Conjuction test part 2

Match the word to its synonym level B1 CEFR. Use the vocabulary exactly adverb precisely except that aside from exist verb to be real existing adjective real, current Example: Flying cars are not practical with existing technology. existence noun reality Example: The existence of black holes has been confirmed by indirect observation. extraordinary adjective unusual feature noun important part of something Example: The Ramon Crater is a unique feature of the Negev Desert. feedback noun reaction figure noun shape Example: I can’t tell if that figure in the shadows is a man or a woman. figure out verb understand Example: I just can’t figure out how the magician did that amazing trick. financial adjective related to money Example: Her family is having financial problems so they can’t travel overseas this year. finance verb pay for Example: If I can’t get a loan from the bank, I won’t be able to finance a new apartment. finance noun money Example: An expert in finance predicts a global recession. finding/findings noun discoveries; results of a study Example: According to the findings of the police investigation, this is the gun which fired the fatal bullet. flexibility noun willingness to change flexible adjective adjusts easily Example: I’d prefer to meet on Monday morning but I can be flexible depending upon your schedule. flood noun a lot of water flood verb to cover with too much water flu noun type of sickness focus on/upon verb pay attention to Example: You should focus on your schoolwork if you want to improve your grades. focus noun attention People with attention deficit disorder lose focus easily. frequency noun how often frequent adjective very often Example: Hanah is a frequent customer and everyone at the store knows her. fresh adjective new Example: We need some fresh ideas if we’re going to solve this problem. frighten verb scare from preposition position, starting point gain verb make an increase, profit, earn Example: I have nothing to gain by choosing sides so I shall remain neutral. gain noun profit, amount earned generate verb create, make Example: Chat GPT can generate text written in any style you choose. guidance noun help, advice hopeful adjective optimistic, having a positive outlook Example: The farmers are hopeful that we will have rain this winter. hopefully adjective with luck ideal adjective best, most preferable Example: Nuclear power may not be an ideal solution to global warming, but it’s certainly worth considering. illness noun sickness, disease illustrate verb draw pictures illustration noun picture, image Example: Children’s storybooks have colorful illustrations. image noun picture, especially on film or television Example: The mother of the pop singer cried when she first saw her daughter’s image on television. in preposition within, inside, into in terms of regarding Example: That company makes a great product but they’re lacking in terms of customer service. in actual fact in truth Example: The mayor says the city is a safe place to live, but in actual fact the violent crime rate is very high. in connection with about Example: Police arrested four men in connection with the robbery. in that case if that is true Example: Billy Bob: “Traffic could be heavy tomorrow.” Peggy Sue: “In that case, we better leave early.” in the meantime while, during Example: The new computers won’t arrive until next week, but we can keep using the old ones in the meantime. initial adjective first Example: Her initial reaction to that song was negative, but over time she’s come to like it. initially adverb at first instruction noun teaching, order Example: Most new electronic devices come with a set of instructions. intelligence noun smartness Example: Since you have a degree from a good university, I assume you have sufficient intelligence to understand this problem. intelligent adjective smart Example: Joe isn’t very intelligent, but he is a kind person with a warm heart. interest noun attraction Example: Yossi has little interest in politics, whereas his wife goes to all the protests and demonstrations. interest verb to attract Example: Sports don’t really interest me, but my brother is a big basketball fan. introduce verb to show something new Example: Today in class I will introduce the basic concepts of literary analysis. invest verb to put money into something in order to earn money Example: Joe invested in cryptocurrency and lost a lot of money. investor noun one who puts money into something in order to earn money Example: Venture capitalists are investors who put money into risky start-up businesses. investment noun putting money into something in order to earn money Example: Buying real estate in Israel is a very safe investment because the value never goes down. investigate verb research, study Example: The police collected evidence to investigate the murder. investigation noun study Example: The police don’t have a suspect for the murder as the investigation isn’t finished yet. investigator noun detective Example: Detective Schmendrick is the lead investigator for the murder case. just about almost Example: I’m just about done here so I’ll be there shortly. keep on doing verb continue Example: You’re crazy if you keep on doing the same thing and expect different results. kind of type of Example: What kind of dog is that, a poodle? knowledge noun awareness Example: John failed the test due to lack of knowledge of the material. lack verb not having, missing Example: John failed the test due to lack of knowledge of the material. landscape noun the view of the land likely adjective, adverb probably Example: When we learn from our mistakes, we’re not likely to forget. limited adjective restricted Example: We should go to the store today because the sale is for a limited time only. limitation noun restriction little adjective small, not a lot Example: She always tells the truth. I have little reason to doubt her. look at verb see Example: People used to read newspapers on the train. Nowadays they just look at their phones. low adverb to a small amount or level Example: I have to charge my phone because the battery is running low. material noun documents, information Example: We have a lot of material to cover before the end of the semester. meaning noun significance mean verb to have significance or purpose means noun form of, by the use of Example: They communicate by means of radio. measure noun step Example: The teacher took measures to prevent cheating during the test mention verb to say, point out Example: The coach said the team played very well today but didn’t mention any player specifically. miss verb (1) fail to catch (2) wishing to see somebody Examples: (1) The football player kicked the ball but missed the goal. (2) Wow, it’s good to see you! I’ve missed you so much! misunderstand verb understand incorrectly Example: I’m afraid I misunderstood the instructions. Could you repeat them please? more or less approximately, somewhat, to a varying degree Example: This is more or less a religious neighborhood, though there are a few secular families. must modal verb have to naturally adverb as expected, normally nature noun (1) open air (2) character Examples: (1) We like to go hiking in nature reserves. (2) Pit bulls are aggressive by nature.

