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______ the sun set, the temperature began to drop. A) After B) While C) Since She studied all night for her test. ______, she was confident when she walked into class. A) Meanwhile B) As a result C) Before We arrived at the park early. ______, we set up our picnic and waited for the others to arrive. A) First B) Later C) Then The alarm rang loudly. ______, I jumped out of bed and rushed to get ready. A) Before B) Immediately C) Eventually The Wright brothers made their first successful flight in 1903. ______, air travel has advanced significantly. A) Since then B) Before C) Meanwhile Example Paragraphs (Choose the Best Transition Word) Cooking Instructions First, preheat the oven to 375°F. ______, mix the flour, sugar, and baking powder in a large bowl. Next, add the eggs and milk, stirring until smooth. (Options: Then, Before, While) Historical Events The Declaration of Independence was signed in 1776. ______, the United States officially became a separate nation from Britain. (Options: As a result, Before, However) Personal Narrative I packed my bags and headed to the airport. ______, I realized I had forgotten my passport at home. (Options: Later, Suddenly, Before) Daily Routine Every morning, I wake up at 6 AM. ______, I brush my teeth and make a cup of coffee. (Options: First, Afterward, Meanwhile) Science Explanation The caterpillar forms a chrysalis. ______, it undergoes metamorphosis and transforms into a butterfly. (Options: Eventually, Meanwhile, Before)

Write questions similar to ______ the sun set, the temperature began to drop. A) After B) While C) Since She studied all night for her test. ______, she was confident when she walked into class. A) Meanwhile B) As a result C) Before We arrived at the park early. ______, we set up our picnic and waited for the others to arrive. A) First B) Later C) Then The alarm rang loudly. ______, I jumped out of bed and rushed to get ready. A) Before B) Immediately C) Eventually The Wright brothers made their first successful flight in 1903. ______, air travel has advanced significantly. A) Since then B) Before C) Meanwhile Example Paragraphs (Choose the Best Transition Word) Cooking Instructions First, preheat the oven to 375°F. ______, mix the flour, sugar, and baking powder in a large bowl. Next, add the eggs and milk, stirring until smooth. (Options: Then, Before, While) Historical Events The Declaration of Independence was signed in 1776. ______, the United States officially became a separate nation from Britain. (Options: As a result, Before, However) Personal Narrative I packed my bags and headed to the airport. ______, I realized I had forgotten my passport at home. (Options: Later, Suddenly, Before) Daily Routine Every morning, I wake up at 6 AM. ______, I brush my teeth and make a cup of coffee. (Options: First, Afterward, Meanwhile) Science Explanation The caterpillar forms a chrysalis. ______, it undergoes metamorphosis and transforms into a butterfly. (Options: Eventually, Meanwhile, Before)

Electrostatics The section of CBSE Class 12 Physics electrostatic potential and capacitance notes mainly deals with the in-depth analysis of electromagnetic phenomena when they are not performing any movements. Additionally, it is divided into ten further sub-topics to study the companion processes of reaching the state. These are - 1. Electric charge In this section of Physics ch 2 Class 12 notes, you get to learn about the basic features of electric charge and its expression in Physics. Along with its basics, the sections help to understand the full potential of charge. Different aspects of Charge included in Class 12 Physics Chapter 2 notes are - Definition Type: Positive and Negative Charge Unit and dimensional formula Point Charge Properties of Charge Comparison of Charge and Mass Methods of Charging Electroscope 2. Coulomb's Law Force is created when charges of opposite signs attract each other, and they repulse if the signs are the same. Coulomb's law tries to define this phenomenon through a mathematical formula, explicitly mentioned in Physics Class 12 notes Chapter 2. Moreover, there is key information about the variation of the constant k and its effect on a medium. Coulomb's law's vector form and the principle of superimposition are also explained in ch 2 Physics Class 12 notes. (Image will be uploaded soon) 3. Electric Field As stated in Class 12 Physics Chapter 2 notes, every positively or negatively charged particle has their respective electric fields. It feels a force at the time of interaction which might be attraction or repulsion. As it arises from electric charge, it is crucial to know about its different parts like - Electric field intensity Relation between electric force and electric field Super imposition of electric field Point charge Continuous charge distributions Properties of Electric Field Lines Motion of Charged Particles in an Electric field Learning more about the electric field from electric potential and capacitance notes Class 12 helps a student to get a grasp of upcoming chapters. 