3-5. FACTORS WHICH INFLUENCE DRUG DOSAGE EFFECTS

3-5. FACTORS WHICH INFLUENCE DRUG DOSAGE EFFECTS

Many factors influence how a dose of a particular drug will affect a patient. Since not all patients are the same size, weight, age, and sex, it would be wise to consider how these factors might influence how much drug a person should receive and the effect(s) that drug might have on the patient. The usual recommended adult dose of medication, as found in standard references, is based on the assumption that the patient is a "normal" adult. Such a "normal" (or average) adult is said to be 5 feet 9 inches (173 centimeters) tall and weigh 154 pounds (70 kilograms). However, many people do not fit into this category. Therefore, the following factors should be considered when patients receive drugs:

a. Weight. Obese (overweight) patients may require more medication than thin patients may because the drug has more tissue to which it can go. The dosage of many drugs is calculated on a weight basis. For example, a person might be prescribed a drug that has a dosage of 5 milligrams of drug per pound of patient body weight.

b. Surface Area. A person's height and weight are related to the total surface area of his body. The "normal" (average) adult has a body surface area of approximately 1.73 square meters. A nomogram  is used to determine the surface area of a patient. The dosage of certain drugs (for example, the anticancer drugs) is determined by the patient's body surface area.

c. Age. As a rule, the very young and the elderly require less than the normal adult dose of most medications. Part of this requirement for less medication is due to the altered metabolism of the drug. Since body enzyme systems greatly influence drug metabolism, considering the differences in these enzyme systems based upon age is important. In the infant, some enzyme systems are not yet fully developed. On the other hand, the enzyme systems of the elderly may not function as well as in the past. Although several formulas are available for calculating a child's dose of medication, the two most accepted methods are those based upon the patient's weight (that is, milligrams per kilogram of body weight) or body surface area (that is, milligrams per square meter of surface area).

d. Sex. Physiological differences between the sexes may influence the dose or the requirement for drugs. Since females have proportionately more fat tissue than males, drugs, which have a high affinity (likeness) for fat, may require larger doses in females. Moreover, estrogen and testosterone, two sex hormones, can affect the patient’s rate of metabolism which can, in turn, influence the rate at which a drug is metabolized, absorbed, or excreted from the body. The requirement for iron is much higher in the female than in the male, because of the loss of blood in each menstrual cycle.

e. Genetic Factors. Various racial and ethnic groups have differences in some metabolic and enzyme systems which can affect the utilization of drugs.

f. Physical Condition of the Patient. The physical condition of the patient influences how a particular drug might act. Consequently, the weak or debilitated patient might require smaller doses of some medications. Patients who are in extreme pain may require larger doses of analgesic agents than those patients who are in less pain.

g. Psychological Condition of the Patient. The patient’s attitude about his disease or treatment can influence the effectiveness of a drug. It has been shown that patients receiving placebo tablets (tablets that contain no active ingredient) sometimes have the same side effects as the patients who were taking tablets of the same appearance that did contain the drug. In some cases, both types of patients (those taking the placebo and those taking the drug) recovered at the same time.

h. Tolerance. The therapeutic effects of some drugs are lessened in individuals after the drugs have been used for long periods. Thus, an individual who has used such a drug for a long time needs larger doses of the drug than he did when he first began to take it in order to obtain the same effect. This effect is called tolerance. Persons who use opium, heroin, cocaine, amphetamines, and barbiturates develop a tolerance to these substances. Cross-tolerance occurs when the use of one drug causes a tolerance to another drug. Alcoholics, barbiturate addicts, and narcotic addicts develop a cross-tolerance to sedatives and anesthetics.

i. Time of Administration. The time when a drug is administered is important. Some orally administered medications should be taken before meals (that is, on an empty stomach) to increase the amount of drug absorbed into the system. Other oral medications (that is, those that cause irritation to the gastrointestinal tract) should be taken after meals on a full stomach.

j. Drug Interaction. The interaction between two or more drugs may influence the overall effectiveness of each of the drugs.

(1) Synergism. Synergism is the joint action of drugs. That is, their combined effects are greater than the sum of their independent effects. Concurrent administration (giving both drugs at the same time) of synergists may require that the dose of each drug be lowered. In the case of synergism, 1 + 1 = 2 1/2. Synergism may be beneficial or harmful. Beneficial effects may be obtained when combining two potentially toxic drugs to achieve the desired therapeutic effect without causing harm to the patient. Harmful effects may occur when alcohol and some depressants are combined.

