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Question,Correct Answer,Option 2,Option 3,Option 4 You just saw your crush trip, but you imagine it in slow‑motion as if in a movie. What are you doing?,Visualizing,Ignoring,Running away,Screaming Your best friend says your outfit is “trash” but you think it’s ICONIC! This shows —,Perception,Precision,Symmetry,Association A butterfly’s wings are perfectly matching on both sides. They are —,Symmetrical,Random,Loud,Vague You always think of pizza when you hear “Friday night.” This is a(n) —,Association,Obsession,Illustration,Symmetry You carefully measure 10 candies for lunch. This shows —,Precision,Obsession,Symmetry,Association A teacher draws a big volcano on the board to explain it. She is —,Illustrating,Guessing,Visualizing,Ignoring Two students react differently to the same horror movie. This shows —,Perception,Symmetry,Precision,Obsession You measure your eyeliner perfectly on both eyes. This is —,Symmetry,Visualizing,Association,Individualized A student redoes ONE sentence 17 times all night. She is —,Obsessive,Relaxed,Careless,Confused A loud, clear knock on the door is —,Distinct,Vague,Random,Individualized You picture your future life as a superhero saving the world. You are —,Visualizing,Associating,Obsessing,Measuring A quiz made just for ONE student is —,Individualized,General,Random,Symmetrical Two students get the same task but react differently. This shows differences in —,Perception,Symmetry,Association,Obsession Your friend always folds napkins perfectly before dinner. That is —,Obsessive,Relaxed,Visualizing,Association A student triple‑checks a ruler, erases tiny mistakes, and won’t submit. Which TWO describe her? (Choose best single answer),Obsessive and Precise,Relaxed and Calm,Confused and Random,Symmetrical and Vague Which shows BOTH perception AND association?,Thinking rain is sad because you cried in it,Measuring carefully,Folding paper,Drawing a volcano The **funniest way to show symmetry** in class would be —,Balancing a pencil on your nose randomly,Throwing paper randomly,Screaming at the board,Balancing a pencil perfectly on your nose You hear a scary clear knock and spill your water. That knock is —,Distinct,Vague,Individualized,Symmetry Which is NOT individualized?,Standard school uniform,Custom shoes,Test for one student,Personalized notebook Two students measure carefully. One is calm and exact, the other keeps freaking out. The calm student shows —,Precision,Obsession,Association,Illustration The same scenario: The freaking‑out student shows —,Obsession,Symmetry,Visualizing,Precision

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LESSON 4. Cellular Respiration • Define cellular respiration • Identify the stages of clan respiration You have just learned how the energy from the sun is captured, processed, and stored in the form of glucose. Cellular respiration, another important life process, is the means by which cells release the stored energy in glucose to make adenosine triphosphate (ATP). The primary goal of this life process is to convert stored energy into usable form, such as ATP, for the cells to carry out their functions. Cellular respiration involves several chemical reactions. The reactions can be summed up in the following equation: C6 H12 O6 + 602 ----- 6 CO₂ +6H₂O + ATP Glucose oxygen carbon dioxide water energy Aerobic respiration reactions, or cellular respiration that takes place in the presence of oxygen, can be grouped into three stages glycolysis, Krebs cycle, and electron transport chain (ETC). Stage 1: Glycolysis Glycolysis is the process that breaks down one molecule of 6-C glucose into 3-C pyruvates or pyruvic acids. It also releases four molecules of ATP. This process occurs in the cytoplasm of the cell. The following is the step-by-step process of glycolysis. Take note that several enzymes are involved in this process. 1. The first step of glycolysis requires energy. It can only proceed when the two ATP molecules donate energy to the glucose by transferring a phosphate group with the help of an enzyme, producing glucose 6-phosphate 2. Then, a specific enzyme promotes the rearrangement of the atoms, producing the fructose 6-phosphate. 3. The action of the enzyme in step 2 promotes the transfer of a phosphate group from another ATP molecule, forming fructose 1,6-bisphosphate. 4. The resulting fructose 1,6-bisphosphate molecules, with the help of another enzyme, splits into two molecules, each with three carbon backbones. These two sugars are dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. 