4. Electric Potential Energy When energy helps a charge to move from an electric field, it is known as the Electric Potential Energy. This section of electrostatic chapter Class 12 notes requires a student to study the Electron volt (eV), and the potential energy that an n number of charges can hold. 5. Electric Potential This section of Class 12 Physics Chapter 2 notes focuses on in-depth learning of Electric Potential or Voltage. Basically, it defines the potential movement of energy. 6. Relation between Electric Field and Potential Apart from knowing more about the relationship between the two values, Physics Class 12 Chapter 2 notes also discuss equipotential surfaces. 7. Electric Dipole Essentially, 'Dipoles' are two opposite points of charge represented with q and –q, with their distance between each other being 2a. Electric Dipoles are crucial in your study of Physics Class 12 Chapter 2 notes to learn more about electric fields and their potential. Additionally, Class 12 Physics Chapter 2 notes focus on the influence of electric dipoles on a uniform electric field mainly through Force and Torque, Work, and Potential Energy. In the last part of Electrostatics, further focus is on using the formulas to their fullest potential. It includes subsections of Electric Field, Electric Potential Energy, Electric Potential, and Electric Dipole. In the notes for electrostatic potential and capacitance, you will find proper solutions accompanied by clear and crisp diagrams for better understanding. 8. Gauss's Law Apart from just discussing the Gauss's Law, in Physics Class 12 ch 2 notes there is a thorough explanation of its properties and applications. The Gauss' Law states that net electric flux passing through a hypothetical closed surface is equal to the net electric charge present within the same closed surface. Being a broad part of the whole chapter, you may need to spend a little more time on it. Moving forward, it starts discussing the properties of conductors in relation to Gauss's Law. The Class 12 Physics notes Chapter 2 perfectly defines the journey to Gauss' Law from Coulomb's Law. Here is the Gauss's Law present in the Class 12 Physics ch 2 notes, (image will be uploaded soon) 9. Capacitors There is a dedicated section about Capacitors in the Class 12 Physics Chapter 2 notes elucidating its functions and importance as storage of potential electric energy. After explaining the structure of a capacitor, it points out the different types, parallel plate, spherical and cylindrical. The section of Chapter 2 notes of Physics Class 12 is further divided into subheads like: Properties of an ideal battery Grouping of capacitors Simple circuits (Series and Parallel) Dielectric Van de Graaff generator Combination of drops Charge distribution method Wheatstone Bridge-based circuit Extended Wheatstone Bridge Infinite network of capacitors Redistribution of charge between two capacitors Vedantu prepares the Class 12 Physics Chapter 2 notes with help from subject matter experts. In the PDF, you get a comprehensive idea of the topic along with potential answers to the most asked questions. Furthermore, the detailed explanation on each section and subsections are written in a simple language allows a student to ace their exams with wholesome knowledge. These Physics Chapter 2 Class 12 notes are going to be one of the best supplementary study materials besides a student’s textbooks. Visit the Vedantu website or download the app to get your hands on all important notes! Important Questions A charge of 4 × 10–8C is uniformly distributed on the surface of a spherical conductor, having a radius of 15 cm. Determine the electric field just outside this sphere at a point that is 15 cm from the centre of this sphere. Determine the capacitance given that the distance between the two plates has been reduced by half and the parallel plate capacitor holds a capacitance of 20 pF (where 1pF = 10-12 F) having air between the two plates. What will be the total capacitance of a combination where three capacitors, each having a capacitance of 20 pF, are connected in series. A square having a side of 10 cm has a 500 µC charge at its centre. Determine the work done to move a charge of 10 µC between two points that are diagonally opposite each other on the square. At an equatorial point, what will be the electrostatic potential because of an electric dipole? Calculate the work done to move a test charge, q, through a length of 1 cm along the equatorial axis of an electric dipole? Polarisation A capacitor has its plates enclosed in a medium that can be filled by insulating substances. A net dipole moment is then induced by an electric field in the dielectric. This event causes the field in an opposite direction. Equipotential Surface An equipotential surface is a type of surface where the potential always has a constant value. If considered as a point charge, the concentric spheres that are centred at a particular area of this charge are basically equipotential surfaces. Advantages of Vedantu's Revision Notes: A Comprehensive Resource for Effective Learning There are several reasons why one may refer to Vedantu's revision notes for studying a subject like Electrostatic Potential and Capacitance. Here are some key points: Comprehensive Coverage: Vedantu's revision notes provide a comprehensive coverage of the entire topic, ensuring that all important concepts and subtopics are included. Concise and Organized: The notes are designed to be concise, focusing on the key points and core ideas. They are organized in a structured manner, making it easy for students to navigate and revise the content. Simplified Explanation: The revision notes offer simplified explanations of complex concepts, making them more accessible and easier to understand. This helps students grasp the material more effectively. Key Formulas and Equations: The notes highlight the key formulas and equations relevant to the topic, ensuring that students have a clear understanding of the mathematical aspects of Electrostatic Potential and Capacitance. Examples and Illustrations: Vedantu's revision notes often include examples and illustrations that help clarify concepts and provide practical applications, enabling students to better relate theory to real-world scenarios. Quick Recap: The revision notes serve as a quick recap of the important points, allowing students to review the material efficiently before exams or assessments. Exam-Oriented Approach: Vedantu's revision notes are designed with an exam-oriented approach, focusing on the topics and concepts that are frequently asked in examinations. This helps students prepare effectively and increase their chances of scoring well. Accessible Anytime: Vedantu's revision notes are easily accessible online, allowing students to study at their convenience and revise the material anytime, anywhere.

Fed. 51: To the People of the State of New York: TO WHAT expedient, then, shall we finally resort, for maintaining in practice the necessary partition of power among the several departments, as laid down in the Constitution? The only answer that can be given is, that as all these exterior provisions are found to be inadequate, the defect must be supplied, by so contriving the interior structure of the government as that its several constituent parts may, by their mutual relations, be the means of keeping each other in their proper places. Without presuming to undertake a full development of this important idea, I will hazard a few general observations, which may perhaps place it in a clearer light, and enable us to form a more correct judgment of the principles and structure of the government planned by the convention. In order to lay a due foundation for that separate and distinct exercise of the different powers of government, which to a certain extent is admitted on all hands to be essential to the preservation of liberty, it is evident that each department should have a will of its own; and consequently should be so constituted that the members of each should have as little agency as possible in the appointment of the members of the others. Were this principle rigorously adhered to, it would require that all the appointments for the supreme executive, legislative, and judiciary magistracies should be drawn from the same fountain of authority, the people, through channels having no communication whatever with one another. Perhaps such a plan of constructing the several departments would be less difficult in practice than it may in contemplation appear. Some difficulties, however, and some additional expense would attend the execution of it. Some deviations, therefore, from the principle must be admitted. In the constitution of the judiciary department in particular, it might be inexpedient to insist rigorously on the principle: first, because peculiar qualifications being essential in the members, the primary consideration ought to be to select that mode of choice which best secures these qualifications; secondly, because the permanent tenure by which the appointments are held in that department, must soon destroy all sense of dependence on the authority conferring them. It is equally evident, that the members of each department should be as little dependent as possible on those of the others, for the emoluments annexed to their offices. Were the executive magistrate, or the judges, not independent of the legislature in this particular, their independence in every other would be merely nominal. But the great security against a gradual concentration of the several powers in the same department, consists in giving to those who administer each department the necessary constitutional means and personal motives to resist encroachments of the others. The provision for defense must in this, as in all other cases, be made commensurate to the danger of attack. Ambition must be made to counteract ambition. The interest of the man must be connected with the constitutional rights of the place. It may be a reflection on human nature, that such devices should be necessary to control the abuses of government. But what is government itself, but the greatest of all reflections on human nature? If men were angels, no government would be necessary. If angels were to govern men, neither external nor internal controls on government would be necessary. In framing a government which is to be administered by men over men, the great difficulty lies in this: you must first enable the government to control the governed; and in the next place oblige it to control itself. A dependence on the people is, no doubt, the primary control on the government; but experience has taught mankind the necessity of auxiliary precautions. This