bleeding can result if the dose is not reduced. Many other drugs are affected, such as antihypertensives (calcium channel blockers), antiarrhythmics (quinidine), and anticonvulsants (phenytoin). One drug can also decrease the renal excretion of another. Sometimes this effect is used to advantage, as, for example, when probenecid is given with penicillin to decrease its removal and thereby increase its concentration in the blood. But this type of interaction can be deadly: quinidine, for instance, can reduce the clearance of digoxin, a drug used to treat heart failure, potentially increasing its concentration to dangerous levels. Two drugs can also have additive effects, leading to toxicity, though either one alone would be therapeutic.

      Problems with drug interactions can occur when a patient is being treated by different physicians, and one physician is not aware of the drug(s) that another has prescribed. Sometimes a physician may prescribe a drug to treat a symptom that actually is a side effect of another drug. Of course, discontinuing the first drug is preferable to adding another that may have side effects of its own. When a new symptom occurs, a recently initiated drug should be suspected before other causes are investigated. Patients should inform their physicians of any new drugs they are taking, as well as consult with the pharmacist about possible interactions that a nonprescription drug might have with a prescription drug already being taken. Having a personal physician who monitors all the drugs, both prescription and nonprescription, that the patient is taking is a wise course to follow.

      In the United States, responsibility for assuring the safety and efficacy of prescription drugs is delegated to the Food and Drug Administration (FDA). This includes the approval of new drugs, identification of new indications, official labeling (to prevent unwarranted claims), surveillance of adverse drug reactions, and approval of methods of manufacture. Before an investigational new drug (IND) can be tested in humans, it must be submitted to and approved by the FDA. If clinical trials are successful, a new drug application (NDA) must be approved before it can be licensed and sold. This process usually takes years, but if the drug provides benefit to patients with life-threatening illnesses when existing treatments do not, then accelerated approval is possible. Physicians can receive permission to use an unapproved drug for a single patient. This consent, called emergency use and sometimes referred to as single-patient compassionate use, is granted if the situation is desperate and no other treatment is available. The FDA also sometimes grants approval to acquire drugs from other countries that are not available in the United States if a life-threatening situation seems to warrant this action. Another way to gain access to an investigational drug is to participate in a clinical trial. If it is a well-controlled, randomized, double-blind trial rather than an “open trial”—in which the investigator is not “blinded” and knows who is the subject and who is the control—the patient runs the risk of being given a placebo rather than the active drug.

      The Federal Trade Commission (FTC) has responsibility for “truth in advertising” to assure that false or misleading claims are not made about foods, over-the-counter drugs, or cosmetics.

      A rare disease presents a unique problem in treatment because the number of patients with the disease is so small (fewer than 200,000 in the United States) that it is not worthwhile for companies to go through the lengthy and expensive process required for approval and marketing. Drugs produced for such cases are made available under the Orphan Drug Act of 1983, which was intended to stimulate the development of drugs for rare diseases. More than 400 orphan drugs have been designated, but there are about 5,000 rare diseases that remain without treatment.

      Controlled substances are drugs that foster dependence (chemical dependency) and have the potential for abuse. The Drug Enforcement Administration (DEA) regulates their manufacture, prescribing, and dispensing. Controlled substances are divided into five classes, or schedules, based on their potential for abuse or physical and psychological dependence. Schedule I encompasses heroin and other drugs with a high potential for abuse and no accepted medical use in the United States. Schedule II drugs, including narcotics such as opium and cocaine and stimulants such as amphetamines, have a high potential for abuse and dependence. Schedule III includes those drugs such as certain stimulants, depressants, barbiturates, and preparations containing limited amounts of codeine that cause moderate dependence. Schedule IV contains drugs that have limited potential for abuse or dependence, and includes some sedatives, antianxiety agents, and nonnarcotic analgesics. Schedule V drugs have an even lower potential for abuse than do schedule IV substances. Some, such as cough medicines and antidiarrheal agents containing limited amounts of codeine, can be purchased without a prescription. Physicians must have a DEA registration number to prescribe any controlled substance. Special triplicate prescription forms are required in certain states for schedule II drugs, and a patient's supply of these drugs cannot be replenished without a new prescription.

Systemic drug therapy
      Systemic drug therapy involves treatment that affects the body as a whole or that acts specifically on systems that involve the entire body, such as the cardiovascular, respiratory, gastrointestinal, or nervous systems. Psychiatric disorders also are treated systemically.

The cardiovascular (cardiovascular disease) system
       atherosclerosis, the most common form of arteriosclerosis (generally called hardening of the arteries (artery)), is the thickening of large and medium-size arterial walls by cholesterol deposits that form plaques, causing the size of the arterial lumen to diminish. This narrowing compromises the artery's ability to supply blood to tissues and is most serious when the coronary arteries (those feeding the heart muscle) become clogged. A heart attack, with the death of a portion of the heart muscle, results; if the damage is extensive, sudden death will follow. The arteriosclerotic process can be slowed or even reversed by lowering serum cholesterol, especially the low-density lipoprotein (LDL) component. Cholesterol-reducing drugs, a low-cholesterol diet, exercise, and weight control can help. One form of cholesterol, high-density lipoprotein (HDL), is actually beneficial and helps to carry the harmful cholesterol out of the arterial wall. While some drugs will raise blood levels of high-density lipoprotein cholesterol, the most effective means of increasing it is to avoid cigarette smoke and increase exercise.

