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Medication Administration

Vol. 15 Issue 4 April 2014

Basic Pharmacology: Drug Elimination

Peak Development Resources P.O. Box 13267 Richmond, VA 23225 Phone: (804) 233-3707 Fax: (804) 233-3705 Email: editor@peakdev.com

After completion the learner should be able to: 1. Identify mechanisms of drug elimination. 2. Describe factors affecting drug elimination. 3. Discuss nursing implications related to drug elimination. In order for drugs to have the desired therapeutic effect, in most cases they must be taken in, transported through body tissues, metabolized, and then eliminated from the body. These are the processes of pharmacokinetics, also described as the bodys effects on the drug. These processes include drug absorption, distribution, metabolism and elimination or excretion. This is in contrast to the principles of pharmacodynamics, which determine how a drug acts on the body, such as its therapeutic and adverse effects. The processes of pharmacokinetics are very important, since they determine when the drugs effects begin, how long the drug lasts in the body, the intensity of its effects, whether it crosses the placenta or enters breast milk, the dosing schedule, and the appropriate route of administration. Drug elimination, or excretion, is the final step in the pharmacokinetic process. It can be defined as the final removal of a drug or metabolite from the body. Mechanisms of Drug Elimination Drugs are eliminated, or excreted, from the body as unchanged drug molecules and/or as metabolites of the drug. The main route of drug elimination is via the kidneys, with the drug and/ or its metabolites exiting the body in the urine. The kidneys serve a protective function by removing wastes and toxins from the body and help to maintain proper fluid and electrolyte balance. To understand how this occurs, a brief review of kidney function is helpful.

Peak Development for Medication Administration and Competency Assessment Tool for Medication Administration are components of a site license for the Peak Development Resources Competency Assessment System for Medication Administration and may be reproduced for this individual facility only. Sharing of these components with any other freestanding facility within or outside the licensees corporate entity is expressly prohibited.

The information contained in Peak Development for Medication Administration is intended only as a guide for the practice of licensed nursing personnel who administer medications. Every effort has been made to verify the accuracy of the information herein. Because of rapid changes in the field of drug therapy, the reader is advised to consult the package insert, facility pharmacist or patients physician for relevant information. This is particularly important for new or seldom used drugs. Use of professional judgment is required in all patient care situations. It is the readers responsibility to understand and adhere to policies and procedures set forth by the employing institution. The editor and publisher of this newsletter disclaim any liability resulting from use or misuse of information contained herein. Copyright 2014

The kidneys filter up to 150 liters of blood daily, illustrating the constant filtering of the average adults 4-6 liter blood volume. The kidneys are comprised of nephrons, the functional unit of the kidneys. Nephrons form complex filters containing the glomerulus, with Bowmans capsule, and the various sections of the long renal tubule. As blood flows into the capillaries of the glomerulus under pressure, fluid from the blood flows into the Bowmans capsule. This process, called glomerular filtration, keeps large substances, such as proteins and cells, in the blood, but allows water, electrolytes, glucose, wastes and other substances to filter out into the resulting fluid. This glomerular filtrate then enters the tubule, traveling through the proximal convoluted tubule, Loop of Henle, and distal convoluted tubule. It then enters the collecting duct. The vast majority, 99%, of the glomerular filtrate is reabsorbed by the tubule and collecting duct and returned to the circulation, a process called tubular reabsorption. The tubules also add substances to the filtrate as needed, to excrete them from the body, such as potassium and hydrogen ions, creatinine and urea. This process is tubular secretion. The remaining 1% of filtrate continues as urine from the collecting duct into the ureters and bladder, resulting in the 1-2 liters of urine produced daily by adults. As with the filtration of other substances, drug elimination is affected by three major functions in the kidneys: Glomerular filtration: Molecules of low molecular weight are filtered out in the glomerulus, including most drugs. The higher the glomerular filtration rate, an indicator of renal function, the more rapidly these drugs are filtered out. Due to the large size of protein molecules, drugs that are protein-bound do not filter out here.

Active tubular secretion: This occurs primarily in the proximal tubule, where active transport systems move some drug molecules from the circulation into the tubular fluid. These transport systems can break the attachment of drugs bound to protein molecules, allowing for elimination of protein-bound drugs. Passive tubular reabsorption: As water in the descending tubule is reabsorbed into the circulation, the concentration of drug in the tubule increases. This promotes passive diffusion of the drug from the tubule fluid back into the circulation, decreasing the elimination of the drug in urine. Only drugs that are water-soluble can be excreted in urine. Lipid-soluble drugs in the filtrate are easily reabsorbed through the lipid-permeable membrane. These drugs may undergo further metabolism by the liver for conversion to a water-soluble form. Or, they may be eliminated from the body through other routes, such as bile. Another factor affecting drug reabsorption is the acid-base balance of the drug and the urine. Urine pH can normally range from 4.6 (acidic) to 8 (basic or alkaline). Generally, drugs that are weakly acidic are more highly reabsorbed (and thus, retained in the body) when the urine is acidic. Likewise, weakly basic drugs have greater reabsorption when the urine is basic. The urine pH can be modified to alter the elimination of some drugs. For example, an overdose of an acidic drug, such as aspirin or phenobarbital, may be treated by administering sodium bicarbonate to alkalinize the urine. This decreases reabsorption and promotes drug elimination. Other Routes of Drug Elimination In addition to the kidneys, drugs may be eliminated via the GI tract, in stool and bile, and via the lungs, sweat, saliva, tears, hair and breast milk. Of these routes, drug elimination by routes other than the kidneys and GI tract/bile are not usually clinically significant to the patient, although drug excretion in saliva may cause oral effects, such as altered taste, and drug excretion via breast milk may affect the breastfeeding infant. GI tract: Some drugs metabolized by the liver may be eliminated by transfer into bile, which then enters the small intestine. This is particularly true for drugs of higher molecular weight, usually over 300, such as morphine, indomethacin and chloramphenicol. Once in the intestine, the drug may be excreted in stool. Or, the drug may be altered by intestinal bacteria and reabsorbed back into the circulation for a return passage through the liver, which delays elimination from the body. This process is known as enterohepatic recirculation, and can prolong a drugs effect on the body. Lungs: The lungs are a major route of elimination for gaseous and volatile drugs, such as inhaled anesthetics.