policy of supplying, by opposite and rival interests, the defect of better motives, might be traced through the whole system of human affairs, private as well as public. We see it particularly displayed in all the subordinate distributions of power, where the constant aim is to divide and arrange the several offices in such a manner as that each may be a check on the other that the private interest of every individual may be a sentinel over the public rights. These inventions of prudence cannot be less requisite in the distribution of the supreme powers of the State. But it is not possible to give to each department an equal power of self-defense. In republican government, the legislative authority necessarily predominates. The remedy for this inconveniency is to divide the legislature into different branches; and to render them, by different modes of election and different principles of action, as little connected with each other as the nature of their common functions and their common dependence on the society will admit. It may even be necessary to guard against dangerous encroachments by still further precautions. As the weight of the legislative authority requires that it should be thus divided, the weakness of the executive may require, on the other hand, that it should be fortified. An absolute negative on the legislature appears, at first view, to be the natural defense with which the executive magistrate should be armed. But perhaps it would be neither altogether safe nor alone sufficient. On ordinary occasions it might not be exerted with the requisite firmness, and on extraordinary occasions it might be perfidiously abused. May not this defect of an absolute negative be supplied by some qualified connection between this weaker department and the weaker branch of the stronger department, by which the latter may be led to support the constitutional rights of the former, without being too much detached from the rights of its own department? If the principles on which these observations are founded be just, as I persuade myself they are, and they be applied as a criterion to the several State constitutions, and to the federal Constitution it will be found that if the latter does not perfectly correspond with them, the former are infinitely less able to bear such a test. There are, moreover, two considerations particularly applicable to the federal system of America, which place that system in a very interesting point of view. First. In a single republic, all the power surrendered by the people is submitted to the administration of a single government; and the usurpations are guarded against by a division of the government into distinct and separate departments. In the compound republic of America, the power surrendered by the people is first divided between two distinct governments, and then the portion allotted to each subdivided among distinct and separate departments. Hence a double security arises to the rights of the people. The different governments will control each other, at the same time that each will be controlled by itself. Second. It is of great importance in a republic not only to guard the society against the oppression of its rulers, but to guard one part of the society against the injustice of the other part. Different interests necessarily exist in different classes of citizens. If a majority be united by a common interest, the rights of the minority will be insecure. There are but two methods of providing against this evil: the one by creating a will in the community independent of the majority that is, of the society itself; the other, by comprehending in the society so many separate descriptions of citizens as will render an unjust combination of a majority of the whole very improbable, if not impracticable. The first method prevails in all governments possessing an hereditary or self-appointed authority. This, at best, is but a precarious security; because a power independent of the society may as well espouse the unjust views of the major, as the rightful interests of the minor party, and may possibly be turned against both parties. The second method will be exemplified in the federal republic of the United States. Whilst all authority in it will be derived from and dependent on the society, the society itself will be broken into so many parts, interests, and classes of citizens, that the rights of individuals, or of the minority, will be in little danger from interested combinations of the majority. In a free government the security for civil rights must be the same as that for religious rights. It consists in the one case in the multiplicity of interests, and in the other in the multiplicity of sects. The degree of security in both cases will depend on the number of interests and sects; and this may be presumed to depend on the extent of country and number of people comprehended under the same government. This view of the subject must particularly recommend a proper federal system to all the sincere and considerate friends of republican government, since it shows that in exact proportion as the territory of the Union may be formed into more circumscribed Confederacies, or States oppressive combinations of a majority will be facilitated: the best security, under