NR565 / NR 565 Midterm Exam Study Guide (Latest 2024 / 2025): Advanced Pharmacology Fundamentals - Chamberlain

NR 565 Midterm Study Guide Sept 2022 Advanced Pharmacology Fundamentals (Chamberlain University)Week 1 • Which schedule drugs can APRNs prescribe? • DEA license will allow for prescribing of Schedules 2-5. There can be restrictions as noted in collaborative agreement. May be facility/state dependent. • Who determines and regulates prescriptive authority? • Determines: Also known as independent prescribing. APRNS can prescribe without limitation and is state dependent. Includes "legend" (prescription) and controlled drugs, health/medical services, DME, etc. Regulates: regulated by health professional board, state board of nursing or the State Board of Medicine, or the State Board of Pharmacy, as determined by each state. Federal government controls drug regulations but has no control over prescriptive authority. • Prescriptive authority is the legal right to prescribe drugs. • How does limited prescriptive authority impact patients within the healthcare system? • Limited prescriptive authority creates numerous barriers to quality, affordable, and accessible patient care. For example, restrictions on the distance of the APRN or PA from the physician providing supervision or collaboration may prevent outreach to area of greatest need. An increase in patient waits. • What are the key responsibilities of prescribing? The ability to prescribe medications is both a privilege and a burden. Have a documented provider-patient relationship, do not prescribe medications to family or friends or yourself, Document a thorough history and physical examination, include any discussions you have with the patient about risk factors, side effects, or therapy options, have documented plan regarding drug monitoring or titration, if you consult additional providers not that you did so. Use the references provided in the following boxes to assist in safely and rationally choosing one medication over another. Be sensible, accept responsibility, do not fear it, know constraints and limitations, always learn and update, keep Rx pads in safe place, confirm allergies, verify medication list with patient, do not let insurance dictate quantity of Rx, Charting is key (particularly with off label use), Provide use and rationale. • What should be used to make prescribing decisions? • The best way to keep your patients (and yourself) safe is to be prudent and deliberate in your decision-making process. Cost, availability, current practice guidelines, medication interactions including interactions with food, side effects, need for monitoring, how drug is metabolized (hepatic or renal), special populations (pregnancy, nursing, older adults) Cost: It is of critical importance that providers ask patients if they have difficulty obtaining their medication because it is cost-prohibitive.Guidelines: It is the provider's responsibility to keep abreast of new recommendations or changes in guidelines and to incorporate these into their prescribing practices. Availability: The drug you want may not be available in your facility or at a specific pharmacy. This can affect your choice of medications. Interactions: There are very few medications that do not interact with either another medication or food. Polypharmacy greatly increases the risk of interactions. Some of these interactions are negligible, but some can have life-threatening consequences. Side Effects: All drugs have side effects. Some are adverse, and some may be beneficial. Allergies: Unfortunately, your patient may have an allergy to that medication or class of drug. It is of critical importance to determine the type of reaction and to document it in the patient's chart. Then, the selection of an appropriate drug may begin. Hepatic and Renal Function: Many drugs are metabolized and eliminated by the liver and kidneys. If these systems are impaired, this can lead to increased adverse effects and possible medication overdose. Need for monitoring: Some drugs require frequent monitoring at initiation or throughout the duration of treatment. Special Populations: Populations that deserve special mention when thinking about medications include pregnant or nursing mothers and older adults. • Be familiar with pharmacokinetic and pharmacodynamic changes of older adults and how that would translate to baseline information needed to prescribe. • Pharmacokinetic is the study of drug absorption, distribution, metabolism, and excretion in the body; what the body does to the drug. Pharmacodynamic is what the drug does to the body. • The ability of older adults to metabolize drugs is commonly decreased. Drug dosages may need to be reduced to prevent drug toxicity. • Physiologic Changes That Can Affect Pharmacokinetics in Older Adults • Absorption of Drugs • Increased gastric pH • Decreased absorptive surface area • Decreased splanchnic blood flow• Decreased gastrointestinal motility • Delayed gastric emptying • Distribution of Drugs • Increased body fat • Decreased lean body mass • Decreased total body water • Decreased serum albumin • Decreased cardiac output • Metabolism of Drugs • Decreased hepatic blood flow • Decreased hepatic mass • Decreased activity of hepatic enzymes • Excretion of Drugs • Decreased renal blood flow • Decreased glomerular filtration rate • Decreased tubular secretion • Decreased number of nephrons • Measures to Reduce Adverse Drug Reactions in Older Adults • Take a thorough drug history, including over-the-counter medications, herbal remedies, and dietary supplements • Account for the pharmacokinetic and pharmacodynamic changes that occur with aging • Initiate therapy with low doses and titrating upward gradually (“start low and go slow”) • Monitor clinical responses and plasma drug levels to provide a rational basis for dosage adjustment • Employ the simplest medication regimen possible • Monitor for drug–drug interactions and iatrogenic illness • Periodically review the need for continued drug therapy, and discontinue medications as appropriate • Encourage the patient to dispose of old medications • Take steps to promote adherence • Avoid drugs included in Beers Criteria for Potentially Inappropriate Medication Use in Older Adults (the Beers list) unless benefits outweigh risks. • • Beer’s Criteria o What is it? • Guidelines for prescribing medications to patients 65 & older. Drugs on the list should be avoided in patients over 65 expect when the benefits significantly outweigh the risks. The Beers Criteria includes five lists that describe certain medications and situations and include: potentially inappropriate medication (PIM) use in older adults, PIM use in older adults due to medication-disease or medication-syndrome interactions that mayexacerbate the disease or syndrome, medications to be used cautiously in older adults, clinically significant drug interactions that should be avoided in older adults, medications to be avoided or dosage decreased in the presence of impaired kidney function in older adults. o Why is it important? • It provides a list of medications that are potentially harmful in elderly. List that identifies drugs with a high likelihood of causing adverse effects in older adults. Beers Criteria are recommendations; ultimately prescribers must determine whether a medication is appropriate for use or not. These guidelines are not intended to limit the use of medications or apply to all older adults. Safe and judicious prescribing is crucial in the older adult to optimize pharmacotherapy. • Impacts/outcomes of polypharmacy • polypharmacy (the use of five or more medications daily) • Polypharmacy greatly increases the risk for interactions. Drug interactions with mild side effects to life-threatening consequences. Elderly is at a higher risk of polypharmacy due to taking five or more medications daily. • CYP450 inhibitors • CYP450 are