      Narrowing of the coronary arteries can reduce the flow of blood to the heart and cause chest pain ( angina pectoris). This condition can be treated with drugs such as nitroglycerin that primarily dilate the coronary arteries or by those such as the beta-blockers and calcium channel blockers that primarily reduce myocardial oxygen requirements.

      Drugs that increase the strength of the heart muscle have been used to treat congestive heart failure for more than 200 years. digitalis, derived from the foxglove plant, was the first drug found to have a positive inotropic effect (affects the force of muscular contraction) on the heart. Digoxin, the most commonly used form of this substance, can be given orally or intravenously. Digitalis has a relatively narrow therapeutic range: too much is toxic and can cause cardiac arrhythmias. Because toxicity is increased if the patient's serum potassium is low, close attention is paid to maintaining adequate potassium levels.

      Drugs that dilate arterial smooth muscle and lower peripheral resistance (vasodilators) are also effective in treating heart failure by reducing the workload of the heart. The angiotensin converting enzyme (ACE) inhibitors are vasodilators used to treat heart failure. They also lower blood pressure in patients who are hypertensive.

      The majority of cases of hypertension are due to unknown causes and are called essential, or primary, hypertension. Approximately five percent of all hypertensive patients have secondary hypertension, which is high blood pressure that results from a known cause (e.g., kidney disease). While the first treatment of hypertension should be to have the patient achieve normal weight, exercise, and reduce sodium in the diet, a wide variety of drugs are available to lower blood pressure, whether it be the systolic or diastolic measurement that is too high. A stepped-care approach has traditionally been used, starting with a single, well-tolerated drug, such as a diuretic. If it proves inadequate, a second drug is added and the combination manipulated until the most effective regimen with the fewest side effects is found. Occasionally, a third drug may be necessary.

The respiratory (respiratory disease) system
      The drugs most frequently used for respiratory treatment are those that relieve cough in acute bronchitis. Antibiotics are effective only if the cause is bacterial. Most often, however, a virus is responsible, and the symptoms rather than the cause of the disease are treated, primarily with drugs that loosen or liquefy thick mucus (expectorants) and humidification (steam) that soothes the irritated mucous lining. While these treatments are widely prescribed, they have not been proven effective clinically. Cough suppressants are used to reduce unnecessary coughing but should not be employed excessively to subvert the cough's natural protective mechanism of ridding the airway of secretions and foreign substances. Dextromethorphan is a nonopioid cough suppressant nearly as effective as codeine and is available in over-the-counter preparations. If nasal congestion and postnasal drainage are present, an antihistamine and decongestant may be useful (see above Treatment of symptoms: Cough (therapeutics)).

       asthma is a narrowing of the airways characterized by episodic wheezing. Bronchodilators are effective in a mild to moderate attack. Frequent attacks require long-term treatment with anti-inflammatory drugs such as cromolyn sodium, nedocromil sodium, or a corticosteroid.

      Chronic obstructive pulmonary disease (COPD) manifests itself late in life with chronic cough and shortness of breath. Although most of the damage has already occurred, some benefit can still be obtained by stopping smoking, using bronchodilators, and administering antibiotics early when superimposed infection occurs. Supplemental oxygen therapy is used in severe cases.

The gastrointestinal system (digestive system disease)
      Drugs are frequently used to reduce lower bowel activity when diarrhea occurs or to increase activity if constipation is the problem. Laxatives (laxative) in the form of stimulants (cascara sagrada), bulk-forming agents (psyllium seed), osmotics (milk of magnesia), or lubricants (mineral oil) are commonly used. Diarrhea must be treated with appropriate antibiotics if the cause is bacterial, as in traveler's diarrhea, or with an antiparasitic agent if a parasite is to blame. Antidiarrheal agents include narcotics (codeine, paregoric), nonnarcotic analogs (loperamide hydrochloride), and bismuth subsalicylate (Pepto-Bismol [trademark]; see above Treatment of symptoms: Diarrhea (therapeutics)).

      Chronic gastritis and recurrent peptic ulcer often result from infection with Helicobacter pylori and are treated with antibiotics and bismuth. Ulcers not caused by H. pylori are treated with drugs that reduce the secretion of gastric acid, such as the H2-receptor antagonists (cimetidine), or agents that form a barrier protecting the stomach against the acid (sucralfate). Antacids are used for additional symptomatic relief.

       nausea and vomiting are protective reflexes that should not be totally suppressed without the underlying cause being known. They may be psychogenic or caused by gastrointestinal or central nervous system disorders, medications, or systemic conditions (pregnancy or diabetic acidosis). Among the most widely used antiemetics are the phenothiazines (Compazine [trademark]), but new drugs continue to be developed that help control the vomiting related to cancer chemotherapy.

The nervous system (nervous system disease)
      Alzheimer's disease (Alzheimer disease) is the most prevalent form of dementia (loss of intellectual function), and treatment had been primarily supportive until drugs that show modest promise for improving cognition (tacrine) were developed. Evidence that the continual use of cognitive faculties slows memory loss in the elderly has been supported by research showing that older persons who are stimulated regularly with memory exercises retain information better than those who are not.

       parkinsonism is named after James Parkinson, the English surgeon who in 1817 described “the shaking palsy.” Although no treatment is known to halt the advance of the disease, levodopa and other drugs can significantly relieve the symptoms of tremor, muscular rigidity, and postural instability.

       migraine headache can be alleviated by one of the many forms of ergotamine and nonsteroidal anti-inflammatory drugs. Sumatriptan is a drug that has significantly improved the treatment of severe migraine attacks, causing fewer side effects than ergotamine or dihydroergotamine, but it is expensive.

