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NR508 Midterm Outline
Chapter 1: The Role of the Advanced Practice Nurse as Prescriber
Roles and responsibilities of APRN prescribers
- The responsibility for the final decision on which drug to use and how to use it is in the hands of the APRN prescriber.
- The degree of autonomy in this role and the breadth of drugs that can be prescribed vary from state to state based on the nurse practice act of that state.
Clinical judgement in Prescribing
- Prescribing drug results from o clinical judgment based on a thorough assessment of the patient and the patient's environment, o the determination of medical and nursing diagnoses, o a review of potential alternative therapies, o specific knowledge about the drug chosen and the disease process it is designed to treat
Collaboration with other providers
- collaborate with physicians, pharmacists, podiatrists, mental health specialists, therapists, and other providers, including APRNs who are not NPs, physician assistants (PAs), and other nurses.
Autonomy and Prescriptive authority
- More states are broadening and expanding the legal, reimbursement, and prescriptive authority to practice for all APRNs, including NPs. Chapter 2: Review of Basic Principles of Pharmacology
How Drugs are Developed
Preclinical Stage: Identification of promising drugs and their testing in animals
- Medicinal chemists - new chemical compounds.
- Preclinical studies are performed on cells, isolated tissues and organs, laboratory animals
- FDA Approval: Drugs approved by the FDA must be both safe and effective. Screened by pharmacologists, toxicologists Clinical Stage: The safety and effectiveness of new products in humans must be established.
- Phase I Clinical Trials: Establish biological effects, safe dosages, and pharmacokinetics in a small number of healthy patients.
- Phase II Clinical Trials: New drugs are used to treat disease in a small number of patients and to determine the potential of the drug to improve patient outcomes. If the drug looks promising phase III will occur.
- Phase III Clinical Trials: Comparison of the new medication to the standard therapy in a larger number of patients at various sites across the country. New drugs must be at least as good or better than other available drugs. Post-Marketing Surveillance: Health professionals- report adverse events -- more people receive the drug than in the clinical trials, and sometimes much more is learned about additional adverse effects that occur infrequently with use of the drug.
Drug Responses
- before a drug can produce a response it must first overcome homeostasis - Dose-Response Curves provide information on the relationship between dosage or concentration and responses for one or more drugs.
o Graphs showing drug responses will show the response on
the vertical axis and the concentration or dose on the horizontal axis.
- Quantal Responses: May or may not occur. For example, seizures occur or they do not. A rash occurs or it does not. A response that is either occurring or absent.
o Prediction of drug dosages or blood levels that produce quantal
effects is more reliable for a population of patients than for an individual patient.
o Data from a population of patients is used to establish
appropriate doses or blood levels to predict quantal effects in a large number of patients. Drug examples: oral contraceptives and seizure medications.
- Graded Responses: Biological effects that can be measured continually up to the maximum responding capacity of the biological system.
o Most drug responses are graded. For example, changes in BP
are measured in mmHg, and patients may experience small or large changes in BP following treatment with drugs. If the patient’s BP is too high or too low, we can adjust the dosage
- Potency: Difference in concentration or dosage of different drugs required to produce a similar effect.
o Drugs that are more potent require a lower dosage or
concentration to produce the same response.
o For example, compare doses of non- prescription drugs that
relieve headache: 200 mg ibuprofen, 325 mg aspirin, and 50 mg ketoprofen. Because ketoprofen requires the lowest dose, it has the highest potency.
- Efficacy: Expresses the ability of a drug to produce a maximum effect at any dosage.
o There are many drugs that will relieve mild pain. No matter
how high we increase the dosage, drugs that work well for mild to moderate pain are usually ineffective for treating more severe cancer-related pain, for example.
o Treatment of severe pain requires the use of stronger drugs,
such as the opioid analgesics morphine or oxycodone. Morphine or oxycodone have higher efficacy for pain relief than ibuprofen.
o Drugs with high efficacy can produce greater effects than
lower-efficacy drugs can.
