A Direct Toxicity

(1) In general terms, toxicity refers to the poison-like effects certain substances can produce in the body. Fortunately, most drugs do not produce toxic effects in most patients. However, when some drugs are administered to a patient over prolonged periods or when some drugs are given in high dosages, direct toxic effects can result. Direct toxicity may involve one or more of the body's systems. Certain parts of the body (that is, bone marrow) produce red and white blood cells. If a toxic accumulation of a substance affects these parts of the body, blood dyscrasias (the formation of malformed or destroyed white or red blood cells) may occur.

(2) The liver has as one of its main functions the detoxification of chemical substances when they are absorbed. If these substances damage the liver significantly, its ability to detoxify them if greatly affected. Of course, if these substances are not detoxified, the concentration of the substance in the body (that is, blood stream) constantly increases. Thus, hepatotoxicity (the destruction of the cells of the liver) can result in the accumulation of toxic products to the point that other body systems are affected.

(3) The kidneys are responsible for eliminating water-soluble toxic products (that is, waste products from cellular respiration) from the bloodstream. If nephrotoxicity

(damage to the kidneys) results, the accumulation of these toxic products can result in death.

(4) Toxic effects may not be limited to the person who is taking the drug. In the past, it has been demonstrated that some drugs will cross the placental barrier and enter the circulatory system of the fetus. Some drugs can exert serious effects on the developing fetus. For example, the fetus may abort or be born with any number of mental or physical defects. Since few mothers are willing to subject themselves and their unborn children to drug testing, the effects of most drugs on the fetus are unknown. Most of what is known about teratogenicity, fetal malformations, has been learned either from experimental studies with animals or from the unfortunate experiences of some mothers. The fetus is particularly susceptible to the adverse effects of medications during the first three months after conception (the first trimester). Unfortunately, many women do not realize they are pregnant until they are well into their first trimester.

b. Allergic Reactions. A few individuals may be allergic, or hypersensitive, to a drug. This allergy may arise because of a prior contact with a particular substance called an allergen (it may even be the drug itself). This acquiring of an allergy is called sensitization. You should understand that the symptoms of an allergy are not related to the ordinary effects of the drug. Allergic reactions to a drug may range from a mildly irritated skin rash to anaphylaxis (a fatal shock). It has been shown that penicillin, a widely prescribed antibiotic, produces varying types of allergic reactions in from 1 to 10 percent of the patients who are administered the drug.

c. Side Effects. Most drugs do not produce only one single effect. Instead, they may produce several physiological responses at the same time. For example, antihistamines, drugs frequently used for their anti-allergic action tend to produce drowsiness. In this case, drowsiness is a side effect of the antihistamines. With some drugs, the side effects are so worrisome and inconvenient that the patient may stop taking the medication.

d. Drug Dependence. All drugs have the potential of producing dependence, the need to have that drug. There are two major types of dependence: psychological and physiological.

(1) Psychological dependence may occur after a patient has been taking a medication for a long time. With psychological dependence, the patient becomes so convinced that he needs the drug (in order to continue to lead an improved life) that he will go to great lengths to ensure that he receives the medication. Patients habituated to amphetamines may demonstrate this type of dependence. Psychological dependence is very difficult to treat.

(2) With physiological dependence, the patient's body develops a real need for the drug over a long period. Since there is a physiological need for the drug, the body reacts by going through withdrawal symptoms (that is, tremors, nausea, vomiting, and convulsions) if the drug is suddenly withheld. The patient habituated to narcotics and barbiturates have physiological dependence.

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