Psychiatric disorders (mental disorder)
      Some of the greatest recent advances in pharmacotherapy have been in the treatment of anxiety disorders and depression. The benzodiazepines have been the mainstay of treatment for anxiety disorders since the 1960s, although their prolonged use incurs the risk of mild dependence. The azaspirodecanediones (buspirone) have little potential for producing dependency and are not affected by alcohol intake. Newer and safer medications are also available for treating panic disorder and obsessive-compulsive disorder.

      Depression is among the most common life-threatening diseases, and considerable advances have been made in managing this very treatable disorder. The selective serotonin reuptake inhibitors (SSRIs) match previous antidepressants (antidepressant) in effectiveness and have fewer unpleasant side effects. They also are safer if an overdose is taken, which is a significant threat in the case of severely depressed patients.

Local drug therapy
      Local anesthetics produce loss of sensation and make it possible for many surgical procedures (surgery) to be performed without a general anesthetic. Barring any complications, the need for the patient to remain overnight in the hospital is obviated. Local anesthetics are also used to anesthetize specific peripheral nerves or larger nerve trunks. These nerve blocks can provide relief in painful conditions like rib fractures, but they are most frequently used to anesthetize an extremity during hand or foot surgery. Spinal anesthesia and epidural anesthesia, in which a local anesthetic is injected into the subarachnoid or epidural space of the lumbar (lower back) area of the spinal canal, provide pain relief during childbirth or surgery that involves the pelvic area yet lack the problems associated with a general anesthetic. Topical anesthetics, a type of local anesthetic, are also used on the skin, in the eye's conjunctiva and cornea, and in the mucous membranes of the nose, mouth, larynx, vagina, or urethra.

      Medications prescribed for dermatologic disorders account for a large amount of local drug therapy, whether it be a substance to stimulate hair growth or to soothe a burning and itching rash. Many different corticosteroid preparations are available to treat eczema, allergic reactions to substances like poison ivy, or seborrheic dermatitis. Sunblocks are used to protect the skin against ultraviolet rays and prevent skin cancer that can result from exposure to such radiation. acne is controlled with skin cleansers, keratolytics to promote peeling, and topical antibiotics to prevent or treat infection. Physicians use various wet dressings, lotions, gels, creams, and ointments to treat acutely inflamed weeping and crusting sores and to moisturize and protect dry, cracked, and scaling skin. Burns (burn) heal more rapidly and with less scarring when treated appropriately with topical preparations like silver sulfadiazine. candida infections of the mucous lining of the mouth (i.e., thrush) or the vagina respond to nystatin or one of the imidazole drugs. The traditional treatment of genital warts has been the topical application of podophyllin, a crude resin, but new technology has made available interferon-α, which is 70 percent effective when injected into the lesion itself or subcutaneously below it.

      Most ophthalmic (eye disease) drugs are local—eye drops to treat glaucoma, steroid-antibacterial mixtures to treat infection, artificial tears for dry-eye syndromes, or mydriatics (drugs causing dilation of the pupil), like atropine, that facilitate refraction and internal examination of the eye.

      Chemotherapy is the treatment of disease using chemical agents that are intended to eliminate the causative organism without harming the patient. In the strict sense, this applies to the use of antibiotics to treat such invading organisms as bacteria, viruses, fungi, or parasites. The term is commonly used, however, to describe the use of drugs to treat cancer, in which case the target is not a causative organism but wildly multiplying cells. The purpose of the therapy is to selectively kill tumour cells and to leave normal cells unharmed—a very difficult task because most drugs have a narrow therapeutic zone beyond which they harm normal cells as well as cancer cells. Approximately 50 different anticancer drugs are available, and an equal number are currently being tested. Anticancer drugs are only relatively selective for cancer cells, and the toughest task for the physician is to select a drug that will destroy the most cancer cells, leave normal cells unharmed, and cause the fewest unpleasant and undesirable side effects. The therapeutic goal is to favourably balance the risk-benefit ratio in which the morbidity of the treatment is weighed against its potential benefits. If a treatment causes patients to be miserable and has only a slight chance of prolonging life, many patients will forego further treatment. However, if the potential for significantly prolonging survival by aggressive therapy exists, the patient may decide to continue with the therapy.

      The effectiveness of chemotherapy depends on the highest possible concentration of the drug being at the tumour site sufficiently long to kill the tumour cells. The maximal opportunity for a cure exists in the early stage of the disease when the tumour is small and localized. The larger and more disseminated the tumour, the more difficult it is to eradicate. The stage the tumour is in will also determine the route of administration, which can be oral, intravenous, intra-abdominal, intrathecal (into the subarachnoid space of the spinal cord), or intra-arterial—specifically, into the artery feeding the tumour.

      Suppression of bone marrow activity, which results in a decrease in blood cell production, represents the most limiting factor in chemotherapy. Because chemotherapy is most effective when used at the highest nontoxic dose, the interval between treatments may need to be prolonged to prevent complete bone marrow suppression. Supportive measures undertaken when bone marrow suppression occurs include repeated platelet transfusions (to combat bleeding caused by diminished platelet production) and white blood cell transfusions (to control infection).

      Adjuvant chemotherapy is the use of drugs to eradicate or suppress residual disease after surgery or irradiation has been used to treat the tumour. This is necessary because distant micrometastases often occur beyond the primary tumour site. Adjuvant chemotherapy reduces the rate of recurrence of some cancers, especially ovarian cancer, osteogenic sarcoma, colon cancer, and Wilms' tumour. The antiestrogen drug tamoxifen has been effective in selected patients with breast cancer.

