Chapter 3 IM

chapter 3 Pharmacokinetics Learning Outcomes: 1. Identify the four primary processes of pharmacokinetics. Suggested Classroom Activity: Divide students into several groups and assign each one a different drug. Have them look up the pharmacokinetics of the drug and the briefly present their findings to the class. Suggested Clinical Activity: Choose a drug that two different patients are receiving, such as a beta blocker or proton pump inhibitor, and have students discuss how the pharmacokinetics of this drug may differ with each patient. Suggested Clinical Activity: Have each student pick one of the medications that an assigned patient has received during the clinical day. Have them discuss the pharmacokinetics of the drug in relationship to the specific patient. Have them identify any factors (diet, liver function, renal function, etc.) in the patient that would impact any of the phases. 2. Explain mechanisms by which drugs cross plasma membranes. Suggested Classroom Activity: Discuss the factors involved in the different mechanisms of drug movement across cell membranes. Suggested Clinical Activity: Choose a patient and review the medications he or she is receiving, exploring how the prescribed drugs for that patient will move across plasma membranes. 3. Discuss factors affecting drug absorption. Suggested Classroom Activity: Divide students into a few groups and assign each group a different drug, choosing some oral and parenteral drugs. Have them research what factors will affect absorption of the drug. Suggested Clinical Activity: Have each student choose one of the drugs an assigned patient is receiving and discuss what factors in that patient will most affect absorption of the drug. 4. Discuss how drugs are distributed throughout the body. Suggested Classroom Activity: Divide students into groups and have each group discuss one of the primary ways drugs cross plasma membranes. Have them identify a few drugs that use each method of distribution. Discuss findings in the large group. Suggested Clinical Activity: Have students pick one of the drugs being taken by an assigned patient and discuss what barriers the patient has, if any, to the distribution of the drug. 5. Describe how plasma proteins affect drug distribution. Suggested Classroom Activity: Divide class into sections and assign each a different drug, choosing ones that have a different protein-binding percentage, such as digoxin, gentamicin, and phenytoin. Discuss how these different percentages affect blood levels of the circulating drug and how the addition of another drug can displace the drug. Suggested Clinical Activity: Have students check the albumin level of an assigned patient and discuss how this will affect drug availability of the medications that are prescribed. 6. Explain the metabolism of drugs and its applications to pharmacotherapy. Suggested Classroom Activity: Compare the differences in oral and intravenous doses of meperidine (Demerol) and/or morphine sulfate to explain the first-pass effect. Suggested Classroom Activity: Explain that some drugs, such as methylphenidate (Ritalin), are available in short-acting as well as extended release formulas. Discuss how this relates to the half-life of the drug. Discuss what some of the advantages and disadvantages of the different doses might be. When might the short-acting formula be chosen over the long-acting one? Suggested Clinical Activity: Have the students choose one patient who is receiving at least three to four drugs and have them check if any of the drugs are CYP substrates. Have them cross-check all the drugs to determine if any of the other drugs are inducers or inhibitors of the same isoenzyme system and discuss the implications it could have for the patient. 7. Identify major processes by which drugs are excreted. Suggested Classroom Activity: Discuss the implications of drugs that are excreted in breast milk for the woman who is breast-feeding. Suggested Classroom Activity: Discuss drugs that are excreted by routes other than the kidney. Suggested Clinical Activity: Have students review the assessment data (I&O, urinary function, etc.) and laboratory values that reflect renal function (creatinine and BUN levels) on an assigned patient and discuss the impact on excretion of medications they are receiving. 8. Explain how enterohepatic recirculation affects drug activity. Suggested Classroom Activity: Discuss the effects of enterohepatic recirculation on drugs with a long half-life, such as amiodarone. Suggested Clinical Activity: Have students examine the role enterohepatic recycling will have on the drugs being taken by one patient. 9. Explain how a drug reaches and maintains its therapeutic range in the plasma. Suggested Classroom Activity: Divide students into a few groups and assign each of them a drug level to monitor, such as lithium, digoxin, or vancomycin levels. Discuss when these levels should be taken and what is done when levels indicate subtherapeutic or toxic levels. Suggested Classroom Activity: Choose one or two drugs, such as digoxin or vancomycin, and discuss why plasma drug levels might be monitored and how the lab results are used to adjust doses. Suggested Clinical Activity: Show students how blood levels are monitored in the clinical setting. If possible, find a drug on which peak and trough level tests are being done and discuss the implications and responsibilities associated with this. 10. Explain the applications of a drug’s plasma half-life (t1/2) to pharmacotherapy. Suggested Classroom Activity: Have students look up the half-life of any drug. Choose a few different ones and correlate the implications of half-life to drug dosing schedules. Suggested Clinical Activity: Have students examine the half-life of drugs prescribed for their assigned patient(s) and correlate this to the schedule of times for administration. 