- Intrinsic Activity: The ability of a drug to produce a response once it has occupied specific receptors.
o some drugs produce the maximum receptor stimulation once
they occupy receptors; their response is limited by how many drug molecules occupy receptor sites.
o Other drugs with lower intrinsic activity can occupy the same
number of receptors but will produce a lesser response.
o Drugs can also occupy receptors and produce no receptor
stimulation; they merely block the action of neurotransmitters or other drugs.
- Drug Selectivity: A ratio of the dose or concentration producing the undesired effect to the dose or concentration producing the desired effect.
o This is the same as determining how many times the
therapeutic dosage needs to be increased to produce the undesired effect.
o A medication that requires one tablet to produce the desired
response and does not produce undesirable effects unless five tablets are used would have a selectivity ratio of 5.
- Therapeutic Index: Ratio of the lethal dose of a drug to the therapeutic dose of a drug.
o The therapeutic index of drugs on the market is, of course,
always greater than 1; a therapeutic index of less than 1 means that the drug kills before it cures.
o The therapeutic index ranges from 2 for some drugs
(cancer chemotherapy, lithium carbonate) to 6,000 for others (penicillin in nonallergic patients)
- Brand vs. Generic Differences between brand and generic preparations can occur in the inactive ingredients of the tablet or capsule, such as coloring or filler materials.
o There are also differences in the speed or rate of absorption.
Receptors: agonists, antagonists
- Receptors are the large molecules, usually proteins, that interact with and mediate the action of drugs. Receptors are important because they determine the relationship between dose and effect, the selectivity of drugs, and the actions of pharmacological antagonists.
- Agonists : Drugs that produce receptor stimulation and a conformational change every time they bind. o Full agonists do not need all of the available receptors to produce a maximum response. Some agonists can produce their maximum response by binding to less than 10% of the available receptors. The receptors that are left over and not needed for a response are called spare receptors.
- Partial Agonists : Bind to receptors, but when they occupy the receptor sites, they stimulate only some of the receptors. This is sometimes called intrinsic activity. o they can act as part agonist and part antagonist. o Partial agonists would require all of the available receptors to produce their full response, and the maximum response for a partial agonist is less than that for a full agonist. o The beta blockers acebutolol, penbutolol, and pindolol are partial agonists. Administration can block the effects of adrenergic nerves on heart rate, but partial agonist activity keeps heart rate from falling too low, as might occur following administration of a pure beta-adrenoceptor antagonist
- Antagonists: Drugs that occupy receptors without stimulating them. o Antagonists occupy a receptor site and prevent other molecules, such as agonists, from occupying the same site and producing a response. o Antagonists produce no direct response. o The response we see following administration of antagonists results from their inhibiting receptor stimulation by agonists. o For example, beta blockers such as propranolol and atenolol act as antagonists at the beta-adrenoceptor. Adrenergic nerve activity can raise heart rate, and patients with high heart rates experience a significant drop in heart rate following administration of beta blockers. The same administration may have little effect on patients who lack adrenergic nerve activity and already have a lower heart rate. o The effect of antagonists is dependent on the background receptor activity that it can block.
- Site of Administration: When medications are administered near their site of action, higher concentrations may be achieved while minimizing unwanted effects in other parts of the body.
- Topical Administration: Allows medication to be concentrated in the skin when patients need an anti-inflammatory (e.g., hydrocortisone) or an antifungal (e.g., clotrimazole) medication for a skin condition. o This is particularly advantageous in that drugs pass more easily through damaged skin, so more drug is available to the areas of the skin that need the medication.
- Multidose Inhalers and Nebulizers: Commonly used to administer drugs (e.g., albuterol) directly into the lungs.
- Ophthalmic Preparations: Sterile preparations suitable for administration to the eye. Because the eye is particularly sensitive, ocular medications are typically buffered and isotonic so that they do not cause discomfort when administered.
- Aural Preparations: Intended for administration into the ear canal, do not meet the buffering and isotonicity requirements for ophthalmic administration.