the republican forms, for the rights of every class of citizens, will be diminished: and consequently the stability and independence of some member of the government, the only other security, must be proportionately increased. Justice is the end of government. It is the end of civil society. It ever has been and ever will be pursued until it be obtained, or until liberty be lost in the pursuit. In a society under the forms of which the stronger faction can readily unite and oppress the weaker, anarchy may as truly be said to reign as in a state of nature, where the weaker individual is not secured against the violence of the stronger; and as, in the latter state, even the stronger individuals are prompted, by the uncertainty of their condition, to submit to a government which may protect the weak as well as themselves; so, in the former state, will the more powerful factions or parties be gradnally induced, by a like motive, to wish for a government which will protect all parties, the weaker as well as the more powerful. It can be little doubted that if the State of Rhode Island was separated from the Confederacy and left to itself, the insecurity of rights under the popular form of government within such narrow limits would be displayed by such reiterated oppressions of factious majorities that some power altogether independent of the people would soon be called for by the voice of the very factions whose misrule had proved the necessity of it. In the extended republic of the United States, and among the great variety of interests, parties, and sects which it embraces, a coalition of a majority of the whole society could seldom take place on any other principles than those of justice and the general good; whilst there being thus less danger to a minor from the will of a major party, there must be less pretext, also, to provide for the security of the former, by introducing into the government a will not dependent on the latter, or, in other words, a will independent of the society itself. It is no less certain than it is important, notwithstanding the contrary opinions which have been entertained, that the larger the society, provided it lie within a practical sphere, the more duly capable it will be of self-government. And happily for the REPUBLICAN CAUSE, the practicable sphere may be carried to a very great extent, by a judicious modification and mixture of the FEDERAL PRINCIPLE. PUBLIUS.

Micromarketing is an advertising strategy that allows a corporation to target a niche group with a particular product or service. With micromarketing, a company defines an audience by a specific trait, such as gender or job title or age range, and then creates campaigns geared toward that specific group. Macro-marketing is a multidisciplinary domain that deals with the impact that marketing has on the economy and society. It specializes in marketing-society interrelationships, such as green marketing, fairness and ethics, social management, market control, consumer conduct, and others. Customer relations refers to the methods, strategies, and processes a company uses to build and maintain customer relationships. Every customer interaction has an impact, and it's more important than ever for companies to consistently meet expectations.s PRODUCT DEVELOPMENT is strategy involves the improvement of current products or services or the development of the new products with the purpose of increasing sales. MARKET DEVELOPMENT is a strategy involves the introduction of existing products or services into a new geographical area or market. STRATEGIC PLANNING a broad process that can address the entire business, or a portion of the business. PLANNING the process of predicting future events and conditions and of determining the best way to attain the goals and objectives of the organization. CUSTOMER VALUE relationship between benefits and the costs including money, stress, and time to sacrifice that is necessary to get those benefits. POLITENESS Saying ”hello”, good afternoon sir/ma’am, and thank you very much are a part of good customer services. PRODUCTION PROCESS it is the process must conform to standards in terms of product quality. RELATIONSHIP MARKETING involves creating, maintaining and enhancing strong relationships with customers and other stakeholders. KEY PERFORMANCE INDICATOR a tool used to check the marketing activities and to track performance to make sure the company is on track to meet specific objectives. REACTIVE salesperson sells the product and encourage the customer to call whenever he or she has any questions or problems. MARKET PENETRATION the objective of this strategy is to increase market share of current products or services in current markets through greater and more intensive marketing efforts. LIQUIDATION this involves selling all of a company’s assets, in parts or as a whole, for their tangible worth. PRICING TEST can be utilized by marketers to calculate a product’s or service’s optimal price, to determine price elasticity. POSITIONING the process of communicating the image of a brand into the minds of consumers. INDUSTRIES business organizations that purchase goods and services for the purpose of producing other products and services or for use in their products and operating processes.