(2) Additive. In an additive drug interaction, the combined effects are equal to the sum of the independent effects of the drugs. In the case of the additive effect, 1 + 1 = 2.

(3) Antagonism. Antagonism is the canceling effect of one drug upon another. A sedative administered with a stimulant may antagonize or cancel the effects of the stimulant. Of course, the degree of antagonism varies from complete cancellation of the effect to varying degrees of reduced effectiveness.

k. Routes of Administration. Drugs may be given to patients using a variety of methods. Some drugs are only effective if they are given in a particular dosage form. Other drugs are administered in forms that enhance or decrease their effect or localize the drug effects.

(1) Oral. Most drugs available today can be administered by mouth (orally). Drugs can be orally administered in the form of tablets, capsules, powders, solutions, or suspensions. Drugs administered by the oral route are usually taken for their systemic effect. These medications must pass through the stomach and be absorbed in the intestinal tract. Orally administered medications are usually easy to take and are usually less expensive than other dosage forms.

(2) Sublingual/buccal. The sublingual/buccal route of administration is closely related to the oral route; however, in the sublingual/buccal route the dosage form is not swallowed. The tablet is to be dissolved under the tongue (sublingual) or in the pouch of the cheek (buccal). The drugs administered in this manner are rapidly absorbed and have the advantage of bypassing the gastrointestinal tract. Nitroglycerin, for heart patients, in tablet form is more likely the most frequently administered sublingual drug.

(3) Rectal. Drugs administered by the rectal route may have a local effect (as for hemorrhoids) or a systemic effect (as in the prevention of nausea and vomiting). The rectal route is convenient to use in pediatric patients (children) or in patients who are unconscious or vomiting. The amount of drug absorbed in the rectal route is usually less than if the drug were administered orally. The absorption of drugs administered rectally is unpredictable and can vary among patients.

(4) Vaginal/urethral. Drugs administered using the vaginal/urethral route are used for their local effect. That is, they are usually given to treat an infection or other pathological condition. Drugs administered in this route should not be irritating since systemic absorption may occur.

(5) Inhalation. Drugs administered by inhalation have either may a local or systemic effect. Anesthetics, like nitrous oxide, are inhaled and exert their effect after absorption into the circulatory system. Sprays for nasal congestion have their effect on the tissue in the nose and do not necessarily enter the general circulation.

(6) Topical. The topical route is probably the oldest route of administration. Topical medications are applied directly upon the skin. As long as the skin is intact (not broken or cut), drugs applied in this manner exert a local effect. The base (vehicle) used to carry the ingredients in the local preparation can influence the action of the drug. For example, dimethylsulfoxide (DMSO) will readily penetrate the skin and carry the active ingredient along with it.

(7) Parenteral. The term parenteral literally means to avoid the gut (gastrointestinal tract). Thus, parenterals are injectable drugs that enter the body directly and are not required to be absorbed in the gastrointestinal tract before they show their effect. Parenteral routes of administration usually have a more rapid onset of action (show their effects more quickly) than other routes of administration. Parenteral products must be sterile (free from living microbes). The parenteral route of administration does have its disadvantages: it hurts, it is not a convenient route, and once administered the injected drug cannot be retrieved.

(a) Intravenous (IV). The injection of a drug directly into the patient's veins is the most rapid route of administration. This type of parenteral route results in the most rapid onset of action.

(b) Intraarterial. In this parenteral route, the drug is injected directly into the patient's arteries. This route is not frequently used.

(c) Intrathecal. The intrathecal route involves the administration of a drug directly into the spine (subarachnoid space) as in spinal anesthesia. The intrathecal route is used because the blood-brain barrier often precludes or slows the entrance of drugs into the central nervous system.

(d) Intramuscular (IM). The intramuscular route is used when drugs are injected deeply into muscle tissue. If the drug is in aqueous (water) solution, absorption is rapid. However, if the drug is in an oily liquid or in the form of a suspension, it can prolong the release of the drug.

(e) Intradermal (ID). In this route, the drug is injected into the (top few layers) of the skin. Ideally, the drug is placed within the dermis. The intradermal route is used almost exclusively for diagnostic agents.

(f) Subcutaneous (Sub-Q/SC). This route involves the injection of the drug under the skin into the fatty layer, but not into the muscle. Absorption of the drug is rapid. Insulin is normally administered subcutaneously.

 Primary Content Providers:  The U. S. Army, The U.S. Navy Ancillary Content and Online Version: David L. Heiserman Publisher: SweetHaven Publishing Services Copyright © 2001, 2004  SweetHaven Publishing Services All rights reserved