Surgical therapy

Major categories of surgery
wound treatment
      Wounds, whether caused by accidental injury or a surgical scalpel, heal in three ways: (1) primary intention (wound edges are brought together, as in a clean surgical wound), (2) secondary intention (the wound is left open and heals by epithelization), or (3) third intention, or delayed closure (the wound is identified as potentially infected, is left open until contamination is minimized, and is then closed).

      Choosing which method is best depends on whether excessive bacterial contamination is present, whether all necrotic material and foreign bodies can be identified and removed, and whether bleeding can be adequately controlled. Normal healing can occur only if the wound edges are clean and can be closely opposed without undue stress on the tissue. An adequate blood supply to the wound is essential. If the tissue is tight and the edges cannot be closed without tension, the blood supply will be compromised. Cutting under the skin to free it from the underlying subcutaneous tissue may allow the edges to be brought together without tension. If direct approximation is still not possible, then skin grafts or flaps are used for closure.

      Wound closure begins with a thorough cleansing of the wound and the installation of a local anesthetic, usually lidocaine, which takes effect quickly and lasts for one to two hours. If the wound is contaminated, further cleansing is performed after instilling the local anesthetic, especially if foreign material is present. If the injury resulted from a fall on gravel or asphalt as in some motorcycle accidents, then aggressive scrubbing is needed to remove the many small pieces imbedded beneath the skin. High-pressure irrigation with saline solution will remove most foreign material and reduce the risk of subsequent infection. Contaminated wounds must be considered to be prone to infection with Clostridium tetani, which causes tetanus, and appropriate immunization should be given.

      Sutures are the most commonly used means of wound closure, although staples and adhesive tissue tape may be more appropriate in certain circumstances. Silk sutures were originally used to close skin wounds, but nylon is stronger and causes less tissue reaction. Ideally, sutures are of the smallest possible diameter that will still maintain approximation of the wound edges. Absorbable sutures made of catgut (made not from cat but from sheep intestines) or a synthetic material such as polyglycolic acid are used to approximate the deeper layers of tissue beneath the skin so that tissue reaction will be lessened. The objective is to eliminate any unfilled space that could delay healing or allow fluid to accumulate. Drains connected to closed suction are used to prevent the collection of fluid when it is likely to accumulate, but drains serve as a source of contamination and are used infrequently. Staples permit faster closure of the skin but are less precise than sutures. When the edges can be brought together easily and without tension, tape is very useful. Although it is comfortable, easy to apply, and avoids the marks left by sutures, tape may come loose or be removed by the patient and is less successful if much wound edema occurs.

      Sutures are removed after 3 to 14 days depending on the area involved, the cosmetic result desired, the blood supply to the area, and the amount of reaction that occurs around the sutures. Sutures on the face should be removed in three to five days to avoid suture marks. Tape is often used to provide support for the remainder of the time the wound needs to heal. Sutures on the trunk or leg will be removed after 7 to 10 days or longer if there is much tension on the wound. Tension and scarring are minimized in surgical procedures by making an incision parallel to normal skin lines, as in the horizontal neck incision for thyroidectomy.

      Dressings protect the wound from external contamination and facilitate absorption of drainage. Because a surgical wound is most susceptible to surface contamination during the first 24 hours, an occlusive dressing is applied, consisting of gauze held in place by tape. Materials like transparent semipermeable membranes permit the wound to be observed without removal of the dressing and exposure of the wound to contamination. Dressings support the wound and, by adding compression, aid healing, as skin grafts do.

      The healing of a wound results in scar formation; a strong yet minimally apparent scar is desirable. In some individuals a keloid, or thick overgrowth of scar, occurs no matter how carefully the wound was closed. The four phases of wound healing are inflammatory, migratory, proliferative, and late. The first, or inflammatory (inflammation), phase occurs in the first 24 hours when platelets form a plug by adhering to the collagen exposed by damage to blood vessels. Fibrin joins the platelets to form a clot, and white blood cells invade the area to remove contamination by foreign material. Local blood vessels dilate to increase blood supply to the area, which hastens healing. In the second, or migratory, phase, fibroblasts (fibroblast) and macrophages infiltrate the wound to initiate reconstruction. Capillaries (capillary) grow in from the periphery, and epithelial cells advance across the clot to form a scab. In the proliferative phase, the fibroblasts produce collagen that increases wound strength, new epithelial cells cover the wound area, and capillaries join to form new blood vessels. In the late phase, the production of new and stronger collagen remodels the scar, blood vessels enlarge, and the epithelium at the surface heals.

      Many factors, including diabetes mellitus or medications, can affect wound healing. In a patient whose diabetes is well controlled, wound healing is essentially normal, but, if the blood glucose level is elevated, it can impair healing and predispose the wound to infection. Kidney or liver failure and malnutrition also will delay wound healing, as will poor circulation owing to arteriosclerosis. Having steroids or anticancer or other drugs in the system can adversely affect the normal healing process.