part of the metabolic pathway, involved in metabolism of drugs in the liver. Metabolism can be inhibited or induced by drugs and once this happens drug-drug interaction can occur. o Examples • Valproate, Isoniazid, Sulfonamides, Amiodarone, Chloramphenicol, Ketoconazole, Grapefruit juice, Quinidineo What do they do? • Slows down metabolism of medications. Inhibitors are medications that inhibit activity of one or more of the CYP450 enzymes. Medications that inhibit an enzyme can potentially slow that enzymes activity required for metabolism of other medications, thereby increasing the levels of medications dependent on that particular enzyme for biotransformation. This inhibition prolongs the pharmacalogical effects, which may result in toxicity. Factors that affect the inhibition include the dose and the capacity to bind to the enzyme Inhibitors act on the liver through a process known as inhibition. By slowing the rate of metabolism, inhibition can cause an increase in active drug accumulation. This can lead to an increase in adverse effects and toxicity. o What do they cause if not used correctly? (aka: What would the patient experience?) • Toxicity. drug build up • Examples of CYP450 inducers o Examples • barbiturates, St Johns wart, carbamazepine, rifampin, alcohol, phenytoin, griseofulvin, phenobarbital, sulfonylureas• o What do they do? • Increase medication metabolism. Inducers are xenobiotics that elevate the CYP450 enzyme activity by increasing the enzyme synthesis. This action leads to additional sites available for biotransformation. The increased number of sites enhances the medication metabolism, decreasing the concentration of the "parent drug" while increasing the metabolite production. The half-life of the inducing drug may cause a delay before enzyme activity increases. A decease in concentration of a medication metabolized by CYP2C9 (responsible for 10% of drug metabolism) usually occurs within 24 hours after the administration of the medication. Inducers act on the liver to stimulate enzyme synthesis. This process is known as induction. By increasing the rate of drug metabolism, the amount of active drug is decreased and plasma drug levels fall. o What do they cause if not used correctly? (aka: What would the patient experience?) If dosage adjustments are not made to accommodate for this, a drug may not achieve therapeutic levels.• What happens when someone has a poor metabolism phenotype? • Slows or increase absorption. Slow the metabolism, keep drug in body longer and increase toxicity. Poor metabolisms affect a high or low therapeutic index: increase drug toxicity, Ex: Plavix: Clots and increase platelets. • Varies depending on life stages: • Pregnancy - hepatic metabolism increases and decreased bowel motility increases absorption of the drug. • Newborns - The drug-metabolizing capacity of newborns is low. As a result, neonates are especially sensitive to drugs that are eliminated primarily by hepatic metabolism. When these drugs are used, dosages must be reduced. • Children - By 1 year, most pharmacokinetic parameters in children are similar to those in adults. children do differ in one important way: they metabolize drugs faster than adults. Because of enhanced drug metabolism in children, an increase in dosage or a reduction in dosing interval may be needed for drugs that are eliminated by hepatic metabolism. • Geriatric - Rates of hepatic drug metabolism tend to decline with age. The principal reasons are reduced hepatic blood flow, reduced liver mass, and decreased activity of some hepatic enzymes. Because liver function is diminished, the half-lives of certain drugs may be increased, thereby prolonging responses. • What does the U.S. Food and Drug Administration regulate when it comes to medications? • Regulates what the pharmacies can sell, requires special alerts and management guidelines, for drugs that cause serious adverse effects, such as QT prolongation. Ensuring pharmaceutical companies thoroughly test new products for efficacy and safety with an aim towards minimizing side effects. They approve or disapprove drugs and have reports published on their website on whether serious problems have been reported to MedWatch. • Medication Guides AKA MedGuides are approved by the FDA to educate about the med to reduce harm for patients. FDA has determined that (1) patient adherence to directions for drug use is essential for efficacy or (2) patients need to know about potentially serious effects when deciding to use a drug. • FDA monitors which meds are safe for pregnant and breast feeding women to take. • Reasons for medication non-adherence 1. patient feels not needed/lack of education of the importance of the medication 2. affordability 3. side effects 4. forgetfulness 5. lack of info 6. lack of disease concern 7. poor social support 8. low reaction satisfaction 9. poor physician relationship• Children: • Not wanting to take the medication, hard to follow the regimen • Geriatrics: • Forgetting to refill their medication, unable to follow the prescribing schedule • Black Box Warnings o What are they? • Concise summaries of adverse effects of concern in a box surrounded by a thick black line. • Black box warnings are issued when a drug is found to have serious or life-threatening risks. These drugs remain eligible for prescribing, but their risk must be carefully considered in discussion with the patient (Rosenthal & Burcham, 2021). o Why are they issued? -Neonate and infant drug absorption -Purpose is to alert the provider to potentially severe side effects and ways to prevent or reduce harm. Provides a concise summary of the adverse effects of concerns. The FDA requires a boxed warning on drugs with serious or lifethreatening risks. The purpose of the warning is to alert providers to (1) potentially severe side effects (e.g., life-threatening dysrhythmias, suicidality, major fetal harm) as well as (2) ways to prevent or reduce harm (e.g., avoiding a teratogenic drug during pregnancy). • Neonate and infant drug absorption o Be familiar with general development and when absorption would reach adult levels • The drug-metabolizing of infants is limited. The liver does not develop its full capacity to metabolize drugs until approximately 1 year after birth. During the time before hepatic maturation, infants are especially sensitive to drugs, and care must be taken to avoid injury • Newborns - The drug-metabolizing capacity of newborns is low. As a result, neonates are especially sensitive to drugs that are eliminated primarily by hepatic metabolism. When these drugs are used, dosages must be reduced. • Children - By 1 year, most pharmacokinetic parameters in children are similar to those in adults. children do differ in one important way: they metabolize drugs faster than adults. Because of enhanced drug metabolism in children, an increase in dosage or a reduction in dosing interval may be needed for drugs that are eliminated by hepatic metabolism. • Common fears with genetic testing • Fear of judgement from employers, insurance, or providers. • Lack of Knowledge: new and developing science, many health care providers do not possess the knowledge or comfort to order or interpret testing and inability to provide patient education. • Financial cost: insurances don't typically cover these services.