NURS 676A STUDY GUIDE QUIZ 1 - DOWNLOAD TO SCORE AN A+

NURS 676A STUDY GUIDE QUIZ 1 - DOWNLOAD TO SCORE AN A+ • How is prescriptive authority regulated for NPs Twenty-one states have fully independent prescribing by nurse practitioners (AANP, 2013b; National Council of State Boards of Nursing, 2015). Some states have full or limited prescribing allowed by CNSs, including Alaska, Colorado, Connecticut, Hawaii, Iowa, Idaho, Minnesota, Montana, Nevada, New Mexico, North Dakota, Oregon, Utah, Vermont, Washington, DC, and Wyoming (National Council of State Boards of Nursing, National Council of State Boards of Nursing recommends licensure as the appropriate level of regulation for the autonomy and authority of the NP role, some states still recognize NPs with certification, endorsement, or through delegated authority from a physician. States have authority under the states’ “police power” to take regulatory action to protect public health, welfare, and safety, including emergency suspension or revocation of practice authority. The courts have consistently upheld professional licensing laws as legitimate use of this power. The purpose of these laws is to ensure that those who provide health- • Who regulates Schedule II drugs and why • Drug Enforcement Administration • DEA is the lead Federal law enforcement agency responsible for enforcing the Controlled Substances Act (CSA). • The most comprehensive federal drug legislation is the Controlled Substances Act of 1970 (FDA, 2010). This law was designed to improve regulation of the manufacturing, distribution, and dispensing of drugs identified as “controlled” drugs by providing a closed system for legitimate providers of these substances. Every person who manufactures, distributes, prescribes, procures, or dispenses any controlled substance must register and obtain a registration number with the U.S. Drug Enforcement Administration (DEA). The Practitioner's Manual: An Informational Outline of the Controlled Substances Act, published in 2006, outlines regulations and requirements for controlled-drug prescribing. This pamphlet is available from the DEA or can be viewed online ( • Many states have controlled substance acts patterned after federal law. Because differences are allowed in the scheduling of drugs among states (a state may be more restrictive but not less restrictive), NPs must become acquainted with the provisions of the regulations in the state in which they are licensed. NPs wanting authority to prescribe controlled substances must apply for state prescriptive authority prior to application for a federal DEA number. Applications for a DEA number may be obtained online through the DEA or though the state regional office. Before applying, it is important to verify with the state board of nursing or pharmacy if a state-issued prescribing number or certificate is also issued separately from the NP license. • For many years the DEA number was inappropriately used for other than controlled substances by pharmacies, primarily to bill insurance or track medications under a provider-unique identifier. Concern over this as well as the plethora of separate numbers used for Medicaid and Medicare billing led to the development and use of the National Provider Identifier number (NPI). The NP should obtain an NPI as soon as it is feasible. Application is free and available online. This number is unique to the provider and is used for all prescriptions that are billed through insurance, as well as for other billing services. • In an effort to control drug distribution, a classification system was developed to categorize drugs as “controlled” based on their potential for abuse, accepted medical use, and diversion potential. NPs must know the different classifications and schedules of controlled drugs as well as the associated prescribing rules and regulations. Controlled drugs are listed in five different schedules— I, II, III, IV, and V—to which different regulations apply. Controlled substance authority for NPs varies from state to state according to ability and autonomy of practice. • Table 4-1 presents the schedules, controls required, and examples of drugs. • Controlled Substance Prescribing Precautions • Prescribers should take precautions with controlled drug prescription pads and information included on the controlled substance prescription to minimize the chance for fraud and diversion of these drugs. The prescription pad (or prescription printer paper) should be stored in a locked area or locked drawer on the printer. Prescriptions should never be signed in advance or used as notepads. The prescriber's name, NPI number, address, and telephone number should be printed on the pads to allow verification by the dispensing pharmacist. Some states also require that the NP's license number appear on the prescription in addition to that of any supervising/collaborating practitioner. The DEA registration number must be designated on all controlled substance prescriptions, though individual states may permit a pharmacist to write in the DEA number if it is not initially provided. The prescription should be dated on the day it is written, indicating any authorized refills as allowed and clinically appropriate. It is helpful to spell out the quantity dispensed as well, using an Arabic numeral (e.g., “forty [40]”) to discourage alterations in the intended