Surgical extirpation
      Extirpation is the complete removal or eradication of an organ or tissue and is a term usually used in cancer treatment or in the treatment of otherwise diseased or infected organs. The aim is to completely remove all cancerous tissue, which usually involves removing the visible tumour plus adjacent tissue that may contain microscopic extensions of the tumour. Excising a rim of adjacent, seemingly normal tissue ensures a complete cure unless there has been extension through the lymphatic system (lymphoma), which is the primary route for cancer to spread. For this reason, local lymph nodes (lymph node) are often removed with the tumour. Pathological examination of the nodes will show whether the cancer has spread. This indicates the likelihood of cure and whether additional treatment such as radiation or chemotherapy is needed. If complete removal of a tumour is not possible, palliative surgery, which provides relief but is not a cure, may be useful to relieve pain or pressure on adjacent structures. Radical surgery may not always be best, as in the early stages of breast cancer. Removal of the entire breast and surrounding structures, including the axillary lymph nodes, has been shown to provide no greater benefit than a lumpectomy (removal of the tumour only) followed by radiation to the area in early stages of breast cancer, while it often causes the patient increased psychological distress. However, because of improvements in breast reconstruction techniques, the trauma of a radical mastectomy is becoming less severe.

      Reconstructive surgery is employed when a significant amount of tissue is missing as a result of trauma or surgical removal. A skin graft may be required if the wound cannot be closed directly. If a large surface area is involved, a thin split-thickness skin graft, consisting of epidermis only, is used. Unfortunately, although these grafts survive transplantation more successfully and heal more rapidly than other types of grafts, they are aesthetically displeasing because their appearance differs markedly from that of normal skin. In a small defect, especially one involving the face or hand, a full-thickness skin graft, consisting of epidermis and dermis, is used, and skin is generally donated from the ear, neck, or groin. Exposure of bone, nerve, or tendon requires a skin flap. This can be a local flap, in which tissue is freed and rotated from an adjacent area to cover the defect, or a free flap, in which tissue from another area of the body is used. An example of a local flap is the rotation of adjacent tissue (skin and subcutaneous tissue) to cover the defect left from removing a skin cancer. A free flap is used when the amount of tissue needed is not available locally, as in an injury to the lower leg from an automobile bumper. The amount and type of tissue needed and the blood supply available determine the type of flap to be used. The blood supply must be adequate to supply the separated flap and wound edge with nourishment.

      Tissue expanders are another way of creating extra tissue that can be used to cover a defect. Inflatable plastic reservoirs are implanted under the normal skin of an adjacent area. For several weeks the reservoir is expanded with saline to stretch the overlying skin, which is then used to cover the defect.

      Reconstructive surgery is performed for a variety of surgical conditions. It may require the fashioning of a new “organ,” as in an artificial bladder, or may involve insertion of prosthetic devices such as artificial heart valves, pacemakers, joints, blood vessels, or bones.

      Prosthetic (prosthesis) devices can be used to replace diseased tissue. They usually perform better than donated tissue because they are made of material that does not stimulate rejection. The first prosthetic device to be used was the Dacron aortic graft developed by Michael E. De Bakey in 1954 to replace aortic aneurysms (dilated vessels that risk rupture and death) or vessels obstructed by arteriosclerotic plaques. Grafts made of similar materials are now employed to replace diseased arteries (artery) throughout the body. Other prosthetic devices include heart valves (made of plastic or taken from a pig) and metal joints (e.g., hip, knee, or shoulder).

      The success of organ transplantation has greatly improved since the advent of the immunosuppressive drug cyclosporine. New and improved immunosuppressive drugs are currently being developed.

      Kidney transplants (kidney transplant) are the most common, with those donated from living relatives ensuring the greatest prospects of long-term survival. The best survival rates are between identical twins. Cadaver transplants are often used, and one-year graft survival rate is 75 to 90 percent. Approximately 50 percent of grafts cease to function after 8 to 11 years, but others last 20 years or more. Kidneys removed from living donors can be preserved for up to 72 hours before they must be implanted, but most are implanted within 24 hours because successful transplantation decreases with time.

      Heart (heart transplant) and heart-lung organs can be preserved for four to six hours, and the success rate with this procedure continues to improve. Extensive matching of blood groups and tissue types is performed to minimize the risk of rejection. The size of the donor and donated organ should match the size of the recipient and the recipient's organ, and the time between pronouncement of death and procurement of the organ should be kept as short as possible.

      In selected patients, liver transplantation has become an accepted treatment for end-stage liver disease. Mortality following surgery is 10 to 20 percent, and survivors still require long-term immunosuppressive therapy.

Surgical techniques
      A laser is a device that produces an extremely intense monochromatic, nondivergent beam of light capable of generating intense heat when focused at close range. Its applications in the medical field include the surgical welding of a detached retina and the stanching of bleeding (called laser photocoagulation) in the gastrointestinal tract that can result from a peptic ulcer. Because a laser beam is absorbed by pigmented lesions, it can be used to treat pigmented tumours, remove tattoos, or coagulate a hemangioma (a benign but disfiguring tumour of blood vessels). Laser surgery has also been found to be effective in treating superficial bladder cancer and can be combined with ultrasonography for transurethral ultrasound-guided laser-induced prostatectomy (TULIP). More recent uses include the treatment of glaucoma and lesions of the cervix and vulva, including carcinoma in situ and genital warts.

      Cryosurgery is the destruction of tissue using extreme cold. Warts, precancerous skin lesions (actinic keratoses), and small cancerous skin lesions can be treated using liquid nitrogen. Other applications include removing cataracts, extirpating central nervous system lesions (including hard-to-reach brain tumours), and treating some heart conduction disorders.

Stereotaxic surgery
      Stereotaxis (precise positioning in space) is a valuable neurosurgical technique that enables lesions deep in the brain that cannot be reached otherwise to be located and treated using cold (as in cryosurgery), heat, or chemicals. In this procedure, the head is held motionless in a head ring (halo frame), and the lesion or area to be treated is located using three-dimensional coordinates based on information from X rays and electrodes.