• Implications and ethics: patient's must understand the implications. Informed consent is necessary for testing, potential results, and options for treatment. Patients must be informed of their results won't be given until weeks later and remain confidential. • Genetic Information Nondiscrimination Act (GINA) was passed Week 2 Some of the information for WK2, noted on this study guide, will come directly from the presentation provided entitled: Applying CDC’s Guidelines for Prescribing Opioids. This presentation will be provided via course announcement in the MAR22 session by the beginning of Week 2. • Guiding principles for prescribers In response to the opioid epidemic. This guideline addresses three main principles to improve opioid prescribing, including: o determining when to initiate or continue opioids for chronic pain o opioid selection, dosage, duration, follow-up, and discontinuation o assessing risk and addressing harms of opioid use TREATING CHRONIC PAIN WITHOUT OPIOIDS o Nonopioid medications (i.e. NSAIDS) and nonpharmacologic treatments (i.e. yoga, heat) are the preferred methods for treating chronic pain such as osteoarthritis (OA). o Use communication techniques to facilitate a patient-centered approach • Compassion • Relationship-building ASSESSING AND ADDRESSING OPIOID USE DISORDER (OUD) o OUD is diagnosed by DSM-5 criteria o Medication assisted therapy (MAT) is available for OUD • Buprenorphine, naltrexone, or methadone • Consider offering naloxone if indicated (i.e. concurrent benzodiazepine use) o Patient and provider resources are available for the treatment of OUD from the CDC REDUCING THE RISKS OF OPIOIDS Objective strategies to monitor for drug diversion o Routine urine drug tests • In general, the medicine being prescribed, should be in the urine. If it is not in the urine, there should be a clear reason why it is not. Additionally, UDT allow for providers to see if there are illicit drugs present as well that could complicate treatment and would need to be discussed.DETERMINING WHETHER TO INITIATE OPIOIDS FOR CHRONIC PAIN o Criteria for prescribing opioids • Establish treatment goals • Determine how effectiveness will be evaluated • Outline a plan for discontinuation o Risks and benefits should be considered and discussed o Strategies to improve patient safety • Use Morphine Milligram Equivalent (MME) calculation to inform dosage changes and reduce overdose risk ▪ Use extra precautions when increasing to ≥50 MME per day ▪ Avoid or carefully justify increasing dosage to ≥90 MME/day USING THE PDMP TO PROMOTE PATIENT SAFETY IN OPIOID PRESCRIBING AND DISPENSING o Utilized by providers, state health departments, and pharmacists o Can help identify high risk patients and send proactive reports to providers • Helps identify if a patient is currently receiving a controlled substance from another provider RENAL AND HEPATIC CONSIDERATION Patients with renal or hepatic insufficiency can experience greater peak effect and longer duration of action for medications, thereby reducing the dose at which respiratory depression and overdose may occur. Similarly, for patients ages 65 years and older, reduced renal function and medication clearance due to age can result in a smaller therapeutic window between safe dosages and dosages associated with respiratory depression and overdose. • Examples of pure opioid agonists o agonist is a drug that binds to the receptor, producing a similar response to the intended chemical and receptor; The pure opioid agonists activate µ receptors and κ receptors to produce: • analgesia, euphoria, sedation, respiratory depression, physical dependence, constipation, and other effects. • Examples: Morphine, codeine, meperidine, and others • When administered alone, the agonist-antagonist opioids produce analgesia. However, if given to a patient who is taking a pure opioid agonist, these drugs can antagonize analgesia caused by the pure agonist. • examples: pentazocine, nalbuphine, butorphanol, and buprenorphine (used for withdrawal symptoms) - used to treat moderate pain. These are mixed because they target differentreceptors in the brain. If given with a full agonist, it competes for the same receptors. • pure opioid antagonists - These drugs do not produce analgesia or any of the other effects caused by opioid agonists; only use is reversal agent for CNS depression induced by opioids. • Naloxone • What is used to calculate a patient’s overdose risk? (An actual calculation won’t be done on the exam) Providers can calculate the morphine milligram equivalent (MME) to help dose medications appropriately and refer to pain specialists as indicated. Clinicians should use caution when prescribing opioids at any dosage, should carefully reassess evidence of individual benefits and risks when considering increasing dosage to ≥50 morphine milligram equivalents (MME)/day, and should avoid increasing dosage to ≥90 MME/day or carefully justify a decision to titrate dosage to ≥90 MME/day (recommendation category: A, evidence type: 3). • How would you know when to refer someone to a pain specialist for pain management? If patients do not experience improvement in pain and function at ≥90 MME/day, or if there are escalating dosage requirements, clinicians should discuss other approaches to pain management with the patient, consider working with patients to taper opioids to a lower dosage or to taper and discontinue opioids (see Recommendation 7), and consider consulting a pain specialist. Some states require clinicians to implement clinical protocols at specific dosage levels. For example, before increasing long-term opioid therapy dosage to >120 MME/day, clinicians in Washington state must obtain consultation from a pain specialist who agrees that this is indicated and appropriate (30). Clinicians should be aware of rules related to MME thresholds and associated clinical protocols established by their states. • Prescription Drug Monitoring Program (PDMP) o What is it? • PDMPs store patient-specific prescription information in a central repository. The information in accordance with state or jurisdictional laws. • PDMPs are valuable tools that facilitate safer opioid prescribing, inform clinical practice, and improve patient safety. • are secure, online, state-based databases that contain information about controlled substance • prescriptions written by clinicians and dispensed by pharmacists within a state or jurisdictionUSING THE PDMP TO POMOTE PATIENT SAFETY IN OPIOID PRESCRIBING AND DISPENSING o Utilized by providers, state health departments, and pharmacists o Can help identify high risk patients and send proactive reports to providers • Helps identify if a patient is currently receiving a controlled substance from another provider o Why is it important? • PDMPs store patient-specific prescription information in a central repository. The information in accordance with state or jurisdictional laws. • PDMPs are valuable tools that facilitate safer opioid prescribing, inform clinical practice, and improve patient safety. • Prescription Drug Monitoring Programs (PDMP) provide the ability to identify patients who might be at higher risk for opioid overdose or OUD and strategies for addressing risk factors. • How renal and hepatic function impact medication levels in the body Patients with renal or hepatic insufficiency can experience greater peak effect and longer duration of action for medications, thereby reducing the dose at which respiratory depression and overdose may occur. Similarly, for patients ages 65 years and older, reduced renal function and medication clearance due to age can result in a smaller therapeutic window between safe dosages and dosages associated with respiratory depression and overdose. • How to assess someone for possible drug diversion REDUCING THE RISKS OF OPIOIDS Objective strategies to monitor for drug diversion o Routine urine drug tests • In general, the medicine being prescribed, should be in the urine. If it is not in the urine, there should be a clear reason why it is not. Additionally, UDT allow for providers to see if there are illicit drugs present as well that could complicate treatment and would need to be discussed. • When should naloxone be prescribed for a patient? -Providers should consider offering naloxone to patients when the following factors that increase risk for an opioid overdose are present -history of nonfatal OD -hx of substance abuse disorder -higher opioid dosages (>50 MME/day) -Concurrent