- Bioavailability: Percentage of the administered dose that does enter the bloodstream. o 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. o 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: Rapid absorption leads to higher peak blood levels, with a risk of greater toxicity and side effects. o So rapid IV administration (e.g., “IV push”) produces immediate drug effects but increases the risk of toxicity and adverse effects. o For these reasons, some medications, such as amino- glycoside 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
- Process of drugs moving throughout the body.
- 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 them
- It is an important principle in pharmacology that passive diffusion through biological barriers occurs most readily when drugs are in the uncharged state. Protein Binding
- Drugs can bind to a variety of proteins that are present in the bloodstream. These are often called plasma proteins.
- Many plasma proteins are produced in the liver, and their presence in the blood reflects liver function, nutritional status, and the effect of aging and disease.
- Albumin is a major protein in the blood and is measured as part of a typical blood analysis. Other plasma proteins include alpha-1-acid glycoprotein, cortisol- binding globulin, sex hormone–binding globulin, and lipoproteins.
- Drugs bound to plasma proteins can freely circulate in the bloodstream rather than be distributed by passive diffusion from their site of absorption, so plasma protein binding helps normalize concentrations throughout the body.
- Drugs that are bound to plasma protein can be protected from metabolism in the liver and from excretion by the kidneys, so plasma protein binding can extend the period of time that drugs remain in the body.
- Alterations in Plasma Proteins: Plasma proteins can be altered by disease states. Patients with poor nutrition may not have the protein building blocks to produce adequate amounts of plasma proteins. Patients with cancer can be undernourished as the cancer cells feed off the body. Patients with liver disease may lack the cellular function to produce one or more of the plasma proteins. Plasma proteins can be affected by myocardial infarction, stress, and infection as well.
- Disadvantages: Protein binding, which may include binding to proteins that are not in the plasma, also prevents the interaction of drug molecules with their site of action. o Plasma protein binding creates a reservoir of bound drug molecules that can unbind at any time to interact with drug receptors and produce responses. o Plasma protein binding occurs in the plasma and encourages retention of drug in the systemic circulation. So it may appear that blood levels of a drug are high, even if the drug is not at its active site. o Binding to proteins is also the basis for a number of drug interactions. Drugs bound to plasma proteins cannot interact with their receptor. If a drug is very strongly bound to plasma proteins, then even a small change in the fraction that is bound can have significant pharmacological effects Metabolism - 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.
- important to know how metabolism affects drug activity and pharmacokinetics and how other drugs might interact to alter drug metabolism.
- 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. o The liver is a major organ for drug metabolism because it contains high amounts of drug-metabolizing enzymes and
encountered by drugs once they are absorbed from the gastrointestinal tract. o 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 that metabolizes drugs. Each of these CYP enzymes is responsible for a single type of metabolic reaction
- Phase I reactions , or nonsynthetic reactions, involve oxidation, reduction, and hydrolysis reactions, which prepare the drug molecule for further metabolism. o 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. o Metabolites are linked, or conjugated, to highly polar molecules such as glucuronic acid, glycine, sulfate, or acetate by specific enzymes. o 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. Half Life
- The rate of drug metabolism depends on the blood levels of drug in relation to the affinity of the drug for its metabolism enzymes.
- Most drugs are present at concentrations below their Km for metabolism (the concentration at which metabolism is half of maximum). o Under these conditions, metabolism is related to drug concentration so that a fixed fraction of drug is metabolized per hour. o This is called first-order metabolism and is characterized by a half- life , the time period over which the drug concentration will decrease by half. o So, blood levels decrease 50% in one half-life, 75% in two half- lives, and 87.5% in three half-lives. As a general rule, drugs tend to be administered at dosing intervals that are close to their half-life.
Cytochrome P450 metabolism
- 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.
- The CYPs are organized into numbered families based on their function.
- Variations in CYPs and in their activity can result in marked differences in drug metabolism between individuals.
- Individual variation in drug metabolism contributes to drug–drug and some drug– food interactions
Excretion
- The principal organs for drug elimination are considered to be the kidneys, lung, biliary system, and intestines.
- Any individual drug may rely on one or more of these sites for elimination or on a different site, such as skin excretion or excretion into saliva or breast milk. Renal
- 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.
