NR 565 MIDTERM STUDY GUIDE LATEST UPDATE 2024 GRADED A, Exams of Nursing

Download NR 565 MIDTERM STUDY GUIDE LATEST UPDATE 2024 GRADED A and more Exams Nursing in PDF only on Docsity! lOMoARcPSD|336 400 06 NR 565 MIDTERM STUDY GUIDE LATEST UPDATE 2024 GRADED A • 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. o Examples Valproate, Isoniazid, Sulfonamides, Amiodarone, Chloramphenicol, Ketoconazole, Grapefruit juice, Quinidine o 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. 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 different receptors 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 • 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 be refilled. 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 of certain 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 also protect 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 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. TABLE 41.3 Classes of Antihypertensive Drugs Recommended for Initial Therapy of Hypertension in | Patients With Certain High-Risk Comorbid Conditions Drug Classes Recommended for Initial Therapy of High-Risk Comorbid Conditions that Constitute Hypertension Compelling Indications for the Drugs Checked = B ACE ape ccp Aldosterone! Blocker Inhibitor Antagonist Heart failure v v v v v Post-myocardial infarction v v v High coronary disease risk v v v v Diabetes v v v viv Chronic kidney disease v v Prevention of recurrent stroke v v ACE, Angiotensin-converting enzyme; ARB, angiotensin II receptor blocker; CCB, calcium |channel blocker. | Adapted from 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/AphA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults.  TABLE 41.4 Comorbid Conditions That Require Cautious Use or Complete Avoidance of Certain Antihypertensive Drugs ‘Comorbid Drugs to Be Avoided or Reason for C Condition __Used With Caution ee Cardiovascular Disorders Heart failure Verapamil These drugs act on the heart to decrease myocardial Diltiazem contractility and can thereby further reduce cardiac output. AVheart block |g Blockers These drugs act on the heart to suppress AV conduction and Labetalot can thereby intensify AV block. Verapamil Diltiazem Coronary artery | Hydralazine Reflex tachycardia induced by hydralazine can precipitate an disease anginal attack. Post- Hydralazine Reflex tachycardia induced by hydralazine can increase cardiac myocardial work and oxygen demand. infarction Other Disorders Dyslipidemia B Blockers These drugs may exacerbate dyslipidemia. Diuretics Renal K*-sparing Use of these agents can lead to dangerous accumulations of insufficiency diuretics potassium. K* supplements Asthma B Blockers B, Blockade promotes bronchoconstriction. Labetalol Depression Reserpine? Reserpine can cause depression.  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. o 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 failureo 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 digoxino 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 Scoreo 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. • 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 https://www.osmosis.org/learn/Osteoarthritis • 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. • 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 reduce joint destruction and slow disease progression because it causes immunosuppression and reduced associated inflammation. Not typically prescribed at primary care offices and more often in rheumatology offices, but it is important to be familiar with these meds because the patients we see may be taking them. • Baseline Assessments: CBC with differential. Signs and symptoms of infection - especially TB and hepatitis. Pregnancy. Malignancies - including on the skin. Liver - important to check. Renal - important to check. • Monitor: CBC with differential. Signs and symptoms of infection - Emphasis should be placed on risk to immunocompetence. New or worsening symptoms or problems. • Contraindicated Immunosuppression - HIV or are on other immunosuppressant drugs. Diabetes. Heart Failure. Liver Dysfunction. Latent TB. Latent HBV. Renal Failure. Recurrent or prone to infections. • Adverse Effects: Infection - commonly occur. Patient education and close monitoring is essential to identify adverse effects in early stages when they can be easily managed. Vaccines to prevent infections are given before starting DMARDs. • So they need a pneumonia, a flu, hepatitis B, HPV and herpes zoster vaccines. • Types: conventional (traditional) DMARDs • Methotrexate is the first medication of choice because it is relatively safe, low cost, and shows 80% improvement and acts faster than all DMARDs (results in 3-6 weeks). • Mechanism of action: Methotrexate is a folate agonist, as it is needed for DNA synthesis and cellular replication. Reduces B and T lymphocytes. • Bassline assessment: Chest x-ray. • Monitor: • Liver function tests. • Renal: Creatinine and BUN. • Pulmonary - done at each visit. • GI - done at each visit. • CBC. • Platelets. • Contraindications: • Pregnant - causing fetal death and abnormalities. • Breast Feeding. • Blood dyscracias. • Immunodeficiencies. • Liver disease. • Live Vaccines. • If it's necessary to give an inactivated or killed vaccine to patients receiving methotrexate, patients should be re vaccinated within three months after therapy is discontinued. Ideally, needed vaccine should be administered prior to starting methotrexate. • Adverse Effects: • Increased risk for hepatotoxicity. • Hepatic fibrosis. • Children and adolescents taking TNF inhibitors have developed lymphoma and other malignancies. • BLACK BOX: • These include serious infections, severe allergic reactions, heart failure, cancer, hematologic disorders, liver injuries, and CNS demyelinating disorders. And our black box warning: patients taking tumor necrosis factor inhibitors are at increased risk for developing serious symptomatic infection and sepsis. targeted DMARDs - Tofacitinib (Xeljanz). Both generic drug names end in n-i-b or "nib." • Mechanism of Action: • Janus kinase inhibitors. JAKs are intercellular enzymes that have a role in initiating cytokine signaling as part of the signal transducer and activation of transcription pathway or the stat pathway. This