quantity. • A prescription for a controlled substance may be directly faxed to the pharmacy as an additional precaution, with the exception of Schedule II controlled substances. A fax cannot be considered the original for Schedule II drugs unless the drug in question is (1) for a nursing home, (2) for a hospice, or (3) for parenteral medication for home IV administration. • As of 2009, tamper-proof prescription pads are required for prescriptions written for patients under Medicaid payment plans. State law incorporates the federal guidelines for what constitutes a tamper-proof prescription into any additional state-specific requirements for controlled substances, such as duplicate prescription pads. A practitioner may find the use of tamper-proof prescription pads or paper to be advisable for all written prescriptions, because many drugs that have abuse potential are not currently federally controlled. Such drugs include tramadol, carisoprodol, and pseudoephederine. No refills permitted No telephone orders unless true emergency and followed up by written prescription within 7 days Electronic prescribing permitted as of 2011 with specific software and secure identification processes Narcotics (morphine, codeine, meperidine, opium, hydromorphone, oxycodone, oxymorphone, methadone, fentanyl) Stimulants (cocaine, amphetamine, methylphenidate) Depressants (pentobarbital, secobarbital) Opioids such as morphine have legitimate clinical usefulness, and the practitioner should not hesitate to prescribe them when indicated for patients who require analgesia or symptomatic relief not provided by other analgesics. Methadone is also used for chronic pain management due to its cost and long half-life. However, methadone also has an extremely variable half-life (7 to 60 or more hours) that differs for individuals based on their metabolism. It therefore should not be a first-line therapy for pain management, especially for the less experienced practitioner. Buprenorphine is another long-acting opioid used for pain management. Both buprenorphine and methadone are legal to prescribe for pain management provided that an NP has his or her own Schedule II authority. However, it is not legal for an NP to prescribe methadone or buprenorphine for narcotic addiction, and such patients should be referred to an MD or a state-registered clinic that specializes in addiction treatment. • What are the key principals of drug metabolism, absorption, excretion and distributions barriers (ie: blood brain barrier). • Absorption • Medications produce little clinical effect when they remain inside the prescription bottle. To produce a biological effect, drugs must enter the body. Once inside the body, drugs can interact with various receptor molecules to produce physiological changes that result in clinical effectiveness. • The way in which medications are presented to the body affects the speed, the extent, and the duration of drug absorption. The route of administration also affects patient compliance, that is, their willingness to follow recommendations for taking a medication (Box 2-4). So choosing the route of administration can have important implications for drug therapy, and it is not surprising that a variety of routes of administration can be chosen based on the chemical properties of an individual drug, the condition of an individual patient, and the goal of drug treatment. • Bioavailability • Because not all of the administered dosage may be dissolved or absorbed or survive liver passage, only a fraction of an administered dosage makes it to the bloodstream. This percentage of the administered dose that does enter the bloodstream is called the bioavailability of the dosage form. Bioavailability can range from less than 10% to more than 90% for oral dosing. When the bioavailability of an oral preparation is low, a higher dose will be given so that the amounts reaching the bloodstream are similar. For example, an oral dose of 500 mg of ciprofloxacin can be substituted for a 400 mg IV dose; ciprofloxacin has about 80% oral bioavailability. • Peak Blood Levels • The speed at which drugs enter the bloodstream affects the maximum blood level that is achieved following drug administration (Fig. 2-8). Rapid absorption leads to higher peak blood levels, with a risk of greater toxicity and side effects. So rapid IV administration (e.g., “IV push”) produces immediate drug effects but increases the risk of toxicity and adverse effects. For these reasons, some medications, such as aminoglycoside antibiotics, are administered by slow IV infusion over 30 to 60 minutes. This allows distribution to occur, keeps the blood level from getting too high, and minimizes toxicity. • Distribution • After a drug is absorbed, it still must reach its site of action to produce an effect. The process of drugs moving throughout the body is called distribution. Distribution of drugs can occur by transfer through the bloodstream and passive diffusion, or their distribution can be promoted or limited by the presence of transport systems that may selectively transport or exclude drugs based on size, charge, or chemical structure. Diffusion can influence the action of drugs; drugs can be effective only if they reach their site of action in adequate concentrations before they are metabolized. • Volume of Distribution • The volume of distribution (VD) is a