      Stereotaxic techniques are also used to focus high-intensity radiation on localized areas of the brain to treat tumours or to obliterate arteriovenous malformations. This technique is also employed to guide fine-needle aspiration biopsies of brain lesions; it requires that only one burr hole be made in the skull with the patient under local anesthesia. Stereotaxic fine-needle biopsy also is used to evaluate breast lesions that are not palpable but are detected by mammography.

Minimally invasive surgery
      Traditional open surgical techniques are being replaced by new technology in which a small incision is made and a rigid or flexible endoscope is inserted, enabling internal video imaging. Endoscopic (endoscopy) procedures are commonly performed on nasal sinuses, intervertebral disks, fallopian tubes, shoulders, and knee joints, as well as on the gall bladder, appendix, and uterus. Although it has many advantages over traditional surgery, endosurgery may be more expensive and have higher complication rates than traditional approaches.

Trauma surgery
      Trauma is one of the leading causes of loss of potential years of life. The explosion in the development of medical instrumentation and technology has made it possible for surgeons to save more lives than ever before thought possible. The intensive care unit contains a complex assortment of monitors and life-support equipment that can sustain life in situations that previously proved fatal, such as adult respiratory distress syndrome, multiorgan failure, kidney failure, and sepsis.

Radiation and other nonsurgical therapies

      Ionizing radiation is the transmission of energy by electromagnetic waves (e.g., X rays) or by particles such as electrons, neutrons, or protons. Interaction with tissue produces free radicals and oxidants that damage or break cellular DNA, leading to cell death. When used properly, radiation may cause less damage than surgery and can often preserve organ structure and function. The type of radiation used depends on the radiosensitivity of the tumour and which healthy organs are within the radiation field. High-energy sources, such as linear accelerators, deposit their energy at a greater depth, sparing the skin but treating the deep-seated tumour. The radiation beam can also come from multiple directions, each beam being focused on the deep tumour, delivering a smaller dose to surrounding organs and tissues. Electron-beam radiation has low penetration and is useful in treating some skin cancers (cancer).

      The basic unit of absorbed radiation is the gray (Gy): one gray equals 100 rads. Healthy organs have varying tolerance thresholds to radiation, bone marrow being the most sensitive and skin the least. The nervous system can tolerate much more radiation than the lungs or kidneys. Total body irradiation with approximately 10 Gy causes complete cessation of development of the bone marrow, and physicians use it to destroy defective tissue before performing a bone marrow transplant.

      Radiation therapy can also be palliative if a cure is not possible; the size of the tumour can be reduced, thereby relieving pain or pressure on adjacent vital structures. It also can shrink a tumour to allow better drainage of an area, such as the lung, which can help to prevent infection and decrease the chance of bleeding.

      Radioactive implants in the form of metal needles or “seeds” are used to treat some cancers, such as those of the prostate and uterine cervix. They can deliver high doses of radiation directly into the tumour with less effect on distant tissues.

      An organ can also be irradiated by the ingestion of a radioactive substance. hyperthyroidism can be treated with iodine-131, which collects in the thyroid gland and destroys a percentage of glandular tissue, thereby reducing function to normal. The drawback to this procedure is the difficulty in calculating the correct dose.

      Irradiation is less effective in treating tissues that are poorly oxygenated (hypoxic) because of inadequate blood supply than it is in treating those that are well oxygenated. Some drugs enhance the toxic effect of radiation on tumour cells, especially those that are hypoxic.

Other noninvasive therapies
      Some tumours are more sensitive than the surrounding healthy tissue to temperatures around 43° C (109.4° F). Sensitivity to heat is increased in the centre of tumours, where the blood supply is poor and radiation is less effective. A tumour may be heated using microwaves or ultrasound. Hyperthermia may enhance the effect of both radiation and chemotherapy; it is one form of nonionizing radiation therapy.

Photodynamic therapy
      Another form of nonionizing radiation therapy is photodynamic therapy (PDT). This experimental technique involves administering a light-absorbing substance that is selectively retained by the tumour cells. The cells are killed by exposure to intense light, usually laser beams of appropriate wavelengths. Lesions amenable to PDT include tumours of the bronchus, bladder, skin, and peritoneal cavity.

Extracorporeal shock wave lithotripsy
      The use of focused shock waves (shock wave) to pulverize stones in the urinary tract, usually the kidney (kidney stone) or upper ureter, is called extracorporeal shock wave lithotripsy (ESWL). The resultant stone fragments or dust particles are passed through the ureter into the bladder and out the urethra. The patient is given a general, regional, or sometimes even local anesthetic and is immersed in water, and the shock wave is applied to the flank over the kidney. If the stone is small, submersion in a water bath is not necessary; shock waves are transmitted through the skin via a water-filled rubber bulb positioned over the stone site. Stones that are too large to be treated in this manner are removed by passing an endoscope into the ureter.

Drug therapy
      The use of drugs to treat emotional disorders has expanded dramatically with the development of new and more effective medications for a variety of disorders that formerly were not treatable. Drugs that affect the mind are called psychotropic and can be divided into three categories: antipsychotic drugs, antianxiety agents, and antidepressant drugs.

Antipsychotic agents
      The advent of antipsychotic, or neuroleptic, drugs such as Thorazine (trademark) enabled many patients to leave mental hospitals and function in society. The primary indication for the use of antipsychotics is schizophrenia, erroneously called split personality. This is a severe mental disorder characterized by delusions, hallucinations, and sometimes bizarre behaviour. One form, paranoid schizophrenia, is marked by delusions that are centred around a single theme, often accompanied by hallucinations. The most effective drug to use may depend on an individual patient's metabolism of the drug or the severity and nature of the side effects.

