Drug dosage refers to the determination and regulation of the amount, frequency, and number of times a specific quantity of medication is to be administered. For legal purposes in the United States, a drug is considered to be any substance (other than a food or a device) intended for use in diagnosis, cure, relief, treatment, or prevention of disease, or to affect the structure or function of the body. However, a simple, working definition of a drug is any chemical that affects the processes of the mind or body, and the dose is the amount to be administered at one time.
The selection of a drug for use in an individual requires two primary considerations: pharmacodynamics (what the drug does to the body) and pharmacokinetics (what the body does to the drug over time). Pharmacodynamics not only involves considering what the drug does as in lowering blood pressure , relieving pain , or fighting an infection , but where (the site) and how (mechanism of action) the drug acts on the body. Often, what the drug does is immediately obvious, but the exact site and mechanism of action may not be understood until after many years of use.
For a drug to work, it has to get to the place in the body where it is needed, and this requires the science of pharmacokinetics. Sufficient amounts of a drug must stay at the site of its required action until the job is completed, but not so much that severe side effects or toxic reactions
Conjugations —The joining of a chemical substance with another to form a new product.
Hydrolysis —The breaking up of a chemical compound by the addition of water.
Lipids —A group of substances composed of fatty, greasy, oily, and waxy compounds that are insoluble in water and soluble in nonpolar solvents or most organic solvents.
Metabolism —The sum of the physical and chemical processes by which living organized substance is built up and maintained and by which large molecules are broken down into smaller molecules to make energy available to the organism.
Oxidation —The chemical reaction whereby electrons are removed from the atoms of a substance for transferal.
Perfused —The act of the passage of a fluid through the vessels of a specific organ or tissue.
Phospholipids —Any lipid or fatty substance that contains phosphorus; the major lipids in cell membranes.
Reduction —The gaining of electrons during a chemical reaction.
Semi-permeable —Permitting passage only of certain molecules.
Therapeutic window —A drug's ability to maintain a specific level of action over a specific period of time.
are produced. Many drugs get to their site of action through the bloodstream. Therefore, how much time they need to work and how long their effects will last can depend on how fast they get into the bloodstream, how much gets into the bloodstream, how fast they leave the bloodstream, how easily and efficiently they are broken down (metabolized) by the liver , and how soon they are eliminated by the kidneys and intestines.
Drugs affect only the speed of biologic functions and do not change the basic character of existing processes nor generate new functions. This means that drugs can either speed up or slow down biochemical reactions in the body, as in how fast or slow a nerve may transmit a message, or how fast or slow a muscle may contract. Although drugs can change the rate of a biological process, they cannot re-establish a system that is injured beyond repair.
Every person responds to a drug differently. Thus, it is difficult to determine what dosage of a drug should be administered to each individual. Since drugs undergo testing in animals and trials in humans, an average dose is determined from these studies. An appropriate response to a drug requires the appropriate concentration of the drug at the site of action. The appropriate concentration and dosage regimen depend on individuals' clinical state, the severity of their disorder, the presence of a diseased state, the use of other drugs, as well as other considerations. Drug administration must be determined by each individual's needs, which requires an accurate evaluation of drug dosage.
All drugs can harm as well as help, so the safety and effectiveness (efficacy) of a drug are relative. Since most drugs cannot maintain a specific level of action for a certain period of time (therapeutic window), their effect can sometimes be either too strong or too weak, depending on the individual's condition who is receiving the drug.
Unwanted drug effects are called side effects or adverse reactions. A drug may affect several functions even though it is prescribed for only one. As an example, most antihistamines are targeted for the function of relieving allergy symptoms, yet one of the many side effects is sleepiness. In turn, this side effect is utilized to target the function of an inability to sleep when offered as a sleep aid.
The best drugs are both safe and effective. However, some drugs may be used despite having a very narrow margin of safety because there might be no safer alternative. Although it is impossible to know everything about every drug, understanding the general principles of drug action is an essential precaution in drug administration.
Utilization of drug treatment for any condition requires the drug to be capable of getting into the body's system (administration), moving into the bloodstream (absorption), and traveling to the specific site where it is needed (distribution). Following the administration, absorption, and distribution, the drug leaves the body (elimination) either in the urine or by conversion to another substance.