hypothetical value that reflects the volume in which a drug would need to be dissolved to explain the relationship between dosage and blood levels. If we administer a dose of 100 mg and the plasma concentration is 2 mg/L, then it appears as though the drug is distributed in 50 liters. If we administer the same dose and the plasma concentration is 20 mg/L, then it appears as though the drug is distributed in a volume of 5 liters (Fig. 2-9). • Volume of distribution is important not only because it relates dosage to blood level but because it tells us something about where a drug might be distributed. Drugs that are confined to the bloodstream will have a volume of distribution equal to the blood volume. The plasma volume is really the smallest volume of distribution we will encounter, since it is not possible for drugs to confine themselves to part of the circulation volume. Plasma makes up about 4.5% of body weight, or about 3 L for an average person. Total body water is about 50% to 60% of body weight (35 to 40 L), depending on gender and body fat. Total body water is about two-thirds intracellular and one-third extracellular. • Volume of distribution is hypothetical, however, so it may also be higher than the amount of volume. For example, a volume of distribution can represent distribution into an amount of water greater than the total body volume; this suggests that much of the drug is bound somewhere outside the bloodstream. • Metabolism is an important factor in determining drug activity. When drugs are metabolized, they are chemically altered by enzymes into new molecules, called metabolites. Metabolism can increase or decrease the onset, duration of action, and toxicity of a medication. So it is important to know how metabolism affects drug activity and pharmacokinetics and how other drugs might interact to alter drug metabolism. • The body is a large container of enzymes that catalyze many different chemical reactions that are required to maintain life. If you think about it, one of the requirements for sustainable life is the ability to maintain a constant internal environment. All organisms are exposed to molecules that cannot be used for food or energy. If an organism cannot rid itself of a certain molecule, then that molecule can accumulate until it causes some sort of toxicity. Therefore, the human body has developed a series of enzymatic reactions directed at all sorts of molecules encountered during life. Drugs that are lipid soluble or weakly acidic or basic may not readily be excreted from the body. In general, the idea is to make these molecules more water soluble so they can be excreted by the kidneys. • Metabolism is the process of changing one chemical into another, and the process usually either creates or uses energy. Metabolism of drugs can occur in every biological tissue, but it occurs mostly in the smooth endoplasmic reticulum of cells in the liver. The liver is a major organ for drug metabolism because it contains high amounts of drug- metabolizing enzymes and because it is the first organ encountered by drugs once they are absorbed from the gastrointestinal tract. Metabolism by the liver following oral administration is called first-pass metabolism and is important in determining whether a drug can be orally administered. • There is a “family” of enzymes, cytochrome P450 (CYP; pronounced sip), that metabolizes drugs. Each of these CYP enzymes is responsible for a single type of metabolic reaction. A drug may undergo several of these biological transformations, or biotransformations, sometimes in different body tissues, before being excreted. Understanding drug metabolism through these CYPs can provide a framework for understanding metabolism in individual patients, as well as drug interactions with other medications and with food. Drug metabolism utilizes two types of reactions that prepare and tag molecules for excretion. Phase I reactions, or nonsynthetic reactions, involve oxidation, reduction, and hydrolysis reactions, which prepare the drug molecule for further metabolism. Phase I reactions introduce or unmask polar groups that, in general, improve water solubility and prepare drug molecules for further metabolic reactions. Phase I metabolism can result in metabolites with greater or lesser pharmacological activity. Many phase I metabolites are rapidly eliminated, whereas others go on to phase II reactions Phase II reactions are called synthetic or conjugation reactions because drug molecules are metabolized and something is added to the drug to synthesize a new compound. Metabolites are linked, or conjugated, to highly polar molecules such as glucuronic acid, glycine, sulfate, or acetate by specific enzymes. Conjugation to these molecules makes metabolites more water soluble and more easily excreted by the kidneys. So the presence or activity of these enzymes can influence the pattern of drug activity and the duration of action for drugs. The most thoroughly studied drug metabolism reaction is the CYP P450 mixed- function oxidase reaction. This reaction catalyzes the metabolism of a large number of diverse drugs and chemicals that are highly lipid soluble. CYP transfers electrons from the oxidation of drugs to the electron transport system of the endoplasmic reticulum, a cell organelle. There are many forms of CYP that are products of separate and distinct genes