5. Another important enzyme then rapidly interconverts the molecules of dihydro-xyacetone phosphate and glyceraldehyde 3-phosphate. This produces two molecules of glyceraldehyde 3-phosphate or 3-phosphoglyceraldehyde (PGAL) 6. The succeeding step involves another enzyme-mediated action. The hydrogen (H) from PGAL is transferred to the oxidizing agent, nicotinamide adenine dinucleotide (NAD), which forms NADH. A phosphate (P) is also added from the cytosol of the cell to oxidize the two molecules of PGAL, forming two 1.3-bisphosphoglycerate. 7. A phosphate (P) from 1,3-biphosphoglycerate is transferred to ADP to form ATP. This happens for each of the two 1,3-bisphosphoglycerate. resulting to a yield of two ATP and two 3-phosphoglycerate molecules. 8. A phosphate is transferred from 3-phosphoglycerate molecules from the third carbon to the second carbon, forming 2-phosphoglycerate molecules A hydrogen atom and a hydroxyl ((OH) group is released, which then combines to form water (H2O). The removal of H2O from 2-phosphoglycerate results in the formation of 2- phosphoglycerate molecules. 9. A hydrogen atom and a hydroxyl ((OH) group is released, which then combines to form water (H2O). The removal of H2O from 2-phosphoglycerate results in the formation of two phosphoenolpyruvic acid (PEP) 10. Phosphate (P) from PEP is transferred to ADP (and forms ATP) and the final product, pyruvic acid. This reaction yields two molecules of pyruvic acid and two ATP molecules In summary, a single glucose molecule that undergoes the process of glycolysis produces two molecules of pyruvic acid, four molecules of ATP, two molecules of NADEL and two molecules of H.O. However, only two molecules of ATP are counted as net products since two molecules of ATP are spent throughout the process. Stage II: Krebs Cycle The Krebs cycle, named after its proponent Sir Hans Adolf Krebs, is a cyclical series of enzyme-controlled reactions. This stage of cellular respiration occurs in the matrix of the mitochondria. It is sometimes. called the citric acid cycle (CAC) since it produces citric acid. Citric acid contains three carboxyl (COOH) groups; hence, it is also called the tricarboxylic acid cycle (TCA). This requires the pyruvic acids produced during glycolysis. The main function of this cycle is to produce high-energy-yielding molecules, namely, NADH and flavin adenine dinucleotide (FADH) that will later on be used in the electron transport chain reaction. Figure 6-7. Summary of glycolysis and corresponding products in each reaction presented (See Appendix F on page 285 for an enlarged and complete version of the image.) An initial process is needed for the Krebs cycle to begin. As a pyruvate molecule from glycolysis enters the mitochondrion, it undergoes an important preliminary ate to form acetyl-CoA reaction. Coenzyme-A (COA) combines with pyruvate help of an enzymatic complex. This conversion also produces CO, and NADH. The Krebs cycle is summarized as follows. Take note that several enzymes are involved in this process. 1. The Krebs cycle technically begins when the acetyl-CoA combines with oxaloacetic acid (OAA), a 4-C molecule, to produce citric acid, a 6-C molecule. 2. With the aid of an enzyme, the citric acid now goes through a series of reactions that releases energy. Water molecule is removed from the citric acid and is returned in a different location. The-OH group is repositioned, forming the molecule isocitrate. 3. Isocitrate is then oxidized, forming the a-ketoglutarate, a 5-C molecule. The byproducts of this reaction are NADH and CO, 4 The a-ketoglutarate loses its CO, and a coenzyme-A is added in its place. The decarboxylation occurs with the help of NAD, which then becomes NADH. The resulting molecule is called succinyl-CoA. 5. Succinyl-CoA is converted into succinate. Also in this reaction, a molecule of guanosine triphosphate (GTP) is synthesized. The GTP molecule has similar structure and energy properties to that of ATP and is used by cells the same way. The free phosphate group attacks the succinyl-CoA molecule, which detaches the COA. Then, phosphate is attached to GDP to come up with GTP, similar to the process that occur in ATP synthesis (from ADP to ATP). 6. Two hydrogens are removed from succinate, A molecule of flavin adenine dinucleotide (FAD), a coenzyme similar to NAD, is reduced to FADH, as it takes the hydrogens from the succinate. This reaction produces the fumarate. 