A solution is a mixture in which one or more substances are uniformly distributed in another substance. Solutions can be mixtures of liquids, solids, or gases. For example, plasma, the liquid part of blood, is a very complex solution. It is composed of many types of ions and large molecules, as well as gases, that are dissolved in water. A solute (SAHL-YOOT) is a substance dissolved in the solvent. The particles that compose a solute may be ions, atoms, or molecules. The solvent is the substance in which the solute is dissolved. For example, when sugar, a solute, and water, a solvent, are mixed, a solution of sugar water results. Though the sugar dissolves in the water, neither the sugar molecules nor the water molecules are altered chemically. If the water is boiled away, the sugar molecules remain and are unchanged. Solutions can be composed of various proportions of a given solute in a given solvent. Thus, solutions can vary in concentra- tion. The concentration of a solution is the amount of solute dis- solved in a fixed amount of the solution. For example, a 2 percent saltwater solution contains 2 g of salt dissolved in enough water to make 100 mL of solution. The more solute dissolved, the greater is the concentration of the solution. A saturated solution is one in which no more solute can dissolve. Aqueous (AY-kwee-uhs) solutions—solutions in which water is the solvent—are universally important to living things. Marine microorganisms spend their lives immersed in the sea, an aqueous solution. Most nutrients that plants need are in aqueous solutions in moist soil. Body cells exist in an aqueous solution of intercellu- lar fluid and are themselves filled with fluid; in fact, most chemical reactions that occur in the body occur in aqueous solutions. Copyright © by Holt, Rinehart and Winston. All rights reserved. Liquid water Solid water Ice (solid water) is less dense than liquid water because of the structure of ice crystals. The water molecules in ice are bonded to each other in a way that creates large amounts of open space between the molecules, relative to liquid water. FIGURE 2-12 solvent from the Latin solvere, meaning “to loosen” Word Roots and Origins CHEMISTRY OF LIFE 43 ACIDS AND BASES One of the most important aspects of a living system is the degree of its acidity or alkalinity. What do we mean when we use the terms acid and base? Ionization of Water As water molecules move about, they bump into one another. Some of these collisions are strong enough to result in a chemical change: one water molecule loses a proton (a hydrogen nucleus), and the other gains this proton. This reaction really occurs in two steps. First, one molecule of water pulls apart another water molecule, or dissociates, into two ions of opposite charge: H2O ∏ H OH The OH ion is known as the hydroxide ion. The free H ion can react with another water molecule, as shown in the equation below. H H2O ∏ H3O The H3O ion is known as the hydronium ion. Acidity or alkalin- ity is a measure of the relative amounts of hydronium ions and hydroxide ions dissolved in a solution. If the number of hydronium ions in a solution equals the number of hydroxide ions, the solution is said to be neutral. Pure water contains equal numbers of hydro- nium ions and hydroxide ions and is therefore a neutral solution. Acids If the number of hydronium ions in a solution is greater than the number of hydroxide ions, the solution is an acid. For example, when hydrogen chloride gas, HCl, is dissolved in water, its mol- ecules dissociate to form hydrogen ions, H, and chloride ions, Cl, as is shown in the equation below. HCl ∏ H Cl These free hydrogen ions combine with water molecules to form hydronium ions, H3O. This