benzo use-high risk of returning to a dose to which tolerance is no longer expected, such as when a pt is released from jail If a patient’s opioid dosage for all sources of opioids combined reaches or exceeds 50 MME/day, clinicians should implement additional precautions, including increased frequency of follow-up (see Recommendation 7) and considering offering naloxone and overdose prevention education to both patients and the patients’ household members (see Recommendation 8). • Behaviors that predict controlled substance addiction Illegal drug use; prescription drug use for nonmedical reasons. History of substance use disorder or overdose. Mental health conditions (eg, depression, anxiety). Sleep-disordered breathing. Concurrent benzodiazepine use. This disorder is manifested by specific criteria such as unsuccessful efforts to cut down or control use and use resulting in social problems and a failure to fulfill major role obligations at work, school, or home (20). This diagnosis has also been referred to as “abuse or dependence” and “addiction” in the literature, and is different from tolerance (diminished response to a drug with repeated use) and physical dependence (adaptation to a drug that produces symptoms of withdrawal when the drug is stopped), both of which can exist without a diagnosed disorder. According to the National Institutes of Health, drug dependence means that a person needs a drug to function normally. Abruptly stopping the drug leads to withdrawal symptoms. Drug addiction is the compulsive use of a substance despite its negative or dangerous effects. ASSESSING AND ADDRESSING OPIOID USE DISORDER (OUD) o OUD is diagnosed by DSM-5 criteria o Medication assisted therapy (MAT) is available for OUD • Buprenorphine, naltrexone, or methadone • Consider offering naloxone if indicated (i.e. concurrent benzodiazepine use) o Patient and provider resources are available for the treatment of OUD from the CDC • Schedule II drugs o Rules around prescribing Cost, guidelines, availability, interactions, side effects, allergies hepatic and renal function, need for monitoring, special populations -All prescriptions for Alternatively, prescribers may submit prescriptions using an electronic prescribing procedure. Oral prescriptions may be called in but only in emergencies, and a written prescription must follow within 72 hours. Prescriptions for schedule II drugs cannot berefilled. However, a DEA rule allows a prescriber to write multiple prescriptions on the same day—for the same patient and same drug. o Schedule II drugs cannot be prescribed or refilled by phone o The exception to this question is with schedule II medications. These are not eligible for refills and must have a new prescription each renewal period. When changing or adding to current medication regimens, it is prudent to follow up with the patient by phone or in person to assess changes. This time can be used to discuss new or increased side effects, check vital signs, obtain laboratory work, or make further adjustments. o Examples o Substances, or chemicals are defined as drugs with a high potential for abuse, with potentially leading to severe psychological or physical dependence. • Combination products with less than 15 milligrams of Hydrocodone per dosage unit (Vicodin), Opioids, Alfentanil, Codeine, Fentanyl, Hydrocodone, Methamphetamine, Barbiturates, Cocaine, Dexedrine, Adderall, Ritalin • US Drug Enforcement Administration description of the scheduled drugs The U.S. Department of Justice Drug Enforcement Agency (DEA) coordinates with local, state, and federal agents to reduce illicit drug use. The DEA enacted the Controlled Substances Act (CSA) in 1970 to regulate drugs and other substances based on their potential for abuse and dependency. Five schedules of controlled substances were created that are updated annually. Classes of scheduled substances include narcotics, depressants, stimulants, hallucinogens, and anabolic steroids. The DEA issues eligible providers with a registration number to write prescriptions for controlled substances. o Schedule I - Schedule I drugs, substances, or chemicals are defined as drugs with no currently accepted medical use and a high potential for abuse. o Schedule II - Schedule II drugs, substances, or chemicals are defined as drugs with a high potential for abuse, with use potentially leading to severe psychological or physical dependence. These drugs are also considered dangerous. o Schedule III drugs, substances, or chemicals are defined as drugs with a moderate to low potential for physical and psychological dependence, abuse and addiction. o Schedule IV drugs, substances, or chemicals are defined as drugs with a low potential for abuse and low risk of dependence. o Schedule V drugs, substances, or chemicals are defined as drugs with lower potential for abuse than Schedule IV and consist of preparations containing limited quantities ofcertain narcotics. Schedule V drugs are generally used for antidiarrheal, antitussive, and analgesic purposes. • Treatment of Chronic Pain DETERMINING WHETHER TO INITIATE OPIOIDS FOR CHRONIC PAIN o Criteria for prescribing opioids • Establish treatment goals • Determine how effectiveness will be evaluated • Outline a plan for discontinuation o Risks and benefits should be considered and discussed o Strategies to improve patient safety • Use Morphine Milligram Equivalent (MME) calculation to inform dosage changes and reduce overdose risk • Use extra precautions when increasing to ≥50 MME per day • Avoid or carefully justify increasing dosage to ≥90 MME/day o Example: How should something like osteoarthritis be treated? TREATING CHRONIC PAIN WITHOUT OPIOIDS o Nonopioid medications (i.e. NSAIDS) and nonpharmacologic treatments (i.e. yoga, heat) are the preferred methods for treating chronic pain such as osteoarthritis (OA). o Use communication techniques to facilitate a patient-centered approach • Compassion • Relationship-building • Risk factors for Opioid Use Disorder -Risk Evaluation and Mitigation Strategy (REMS)-reinforces safe medication use. Goal of REMS is to ensure that medication is used according to FDA approved prescribing. -Requires drug manufacturers to add recs about naloxone o The patient requests refills before the prescription runs out o The patient fails to disclose pertinent information, such as current o opioid prescriptions o The patient makes unreasonable excuses for losing medications o The patient may show physical signs of opioid withdrawal, such as anxiety, nausea, vomiting, or abdominal pain. If any of the above signs are noticed during a patient exam, you may need to assess your patient for OUD. Patients who are prescribed opioids for long term use are at increased risk for opioid use disorder (OUD). OUD is diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Addition (DSM-5) assessment criteria and not speculation alone. Documenting according to DSM-5 criteria will help not only identify the condition but alsoprotect practitioners legally in making such a diagnosis. However, when a patient is diagnosed with OUD, there are treatment options available which does include medication assisted therapy (MAT). Prescription Drug Monitoring Programs (PDMP) provide the ability to identify patients who might be at higher risk for opioid overdose or OUD and strategies for addressing risk factors. • Severity: Mild: 2-3 symptoms. Moderate: 4-5 symptoms. Severe: 6 or more symptoms o Opioids are often taken in larger amounts or over a longer period of time than intended. o There is a persistent desire or unsuccessful efforts to cut down or control opioid use. o A great deal of time is spent in activities necessary to obtain the opioid, use the opioid, or recover from its effects. o Craving, or a strong desire to use opioids. o Recurrent opioid use resulting in failure to fulfill major role obligations at work, school or home. o