7. Fumarate is then converted into malate as the addition of a water molecule is catalyzed. The final reaction is the regeneration of oxaloacetate. The resulting byproduct of this regeneration is NADH Recall that two pyruvate molecules were produced during glycolysis, causing the Krebs cycle to turn twice. Each tuts produces three molecules of NADH, single ATH one FADIH, and the by-product CO, which is exhaled. Stage III: Electron Transport Chain The electron transport chain (ETC) is a series of photon pumps on the inner membrane of the mitochondrion. Electron transport is the last stage of the cellular respiration. In this stage, the energy from NADH and FADH, from the Krebs cycle is transferred to ADP to produce ATP. This process is generally known as oxidative phosphorylation. This energy coupling mechanism in the cell was revealed by the work of Peter stored energy in the form of proton (1) gradient to phosphorylate (add phosphate) ADP and produce ATP. The pumping of hydrogen sons across the inner membrane creates higher concentration ions in the inner membrane than on the outside of the membrane. This chemiosmotic gradient causes the ions to flow back across the membrane where the concentration of ions is lower. ATP synthase lined in the matrix serve as a channel protein, helping the ions to move across the membrane. The chemiosmotic gradient powers the phosphorylation of ADP to ATP, which also occurs in the ATP synthase. After passing through the ETC, the oxygen, being the final hydrogen acceptor, combines with two electrons and two protons, forming a water molecule. Water is a by-product of cellular respiration and is excreted. MINI TEST 6-3 1. Which energy-releasing pathway yields the most ATF in each glucose molecule? 2. Briefly describe the two stages of aerobic respiration that follow glycolysis: (a) Krebs cycle (b) Electron transport chain Anaerobic Respiration Most cells carry out arrobic respiration when oxygen is present. Aerobic respiration is an efficient process that yields a lot of ATP. However, many organisms thrive in mud, marshes, animal gut, canned goods, sewage treatment pond, and deep oceans where oxygen is scarce. Organisms that can live without oxygen are called anaerobes. Cellular respiration that proceeds without the presence of oxygen is called anaerobic respiration. In the event that the oxygen supply becomes low, aerobic cells also perform fermentation and lactic acid fermentation anaerobic pathways. There are two common anaerobic pathways in these cells, alcoholic fermentation and lactic acid fermentation. In alcoholic fermentation, ethyl alcohol and carbon dioxide are produced by some cells using the pyruvate from glycolysis. Each pyruvate molecule is rearranged into acetaldehyde and carbon dioxide, which is eventually released. NADII gives up electrons to acetaldehyde to form ethanol Fermentation is widely used in the industry. Yeast, a fungus used in making bread. can undergo anaerobic respiration. Bakers aux sugar, flour, water, and yeast to form the bread dough. The dough rises due to the carbon dioxide and alcohol released by the yeast cells trapped in air bubbles. Beer and wine manufacturers, we yeast to ferment the sugars in wheat and grape juice, forming alcoholic beverages such as beer and wine. In some cells, glycolysis produces two pyruvates, two NADH molecules, and two ATP molecules. Pyruvate itself becomes the final acceptor of the electrons from the NADH that produces the final product: lactate. Oftentimes, this product is called lactic acid. Human skeletal muscles can carry out fermentation when the blood cannot supply the cells with adequate oxygen during strenuous activities. When lactic acid builds up in the muscles, fatigue, burning sensation, and cramps result. Lactic acid will continue to build up until there is adequate supply of oxygen. Lactic acid is then converted back into pyruvate in the liver. Muscles also restore normal functions. Have you ever wondered why milk or cream turns sour after some time? Bacterial cells that undergo fermentation are responsible in producing lactate that turns the milk sour. These bacteria are used in manufacturing yogurt and sour milk products. Fermentation pathways do not breakdown and utilize the glucose completely. ATP is no longer produced beyond the process of glycolysis. Thus, energy produced is just enough for some single-celled organisms, or the energy can only be used by multicellular organisms for a short period.