aqueous solution contains many more hydronium ions than it does hydroxide ions, making it an acidic solution. Acids tend to have a sour taste; how- ever, never taste a substance to test it for acidity. In concentrated forms, they are highly corrosive to some materials, as you can see in Figure 2-13. Bases If sodium hydroxide, NaOH, a solid, is dissolved in water, it dissociates to form sodium ions, Na, and hydroxide ions, OH, as shown in the equation below. NaOH ∏ Na OH Copyright © by Holt, Rinehart and Winston. All rights reserved. Eco Connection onnection Acid Precipitation Acid precipitation, more commonly called acid rain, describes rain, snow, sleet, or fog that contains high levels of sulfuric and nitric acids. These acids form when sulfur dioxide gas, SO2, and nitrogen oxide gas, NO, react with water in the atmosphere to produce sulfuric acid, H2SO4, and nitric acid, HNO3. Acid precipitation makes soil and bodies of water, such as lakes, more acidic than normal. These high acid levels can harm plant and animal life directly. A high level of acid in a lake may kill mollusks, fish, and amphibians. Even in a lake that does not have a very elevated level of acid, acid precipitation may leach aluminum and magnesium from soils, poisoning water- dwelling species. Reducing fossil-fuel consump- tion, such as occurs in gasoline engines and coal-burning power plants, should reduce high acid levels in precipitation. Sulfur dioxide, SO2, which is produced when fossil fuels are burned, reacts with water in the atmosphere to produce acid precipitation. Acid precipitation, or acid rain, can make lakes and rivers too acidic to support life and can even corrode stone, such as the face of this statue. FIGURE 2-13 44 CHAPTER 2 This solution then contains more hydroxide ions than hydronium ions and is therefore defined as a base. The adjective alkaline refers to bases. Bases have a bitter taste; however, never taste a substance to test for alkalinity. They tend to feel slippery because the OH ions react with the oil on our skin to form a soap. In fact, commercial soap is the product of a reaction between a base and a fat. pH Scientists have developed a scale for comparing the relative con- centrations of hydronium ions and hydroxide ions in a solution. This scale is called the pH scale, and it ranges from 0 to 14, as shown in Figure 2-14. A solution with a pH of 0 is very acidic, a solution with a pH of 7 is neutral, and a solution with a pH of 14 is very basic. A solution’s pH is measured on a logarithmic scale. That is, the change of one pH unit reflects a 10-fold change in the acidity or alkalinity. For example, urine has 10 times the H3O ions at a pH of 6 than water does at a pH of 7. Vinegar, has 1,000 times more H3O ions at a pH of 3 than urine at a pH of 6, and 10,000 times more H3O ions than water at a pH of 7. The pH of a solution can be measured with litmus paper or with some other chemical indicator that changes color at various pH levels. Buffers The control of pH is important for living systems. Enzymes can function only within a very narrow pH range. The control of pH in organisms is often accomplished with buffers. Buffers are chemi- cal substances that neutralize small amounts of either an acid or a base added to a solution. As Figure 2-14 shows, the composition of your internal environment—in terms of acidity and alkalinity— varies greatly. Some of your body fluids, such as stomach acid and urine, are acidic. Others, such as intestinal fluid and blood, are

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.

Conjuction test

Conjunction test

Pre-test Conjunction

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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