- 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 Biliary
- 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
- 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 Other (eg for volatile drugs)
Ensure drug/dose/scheduling is accurate Check drug costs (for the patient) Step 5 Educate the patient: To improve adherence ● ● Tailored to patient in plain language (5-6th grade level) Include purpose, instructions, side effect Step 6 Monitor effectiveness. ● Passive monitoring: pt educated and told to contact provider if not effective or adverse reactions (common in short term treatments, no test of cure required) Active monitoring: needs follow up exam to eval effectiveness evaluating blood levels, dosage adjustments, monitoring parameters
Patient education
- Up to 50% of patients do not take their medications as prescribed or they do not take them at all
- Poor medication adherence leads to worsening disease and death, as well as increased health-care costs
- Patient education regarding the purpose of the medication, instructions for administration, and potential adverse drug effects will improve adherence to the medication regimen.
- Patient education should be tailored to the patient and presented in plain language (fifth- or sixth-grade-reading level), with an understanding that nine out of 10 adults have difficulty reading health information
Monitor effectiveness
- Once the patient begins taking the prescribed medication, the chosen drug needs to be monitored for effectiveness.
- Passive monitoring occurs when the patient is educated on the expected outcome of the drug therapy and is instructed to contact the provider if the treatment is not effective or if adverse drug effects occur. o This is common when short-term treatment, such as an antibiotic, is prescribed, and no test of cure is required.
- Active monitoring occurs when the provider schedules a follow-up examination to determine the effectiveness of the drug therapy o may include evaluating therapeutic blood levels and making dosage adjustments, as is necessary in anticoagulant therapy or patients taking an antiseizure medication. o may also include adding or subtracting medications from the treatment regimen based on the effectiveness of the treatment. o Monitoring parameters are often published for a drug but may need to be adjusted based on age or concurrent disease processes.
Drug, Patient, and Provider factors that influence drug selection
- Evidence-based guidelines are the gold standard for initial drug selection, but providers need to examine the drugs recommended in the guideline for their clinical utility with the individual patient.
- Selecting the appropriate drug treatment requires that the provider consider multiple factors regarding the drug and the patient who will be receiving the medication: pharmacokinetics, pharmacodynamics, therapeutic issues, safety, and cost
- Additionally, individual patient and provider factors may influence drug choice. The nurse practitioner should review and consider all seven of these criteria prior to prescribing Pharmacodynamic Factors
- 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
- The ease of titration is influenced by the dose–response curve of the drug
- 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. Pharmacokinetic Factors
- When deciding what drug in a class to prescribe, the pharmacokinetic properties of a drug may influence drug selection.
- The FDA has a tiered system of safety announcements to promote drug safety. information sheet to provide specifics about the safety issue and factors to consider when making treatment decisions.
- When drugs are determined by the FDA to have serious safety issues, particularly ones that may lead to serious injury or death, the FDA may require a warning to be displayed prominently on the drug monograph, often referred to as a “Black Box” warning. Prescribers are responsible for keeping up-to-date on the latest drug safety information. Cost
- When prescribing, the nurse practitioner must consider the costs to the patient and the cost to the health-care system or to society at large.
- The cost to patients may be so high that they cannot afford prescriptions, and cost then becomes a barrier to adherence.
- Many insurance policies do not cover the cost of drugs, and patients must therefore pay out of pocket for their medications.
- Prescribing generics when possible and knowing what drugs are on the $4 retail pharmacy prescription lists assists in keeping costs reasonable for the patient. Patient Factors
- Patient factors that may affect prescribing include drug adverse effects that influence adherence, health beliefs, values, and current drug therapy that may interfere with the new drug
- unnecessary duplications with other drugs being taken may occur. Any time a regimen can be simplified by reducing duplication, adherence is more likely.
- Other patient factors that affect prescribing are the patient's age (children and older adults), pregnancy, mental health diagnosis, or another disease. Provider Factors
- Ease of Prescribing or MonitoringProviders often develop a personal formulary of drugs with which they are familiar and that they are comfortable prescribing
- Unfamiliar medications require providers to research the drug and educate themselves in order to prescribe the drug safely.