Alcohol is also excreted via the lungs, which is the basis for the alcohol breath test commonly used to determine the presence and amount of alcohol in the body. Implications for Care Because the majority of drug elimination is handled by the kidneys, any reduction in normal renal function may affect this process, leading to possible drug accumulation and increased risk of adverse effects and toxicity. Renal function tends to decrease with age, therefore, the elderly are at increased risk for drug elimination and toxicity issues. Newborns and young infants are also at risk, due to immaturity of renal function, particularly glomerular filtration and tubular secretion and reabsorption. These normally reach adult levels by one year of age. Other factors that place the patient at risk for impaired drug elimination include acute or chronic kidney disease, poor renal perfusion, hypertension, heart failure, dehydration, diabetes and atherosclerosis. The liver plays an important role in converting drugs to a water-soluble form, which allows for elimination by the kidneys. Also, the liver manufactures bile, which is another route of excretion for some drugs. Therefore, decreased hepatic function, such as from cirrhosis, hepatitis or other liver conditions, may also decrease drug elimination. The patients renal function, determined by creatinine clearance and/or estimated glomerular filtration rate, should be used by the prescriber to determine the appropriate drug dosage and timing, for drugs that are cleared renally. Based on these values, the prescriber may choose to reduce the drug dosage and/or increase the time between doses, for patients with reduced renal function. This allows more time for the drug to be eliminated, reducing the risk of drug build-up and toxicity. Patients at risk for impaired drug elimination should be carefully assessed for therapeutic and adverse drug effects, and signs of drug toxicity. This is especially important when drugs with a narrow therapeutic index are prescribed. These are drugs whose therapeutic levels are fairly close to levels that may produce toxicity, such as digoxin, warfarin, lithium, phenytoin and theophylline. Serum drug levels should be obtained and evaluated as indicated. Assessment should also include any over-the-counter or herbal drugs used by the patient that may affect renal function or interact with currently prescribed medications. Drug elimination is an important process in pharmacokinetics, as this plays an important role in maintaining therapeutic drug levels and reducing adverse effects. An understanding of drug elimination and the factors affecting this process promotes safe and effective drug therapy.

Peak Development for Medication Administration Basic Pharmacology: Drug Elimination Page 2

Peak Development for ... Medication Administration Competency Assessment Tool

Vol. 15 Issue 4 April 2014

Basic Pharmacology: Drug Elimination

NAME: DATE: UNIT:

Directions: Place the letter of the one best answer in the space provided.
_____1. The processes of drug absorption, distribution, metabolism and elimination are known as: A. pharmacodynamics B. pharmacokinetics C. pharmacocompatibility D. pharmacodiffusion _____2. Most drugs are eliminated from the body by which of the following organs: A. liver B. intestines C. kidneys D. lungs _____3. The lungs are primarily responsible for the elimination of: A. drugs comprised of large molecules B. all lipid-soluble drugs C. protein-bound drugs D. gases and volatile drugs _____4. The functional unit of the kidney, where glomerular filtration and other functions occur, is the: A. renal calyx B. nephron C. papilla D. pyramid

_____5. In which of the following renal functions do fluid, drugs and other substances move from the tubule fluid into the bodys circulation: A. tubular secretion B. glomerular filtration C. tubular reabsorption D. none of the above _____6. The pH of urine can normally range from acidic to basic (alkaline). A. True B. False _____7. Elimination of a weakly acidic drug via the kidneys is most effective when the urine pH is: A. basic B. acidic C. neutral D. none of the above pH does not affect drug elimination _____8. Which of the following patients is at greatest risk for impaired drug elimination: A. Mrs. W, age 62, who has fibromyalgia B. James, age 2, having a procedure to relieve a urethral stricture C. Mr. G, age 84, who has heart failure and diabetes D. Mr. F, age 70, having surgery for an inguinal hernia _____9. If drug dosage modifications are needed for a patient with reduced renal function, which of the following is most appropriate: A. increased dosage B. increased time between doses C. decreased time between doses D. decreased dosage and decreased time between doses _____10. Drug toxicity due to impaired elimination is most likely to occur with drugs that: A. are administered orally B. affect the central nervous system C. are protein-bound D. have a narrow therapeutic index
Competency Assessment Tool Basic Pharmacology: Drug Elimination

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