and that catalyze different reactions. Over 50 human CYPs have been isolated so far. The CYPs are organized into numbered families based on their function. For example, the CYP1, CYP2, and CYP3 families metabolize a variety of drugs and steroids (Box 2-5). Subfamilies are designated by additional letters and individual enzymes by numbers. The CYP3As are the major subfamily expressed in the human liver and consist of three forms: CYP3A4, CYP3A5, and CYP3A7. The CYP3A7 enzyme is present in the fetus and appears to be discontinued after birth. CYP3A4 is a major drug-metabolizing enzyme, whereas CYP3A5 metabolizes the same drugs but is less active. Prodrugs are inactive compounds that rely on metabolism to become active. Prodrugs have advantages and disadvantages. The advantages may be in terms of their absorption or distribution. L-DOPA is a prodrug used to treat Parkinson's disease. The problem in Parkinson's disease is a lack of dopamine in the striatum of the brain. Dopamine, however, cannot pass through the blood–brain barrier, so it cannot be used to treat the neurotransmitter shortage in the brain. L-DOPA can pass into the brain and enter into cells, where it can be converted into dopamine. Prodrugs can also have disadvantages. Terfenadine was one of the first nonsedating antihistamines and was quite popular at one time. First- pass metabolism by CYP3A4 biotransforms terfenadine, which is cardiotoxic, into fexofenadine, an effective antihistamine. When it was realized that inhibition of CYP3A4 could result in toxicity and death in some patients, terfenadine was withdrawn and replaced with fexofenadine, its active metabolite. Renal Excretion The kidney is the primary organ of excretion for most drugs. The general theme of metabolism is to produce drug metabolites that are more water soluble and more easily removed by the kidneys. The kidney can then remove these substances from the plasma and excrete them in the urine. The kidney is a complex organ with several important functions, including excretion of waste products and maintenance of fluid and electrolyte balance in the body. The strategy of the kidney is to allow removal of a large volume of plasma and then to take back the substances that the body needs. The result is urine. There are also transport mechanisms that can secrete substances into the urine. We will consider how drugs manage to end up in the urine. Production of urine begins in the glomerulus of the kidney. The operational unit of the kidney is the nephron, and each of the approximately 1 million nephrons begins with a glomerulus (Fig. 2-12). The glomerulus is a specialized area of the nephron adapted for ultrafiltration, a process in which substances in the plasma pass through small holes, or pores, in the glomerular capillary membrane based on their size and charge. The structure of the glomerular capillary membrane permits filtration of smaller molecules while restricting the passage of compounds with larger molecular weights. As blood flows through the kidney and encounters the glomerulus, much of the fluid portion of the blood is filtered into the lumen, or center, of the nephron. The kidney is exceptionally efficient at what it does. Approximately 125 mL of blood flows through the glomeruli in the kidneys per minute, the glomerular filtration rate (GFR), and it is an important measure of renal function. Glomerular filtration is the first step toward production of urine containing excreted drug. Filtration preserves plasma proteins while removing free drugs and other waste products from the plasma. The large volume of fluid filtered through the glomerulus is an ideal vehicle for drug removal. As the ultrafiltrate is formed, drugs that are free in the plasma and not bound to plasma proteins or blood cells are filtered. Filtration may be slower for drugs that are large because of the size of the pores through which filtration occurs; very large drugs may not be filtered at all. The pores of the glomerulus contain a fixed negative charge, so filtration may also be affected by drug charge. The glomerular filtrate in the nephron contains a variety of smaller molecules, including excreted drug and metabolites. As the filtrate moves through the lumen of the nephron, molecules are reabsorbed from the lumen into the blood. The extent to which a drug diffuses back across the nephron to reenter the circulation is one of the factors that determine urinary excretion of drug. The passive diffusion of substances back into the circulation is encouraged by the reabsorption of water that occurs along most of the nephron, creating a concentration gradient promoting reabsorption if the lipid solubility and ionization of the drug are appropriate. The unionized or uncharged form of the drug will diffuse more readily, and the acidity of urine can influence the ionization and reabsorption of drugs. Acidification of the urine creates a situation that favors the excretion of basic drugs and metabolites, whereas basic urine encourages the excretion of acidic drugs and metabolites. Effects of urine acidity on drug elimination can have important clinical implications. Urine can be made acidic by administration of ammonium chloride and can be made basic by administration of sodium bicarbonate. Tubular Reabsorption In addition to reabsorption by passive diffusion, some substances filtered at the