pathway is involved in inflammatory and immune responses. Therefore, by inhibiting Jaks, these DMARDs reduce immune and inflammatory responses that underline the pathology of RA. • Indicated for treatment of moderately to severe active RA in patients who cannot take methotrexate, and for patients who have not experienced an adequate response to methotrexate. So you do not give it with methotrexate. • Biologic DMARDs have an additive toxic effect when combined with Xeljanz. • Baseline assessment: heart rate and blood pressure, a lipid panel, ALT and AST, which are both liver function test with an emphasis on cardiac, pulmonary and GI status. • Metabolized by CYP3A4 and CYP2C19 iso enzymes, therefore, drugs that act as CYP3A4 or CYP2C19 inhibitors can increase Xeljanz levels. • Monitoring: • Infection • Cautions and contraindications: • Xeljanz can increase immunosuppression when combined with other drugs having immunosuppressant effects. • Decreases the efficacy of inactivated vaccines. If vaccinations are needed, They should be given two weeks before starting Xeljanz. Herpes zoster vaccines are recommended for older adults, and live or attenuated vaccines can cause serious complications and adverse reactions when administered to patients taking Xeljanz. • Adverse Effects: • So approximately 20 percent of people taking Xeljanz develop infection; most common infection in clinical trials was nasopharyngitis, though other infections such as herpes zoster and gastroenteritis were documented. • headache, increased serum cholesterol, increased creatine phosphokinase, and skin rashes. Less common, but serious adverse effects have occurred. One of the most concerning is bone marrow suppression. • Decreases and lymphocytes, neutrophils and erythrocytes occur most often, but significant decrease in platelets. • Bradycardia with prolonged PR interval, interstitial lung disease, GI perforations, drug induced liver injury, hyperlipidemia, and increased occurrence of malignancies. • Patients taking Xeljanz have developed lymphoma and other malignancies. • BLACK BOX: • Increases the risk for developing serious and potentially fatal infections, including tuberculosis. DMARDs Across the LifeSpan: • Children: Biologic DMARDs, children and adolescents taking TNF inhibitors have developed lymphoma and other malignancies. • Pregnant women: Conventional DMARDs, the methotrexate, can cause fetal death and congenital abnormalities. The biologic DMARDs, research is limited for all biologics. The targeted DMARDs, fetal death and congenital abnormalities have occurred in animal studies, and until more is known, targeted DMARDs are not recommended for pregnant women. • Breastfeeding: DMARDs are not recommended. • In older adults, elderly patients may be at greater risk for infection, secondary to the immunosuppressive effects of DMARDs • Gout o Complications of untreated gout Untreated gout from urate crystals may cause erosion and irreversible joint damage, renal damage, and tophi. o Treatment of acute flare with colchicine • NSAIDs are used first, usually. • First, it can be used short-term to treat an acute gouty attack. And second, it can be used long-term to prevent attacks from occurring. • 1.2 first. Then, 0.6. Max 1.8/24hour § Patient education • Anti-inflammatory drug: colchicine is generally reserved for patients who are unresponsive to or intolerant of safer agents. • Don't take this medication with statin meds because of risk for rhabdomyolysis. § Adverse effects • The most characteristic side effects are nausea, vomiting, diarrhea, and abdominal pain. These responses which occur during the treatment of acute gouty attacks result from the injury to the rapidly proliferating cells of the GI epithelium. With the high doses used in the past, these GI effects were developed in nearly all patients. However, with lower doses used today, GI toxicity is much less common. • If GI symptoms occur, colchicine should be discontinued immediately regardless of the status of the joint pain. And that is patient teaching that you need to be very clear with your patients about when you're prescribing colchicine. • Injury to rapidly proliferating cells can also suppress bone marrow function and thereby cause leukopenia, granulocytopenia, thrombocytopenia and pancytopenia. Accordingly, colchicine should be used with caution in patients with hematologic disorders. • colchicine can cause rhabdomyolysis, which is a muscle breakdown during long-term low dose therapy. • Risk is increased in patients with renal and hepatic impairment and in those taking Statin drugs, which can cause rhabdomyolysis on their own. • Life-threatening reactions have occurred when colchicine was combined with two classes of drugs: P glycoprotein (PGP) inhibitors and inhibitors of CYP3A4. PGP is a transporter protein that can reduce plasma drug levels through effects in the liver, kidney, and intestine; hence by inhibiting PGP, Drugs such as cyclosporine and ranolazine can cause colchicine to accumulate to toxic levels. • So similarly, by inhibiting CYP3A4, drugs such as ketoconazole, clarithromycin, and HIV protease inhibitors can cause colchicine levels to rise. Accordingly, combined use of colchicine with strong inhibitors of either PGP or CYP3A4 should generally be avoided and is contra-indicated in patients with hepatic or renal impairment. o Long-term use of allopurinol • Allopurinol is the current drug of choice for chronic tophaceous gout. By reducing blood uric acid levels, allopurinol prevents the formation of new tophi and causes regression of the tophi that have already formed. And when we say tophi, it's the big red swollen area on the joint, that is the tophi. And this allows joint function to improve. Reversal of hyperuricemia also decreases the risk for nephropathy from the deposition of urate crystals in the kidneys by inhibiting xanthine oxidase, an enzyme required for uric acid formation. § What condition can be developed? • Allopurinol is generally well tolerated. Mild side effects include GI reactions from nausea, vomiting, diarrhea, and abdominal discomfort, and neurological effects such as drowsiness, headache, and a metallic taste. • Prolonged use of allopurinol, say more than three years, may lead to the formation of cataracts.