Continued opioid use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of opioids. o Important social, occupational or recreational activities are given up or reduced because of opioid use. o Recurrent opioid use in situations in which it is physically hazardous o Continued use despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by o opioids. o *Tolerance, as defined by either of the following: o (a) a need for markedly increased amounts of opioids to achieve intoxication or desired effect o (b) markedly diminished effect with continued use of the same amount of an opioid o *Withdrawal, as manifested by either of the following: o (a) the characteristic opioid withdrawal syndrome o (b) the same (or a closely related) substance are taken to relieve or avoid withdrawal symptoms • Methadone o (Diskets, Dolophine, Methadose) has pharmacologic properties very similar to those of morphine. Used for pain and opioid addiction. o Black Box Warning prolongs the QT interval and hence may pose a risk for potentially fatal dysrhythmia. Torsades de pointes has developed in patients taking 65 to 400 mg/day. To reduce risk, methadone should be used with great caution—if at all—in patients with existing QT prolongation or a family history of long QT syndrome and in those taking other QT- prolonging drugs. In addition, methadone causes severe respiratory depression that can be potentially fatal.o Benefits of use in opioid use disorder By taking methadone, the addict avoids both withdrawal and the need to procure illegal drugs. Maintenance dosing is done once a day. Maintenance is most effective when done in conjunction with nondrug measures directed at altering patterns of drug use. Suppressive therapy is done to prevent the reinforcing effects of opioid-induced euphoria. Suppression is achieved by giving the addict progressively larger doses of methadone until a very high dose (120 mg/day) is reached. Building up to this dose creates a high degree of tolerance, and hence no subjective effects are experienced from the methadone itself. Because cross-tolerance exists among opioids, after the patient is tolerant to methadone, taking street drugs, even in high doses, cannot produce significant desirable effects. As a result, individuals made tolerant with methadone will be less likely to seek out illicit opioids. • Buprenorphine and Naloxone/Benefit of using this combination -Buprenorphine is an opioid partial agonist. The partial agonist effect relieves withdrawal symptoms resulting from cessation of opioids. -Buprenorphine should be started at 6-12 hours after the last dose of heroin or immediate release opioids and longer after ER. At least 36 hours after the last dose of methadone -providers must have board certification in addiction medication and complete special training to qualify for the federal waiver to prescribe Buprenorphine NALOXONE; is an opioid antagonist. Is added with Buprenorphine to make the product less likely to be abused by injection. The naloxone component will have no effect if taken in tablet form. If injected then naloxone will precipitate withdrawal. • Three kinds of drugs are used for long-term management: opioid agonists, opioid agonist-antagonists, and opioid antagonists. Opioid agonists (methadone) and agonistantagonists (buprenorphine) substitute for the abused opioid and are given to patients who are not yet ready for detoxification. In contrast, opioid antagonists (naltrexone) are used to discourage renewed opioid use after detoxification has been accomplished. o opioid agonist or partial agonist treatment with methadone maintenance therapy or buprenorphine has been shown to be more effective in preventing relapse among patients with opioid use disorder (151–153) o maintenance therapy with buprenorphine and buprenorphine-naloxone effective in preventing relapse (216,217). o For pregnant women with opioid use disorder, medication-assisted therapy with buprenorphine or methadone has been associated with improved maternal outcomes and should be offered (202) (see Recommendation 12). • Treatment of chronic pain o Use of pregabalin o treats neuropathic paino Selected anticonvulsants such as pregabalin and gabapentin can improve pain in diabetic neuropathy and post-herpetic neuralgia (contextual evidence review). Pregabalin, gabapentin, and carbamazepine are FDA-approved for treatment of certain neuropathic pain conditions, and pregabalin is FDA approved for fibromyalgia management. o Abrupt discontinuation can cause insomnia, nausea, headache, diarrhea, and other symptoms that suggest physical dependence. To avoid withdrawal symptoms, pregabalin should be discontinued slowly, over 1 week or more. o Sedation, dizziness, and ataxia are more commonly linked to pregabalin. Gastrointestinal bleeding may be caused by COX-2 inhibitors and NSAIDs. Tricyclics (TCAs) and SNRIs treats neuropathies pain -contraindicated in severe cardiac disease, particularly conduction issues -anticholinergic effects Week 3 • How to treat hypertension o Order HTN medications are typically prescribed in o Which is best for someone with diabetes• Preferred antihypertensive drugs in patients with diabetes are ACEIs, ARBs, CCBs, and diuretics (in low doses). o Diabetic nephropathy? ACEIs and ARBs can slow the progression of renal damage and reduce albuminuria. o Anti-Hypertensives and DM Warnings: o β blockers can suppress glycogenolysis and mask early signs of hypoglycemia; therefore they must be used with caution. o Thiazides and loop diuretics promote hyperglycemia and hence should also be used with care. o Why not CCB rather than ACE-I? CCB's increase the risk for MI.o Best approach or drug to use during pregnancy or someone wishing to become pregnant • Stay away from: ACEIs, ARBs, and DRIs are contraindicated owing to their potential for harm (fetal growth delay, congenital malformations, neonatal renal failure, neonatal death). o ACE-I: o Pregnancy: Category C and D • Category C during first trimester • Category D during second and third trimester o CCB: o Require special consideration for use in pregnancy and breastfeeding women • According to guidelines issued by the American College of Obstetricians and Gynecologists (ACOG), “severe” hypertension ( SBP >160 mm Hg or DBP >110 mm Hg ) requires treatment, whereas “mild” hypertension (SBP 140 to 159 mm Hg or DBP 90 to 109 mm Hg) generally does not.o When drug therapy is initiated during pregnancy, methyldopa and labetalol are the traditional agents of choice. o Therapeutic action of drug classifications used Diuretics are medications that act on the kidneys to increase production of urine, therefore elimination of water from the body.Alright, so thiazide and thiazide-like diuretics are taken perorally, and once in the blood, they travel to the kidneys where they are secreted by the proximal convoluted tubule into the lumen of the renal tubule. An important point to make here is that they are secreted by the same secretory system that secretes uric acid into the tubule, so they compete with the secretion of uric acid, therefore increasing uric acid levels in the blood. Next, they travel along with the filtrate until they reach the distal convoluted tubule. This part of the nephron is lined by epithelial cells. All diuretics decrease blood volume, venous pressure, and preload. More specifically, thiazide diuretics block the sodium-chloride channel in the kidney, decreasing the cross of sodium over the luminal membrane, which in turn decreases the action of the sodiumpotassium pump and sodium and water passage to the renal interstitium. These changes increase urinary output and require the monitoring of potassium and other electrolytes to prevent adverse effects. All thiazides contain sulfa compounds; therefore, these medications should be avoided in patients allergic to sulfa. Thiazide diuretics are also used to manage osteopenia or osteoporosis, as they slow