Antianxiety agents
      Drugs that combat anxiety have been called tranquilizers, an inexact term in that they do not tranquilize as much as reduce anxiety and enable dysfunctional patients to cope more effectively with life's vicissitudes and lead more rewarding lives. This class of drugs include the barbiturates (barbiturate), benzodiazepines, nonbenzodiazepine-nonbarbiturates, and hypnotics. The barbiturates phenobarbital, amobarbital, pentobarbital, and secobarbital have been around the longest and are used primarily as sedatives or for seizure disorders (phenobarbital).

      The benzodiazepines have become the drugs of choice for acute anxiety. The first to be developed was chlordiazepoxide (Librium [trademark]), followed by a large variety of benzodiazepines that each has slightly different properties. Some are used primarily as sleeping pills (hypnotics) to treat insomnia. Before the development of the benzodiazepines, the only available antianxiety drugs were the barbiturates and meprobamate. The benzodiazepines have fewer unfavourable side effects and less abuse potential and have replaced barbiturates and meprobamate in the treatment of anxiety. They also are useful in treating alcohol withdrawal, calming muscle spasm, and preparing a patient for anesthesia. Drug dependency is a potential problem, however, especially in persons with a history of dependence on alcohol or other psychoactive drugs.

      The nonbenzodiazepine-nonbarbiturate drugs include meprobamate (see above), which is rarely used today, and a new class of drugs, the azaspirodecanediones (buspirone), that have some advantages over the benzodiazepines. The most significant advantage is the absence of the potential for abuse, which renders these drugs safe in the long-term treatment of chronic problems such as generalized anxiety disorder. They also have no sedative effects and thus are safe for patients to use when driving or operating machinery. New drugs like buspirone that are effective but avoid many of the unfavourable side effects of earlier agents will continue to be developed.

      Hypnotic agents (nonbenzodiazepines) include chloral hydrate, some sedating antidepressants, and sedating antihistamines, such as diphenhydramine (Benadryl [trademark]) and hydroxyzine (Atarax [trademark]). These are used less frequently than the benzodiazepine hypnotics because of an increased morning hangover effect and other side effects. The distinction between antianxiety drugs and hypnotics is not clear, because many can serve both functions. Small doses of hypnotic benzodiazepines are effective antianxiety agents, and in many persons, especially the elderly, antianxiety benzodiazepines can induce sleep.

       depression, the most common emotional disorder, is classified as an affective disorder, the term affect referring to emotions and feelings. Affective disorders, also called mood disorders, include major depression and bipolar (manic-depressive) disorder.

      Many drugs are available to treat depression effectively. One is selected over another based on side effects or safety. The main classes of antidepressants are the tricyclics, selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), and others that are often called heterocyclics (trazodone, bupropion). The most recently developed antidepressants are the SSRIs, such as fluoxetine (Prozac [trademark]), sertraline, and paroxetine. They have no sedating effect, anticholinergic activity, associated weight gain, or cardiac toxicity, but they can cause nervousness. The oldest and best-studied class is the tricyclics, which are divided into tertiary amines and secondary amines. Most tricyclics have a sedating effect, cardiac toxicity, and varying degrees of anticholinergic side effects, which some individuals, especially the elderly, have difficulty tolerating. Anticholinergic effects, which result from the blockage of parasympathetic nerve impulses, include dry mouth, constipation, difficulty urinating, and confusion. Monoamine oxidase inhibitors have the potential to produce dangerous drug interactions. This is especially true of tyramine, which can cause hypertension and severe headache. Tyramine is found in many foods, which forces patients who take it to adhere to a specific diet.

       bipolar disorder is characterized by severe mood swings, from excessive elation and talkativeness to severe depression. The predominantly favoured mood-stabilizing drug is lithium, which requires regular monitoring of blood concentrations to achieve optimum effect. If the patient experiences episodes of mania or depression while taking lithium, additional drugs may be necessary.

Behavioral therapy (behaviour therapy)
      Behavioral therapy, also called behavioral modification, uses psychological counseling to change activity that is undesirable or potentially harmful. Treatment most often is directed toward changing harmful habits, such as discontinuing cigarette smoking, dieting to lose weight, controlling alcohol abuse, or managing stress more effectively.

      Several types of behavioral therapy are used. Rational emotive therapy aims at altering inaccurate or irrational thoughts that lead to negative emotions or maladaptive behaviour. Other behavioral approaches attempt to modify physical responses. biofeedback, for example, uses sensitive electronic devices and the principles of reinforcement to provide continuous visual or auditory “feedback,” which helps patients learn to control subtle physical processes. Relaxation training, like deep muscle relaxation exercises, is a stress-reducing technique that can be used conveniently any time of the day. These cognitive behavioral techniques have been used to treat insomnia, hypertension, headaches, chronic pain, and phobias.

      Behavioral therapies have been developed for common problems of both childhood (e.g., academic performance, enuresis, stuttering) and adulthood (e.g., marital discord).

      Psychotherapy in which an experienced therapist—a psychiatrist, psychologist, social worker, or member of the clergy—works with a group of patients or relatives is called group therapy. The process uses the interaction of group members to benefit each member of the group. Behavioral modification through group interaction and support can be used to change eating behaviours, which can lead to a reduction in weight. Support groups are available to assist patients and families in dealing with cancer, alcoholism, abuse, bereavement, and many other crises.

