A genuine ALLERG
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Y may cause rash; hives; itching; wheezing or other breathing difficulty; diarrhea and vomiting; swelling of the
hands, feet, and face; fainting; shock; or other serious physical disturbance.
drugs taken orally seldom produce severe allergic responses, compared to those given by injection. Because injection puts the
drug into the body more quickly, a powerful and rapid allergic reaction may occur.Allergies to
drugs occur in the same way as do allergies to any other foreign substance. For some reason the
drug becomes an ANTIGEN, a substance that stimulates the formation of protein compounds called antibodies (see ANTIBODY). This is a vitally important defense mechanism when infection occurs. The body produces antibodies in reaction to infectious
agents, either destroying the
agents or making them more susceptible to other body defenses. These combine with the antigen to render it physiologically inert and harmless. Vaccines for
smallpox, diphtheria,
tetanus, polio, and other diseases stimulate the body to produce antibodies against specific disease-causing organisms. In the allergic state, however, the antigen-antibody combination does not result in an inert compound; instead it causes undesirable physiological actions.Allergies take time to develop, as the body cannot instantaneously form antibodies. Consequently, it is impossible to be allergic to a
drug the first time it is given, unless one is already allergic to a similar
drug. Such an allergy is caused by a process called
cross-sensitization. A
drug in circulation attaches to plasma proteins and becomes antigenic. As the
drug-plasma protein passes through the lymphatic system, it comes in contact with tissue formations called lymph nodes.
cells in the lymph nodes are stimulated to form antibodies, which then enter the general circulation and attach to
cell membranes in the
skin, blood vessels, and other tissues. If the patient now receives another dose of the
drug to which he or she has become allergic, it attaches to plasma protein, and eventually some of the
drug combines with the waiting antibodies. (Antigens and antibodies combine only with each other or with almost identical compounds.)If the antigen-antibody meeting occurs on the surface of the
cell, the
cell membrane may be damaged, causing the
cell to release various chemical compounds, including histamine. Histamine causes itching, spasm of muscles in the intestine and respiratory tract, leakage of fluid from capillaries, and other effects. This then causes the observable allergic signs of rash, intestinal and breathing disturbances, and tissue swelling; in extreme
cases shock occurs as blood
pressure falls.Other forms of allergy exist. If a
drug becomes antigenic, allergic mechanisms may affect blood
cell formation in the bone marrow. Because of reduced production or destruction of important blood-
cell types, the allergic patient may become unable to fight infections effectively and may die of an infection that normally would have caused only a brief illness.
drug-induced allergy may also affect the blood's clotting ability, causing serious bleeding problems.It should be reemphasized that some
drug-induced blood problems are not allergic but are due to direct toxic effect of the
drug on the bone marrow where blood
cells are manufactured. Chloramphenicol, an antibiotic, may cause death by producing aplastic anemia, a disease in which red
cell production is reduced or stopped.
drug allergies rarely occur, however, and both physician and patient should be aware of the patient's allergies and the difference between the true allergies and side effects.
drug TOXICITYNo substance is free of possible harmful effects--even an excess of water can poison--and
drugs can cause harm in smaller quantities than most ingested materials.
drug toxicity may occur immediately or after the
drug has been taken for a long period. Some forms of toxicity are simply extensions of desired effects--for example, excessive drowsiness from a tranquilizer. Most incidents of
drug toxicity are the result of excessive dosage and can be treated by stopping the medication temporarily or by lowering the dose.Types of ToxicityBecause the
liver is exposed to
drugs in high concentration, it is vulnerable to the direct effects of
drugs. This may produce chemical hepatitis.The kidney, too, may become
drug-saturated in its work as an excretory
organ. The less soluble sulfonamides may precipitate into
crystals in the
kidneys and cause tissue damage. If an antihypertensive
drug lowers the blood
pressure too far, kidney damage may occur.