- The amount of provider follow-up required, whether it is titrating doses or therapeutic monitoring, may influence prescribing decisions
- FormulariesNurse practitioners need to be familiar with the formulary of medications they are allowed to prescribe from and to keep themselves updated as formularies change
Influences on Rational Prescribing: Pharmaceutical Promotion
- Pharmaceutical promotion o Gifts and freebies to influence prescribers: prescribers must be aware of the influences of marketing on their prescribing
When Prescribing Recommendations Change: antibiotic resistance
and overprescribing of antibiotics for URIs
- Current guidelines change, and providers must be up-to-date on these practice changes
- prior to 1990’s antibiotics were widely prescribed for URIs. The excessive and inappropriate overuse and anti-infectives become a major factor in drug resistance Chapter 4: Legal and Professional Issues in Prescribing
New Drug Approval process including Clinical Phases
- costs a company approximately $2.6 billion
- takes 8.5 years on average for an experimental drug to travel from laboratory preclinical trials to FDA approval Preclinical Research
- process of synthesis and extraction identifies new molecules with the potential to produce a desired change in a biological system
- produced through artificial synthesis or extracted from natural sources
- Biological screening and pharmacological testing use nonhuman studies pharmacological activity and therapeutic potential of compounds-- animals, isolated cell cultures and tissues, enzymes, and cloned receptor sites, as well as computer models.
- Pharmaceutical dosage formulation and stability testing make up the process of turning an active compound into a form and strength suitable for human use.
- Toxicology and safety testing determines the potential risk a compound poses to people and the environment. Clinical Studies - investigational new drug (IND) application is filed with the FDA prior to human testing--description of the clinical research plan -- clinical tests can begin 30 calendar days after submission. - three phases:
indications and contraindications, means of administration, dosages, side effects, adverse reactions, how the drug is supplied, and any other pertiant information for safe and effective delivery
- The FDA is concerned with the marketing and availability of drugs that have demonstrated substantial evidence of an acceptable risk/benefit ratio for labeled indications. The proper and efficacious therapeutic use of these drugs is the responsibility of the prescriber. off-label use of drugs - use of an FDA-approved drug in a dose or route for which it was not approved or for a clinical indication other than the FDA-approved use. - NPs are responsible for knowing the FDA indication and approval status of any drug they prescribe. - clinical support can be demonstrated for off label use if the proposed use is based on rational scientific theory or controlled clinical studies - ex: trazadone not FDA approved for insomnia but often prescribed for this use - FDA labeling is not intended to set the standard for good clinical judgement
Controlled Substance Laws
- The most comprehensive federal drug legislation is the Controlled Substances Act of 1970
- 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)
- NPs wanting authority to prescribe controlled substances must apply for state prescriptive authority prior to application for a federal DEA number--National Provider Identifier number (NPI). The NP should obtain an NPI as soon as it is feasible
- NPs must know the different classifications and schedules of controlled drugs as well as the associated prescribing rules and regulations.
- Some states --NP's license number appear on the prescription in addition to that of any supervising/collaborating practitioner
- DEA registration number must be designated on all controlled substance prescriptions--prescription should be dated on the day it is written, indicating any authorized refills as allowed and clinically appropriate.
- As of 2009, tamper-proof prescription pads are required for prescriptions written for patients under Medicaid payment plans.
Controlled Drug DEA schedules (Table 4-1)
Schedul e Controls Required Drug Examples I No accepted medical use No legal use permitted For registered research facilities only Heroin, LSD, mescaline, peyote, marijuana ***** II 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) III Prescription must be rewritten after 6 mo or 5 refills Telephone or fax prescription okay Narcotics (codeine in combination with non-narcotic ingredients not to exceed 90 mg/tab; hydrocodone not to exceed 15 mg/tab) Stimulants (benzphetamine, chlorpheniramine, diethylpropion) Depressants (butabarbital) Anabolic steroids, testosterone IV Same as Schedule III Penalties for illegal possession Pentazocine, phentermine, benzodiazepines, meprobamate