Family and systemic therapy
      General systems theories emerged in the biological and social sciences following World War II. This led to the conceptualization of the individual as an interdependent part of larger social systems. Systemic therapy does not focus on how problems start, but rather on how the dynamics of relationships influence the problem. The therapist's goal is to alter the dynamics of the relationships rather than to focus only on the behaviour or internal dynamics of individuals. For example, if a child is having temper tantrums, attention would be given to the stage of family development, the quality of communication between its members, and the clarity and flexibility of family roles.

       family counseling brings the entire family together to discuss specific problems of one or more family members, including adolescent discipline problems, marital discord, drug abuse, or relationship problems in families that can arise from remarriage.

Psychodynamic therapies
      Sigmund Freud (Freud, Sigmund) held that all behaviour is influenced by unconscious motivations and conflicts. Personality characteristics are thought to be shaped from the earliest childhood experiences. Psychological defenses are seen mainly as unconscious coping responses, the purpose of which is to resolve the conflicts that arise between basic desires and the constraints of external reality. Emotional problems are seen as maladaptive responses to these unconscious conflicts.

      Psychodynamic therapies emphasize that insight is essential to lasting change. Insight means understanding how a problem emerged and what defensive purpose it serves. A classic form of psychodynamic therapy is psychoanalysis, in which the patient engages in free association of ideas and feelings and the psychoanalyst offers interpretations as to the meaning of the associations. Another form is brief, dynamic psychotherapy, in which the clinician makes recommendations based on an understanding of the situation and the reasons for resisting change.

      Psychotherapy, the use of mental rather than physical means to achieve behavioral or attitudinal change, employs suggestion, persuasion, education, reassurance, insight, and hypnosis. Supportive psychotherapy is used to reinforce a patient's defenses, but avoids the intensive probing of emotional conflicts employed in psychoanalysis and intensive psychotherapy.

      Experienced clinicians usually draw on various counseling theories and techniques to design interventions that fit a patient's problem. The format of therapy (e.g., individual, couple, family, or group) will vary with each patient. Many patients respond best to a combination approach. Depression, for example, is frequently alleviated by medication and cognitive-behavioral therapy. There is growing interest in primary prevention to increase the coping abilities and resilience of children, families, and adults who are at risk for mental health problems.

Robert Edwin Rakel

Additional Reading
Ralph H. Major, A History of Medicine, 2 vol. (1954), covers medical history from its beginnings to modern times; unlike many history books, it is easy reading. An unusual reference containing technical information not found in standard medical dictionaries is James L. Bennington, Dictionary & Encyclopedia of Laboratory Medicine and Technology (1984). Robert E. Rakel, Textbook of Family Practice, 4th ed. (1990), is the standard textbook for family physicians covering the breadth of the discipline and emphasizing clinical diagnosis and treatment. Annually an issue of JAMA, the journal of the American Medical Association, is devoted to recent discoveries in every medical discipline and is an excellent source of up-to-date information on new developments in medicine; one such development is treated in Richard C. Reba, “Nuclear Medicine,” JAMA, 270(2):230–232 (July 14, 1993). An expert panel reviewed the scientific literature and developed recommendations for prevention in 60 conditions that represent the leading causes of death and disability in the United States; these recommendations are found in U.S. Preventive Services Task Force, Guide to Clinical Preventive Services (1989). Manual of Clinical Dietetics, 4th ed. (1992), published by the American Dietetic Association, is an excellent reference for diets and nutritional contents of foods. Drug Facts and Comparisons (annual), contains detailed information about all prescription drugs. Drug Evaluations Annual is a well-written evaluation of the clinical use of specific drugs, including comparative evaluations. Conn's Current Therapy (annual), provides a concise reference for the treatment of most medical and surgical diseases. Scientific American Medicine (monthly), published in loose-leaf format, covers all major areas of internal medicine. Douglas Wilmore (ed.), Care of the Surgical Patient, 2 vol. (1989), is a regularly updated loose-leaf publication from the Committee on Pre and Postoperative Care of the American College of Surgeons; vol. 1 is devoted to critical care and vol. 2 to elective surgery. Current Medical Diagnosis & Treatment (annual), contains concise diagnostic information and treatment for a large number of medical diseases. James B. Wyngaarden, Lloyd J. Smith, Jr., and J. Claude Bennett, Cecil Textbook of Medicine, 19th ed. (1992), is one of the best standard textbooks of medicine, compiled by leading authorities and containing thorough information on common and rare diseases. Richard D. DeShazo and David L. Smith (eds.), “Primer of Allergic and Immunologic Diseases,” JAMA, 268(20):2785–2996 (Nov. 25, 1992), is an entire issue devoted to allergy and immunology, containing articles ranging from the basics of the immune response to autoimmune diseases and immunization; prepared by the American Academy of Allergy and Immunology, it provides complete coverage of the subject.Robert Edwin Rakel

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Universalium. 2010.

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  • therapeutics — noun plural but singular or plural in construction Date: 1671 a branch of medical science dealing with the application of remedies to diseases …   New Collegiate Dictionary

  • therapeutics — noun The treatment of disease; the science of healing. See Also: therapeutic …   Wiktionary

  • therapeutics — ther|a|peu|tics [ˌθerəˈpju:tıks] n [U] technical the part of medical science relating to the treatment and cure of illness …   Dictionary of contemporary English

  • therapeutics — ther·a peu·tics || ‚ðerÉ™pjuːtɪks n. branch of medicine dealing with healing remedies …   English contemporary dictionary

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