glomerulus are reabsorbed by active transport systems located primarily in the proximal tubule of the nephron. Active transport is important for endogenous substances that the body needs to recover from the glomerular filtrate, such as ions, amino acids, and glucose. The active transport systems are located on the luminal cell surface and transport substances into the cell, where they are passively transported into the plasma. A small number of drugs may be actively reabsorbed. It is more common that drugs acting on tubular secretion do so by inhibiting active transport. Uricosuric agents such as probenecid and sulfinpyrazone inhibit the active reabsorption of uric acid. Substances that are actively reabsorbed can also be actively secreted and drugs may inhibit both processes. For example, low doses of salicylates, such as aspirin, inhibit tubular secretion and decrease total urate excretion, whereas higher doses inhibit tubular reabsorption and result in increased excretion of uric acid. Tubular Secretion The nephron also contains active secretory systems that transport drugs from the blood into the lumen of the nephron. There is a transport system that secretes organic anions and a transport system that secretes organic cations. The transporters are present on the plasma side of the tubular cells of the nephron, where they actively pump anions or cations into the cell. The substances then pass into the lumen by passive transport. The secretory capacity of these transporters can be saturated so that less drug is excreted at high drug concentrations. When two drugs are substrates for the same transporter, they compete with one another and decrease the rate at which each is excreted. Active secretory systems for anions and cations are important because charged anions and cations are often strongly bound to plasma proteins and may not be readily excreted by glomerular filtration. Tubular secretion often contributes to the renal elimination of drugs that have short half-lives. Hydrochlorothiazide, furosemide, penicillin G, and salicylates are among the substrates for the organic anion transport system. The organic cation transport system actively secretes atropine, cimetidine, morphine, and quinine. Renal Excretion of Drugs The rate at which a drug is excreted by the kidneys depends on several factors. Renal blood flow influences the GFR, which is how much plasma is filtered per minute by the glomerulus. Filtration in the glomerulus depends on the molecular size, the charge, and the degree of protein binding, each of which influences how much drug passes through the glomerular basement membrane. Tubular acidity will influence the degree of reabsorption. Active reabsorption or active secretion into the urine may also influence excretion rate. Renal excretion of drugs is typically well characterized. What is variable, however, is the level of renal function in an individual patient receiving a renally excreted medication. It is common to monitor renal function of patients in the clinical setting and to adjust dosages based on renal function and the renal contribution to drug excretion. Renal function is typically assessed from patient serum creatinine along with height, weight, age, and gender. Biliary Excretion In addition to metabolizing many drugs, the liver secretes about a liter of bile each day. Drugs can enter the bile and be excreted into the intestinal tract when bile is released to help digest food. Only small amounts of drug enter the bile by diffusion; instead, biliary excretion contributes to removal of some drugs. The biliary system includes three types of active transport. Organic cation and organic anion transporters are similar to those found in the renal tubules. The additional system is the bile acid transport system. Conjugated metabolites of drugs generally have enhanced biliary excretion. Cardiac glycosides, such as digoxin, are an example of drugs secreted into the bile. Some drugs that are excreted in bile can be reabsorbed in the intestine. This creates a phenomenon called enterohepatic cycling, in which drug is excreted in the bile, absorbed from the intestines, and then excreted in the bile again. Enterohepatic cycling decreases the amount of drug that is actually excreted and extends the time that a drug remains in the body. Other Sites of Excretion Drug excretion is not limited to the kidneys and liver. Drugs can diffuse out of the body at various sites, and while these excretion sites are typically not major, they can be important for forensic or clinical reasons. Pulmonary excretion can occur for any volatile material present in the body. Pulmonary excretion is important for anesthetic gases, such as nitrous oxide. Pulmonary excretion is also important following alcohol consumption. Ethanol distributes throughout the body and is readily excreted each time we breathe. Because the amount of ethanol exhaled in each breath is proportional to blood level, the Breathalyzer can be used to estimate blood levels of ethanol. Pulmonary excretion is also important for volatile ketones, which are produced in diabetic patients who are poorly controlled; the smell of ketones on a patient's breath can be an important clue that the patient may have diabetes and be at risk for diabetic ketoacidosis. Substances can be excreted through the skin, although this is often a minor route of