drugs may cause tragic malformations of unborn infants. This form of toxicity is called teratogenicity. For this reason,
drugs are avoided whenever possible during pregnancy, especially in the first 3 months. The long-term use of
drugs by women of child-bearing age is not recommended. The tranquilizer THALIDOMIDE caused many
cases of limb defects among infants.Tranquilizers, sedatives, and other similar
drugs may cause alteration of feelings and moods, decreased motivation,
memory impairment, poor judgment, and reduced motor coordination.The use of opiates,
barbiturates, amphetamines (see
AMPHETAMINE), cocaine,
marijuana, and other sedatives or hypnotic
drugs may result in a state of physical and psychological craving. Withdrawal states of varying degrees occur with some, but not all, addictive
drugs.About 1 million
cases of nonfatal poisonings occur in the
United States each year. Poison
Control centers in many cities advise physicians in the treatment of accidental or deliberate poisonings. The problem has been ameliorated by
drug containers designed to prevent children from opening them. The old cliche, "Keep out of reach of children," remains valid.In research on
drugs, several observations are made to attempt to quantify the
drugs' toxicity. A lethal dose that kills 50 percent of a group of similar animals under standard conditions is represented as LD followed by a subscript
number 50. It is a measurement of immediate toxicity, not a precise value. To determine the chronic toxicity of an experimental
drug, it is given to two species for at least 90 days in at least three different dosage levels. The animals are then examined for
drug effects. Special toxicity tests are routinely made to determine the effects of a
drug on newborn lab animals. Anesthetics are given for 3 hours a day for 5 days, and the effects on
skin, heart, intestinal tract, and other body systems are observed. The therapeutic
index is the ratio between the lethal dose and the dose that will produce a therapeutic response in 50 percent of all animals tested--represented as ED followed by a subscript
number 50. The ratio LH-50/ED-50 is the therapeutic
index. This measurement is of limited use, since animal results cannot be directly applied to humans. More important in clinical work is the dose that produces a limited side effect or the first dangerous toxic sign. This varies from patient to patient. For example, the usual dose of phenobarbital is 30 to 100 mg. Deaths have occurred with fairly small over?oses. A patient who had been taking phenobarbital regularly for
epilepsy, however, survived an overdose of 25,000 mg--250 times the prescribed dose.Risk Versus BenefitWhen prescribing a
drug, the physician usually considers possible toxicity, weighing this risk against the potential benefit to be received from the
drug and the severity of the disease. For example, anticancer
drugs are usually extremely toxic, since they work by disrupting cellular
metabolism and thus affect normal tissue as well as the cancer. The alternative, however, is usually a speedy death.Accusations have been made that physicians regularly misprescribe, and in some
cases this is probably true. Such errors may stem from inadequate training, fatigue, economic motives, laziness, or merely human error, such as inaccurate examination or diagnosis. Sometimes the patient may
pressure the doctor for a shot when none is needed, and the doctor may comply. A serious example of poor prescribing practice occurred during the 1960s. Many physicians continued to give chloramphenicol, which occasionally caused death from aplastic anemia, even after the danger was well known and safer antibiotics were available.Training in
pharmacology is an important part of medical school. At the UCLA School for
medicine, for example, 106 lecture hours of
pharmacology are given in the 2d year, and these are supplemented by outside study and supervised clinical work in the 3d and 4th years. Some believe that medical students gain little knowledge of
pharmacology in medical school, and that 100 to 220 hours of study is not satisfactory. Whatever the truth may be, it is a must for doctors to continue to study
drugs throughout their professional careers in order to remain competent. Other factors reducing
drug dangers include quality research and evaluation and well-regulated production and dispensation of
drugs.
drug DEVELOPMENT AND REGULATIONIt is only in the last century that techniques have existed for the adequate evaluation and regulation of
drugs. In preceding centuries, many ineffective remedies were used by physicians who honestly believed in them.
drugs such as MANDRAKE root were prescribed, and patients improved; thus a worthless medication remained in use.