Chapter 22 Antihypertensive Drugs Hypertension Defined (JNC-8) Pharmacology Overview 7 main categories of drugs to treat HTN Adrenergic drugs (old friend) Angiotensin-converting enzyme (ACE) inhibitors Angiotensin II receptor blockers (ARBs) Calcium channel blockers (CCBs) Diuretics Vasodilators Direct renin inhibitors A. Adrenergic Drugs: 5 Subcategories and where they act A1. Adrenergic neuron blockers (central and peripheral)- we won’t talk about this A2. Alpha1 receptor blockers (peripheral) A3. Alpha2 receptor agonists (central) A4. Beta receptor blockers (peripheral) A5. Combined α and β receptor blockers (peripheral) A2. Peripherally Acting Adrenergic DrugAlpha1 Blockers (we’ve met these) Doxazosin, prazosin, alfuzosin Block alpha1-receptors which causes BP to decrease Reduces peripheral vascular resistance and BP by dilating both arterial and venous blood vessels Main Use: benign prostatic hyperplasia (BPH) Alpha1 Blockers REMEMBER Tamsulosin (Flomax)* is an α1 blocker BUT *Tamsulosin is not used to control BP, just for BPH. A3. Centrally Acting Adrenergic DrugsAlpha 2 agonist Clonidine and methyldopa 1- Stimulate alpha2-adrenergic receptors. in the brain Decreases sympathetic outflow from the CNS which decreases NE production 2. Stimulate alpha2-adrenergic receptors in kidneys remember alpha 2 opposes alpha 1 Dilates peripheral blood vessels → lowers peripheral resistance → Results in decreased BP So ….Clonidine (Catapres) Used primarily for its ability to decrease blood pressure in an urgent setting Also use in opioid withdrawal as previously discussed Oral (multiple times a day), and topical patch formulations Do not stop abruptly as it may lead to rebound hypertension In reality, Clonidine and methyldopa Not prescribed as first-line home antiHTN drugs High incidence of unwanted adverse effects: orthostatic hypotension, fatigue, and dizziness MIGHT be uses as adjunct drugs after other drugs have failed, in conjunction with other antiHTN such as diuretics A4. Adrenergic Drugs Selective Beta 1 Blockers Metoprolol, Atenolol Reduction of HR through β1 receptor blockade (remember adrenergic blocking of this receptor???) HR results in BP Cause reduced secretion of renin = BP A4. Adrenergic Drugs Selective Beta1 Blockers Nebivolol (Bystolic) Uses: hypertension and HF Action: blocks β1 receptors and produces vasodilatation, which results in a decrease in SVR High doses loses selectivity and blocks both β1 and β2 Less sexual dysfunction All BB- Do not stop abruptly; must be tapered over 1 to 2 weeks A4. Adrenergic Drugs NONSelective Beta Blockers Propranolol Acts equally on β1 and β2 Other uses include situational anxiety associated with public speaking, test taking As mentioned on previous slide, nebivolol at high doses becomes beta nonselective A5. Dual-Action Adrenergic Drugs α1 and β Receptor Blockers Dual antihypertensive effects of reduction in heart rate (beta1 receptor blockade) and vasodilation (alpha1 receptor blockade) Examples are carvedilol (common) and labetalol (not as common) A5. Dual-Action Adrenergic Drugs α1 and β Receptor Blockers Carvedilol (Coreg) Widely used drug that is well tolerated Uses: HTN, mild to moderate HF in conjunction with digoxin, diuretics, and ACE inhibitors Contraindications: severe bradycardia or unstable HF, bronchospastic conditions such as asthma, and various cardiac conduction problems Adrenergic Drugs Indications - HTN But also for Glaucoma (topical) BPH: doxazosin, prazosin, and terazosin (2 for 1) Management of severe HF when used with cardiac glycosides and diuretics Contraindications Acute HF- have to stabilize first MOAIs- yeah doesn’t everything interact with MAOIs? Peptic ulcers Severe liver/kidney disease Asthma (with beta blockers) Adrenergic Drugs: Adverse Effects Orthostatic hypotension 1st-dose syncope Rebound hypertension with abrupt discontinuation Most common: Dry mouth, drowsiness, constipation, sedation Interactions- always check for specific drug interactions Can cause additive CNS depression with alcohol, benzodiazepines, opioids Question #1 When administering an