elimination. The skin has a large surface area through which excretion can occur; drugs may be incorporated into the hair and can be excreted through the sweat glands. Excretion of drugs into sweat and saliva is of minor importance for most drugs and depends on the diffusion of uncharged drug across the epithelial cells of sweat and salivary glands. Excretion into hair, sweat, and saliva is quantitatively unimportant but can be used to non-invasively detect drugs in the body. Interestingly, some drugs excreted into saliva can produce changes in taste. Excretion into saliva might help explain part of the pharmacological action of certain drugs, such as antibiotic erythromycin, in throat infections. Drugs can also be excreted into the breast milk of nursing mothers. The concentration in the breast milk depends on drug properties such as lipid solubility and the degree of ionization and on patient properties such as the extent of active secretion into breast milk and the blood level of the drug in the mother. Low-molecular-weight drugs that are unionized can passively diffuse across the epithelial cells of the mammary gland and enter the breast milk. Because breast milk is more acidic than plasma, it tends to accumulate basic drugs. Infants can be exposed to drugs through breast milk. The risk to the infant from drug exposure in breast milk depends on the amount and type of drug involved and the ability of the infant to metabolize the drug. Breastfeeding is discouraged when there is a potential for drug toxicity in the infant. o Think about the organ systems that affect these processes (liver, gut, kidneys) • Understand the principals of drug to drug interactions, therapeutic levels and therapeutic effects • The pharmacodynamics of a drug must be specific and selective to the target tissues affected by the disease to have the greatest therapeutic effect with the least adverse effects (Spector & Vesell, 2002). The ease of titration is influenced by the dose–response curve of the drug (Maxwell, 2009). The relationship between a drug's desired therapeutic effects and its adverse effects is called its therapeutic index (see Chap. 2). Drugs with a low or narrow therapeutic index may require close monitoring for toxicity or adverse effects, whereas drugs with a wide therapeutic index are fairly safe and require less monitoring. Antibiotics, for example, tend to have fairly wide therapeutic indices. Propranolol (Inderal) has such a wide therapeutic index that doses safely range from 20 mg to 320 mg. Similar to genetic differences in metabolism, drug–drug interactions can also affect the rate at which individuals metabolize medications. Some medications bind to certain enzymes in the liver and either speed up (induction) or slow down (inhibition) the rate of metabolism and clearance of drugs that flow through the same enzyme pathway. Both scenarios can cause problems, but most commonly drug inhibition leads to accumulation of drug and higher-than- desired concentrations in the circulation, often leading to ADRs. An additional interaction is the potential for two drugs to compete for metabolism, which increases the concentration of both medications and the risk of side effects. Most drug interactions can be identified by reviewing patient medication profiles and using a drug interaction checker, such as Micromedex, Online Facts and Comparisons, or Lexicomp. These resources also provide recommendations based on the severity of the interaction. A review of therapy should be performed prior to the initiation of new medications. There is also the potential for foods to interact and affect metabolism. The best example of food–drug interactions is grapefruit reducing the clearance of simvastatin and increasing the risk of myopathy, or herbal products such as St. John's wort reducing clearance of cyclosporine (Aronson & Ferner, 2003; FDA, 2009). Some drug–drug interactions can manifest rapidly (within 1 to 2 days). For example, when trimethoprim-sulfamethoxazole is added to warfarin, an anticoagulant, warfarin metabolism is reduced, resulting in an increase in the INR and prothrombin time. Ultimately, this increases the risk of bleeding and should be avoided, if possible, or adjustments should be made in monitoring warfarin frequency and dose. Many interactions, however, may take longer to present. For example, when the antiarrhythmic amiodarone is added to digoxin, amiodarone inhibits the metabolism of digoxin. This interaction can take weeks to months before the full extent of the effect precipitates due to the long half- life of amiodarone. It requires diligence to appropriately adjust the digoxin dose and monitor serum concentrations. Although not all interactions are significant, clinicians should evaluate each interaction and determine clinical importance. • What medications require laboratory monitoring and why is this important • Special considerations when prescribing for geriatric, pregnant and pediatric patients • Pregnant patients pose a challenge to the prescriber. Early in pregnancy, there is a risk for drugs being teratogenic to the fetus. The FDA has historically assigned a pregnancy category to prescription drugs, rating them as Pregnancy Category C, D, or X, known to cause fetal harm (U.S. Food and Drug Administration, 2009). The FDA has proposed a change in labeling to incorporate a pregnancy risk