11. Differentiate between loading and maintenance doses. Suggested Classroom Activity: Discuss the purpose and practical application of drugs that are sometimes prescribed with an initial loading dose, such as azithromycin (the Z pack) and digoxin. Suggested Clinical Activity: Illustrate an example of a loading dose if one is found in the clinical setting. Key Concepts Pharmacokinetics is what the body does to drugs. Pharmaco means “medicines,” and kinetics means “movement.” Drugs face numerous obstacles in reaching their target cells, the greatest of which is crossing the many membranes that separate the drug from its target cells. The four phases of pharmacokinetics are absorption, distribution, metabolism, and excretion. Various mechanisms are used by drugs to reach target tissues. These can involve simple diffusion (passive transport), facilitated diffusion, and active transport. Simple diffusion involves movement from an area of high concentration to one of low concentration. Facilitated diffusion involves utilization of a carrier protein. Active transport involves movement against a concentration gradient, which requires energy. The first phase of pharmacokinetics, absorption, is the process of moving a drug from the site of administration to the bloodstream. Absorption is affected by many different factors. The route of administration is one of the most important variables affecting drug absorption. Enteral drugs are delivered to the GI tract, either orally (PO) or through nasogastric or gastrostomy tubes. Tablets and capsules are the most common forms of oral medication and must dissolve before the drug becomes available to the body for absorption. Enteric-coated tablets are designed to dissolve in the alkaline environment of the small intestine. Extended release tablets or capsules are designed to dissolve slowly, resulting in a longer duration of action. Drugs absorbed from the stomach and small intestine first travel to the liver, where they may be inactivated in a process called the first-pass effect. Sublingual and buccal administrations are enteral routes in which the medications are not swallowed but instead are kept in the mouth. Topical drugs are applied to the skin or mucous membranes. Some drugs are applied topically to produce a local effect, while others are so administered to provide for slow release and absorption to the general circulation. Parenteral drugs are administered by routes other than enteral or topical. Intradermal and subcutaneous drugs are administered into the layers of the skin. Intramuscular drugs are administered directly into large muscles. Intravenous drugs are delivered directly into the bloodstream For almost all drugs, higher doses produce a faster and greater response. The physical and chemical condition of the GI tract plays a significant role in absorption for drugs administered by mouth. For a drug to be absorbed, there must be adequate blood flow to the site of administration. Ionization of the drug affects its ability to cross plasma membranes and to be excreted by the body. Drug–drug and food–drug interactions have the potential to affect absorption. Other factors being equal, drugs will be absorbed faster when applied to regions of the body having a larger surface area. Drug distribution is the second phase of pharmacokinetics. It involves the transportation of the drug through the body. Distribution is affected by drug solubility, tissue storage, amount of blood flow to tissue, and protein binding. Drugs compete for protein-binding sites. Only unbound drugs will reach their target site. The percentage of drug bound to plasma proteins is found in most drug guides. Special barriers to drug distribution include the blood–brain barrier and the fetal–placental barrier. The drug metabolism process is also called biotransformation. In this process, the body chemically changes a drug molecule, which results in functional changes to the drug. Prodrugs are medication that require metabolism to produce their therapeutic actions. For many drugs, metabolism is accomplished by the hepatic microsomal enzyme system in the liver by the CYP, or cytochrome P450, enzyme system Drugs metabolized by CYP are substrates for the enzyme. Some drugs act to inhibit the action of CYP and are called enzyme inhibitors. Some drugs have the ability to cause enzyme induction and are called enzyme inducers. Some drugs have the ability to increase metabolic activity in the liver, a process called enzyme induction. The first-pass effect occurs with many oral drugs. Much of the drug is rendered inactive on the first trip through the liver and does not reach general circulation. Because of this effect, oral doses of drugs often differ from a parenteral dose of the same drug. Infants do not develop a mature microsomal enzyme system until at least 1 year of age and this activity is generally reduced in older adults. CYP activity can be genetically determined. CYP activity is also affected by lifestyle factors such as tobacco use and chronic alcohol consumption. The rate at which a drug is excreted determines the drug concentration’s in the blood. Drugs are excreted primarily via the kidney, but may also be eliminated via pulmonary, fecal, and glandular routes. The renal excretion of drugs is influenced by the pH of the filtrate in the renal tubule. The lungs excrete most drugs in their original unmetabolized form. Drugs may also be excreted by glands into saliva, sweat, or breast milk. Drugs cleared through biliary excretion can be recirculated many times with bile, extending the length of time in the body. Time response relationships illustrate drug plasma levels following administration of a specified dose. These levels reflect a minimum effective dose, the therapeutic range, and toxic concentration. The plasma half-life (t1/2) is the time required for a drug’s plasma concentration to be reduced by one half after being administered. It takes four half-lives for a drug to be considered eliminated from the body. Repeated dosing of a drug allows for the drug to reach a plateau level, which is often desired in order to provide a therapeutic response. Administration of a loading dose of medication may be given to increase the plasma level of the drug and induce a therapeutic response sooner. A maintenance dose is given to keep the drug level in a therapeutic range. Adams and Urban, Pharmacology: Connections to Nursing Practice, 3e Instructor’s Resource Manual Copyright 2016 by Education, Inc. Adams and Urban, Pharmacology: Connections to Nursing Practice, 3e Instructor’s Resource Manual Copyright 2016 by Education, Inc.