alpha-adrenergic drug for hypertension, it is most important for the nurse to assess the patient for the development of what response? Hypotension Hyperkalemia Oliguria Respiratory distress Answer A Hypotension This is a key point in patient education These drugs have strong vasodilating properties and may cause severe hypotension, especially at the beginning of therapy. B. Angiotensin-Converting Enzyme Inhibitorsaka ACE Inhibitors or ACEi Large group of safe and effective drugs Currently are 10 ACEi Often used as first-line drugs for HF and hypertension May be combined with a thiazide diuretic, loop diuretic, or Calcium Channel Blocker (CCB) You need to understand the basics ACE Inhibitors: Review RAAS ACE converts angiotensin I, formed through the action of renin, to angiotensin II Angiotensin 2 is a potent vasoconstrictor and also induces aldosterone secretion by the adrenal glands Aldosterone stimulates sodium resorption (H20 follows Na Both act to raise BP which causes kidneys to reduce renin production ACEi= Great drug to treat HTN BUT contraindicated in pregnancy (2nd,3rd trimester due to fetal renal damage) and breastfeeding first few weeks after birth B. ACE Inhibitors - PRIL Lisinopril (Prinivil) super common, often the 1st drug Enalapril (Vasotec) also common Captopril (Capoten) great if liver disease present Benazepril (Lotensin) Fosinopril (Monopril) Perindopril (Aceon) Quinapril (Accupril) Ramipril (Altace) Trandolapril (Mavik) Primary Effects of the ACE Inhibitors Prevent Na (and H2O) resorption by inhibiting aldosterone secretion (volume reduction) (GO BACK TO RAAS DIAGRAM) blood volume decreases work of the heart preload, or the left ventricular end-diastolic volume which is important in HF ACE SUMMARY OF ACTIVITY 1) Prevent vasoconstriction caused by angiotensin 2 (2) Prevent aldosterone secretion  less sodium and water resorption Cardioprotective Effects of ACEi They slow progression of left ventricular hypertrophy (ventricular remodeling) after MI so considered cardioprotective ACE inhibitors have been shown to decrease morbidity and mortality in patients with HF Renal Protective Effects of ACEi ACE inhibitors: reduce glomerular filtration pressure by volume reduction Cardiovascular drug of choice for patients with diabetes since it helps protect kidneys by reducing pressure. Sometimes used low dose for kidney protection with DM without HTN B. ACEi Enalapril (Vasotec) Only ACEi available in both oral and IV Enalapril IV does not require cardiac monitoring Oral enalapril: prodrug (metabolized in liver) Improves patient’s chances of survival after an MI Reduces the incidence of HF B. ACEi Captopril (Capoten) Uses: prevention of ventricular remodeling after MI; reduce the risk of HF after MI Shortest half-life Must be administered multiple times throughout the day so this limits its use Not a prodrug so good for patient with liver disease Question #2 A patient with diabetes has a new prescription for the ACE inhibitor lisinopril. She questions this order because her provider has never told her that she has hypertension. What is the best explanation for this order? The doctor knows best The patient is confused This medication has cardioprotective properties This medication has a protective effect on the kidneys for patients with diabetes Answer D ACE inhibitors have been shown to have a protective effect on the kidneys because they reduce glomerular filtration pressure. This property makes them the cardiovascular drug of choice for patients with diabetes. Question #3 A patient with a history of pancreatitis and cirrhosis is also being treated for hypertension. Which drug will most likely be ordered for this patient? Clonidine Prazosin Diltiazem Captopril Answer D Captopril Captopril is not a prodrug; therefore, it does not need to be metabolized by the liver to be effective. This is an advantage in patients with liver disease. ACE Inhibitors: Adverse Effects *Dry, nonproductive cough, which reverses when therapy is stopped. This is a class effect Dizziness- Note: First-dose hypotensive effect may occur Headache & Fatigue