Administration of drugs can occur by many different means. Drugs be taken by mouth (oral/p.o.); by injection into a vein (intravenous/IV); by injection into a muscle (intramuscular/IM); beneath the skin (subcutaneous/SQ); placed under the tongue (sublingual); inserted in the rectum (rectal); instilled in the eye (ocular); sprayed into the nose (nasal); sprayed into the mouth (inhalation); applied directly to the skin for a local effect (topical); or applied to the skin for a systemic effect by a patch (transdermal).
Absorption is the process of drug movement from the administration site to the general (systemic) circulation. Although oral administration is the most convenient, the safest, the least expensive, and the most common route, it has its restrictions. The presence of other drugs and food in the stomach affect how drugs are absorbed. Some drugs must be taken on an empty stomach, while others should be taken with food.
For distribution into the general circulation, a drug taken orally is absorbed from the gastrointestinal tract by passing through the intestinal wall and then to the liver. Whereas a drug given IV immediately passes into the general circulation to produce a quicker and more consistent effect, a drug given by most other routes must travel across several semi-permeable cell membranes before reaching the systemic circulation. These membranes are biologic barriers that selectively prevent the passage of drug molecules and are composed of mostly cholesterol and phospholipids. These lipids provide stability to the membrane and determine its permeability characteristics. Drugs cross a biologic barrier by passive diffusion (moving from an area of high concentration to one of low concentration), facilitated passive diffusion (a carrier component combines with the drug to cause rapid diffusion across the membrane), active transport (the cell expends energy to move a drug), or pinocytosis (the cells ingest extracellular fluid and its contents).
Bioavailability refers to the rate and extent to which a drug is absorbed into the bloodstream and thereby gains access to the site of action. The properties of the actual dosage form of a drug, either tablet, capsule, suppository, transdermal patch, or solution, largely determine drug bioavailability.
Drug products may be chemically equivalent, containing the same compound in the same amount, but have dissimilar effects even at the same dose, due to different inactive ingredients, which affect absorption. When drug products contain the same active ingredients and also produce virtually the same blood levels over time, they are termed bioequivalent. If drug products given to the same person in the same dosage regimen produce the same therapeutic effect, they are therapeutically equivalent. Bioequivalent products are expected to be therapeutically equivalent.
A drug product is the actual dosage form of a drug. Drug products contain other substances (additives) that are adjusted to affect the rate and extent of the drug's absorption. Some drug products are designed to release the active ingredient slowly over a long period of time and are called controlled-release dosage forms. This occurs by coating the drug product with a polymer (a chemical substance) of varying thickness that dissolves layer by layer at different times in the gastrointestinal tract. Other additives such as enteric coatings prevent the drug from irritating the stomach lining. Drugs filled with liquids are usually absorbed faster than those filled with solids.
Although a drug rapidly circulates through the body in the bloodstream, this does not mean that it immediately moves into the tissues. Drugs are distributed to different tissues at different rates, depending on their ability to cross membranes, the rate of blood flow to a particular tissue, and the tissue mass. Most drugs do not spread evenly throughout the body; some tend to stay in the plasma (watery tissue of the blood) and muscle, others concentrate in specific areas such as the kidneys, liver, and thyroid. A balance between entry and exit rates (distribution equilibrium) is reached more rapidly in highly vascularized areas than in areas that are poorly perfused. There are drugs that bind tightly to blood proteins and leave the bloodstream very slowly, and others that exit quickly to the tissues. Some tissues build up high levels of a drug and serve as reservoirs of extra drug, which prolongs their distribution. Those drugs that accumulate in fatty tissues exit slowly and will continue to circulate in the bloodstream for days following the last administration.
It is possible for drugs to reach the central nervous system (CNS) through the brain capillaries and the cerebral spinal fluid (CSF). However, despite the fact that the brain receives approximately one-sixth of the blood circulation, distribution of drugs to brain tissues is restricted. Fat-soluble drugs can enter the brain and exert their effects rapidly, but the water-soluble drugs enter the brain slowly. The CNS is well perfused so the major factor of drug distribution rate in it is permeability, whereas for most tissues, perfusion is the major determinant of distribution.
The liver is the principal site of drug metabolism , and some of the metabolites are active forms of the drug administered. An inactive substance that produces an active metabolite, once it is absorbed, is called a pro-drug. All drugs are either metabolized or excreted intact. Enzymes in the liver assist with chemical reactions (oxidation, reduction, hydrolysis), and some enzymes attach substances to the drugs, producing reactions called conjugations, which enable a drug to be excreted in the urine.