Growing up in Sioux Falls, South Dakota, a small city surrounded by endless plains, I've found unexpected echoes of home in China's smaller towns — from the warmth of locals in Huaihua, Central China's Hunan province, to the quiet charm of Yangshuo, South China's Guangxi Zhuang autonomous region. With an itch to see more of China's lesser-visited regions, I began planning a trip to the northwest with seven friends — five Americans, one Pakistani, one Zimbabwean, and one Colombian. We bought round-trip tickets from Shanghai to Yinchuan, Ningxia Hui autonomous region, for less than $120 each. From there, we planned to rent a car and drive to Xining in Qinghai, then on to Qinghai Lake, and finally to Lanzhou, Gansu. To make that possible, several of us applied for Chinese driver's licenses, a process that involved translating our US licenses into Mandarin and passing a short test on traffic laws. Within a day, we were licensed. As we piled into two rental cars in late March to begin our eight-day journey, it became clear that this wasn't just a road trip — it was the culmination of our four years in China, the Mandarin we had so diligently studied, and our ongoing effort to contribute to US-China people-to-people relations. Right away, we drew curious reactions. At the Yinchuan airport, taxi drivers offered us rides into the city, only to stare in astonishment when we told them we had rented cars. "You're driving? In China?" one driver asked, visibly surprised. It was a reaction we'd encountered multiple times during our trip, as foreign drivers are rare in China, especially in remote regions. In Yinchuan, we stocked up on snacks and adjusted to the chilly desert air. From there, we headed west, navigating wide highways framed by dramatic landscapes: arid plains, jagged mountains, and occasionally, a herd of sheep crossing the road. The vastness of the Northwest was humbling — and as someone who grew up on the wide-open prairies of South Dakota, it felt oddly familiar. One of the highlights of our trip was camping by Qinghai Lake, the largest saltwater lake in China. A few summers ago, Santiago Solano, one of my classmates from the US, cycled from Xi'an in Shaanxi to Urumqi in the Xinjiang Uygur autonomous region over the course of a month and met many kind strangers along the way. One of them was Geng San, a Tibetan lamb herder who managed a piece of land right next to Qinghai Lake and graciously invited us to camp there. "That's what China is — it's the people. The quiet generosity of an old Tibetan nomad who, years after we first met, still offered us a place to rest on his land," said Solano, who is also part of the group on this trip. But apparently, we underestimated just how cold it would be to camp next to Qinghai Lake in late March. It was deathly freezing. In preparation for the trip, we had ordered two tent kits and eight sleeping bags. However, when the temperature eventually dropped to — 10 C, all of us piled into the cars and turned the heaters on. So much for camping. From Qinghai Lake, we drove to Lanzhou, where we visited many food markets and tried every type of noodle on offer. Since we are college students, we rented a gaming hotel room — something I've only ever seen in China. At night, instead of attending local parties as we had before, we stayed in the hotel and gamed late into the morning. For me, the trip was as much about the journey as it was about the destinations. Driving through Northwest China gave us a unique perspective on the region's natural beauty and its people. At gas stations, shopkeepers greeted us with curiosity and kindness, often offering recommendations for nearby attractions. At roadside carts, we sampled local specialties, grabbing a quick skewer and a mango for the road. And at every stop, we were touched by the warmth and hospitality that make traveling in China so rewarding. As an American who has lived in China for several years, I'm often asked about my experiences here. Trips like this one remind me of the similarities between the two countries, despite their differences. Just as road trips are a quintessential part of American culture, they've become my favorite way to explore China. Whether it's driving through the rolling hills of South Dakota or the deserts of Ningxia, there's something universal about the freedom and camaraderie that come with having complete control over where you end up. Written by Charlie Howes, a 22-year-old American who has lived in China since 2019. He completed his final year of high school at Beijing No 80 High School and is currently studying at New York University Shanghai. He has founded a company in China focused on facilitating US-China trade and plans to continue living in Shanghai long term. He enjoys road trips, cycling around the world, learning languages, and meeting new people.

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.

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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