calcium loss in bones. o Therapeutic Use: o Essential hypertension: first-choice and usually the only choice in treating hypertension. o Edema: mobilizing edema associated with mild to moderate heart failure. They are also given to mobilize edema, mild to moderate heart failure or associated with hepatic or renal disease.Okay, so next we have the angiotensin converting enzyme inhibitors, or ACE inhibitors, and their names usually end in “-pril” - like captopril, enalapril, or lisinopril. So, by inhibiting the action of ACE, they prevent the formation of angiotensin II, and therefore decreases its level in the blood. With less angiotensin II in the bloodstream, there’s less vasoconstriction and therefore these medications effectively lower the blood pressure. As a result of blocking ACE, bradykinins form and cause the dry cough but can later lead to life-threatening angioedema. In addition, they lower aldosterone release, which causes natriuresis, or excretion of sodium by the kidneys. Because ACE inhibitors are effective in lowering blood pressure, they can be used not only to treat hypertension, but also to treat heart failure, where the heart isn’t strong enough to pump out an adequate amount of blood. In this situation, the decreased vasoconstriction leads to decreased peripheral vascular resistance and afterload, so the heart doesn’t have to pump as hard against that resistance.ACE inhibitors should also be given right after someone suffers an acute myocardial infarction in order to increase the perfusion of the heart to prevent further ischemic damage. Finally, we have the angiotensin II receptor blockers, or ARBS. They bind to angiotensin receptor 1 on vascular smooth muscles and the adrenal glands, which prevent angiotensin II from binding. This results in decreased vasoconstriction and decreased aldosterone synthesis respectively. ARBs ends in “-sartan,” like candesartan, valsartan, and losartan. They have the same indications as ACE inhibitors and can also be used to treat hypertension, heart failure, and MIs. Unlike ACE inhibitors, they don’t increase bradykinin levels in blood, hence they cause less cough and angioedema. Other than that, the adverse effects of angiotensin II receptor antagonists, just like ACE inhibitors, are hyperkalemia and hypotension. Despite having an apparently safer profile than ACE inhibitors, angiotensin II receptor antagonists are the medications of choice only if ACE inhibitors cannot be tolerated.So, let’s start with the dihydropyridines, which are mainly used to treat hypertension by creating vasodilation by blocking voltage-gated calcium channels in both cardiac smooth muscles as well as in blood vessels. They preferentially exert their effects on arterial smooth muscle, and nifedipine is the prototype of this class. Besides treating hypertension, dihydropyridines are also commonly used to treat other disorders. Since they can also dilate coronary arteries, they are effective for preventing angina.o Ethnic groups impacted by certain drug classifications o ACE inhibitors should be avoided by African American/Black and should take thiazides and/or CCBs. o One agent, rosuvastatin reaches abnormally high levels in people of Asian heritage. At usual therapeutic doses, rosuvastatin levels in these people are about twice those in Whites. Accordingly, if rosuvastatin is used by Asians, dosage should be reduced due to lack of CYP3A4 o Carbamazepine (Tegretol), used for epilepsy and bipolar disorder, can cause life-threatening skin reactions in some patients— specifically patients of Asian ancestry who carry genes that code for an unusual human leukocyte antigen (HLA) known as HLA-B*1502. • Prescribing considerations when carbamazepine is prescribed with warfarin o Carbamazepine (Tegretol®) is a potent enzyme inducer and may be metabolized by the same CYP450 enzyme that it induces. o Genetic testing for variants of CYP2C9 and VKORC1 may be done to identify patients who may require a reduction in warfarin dosage o Carbamazepine can enhance the activity of CYP450 which speeds up the metabolism of warfarin and we get an subtherapeutic INR that’s under 2. • Beta blockerso Their use with nitroglycerin and tachycardia o Organic Nitrate o Prototype Drug: Nitroglycerin o Therapeutic Action: Acts directly on vascular smooth muscle (VSM) to promote vasodilation o Beta Blockers o Prototype Drug: Propranolol; Metoprolol o Therapeutic Action: Decreases cardiac oxygen demand through blockade of specific receptors in the heart. o Common side effects of nitrates include flushing, headache, orthostatic hypotension, and reflex tachycardia, which is treated by co-administration of beta blockers. o Know examples o Examples: "pine" ending • nifedipine (Procardia XL) • amlodipine (Norvasc) • felodipine (Plendil) o Risk of stopping them abruptly Nitroglycerin • Tolerance to nitroglycerin-induced vasodilation can develop rapidly (over the course of a single day). • Long-acting preparations (transdermal patches, topical ointment, sustained-release oral tablets or capsules) should be discontinued slowly. If they are withdrawn abruptly, vasospasm may result. • Long-term use of β blockers can sensitize the heart to catecholamines. As a result, if a β blocker is withdrawn abruptly, anginal pain or ventricular dysrhythmias may develop. This phenomenon of increased cardiac activity in response to abrupt cessation of β-blocker therapy is referred to as rebound excitation. The risk for rebound excitation can be minimized by withdrawing these drugs gradually (e.g., by tapering the dosage over a period of 1 to 2 weeks). If rebound excitation occurs, dosing should be temporarily resumed. Patients should be warned against abrupt cessation of treatment. Also, they should be advised to carry an adequate supply of their β blocker when traveling. o What happens when given to someone with asthma? • In patients with asthma, blocking β2 receptors in the lung can cause bronchospasm. Because of its cardiac and pulmonary effects, propranolol should be used cautiously in patients with asthma and is contraindicated in patients with sinus bradycardia, highdegree heart block, and HF. • Diuretics• Different types of thiazides • Indications • Contraindications o Action • See therapeutic action above o Contradictions to thiazide diuretics • Sensitivity to sulfa drugs since all these meds have sulfa • Sensitivity to thiazides o Monitoring needs • Increases uric acid and glucose; pay attention to those who are prone to gout and are diabetic. • Side effects: Hyper ▪ Hyperglycemia (evidence unclear about interactions) ▪ Hyperuricemia (can precipitate gout) ▪ May cause hyperlipidemia; cholesterol & LDL ▪ Hypercalcemia Hypo ▪ Hypokalemia (potentiates digoxin toxicity and increases risk of arrhythmias) • hypokalemia metabolic alkalosis from the loss of potassium and H+ ▪ Hyponatremia (hold diuretic, restrict water intake, replace K+ loss) • Hypovolemia from urinating too much and increases the loss of sodium ▪ Hypomagnesemia • Heart failure o What to prescribe in response to fibrotic changes • ACEI• Influence on cardiac remodeling. With continued use, ACEIs have a favorable influence on cardiac remodeling. Elevation of kinins is largely responsible. This statement is based in part on the observation that, in experimental models, giving a kinin receptor blocker decreases beneficial effects on remodeling. Also, we know that suppression of angiotensin II production diminishes over time, so reduced angiotensin II cannot fully explain long-term benefits. • Not favorable: • However, because ARBs do not increase levels of kinins, their effects on cardiac remodeling are less favorable than those of ACEIs. For this reason and because clinical experience with ACEIs is much greater than that with ARBs, ACEIs are generally preferred. For now, ARBs should be reserved for HF patients who cannot tolerate ACEIs, usually owing to intractable