Excretion refers to the processes by which the body eliminates a drug without further chemical change, and the major organ of excretion is the kidney. The kidneys filter drugs from the bloodstream and excrete them into the urine. Thus, the major limiting factor of excretion is kidney function, and decreasing kidney function is seen in the elderly, or people with high blood pressure, diabetes, and recurring kidney infections. A laboratory determination of kidney function permits the dosage of a drug to be altered as necessary. The liver does excrete some drugs through bile. These particular drugs enter the gastrointestinal tract and end up in the feces if they are not reabsorbed into the bloodstream or decomposed. Individuals with liver disease may need to have the drug dosage adjusted accordingly, although there is no corresponding liver function test comparable to that for kidney function. Likewise, some drugs can be excreted in breast milk, saliva, sweat, or exhaled air.
Once in the body, drugs can affect it in many ways. Interactions with other cells, tissues, or organs may result in side effects or adverse drug reactions. Many drugs bind or attach to cells by means of receptors on the cell surface. Receptors have a specific structure, which permits only those substances that fit it precisely to attach to it. The majority of cells have these surface receptors with which drugs can selectively bind to change the activity of the cell. These receptors possess a natural, physiologic purpose, and drugs take advantage of them.
A class of drugs called agonists activates or stimulates the receptors to trigger a response that either increases or decreases the cell's function. Another class of drugs called antagonists blocks the access of agonists to the receptors. Antagonists are used primarily to block or diminish cell responses to agonists normally present in the body, and this is usually in reference to neurotransmitters.
Other targets of drug action are enzymes, protein substances needed in the body to assist with the control of chemical reactions during metabolism. Drugs that target enzymes are classified as inhibitors or inducers (activators).
Affinity and intrinsic activity are two other drug properties that must be considered in dosage. Affinity refers to the attraction or strength of the bond between a drug and its target, regardless of whether it is a receptor or an enzyme. Intrinsic activity refers to the ability of the drug to produce its desired effect after it is bound to its target. Agonists drugs have both properties because they must bind effectively and produce a response. Antagonists drugs, however, only have an affinity for a target site since their purpose is to block agonists.
Other properties that are important in determining drug dosage include potency, efficacy, tolerance, and resistance. Potency refers to the amount of drug needed to produce a certain effect; it is usually expressed in milligrams (mg). Greater potency does not necessarily mean that one drug is better than another because side effects, toxicity, duration of effectiveness, and cost must also be considered. Efficacy refers to the maximum therapeutic response that a drug can produce and, once again, this is only one factor in the consideration of which drug to use at what dosage. Tolerance to a drug can occur when the body adapts to the continued presence of the drug. It is also possible for tolerance to occur if the number of receptors decreases or their affinity for the drug decreases. The term resistance is generally used to refer to a situation in which an individual no longer responds well to a drug. In these cases, the drug dosage may be increased or an alternative drug may be utilized.
Before administering a new drug or a medication that is prescribed on an as-needed basis, a patient must be assessed in terms of factors that may be pertinent. An initial prediction of increased risk for adverse drug effects can be made by the patient assessment. It is essential to double check the medication ordered, the dosage to be given, the times the drug is to be administered, how it is to be administered, the expiration date on the drug, and that the correct patient receives the correct drug. Many IV medications are now being mixed in the pharmacy to prevent errors in calculations for a patient. It is important that the health care provider discusses with the patient what the medication is, why it is being given, and reviews some potential side effects.
A patient should be continually assessed during the administration of a medication for signs and symptoms of any untoward reaction, as well as to determine if the medication has had the desired effect.
Adverse reactions are one of the main complications of drug administration. Some patients may experience an allergic reaction to a medication that could range from mild to severe. They may experience itching, exhibit a rash, have localized swelling, difficulty breathing, or suffer a complete vascular collapse. Other complications could include a resistance to the drug with a subsequent progression of the initial condition. If the patient's status does not seem to be improving, this should be reported to the physician or nurse practitioner. Severe side effects could be detrimental to the patient, necessitating laboratory tests to monitor the patient's condition.
Results expected with drug administration will vary according to why the drug was given. In all cases, it is essential to determine what end result is expected from the administration of a drug.
Health care team roles
The health care team shares responsibility for providing optimal intervention in the administration of drugs. Since nurses spend more time with patients and are more likely to focus on the patient as an individual, this places them in an optimal position to assess a patient's response to a drug. Any pertinent changes should be immediately reported to the physician or nurse practitioner. The nurse must also ensure that the patient is well informed about the drug being administered.
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Linda K. Bennington, C.N.S.