Possible hyperkalemia ** Angioedema: rare but potentially fatal Not safe in pregnancy-are contraindicated during the second and third trimesters of pregnancy because of increased risk of fetal renal damage C. Angiotensin II Receptor Blockers(ARB) Considered an alternative to ACEi Less likely to cause a dry cough and hyper K+ that is common with ACE inhibitors Angiotensin II Receptor Blockers: Mechanism of Action Go back to RAAS diagram! ARBs affect primarily 2 places 1. Vascular smooth muscle - blocks vasoconstriction 2. Adrenal gland -Selectively blocks the binding of Ang 2 to certain Ang 2 receptors inhibiting secretion of aldosterone Lowers volume retention and BP Angiotensin II Receptor Blockers -ARTAN Losartan (Cozaar)- very common Eprosartan (Teveten) Valsartan (Diovan) Irbesartan (Avapro) Candesartan (Atacand) Olmesartan (Benicar) Telmisartan (Micardis) Azilsartan (Edarbi) C. ARB Losartan (Cozaar) Beneficial in patients with HTN and HF Used with caution in patients with kidney or liver dysfunction and in patients with renal artery stenosis ***Not safe for breastfeeding women and should not be used in pregnancy (Cat C 1st trimester, Cat D 2nd-3rd trimester), potential fetal toxicity Appear to be equally effective for the treatment of hypertension and well tolerated ARBs less likely to cause cough and hyperK+ but can still happen Evidence that ARBs are associated with lower mortality after MI than ACE inhibitors Never take ACEi and ARBs at the same time* 5. Calcium Channel Blockers (CCB) Primary use: HTN, angina, some dysrhythmias Cause smooth muscle relaxation by blocking the binding of calcium to its receptors, preventing muscle contraction Results in: Relaxed blood vessels to the heart Decreased peripheral smooth muscle tone Decreased SVResistance Decreased BP E. Diuretics First-line antiHTN in JNC 8 guidelines Decreases fluid volume The results from diuresis: preload, Peripheral resistance Overall effect  Decreased workload of the heart and decreased BP Thiazide diuretics are the most commonly used diuretics for HTN Ie hydrochlorothiazide (HCTZ), chlorthalidone We will discuss diuretics further in the chapter on diuretics F. Vasodilators Directly relax arterial or venous smooth muscle (or both) Results in: Decreased SVR Decreased afterload Peripheral vasodilation Indicated for treatment of HTN May be used in combination with other drugs F. Vasodilators Hydralazine (Apresoline) Orally: routine cases of essential hypertension Injectable: hypertensive emergencies BiDil: specifically indicated as an adjunct for treatment of HF in African-American patients F. Vasodilators Sodium Nitroprusside (Nitropress) *Sodium nitroprusside and IV diazoxide are reserved for the management of hypertensive emergencies. Contraindications: severe HF, known inadequate cerebral perfusion (especially during neurosurgical procedures) F. Vasodilators Adverse Effects Hydralazine: dizziness, headache, tachycardia, edema, dyspnea, N/V/D, vitamin B6 deficiency, rash Sodium nitroprusside: hypotension, bradycardia, decreased platelet aggregation, rash G. Direct Renin Inhibitors Aliskirin (Tekturna) Blocks the RAS pathway at the point of activation. Inhibiting renin production prevents the downstream production of Ang II (potent vasoconstrictor) Adverse effects: N/V, severe hypotension, hyponatremia, hyperkalemia… Contraindicated in patients with DM taking ACEi or ARB Miscellaneous Antihypertensives Eplerenone (Inspra) Newer class of drugs called selective aldosterone blockers (remember RAAS?) Reduces BP by blocking the actions of aldosterone at its corresponding receptors in the kidney, heart, blood vessels, and brain Indications: routine treatment of hypertension and for post-MI HF Contraindicated if serum potassium levels are high (above 5.6 mEq/L) A Special Form of HTNTreatment of Pulmonary Hypertension Sildenafil and Tadalafil Commonly used for erectile dysfunction Used for pulmonary hypertension but with different trade names Sildenafil: Revatio* (Viagra for ED) Tadalafil: Adcirca* (Cialis for ED)

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