cough. (Because ARBs do not increase bradykinin levels, they do not cause cough.) • Aldosterone Antagonists: • Promotion of myocardial remodeling (which impairs pumping) • Promotion of myocardial fibrosis (which increases the risk for dysrhythmias) o Effects of cardiac glycosides • Digoxin (Lanoxin) belongs to a family of drugs known as cardiac glycosides. • Digoxin has profound effects on the mechanical and electrical properties of the heart. In patients with HF, benefits derive from increased myocardial contractility and from effects on neurohormonal systems. • Uses: Dysrhythmias, HF, digoxin can reduce symptoms, increase exercise tolerance, and decrease hospitalizations. • May be harmful: Does not prolong life, shortens life for women. Toxicity risk. ▪ Need to monitor heart rate and monitor levels. ▪ Second-line therapy for treating heart failure. • Quinidine and digoxin o What happens when they are combined? • Quinidine is an antidysrhythmic drug that can cause plasma levels of digoxin to rise. Quinidine increases digoxin levels by (1) displacing digoxin from tissue binding sites and (2) reducing renal excretion of digoxin. By elevating levels of free digoxin, quinidine can promote digoxin toxicity. Accordingly, concurrent use of quinidine and digoxin should be avoided. • Atherosclerotic Cardiovascular Disease (ASCVD) Risk Score o What is it?• Under the 2018 ACC/AHA guidelines, ASCVD risk assessment is directed at determining the patient's absolute risk for developing clinical coronary disease over the next 10 years. The mode of intervention is then determined by the individual's degree of risk. • If the assessment indicates ASCVD risk, lifestyle changes—especially diet and exercise— should be implemented. If ASCVD risk is high, LDL-lowering drugs should be added to the regimen. o When is it used? • Ages start from 20 to 79 years old. • Identifying atherosclerotic cardiovascular disease risk factors. • Major risk factors that modify LDL treatment goals include positive risk factors (advancing age, black race, hypertension, cigarette smoking, and low HDL cholesterol) and one negative risk factor (high HDL cholesterol). (LDL itself is not listed because the reason for counting these risk factors is to modify treatment of high LDL.) • We know that diabetes is a very strong predictor of developing ASCVD. Accordingly, we no longer consider diabetes to be a risk factor. Instead, for the purpose of risk assessment, diabetes is now considered an ASCVD risk equivalent—that is, having diabetes is considered equivalent to having ASCVD as a predictor of a major coronary event. • Calculating 10-year atherosclerotic cardiovascular disease risk. • The 2018 ACC/AHA cholesterol guideline defines high ASCVD risk as 20% or greater. Patients with existing clinical ASCVD are placed in a “very-high risk” category, despite their screening percentage. For all other people, 10-year risk must be calculated. The instrument employed most often is the Framingham Risk Prediction Score, which takes five factors into account: age, total cholesterol, HDL cholesterol, smoking status, and systolic blood pressure. • Hyperlipidemia o Statin Drugs § At what age can they be prescribed • Most other patients with ASCVD are treated with statins alone. In primary prevention, statins are recommended for patients with severe hypercholesterolemia and in adults 40 to 75 years of age either with diabetes mellitus or at higher ASCVD risk. • In children, adolescents (10 to 19 years of age), and young adults (20 to 39 years of age), priority should be given to estimation of lifetime risk and promotion of lifestyle risk reduction. Drug therapy is needed only in selected patients with moderately high LDL-C levels (≥160 mg/dL [≥4.1 mmol/L]) or patients with very high LDL-C levels (190 mg/dL [4.9 mmol/L]). o Ezetimibe (Zetia) § What is it? • Non-statin agent: Cholesterol Absorption Inhibitors ▪ Ezetimibe (Zetia®)• Lowers LDL-C levels, on average, by 13% to 20% by derive from blocking cholesterol absorption by acting on cells of the brush border of the small intestine to inhibit dietary cholesterol absorption from food and from bile. Treatment reduces plasma levels of total cholesterol, LDL cholesterol, TGs, and apolipoprotein B. In addition, ezetimibe can produce a small increase in HDL cholesterol. • most used non-statin medication § When would it be used? • used in monotherapy or as adjunct therapy with a statin or a fibrate with implementing a modified diet. ▪ When ezetimibe was combined with a statin, the reduction in LDL cholesterol was about 25% greater than with the statin alone. • should not be used in patients with severe hepatic impairment. ▪ Side Effects: Reports of myopathy, rhabdomyolysis, hepatitis, pancreatitis, and thrombocytopenia. o Pharmacological option to minimize side effects § In other words, how would you treat high cholesterol if someone was concerned about or experiencing side effects from other medications? Which drug classification would be a good choice? • Statins are generally well tolerated. Side effects are uncommon. Some patients develop headache, rash, or gastrointestinal (GI) disturbances (dyspepsia, cramps, flatulence, constipation, abdominal pain). However, these effects are usually mild and transient. Serious adverse effects—hepatotoxicity and myopathy—are relatively rare. Some statins pose a greater risk than others, as noted subsequently. ▪ Myopathy and rhabdomyolysis (5% to 10% chance). • rosuvastatin (Crestor). Highest risk but still rare. • Management of muscle pain: replacement of vitamin D and coenzyme Q and switching statins. ▪ Hepatotoxicity (0.5% to 2% chance). • Liver injury, as evidenced by elevations in serum transaminase levels in patients who have been taking this 1 year or longer. • Not to be used with ETOH hepatitis but fatty hepatitis is OK. ▪ Toxicity: The same dose of rosuvastatin, when given to Asian and white subjects, may produce twofold higher blood levels in the Asians. Accordingly, when rosuvastatin is used in Asians, start with the lowest available dosage and monitor diligently. • Bile Acid Sequestrants are used in adjunct to statins. ▪ Constipation is the main complaint. This can be minimized by increasing dietary fiber and fluids. If necessary, a mild laxative may be used. • Niacin ▪ Flushing• Fibric Acid Derivatives (Fibrates) ▪ Gemfibrozil is generally well tolerated. • Increases risk for gallstones because of the increase of cholesterol saturation; not to be used in those with bladder diseases. • Myopathy. • Hepatotoxic and can pose risk for liver cancer. • Monoclonal Antibodies (Proprotein Convertase Subtilisin/Kexin Type 9 [PCSK9] Inhibitors) ▪ Allergic reaction ▪ Immunogenicity. These patients also had a higher incidence of injection site reactions compared with patients who did not develop antibodies. • Angina o Therapeutic action of organic nitrates • The oldest and most frequently used antianginal drugs. These agents relieve angina by causing vasodilation. • Nitroglycerin acts directly on vascular smooth muscle (VSM) to promote vasodilation. The most important aspect of this sequence is the conversion of nitrate to its active form—nitric oxide—in the presence of a sulfhydryl source. • Stable angina. Nitroglycerin decreases the pain of exertional angina primarily by decreasing cardiac oxygen demand but does not affect coronary arteries. • Variant angina. Nitroglycerin acts by relaxing or preventing spasm in coronary arteries. Hence the drug increases oxygen supply. It does not reduce oxygen demand. o Contraindications for ranolazine • It is used for the reduction of cardiac ischemia and the associated pain. • Ranolazine can cause a dose-related increase in the QT interval and may thereby increase the risk for torsades de pointes, a serious ventricular dysrhythmia. Accordingly, the drug is contraindicated for patients with preexisting QT prolongation and for those