summary and clinical considerations to the drug label (U.S. Food and Drug Administration, 2011). Later in pregnancy, drugs may cause fetal adverse effects, such as tachycardia or stroke, or may cause the fetus to abort during premature labor. The National Library of Medicine TOXNET Developmental and Reproductive Toxicology Database (DART) is a Web-based databank of the latest information on the developmental and reproductive effects of drugs (). Drugs in pregnancy are discussed in the Precautions and Contraindications sections for each drug class and in Chapter 49. • • Another significant legislative act was the Pediatric Research Equity Act passed in 2003 (FDA, 2010). This act, referred to as the “Pediatric Rule,” authorized the FDA to request pediatric studies of already marketed drugs or to require studies by others if the manufacturer refuses. Since the passage of the Pediatric Rule, several drugs in common use for children were removed from the market because their safety and efficacy had never been tested in pediatric subjects. • Include the patient weight, especially if pediatric or elderly. atients at the extremes of age, either the very young or the very old, have developmental pharmacokinetic differences that warrant careful prescribing. Infants have immature liver and renal functions that place them at risk for toxicity and ADRs and may require dosage adjustments based on age. Likewise, the elderly population has decreased liver and renal functions related to the physiological changes associated with aging, placing them at risk for increased ADRs. Prescribing for children is discussed in Chapter 50 and prescribing for geriatric patients is discussed in • How is pharmacokinetics affected by ethnicity, gender and age • African Americans (cont’d) ▪ Racial differences in pharmacokinetics and response ▪ Angiotensin-converting enzyme inhibitors may not work as well due to African Americans having less renin-dependent hypertension. ▪ African Americans respond differently to alcohol, psychotropic drugs, and caffeine than do whites; they have higher blood levels, faster therapeutic response, and a higher rate of extra pyramidal effects than do whites. • Asian Americans/Pacific Islanders (cont’d) ▪ Drug pharmacokinetics and response ▪ 2D6 activity is lower in Asians. ▪ Slower metabolism of antidepressants and neuroleptics ▪ May require lower doses ▪ Slower metabolism of drugs requiring 2C19 (diazepam) requiring lower doses ▪ 85% to 90% of Asians have dehydrogenase deficiency. ▪ Decreased alcohol metabolism leading to flushing ▪ East Asians may be “fast acetylators.” ▪ May require a more frequent or higher dose of drugs metabolized by acetylation 1. muscle mass may deteriorate, altering the amount of total body water and volume distribution for certain drugs 2. Albumin level may decline, Malnourished patients affecting protein binding and increasing the amount of free drug 3. Kidney function declines with ae resulting in reduced rate of drug excretion for real cleared drugs 4. Elderly have increased sensitivity to medications. (Start low and go slow) 5. Elderly have more pronounced adverse reactions to meds 1. Neonates have an increased amount of free body water 2. Neonates/infants may not have fully developed enzyme pathways so metabolism may be altered 3. Preterm infants can have altered protein binding 4. Children are constantly growing so volume distribution changes and doses may need frequent adjustmen • Why is the Vaccine Adverse Events Reporting system important? • As health professionals, we have an obligation to provide data to allow the FDA to monitor medication and vaccine safety. MedWatch allows health-care professionals and consumers to report adverse events and serious problems caused by FDA-regulated products. The Vaccine Adverse Events Reporting System (VAERS) is a separate program used to report adverse events related to vaccinations and like MedWatch allows voluntary reporting on adverse events by both healthcare professionals and consumers. The FDA monitors adverse events and can respond with safety announcements, alerts, and/or removal from the market. The FDA publishes alerts in MedWatch (Fig. 5-1) and consumer publications. • To ensure a favorable balance between benefits and risks for certain drugs or biologicals, the FDA requires manufacturers to implement a Risk Evaluation and Mitigation Strategy (REMS). A REMS protocol is composed of various actions (called ETASU: elements to assure safe use), including letters to prescribers; additional patient information; and required patient, prescriber, and/or pharmacy registration and training. REMS are required for many drugs, including those listed • Key points when obtaining a drug history from a patient • Understand the principals for choosing medication routes (sublingual, sustained release, IM, etc) and dose timing (QID vs BID) and why certain medication require a loading dose • US FDA regulation for drug labeling • The FDA regulates what goes on a label. ▪ Labeling on over-the-counter (OTC) drugs ▪ Insert in prescription drugs ▪ Off-label prescribing ▪ Prescribing for a use not indicated on the official FDA label ▪ Legal ▪ Decision is based on ▪ Understanding the medication being prescribed ▪ Rational scientific principles ▪ Expert medical opinion (the literature) ▪ Controlled clinical trials Pharmacotherapeutics for Advanc •