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Pharmacology for Nurses A Pathophysiologic Approach Third Edition CHAPTER 4 Pharmacokinetics Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. NCLEX-RN Review Question 1 A patient has an order for a tetracycline antibiotic and has been instructed to avoid taking the medication with foods, beverages, or drugs that contain calcium, iron, or magnesium. What stage of the pharmacokinetic processes is behind the rationale for this instruction? Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. NCLEX-RN Review Question 1 – Choices 1. 2. 3. 4. Absorption Distribution Metabolism Excretion Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. NCLEX-RN Review Question 1 – Answer 1. 2. 3. 4. Absorption Distribution Metabolism Excretion Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. NCLEX-RN Review Question 1 – Rationale Rationale: Some medications can be affected by foods, beverages, or other drugs. The effect of calcium, iron, and magnesium on a tetracycline antibiotic is an example of a food–drug interaction that occurs in the absorption process. Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. NCLEX-RN Review Question 2 The patient has a malignant brain tumor. What property of pharmacokinetics may cause difficulty in treating her tumor? Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. NCLEX-RN Review Question 2 – Choices 1. 2. 3. 4. Blood–brain barrier Drug–protein complexes Affinity for neoplasms Lack of active transport Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. NCLEX-RN Review Question 2 – Answer 1. 2. 3. 4. Blood–brain barrier Drug–protein complexes Affinity for neoplasms Lack of active transport Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. NCLEX-RN Review Question 2 – Rationale Rationale: The blood–brain barrier may cause difficulty in treating tumors. Most antitumor medications do not cross the blood–brain barrier. Cognitive Level: Analysis Nursing Process: Assessment Patient Need: Physiological Integrity Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. NCLEX-RN Review Question 3 A patient with cirrhosis of the liver exhibits decreased metabolic activity. This will require what possible change in her drug regimen? Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. NCLEX-RN Review Question 3 – Choices 1. A reduction in the dosage of drugs 2. A change in the timing of medication administration 3. An increased dose of prescribed drugs 4. All prescribed drugs must be given by intramuscular injection. Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. NCLEX-RN Review Question 3 – Answer 1. A reduction in the dosage of drugs 2. A change in the timing of medication administration 3. An increased dose of prescribed drugs 4. All prescribed drugs must be given by intramuscular injection. Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. NCLEX-RN Review Question 3 – Rationale Rationale: The liver is the primary site of drug metabolism. Patients with severe liver damage, such as that caused by cirrhosis, will require reductions in drug dosage because of the decreased metabolic activity. Cognitive Level: Analysis Nursing Process: Implementation Patient Need: Physiological Integrity Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. NCLEX-RN Review Question 4 Some drugs may be completely metabolized by the liver circulation before ever reaching the general circulation. This effect is known as what? Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. NCLEX-RN Review Question 4 – Choices 1. 2. 3. 4. Conjugation of drugs Hepatic microsomal enzyme system Blood–brain barrier First-pass effect Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. NCLEX-RN Review Question 4 – Answer 1. 2. 3. 4. Conjugation of drugs Hepatic microsomal enzyme system Blood–brain barrier First-pass effect Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. NCLEX-RN Review Question 4 – Rationale Rationale: Some oral drugs are rendered inactive by hepatic metabolic reactions, during the process known as the first-pass effect. An alternative route may need to be assessed. Cognitive Level: Application Nursing Process: Implementation Patient Need: Physiological Integrity Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. NCLEX-RN Review Question 5 A patient who is in renal failure may have a diminished capacity to excrete medications. It is imperative that this patient be assessed for what development? Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. NCLEX-RN Review Question 5 – Choices 1. 2. 3. 4. Increased creatinine levels Increased levels of blood urea nitrogen Drug toxicity Increased levels of potassium Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. NCLEX-RN Review Question 5 – Answer 1. 2. 3. 4. Increased creatinine levels Increased levels of blood urea nitrogen Drug toxicity Increased levels of potassium Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. NCLEX-RN Review Question 5 – Rationale Rationale: The kidneys are the primary site of excretion. Renal failure increases the duration of the drug’s action because of decreased excretion. The patient must be assessed for drug toxicity. Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. NCLEX-RN Review Question 5 – Rationale (cont'd) Cognitive Level: Analysis Nursing Process: Assessment Patient Need: Physiological Integrity Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. Application of Pharmacokinetics to Clinical Practice • Pharmacokinetics: the study of drug movement throughout the body • Know how the body handles medication • Understand actions and side effects of drugs • Understand obstacles drug faces to reach target cells Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. Drugs in the Body • Greatest barrier for many drugs is crossing many membranes • Enteral route drugs broken down by stomach acids and enzymes • Organs attempt to excrete medicines • Phagocytes may attempt to remove medicines seen as foreign Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. Four Categories of Pharmacokinetics • • • • Absorption Distribution Metabolism Excretion Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. Diffusion or Passive Transport • Molecules move from higher to lower concentration • Usually small, nonionized, or lipid-soluble molecules Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. Active Transport • Chemicals move against concentration or electrochemical gradient • Usually large, ionized, or water-soluble molecules • Cotransport involves the movement of two or more chemicals across the membrane Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. Absorption • Movement from site of administration, across body membranes, to circulating fluids • Primary factor determining length of time for effect of drug to occur Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. Factors Affecting Drug Absorption • • • • • • Route of administration Drug formulation Drug dosage Digestive motility Digestive tract enzymes Blood flow at administration site Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. Factors Affecting Drug Absorption (cont'd) • Degree of ionization of drug – In acid of stomach, aspirin is nonionized and easily absorbed by bloodstream – In alkaline of small intestine, aspirin is ionized and less likely to be absorbed • pH of surrounding environment • Drug-drug/drug-Food interactions • Dietary supplement/herbal product–drug interactions Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. Metabolism (Also Known as Biotransformation) • • • • Changes drug so it can be excreted Involves biochemical reactions Liver—primary site Addition of side chains, known as conjugates, makes drugs more water soluble and more easily excreted by the kidneys Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. Metabolism in the Liver • Hepatic microsomal enzyme system (P450 system) – Inactivates drug – Accelerates drug excretion – some agents, known as prodrugs, have no pharmacologic activity unless first metabolized to active form by body Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. Enzyme Induction • A drug increases metabolic activity in the liver • Changes in the function of the hepatic microsomal enzymes can significantly affect drug metabolism Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. Oral Drugs Enter Hepatic-Portal Circulation (First-Pass Effect) • Drug absorbed • Drug enters hepatic circulation, goes to liver • Drug is metabolized to inactive form • Drug conjugates and leaves liver • Drug is distributed to general circulation • Many drugs rendered inactive by first-pass effect Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. Figure 4.4 First-pass effect: (a) drugs are absorbed; (b) drugs enter hepatic portal circulation and go directly to liver; (c) hepatic microsomal enzymes metabolize drugs to inactive forms; (d) drug conjugates, leaving liver; (e) drug is distributed to general circulation. Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. Metabolism and Pharmacotherapy • Can be decreased metabolic activity in some clients – Infants and elderly – Clients with severe liver disease – Clients with certain genetic disorders – Dosages need to be adjusted in these clients Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. Distribution of Medications • Distribution involves the transport of pharmacologic agents throughout the body – Simplest factor determining distribution is the amount of blood flow to body tissues • Physical properties of drug have big influence • Certain tissues, such as bone marrow, have a high affinity, or attraction, for certain medications Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. Drugs Bind with Plasma Proteins • Many drug molecules form drug–protein complexes – binding reversibly to plasma proteins – and thus never reach target cells • Cannot cross capillary membranes • Drug not distributed to body tissues Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. Figure 4.3 Plasma protein binding and drug availability: (a) drug exists in a free state or bound to plasma protein; (b) drug-protein complexes are too large to cross membranes. Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. Distribution of Medications • Drugs and other chemicals compete for plasma protein–binding sites – Drug–drug and drug–food interactions may occur when one drug displaces another from plasma proteins • Some have greater affinity • Displaced drug can reach high levels – Can produce adverse effects Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. Distribution of Medications (cont'd) • Blood-brain barrier and fetal-placenta barrier: special anatomic barriers that prevent many chemicals and medications from entering – Makes brain tumors difficult to treat – Fetal-placenta barrier protects fetus; no pregnant woman should be given medication without strong consideration of condition Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. Primary Site of Excretion of Drugs Is Kidneys • Free drugs, water-soluble agents, electrolytes, and small molecules are filtered • Drug-protein complexes are secreted into distal tubule • Secretion mechanism is less active in infants and older adults • pH of filtrate can increase excretion Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. Renal Failure Diminishes Excretion of Medications • Drugs retained for extended times • Dosages must be reduced Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. Other Organs Can Be Sites of Excretion • Respiratory system • Glands • Biliary system Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. Enterohepatic Recirculation of Drugs • Drugs excreted in bile • Bile recirculates to liver • Percentage of drug recirculated numerous times • Prolongs activity of drug – Activity of drug may last after discontinuation Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. Drug Plasma Concentration and Therapeutic Response • Concentration of medication in target tissue often impossible to measure, so must be measured in plasma – Minimum effective concentration - amount of drug required to produce a therapeutic effect – Toxic concentration - level of drug that will result in serious adverse effects – Therapeutic range - plasma drug concentration between the minimum effective concentration and the toxic concentration Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. Plasma Half-Life (t1/2) of Drugs • Length of time needed to decrease drug plasma concentration by one half • The greater the half-life, the longer it takes to excrete • Determines frequency and dosages Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. How Drug Reaches and Maintains Therapeutic Range • • • • Repeated doses of drug given Drug accumulates in bloodstream Plateau reached Amount administered equals amount eliminated Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. Loading Dose • Higher amount of drug given • Plateau reached faster • Quickly produces therapeutic response Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved. Maintenance Dose • Keeps plasma-drug concentration in therapeutic range Pharmacology for Nurses: A Pathophysiologic Approach, Third Edition Adams • Holland Copyright ©2011 by Pearson Education, Inc. All rights reserved.