taking other drugs that can increase the QT interval. In addition, ranolazine is contraindicated for patients at risk for developing high levels of the drug—namely, patients with hepatic impairment or those taking drugs that inhibit CYP3A4. • In patients with severe renal impairment, ranolazine can raise blood pressure by about 15 mm Hg. Accordingly, blood pressure should be monitored often in these people. • Moderate or strong CYP3A4 inhibitors should be avoided (grapefruit juice, HIV protease inhibitors (e.g., ritonavir), macrolide antibiotics (e.g., erythromycin), azole antifungal drugs (e.g., itraconazole), and some CCBs.) Increasing the risk for torsades de pointes. • Patients taking drugs that prolong the QT interval (e.g., quinidine, sotalol). Week 4 • Most appropriate treatment approach for OA o Pharmacological and non-pharmacological• Treatment is directed at (1) relieving symptoms (pain, inflammation, and stiffness), (2) maintaining joint function and range of motion, (3) minimizing systemic involvement, and (4) delaying disease progression. To achieve these goals, a combination of pharmacologic and nonpharmacologic measures is used. • Nondrug Measures • Nondrug measures for managing RA include physical therapy, exercise, and surgery. Physical therapy may consist of massage, warm baths, and applying heat to the affected regions. These procedures can enhance mobility and reduce inflammation. • Orthopedic surgery has made marked advances. • A complete program of treatment should include patient education and counseling. • Drug Therapy The antirheumatic drugs fall into three major groups: • Nonsteroidal antiinflammatory drugs (NSAIDs) • Selection of an NSAID is based largely on efficacy, safety, and cost. Do not treat RA with opiods. • NSAIDs provide rapid relief of symptoms but do not prevent joint damage and do not slow disease progression. The NSAIDs are safer than DMARDs and glucocorticoids; thus treatment with NSAIDs requires less vigorous monitoring. • MOA ▪ 1st gen. inhibit COX-1 AND COX-2, , which pose a greater risk for GI ulceration because of inhibiting COX-1. • Aspirin • Ibuprofen • Meloxicam • Naproxen ▪ 2nd gen. (-coxibs) are selective and only inhibit COX-2. • Celecoxib (Celebrex) ▪ Work by inhibiting prostaglandins that produce pain. • Assess baseline: ▪ Renal function before starting NSAIDs but extreme cautions with peptic ulcer disease, bleeding disorders, those taking anticoagulants, older adults with heart failure, renal dysfunction and angina. • Make sure to monitor pain and functional ability. • No other monitoring is needed in terms of labs. • Start patient on a proton pump inhibitor while taking these meds to reduce the risk of GI bleed. • BLACK BOX WARNING: ▪ Risk for thrombotic events (in 2nd generation because it does not block COX-1), GI ulceration and bleeding. • Across the life-span:▪ Reye syndrome is usually associated with children or people that have not had chicken pox. Not for infants and children because of the risk for Reye Syndrome, aspirin should not be given! Acetaminophen and ibuprofen can be used safely in small doses for fever. ▪ Pregnant women: NSAIDs can result in closure of the ductus arteriosus in the baby. Therefore, their use is contra indicated in third trimester of pregnancy. ▪ Breastfeeding women: NSAIDs and acetaminophen appear safe for use in breastfeeding mothers. ▪ And for our older adults, NSAIDs are the most common drugs used to treat chronic pain in older adults. These drugs have been shown to increase hospital admissions in the population, however. And NSAIDs are also blamed for contributing to elevating blood pressure, precipitating CHF decompensation that can provoke renal failure, and caution should be used with NSAIDs in older adults. • Glucocorticoids • A steroid from the adrenal gland, cortisol - glucocorticoids provide rapid relief of symptoms by reducing of protein that are synthesizes the release of leukotrienes and prostaglandins to reduce inflammation and immunosuppression. • In addition, they can slow disease progression. Unfortunately, although glucocorticoids are effective, with long-term use they can cause serious toxicity (e.g., osteoporosis, gastric ulceration, adrenal suppression). As a result, treatment is usually limited to short courses until DMARDs and methotrexate manage the symptoms, but glucocorticoids can be used for exacerbations, too. ▪ Oral: Synthetic glucocorticoids work by removing neutrophils from the blood via demargination and reducing other white blood cells. • Hydrocortisone - Short-acting (8-12 hours) and short duration • Prednisone - Intermediate acting (18-36 hours), 4-5 times more potent. so, less is more. • Dexamethasone - long acting (36-54 hours), 25 times more potent. ▪ Can be given to a specific area if on or two joints are affected via intra-articular injections. Generalized symptoms are treated with oral glucocorticoids. • Assess and monitor: ▪ Neuromuscular and ophthalmic examination. ▪ Determine signs and symptoms of infection, check blood pressure and BMI. ▪ Height and weight for peds where use of medication is for a long period of time. ▪ CBC w/ WBC count and differential, serum glucose, electrolyte, lipid panel, and DEXA for bone mineral density. Assess every 6 to 12 months, if condition is stable. • If complications occur: • consider hyperglycemia and eye exam should be done every six months. Ask about muscle weakness at each visit and assess proximal muscle strength of extremities if weakness is present and determine proximal strength to determine weakness.• Stools for GI bleed if complaints of GI discomfort or black or red stools. • Bone mineral density in a year and 2-3 years after, if stable and does not decline. If decline, every year. ▪ Consider testing for latent TB, especially if a patient is at risk for TB. • Educate: ▪ Those who have recently received live virus vaccines are also at risk. Patients with infections should first be placed on antimicrobial therapy if feasible. ▪ And then medication adjustments may be needed for patients taking potassium depleting diuretics, digoxin, NSAIDs or hypoglycemic drugs, including insulin. • Side effects: ▪ GI ulceration and bleeding is a risk, especially increases with NSAIDs. ▪ Usually from high-doses for a long period of time can result in iatrogenic Cushing syndrome. ▪ Fluid retention, hypertension, hypokalemia. ▪ Hyperglycemia, diabetic, suppression of HPA Axis that causes adrenal cortical atrophy. ▪ Impaired healing. ▪ Muscular myopathy, avascular necrosis of femoral and humeral heads, osteoporosis, and pathological fractures (increased osteoclast activity and decreases osteoblast). ▪ Impaired height in children. ▪ Peptic ulcers ▪ Cataracts • Across the lifespan: ▪ Children: Inhibition of bone growth and stunts their growth, if used for extended periods of time. ▪ Pregnant women: Limit studies, but have shown in the first trimester, cleft palates. Administration later in pregnancy places the neonate at risk for hypoadrenalism. ▪ For some conditions like severe persistent asthma, the risk of not using corticosteroids may cause more harm than using them. It's essential to weigh the risk versus benefits. ▪ Use the smallest dose for the shortest period of time to control symptoms and use inhaled or other non- systemic formulations whenever you can. When systemic use is needed, hydrocortisone is preferred over other glucocorticoids. ▪ Breastfeeding: when physiologic doses or low pharmacologic doses are used, the concentration achieved in milk is probably too low to affect the nursing infant. Large doses have the same effect, such as if it were to be administered for children. ▪ Older adults: Long-term use of glucocorticoids can cause osteoporosis, adrenal insufficiency, and GI ulceration. And these conditions may affect older adults disproportionately. • Disease-modifying antirheumatic drugs (DMARDs)• DMARDs are drugs that re