Chapter 2: But I'm Afraid

Commas Directions: Correct the sentences by adding commas where needed. 1. After the sound of the bell we realized it was a false alarm. 2. Mr. Yoshino the head of the department resigned yesterday. 3. The gentleman with the black umbrella who is an ambassador to the United States said hello to us as we were entering the hotel. 4. Even though we won the game the players unfortunately did not play their best. 5. Heather walked quickly up to the door and knocked hoping that someone would answer. Author’s Purpose 6. An author writes a story about a boy who saves his town from a flood by using his quick thinking. The author includes exciting descriptions of the boy's bravery. What is the author’s most likely purpose for writing this story? A. To inform readers about the dangers of floods B. To entertain readers with a heroic tale C. To explain how to prevent floods D. To persuade readers to prepare for emergencies 7. Which of the following is an example of an author writing to persuade? A. A science textbook chapter explaining the water cycle B. A commercial encouraging people to adopt shelter pets C. A short story about a girl who finds a magical necklace D. A recipe for making chocolate chip cookies 8. Read the following sentence: "Studies show that students who read for 20 minutes a day score higher on tests. Reading is one of the best habits you can develop for success in school and life." What is the author’s purpose in this passage? A. To entertain readers with a fun story B. To persuade readers to read more often C. To inform readers about how books are written D. To explain how to find books to read 9. An author writes a how-to guide titled 10 Easy Steps to Plant a Garden. What is the author’s primary purpose? A. To persuade readers to grow their own vegetables B. To inform readers how to plant a garden C. To entertain readers with funny garden tips 10. Read the excerpt: "Long ago, in a village surrounded by mountains, the people discovered a secret about their water well. Every full moon, the well water turned to gold for just one night. But no one knew why. This mystery brought travelers from far and wide, hoping to uncover the truth." What is the author’s purpose in this excerpt? A. To persuade readers to visit the village B. To inform readers about a historical event C. To entertain readers with a mysterious tale D. To explain the science behind the water Main Idea When I stepped out into the bright sunlight from the darkness of the movie house, I had only two things on my mind: Paul Newman and a ride home. I was wishing I looked like Paul Newman--- he looks tough and I don't--- but I guess my own looks aren't so bad. I have light-brown, almost-red hair and greenish-gray eyes. I wish they were more gray because I hate most guys that have green eyes, but I have to be content with what I have. My hair is longer than a lot of boys wear theirs, squared off in back and long at the front and sides, but I am a greaser and most of my neighborhood rarely bothers to get a haircut. Besides, I look better with long hair. 11. What is the main idea? The narrator likes movies. The narrator wishes he was Paul Newman. The narrator is content with his appearance. The narrator looks better with long hair. 12. The narrator believes. . . looks are important. he should get a haircut. green eyes are bad. that he has red hair. Once there were four girls who shared a pair of pants. The girls were all different sizes and shapes, and yet the pants fit each of them. You may think this is a suburban myth. But I know it's true, because I am one of them, one of the sisters of the Traveling Pants. We discovered their magic last summer, purely by accident. The four of us were splitting up for the first time in our lives. Carmen had gotten them from a secondhand place without even bothering to try them on. She was going to throw them away, but by chance, Tibby spotted them. First Tibby tried them; then me, Lena; then Bridget; then Carmen. By the time Carmen pulled them on, we knew something extraordinary was happening. If the same pants fit and I mean really fit the four of us, they aren't ordinary. They don't belong completely to the world of things you can see and touch. My sister, Effie, claims I don't believe in magic, and maybe I didn't then. But after the first summer of the Traveling Pants, I do. 13. What is the main idea? Four friends were connected through a special pair of pants. A pair of pants called the Traveling Pants. Carmen finding a pair of pants from a second-hand shop. The girls believing in magic. 14. The narrator included that the pants fit all of them to emphasize how the girls become friends. the girls are different sizes. why the pants are special. where the pants came from. If you are interested in stories with happy endings, you would be better off reading some other book. In this book, not only is there no happy ending, there is no happy beginning and very few happy things in the middle. This is because not very many happy things happened in the lives of the three Baudelaire youngsters. Violet, Klaus, and Sunny Baudelaire were intelligent children, and they were charming, and resourceful, and had pleasant facial features, but they were extremely unlucky, and most everything that happened to them was rife with misfortune, misery, and despair. I'm sorry to tell you this, but that is how the story goes. 15. What is the main idea? description about the story to come. A warning about the story and its sad content. A declaration about the Baudelaire family. A beginning for the end of the story. 16. The narrator believes the reader does not like sad stories. likes stories with happy endings. can’t enjoy the story. will find the story unhappy. 17. Read the following sentence: Of course you can exaggerate your story, but what you say must be based on truth. Which word means the same as exaggerate? repeat reveal overstate increase 18. What is the meaning of the word inaugurated, used in the following sentence: Less than two months after Abraham Lincoln was inaugurated President in 1861, he encountered one of the most difficult tasks ever experienced by a United States leader: civil war. elected by a vote brought into office identified by name viewed as an authority 19. What does the phrase “practice your presentation so much that you could do it in your sleep” suggest in the following sentence: The best advice is to practice your presentation so much that you could do it in your sleep. get plenty of sleep the night before giving a presentation give their presentations in front of a small audience first take advice from their teachers on how to write a presentation memorize their presentations before they give them 20. Read the following sentence: The Phoenix Mars Lander is a NASA spacecraft that landed on the Red Planet in May 2009 to study the history of water and potential for life on the planet. What is another word for potential? existence situation possibility qualification

Hi, I'm John Green, this is Crash Course U.S. History, and today, we're going to talk about slavery, which is not funny. 0:06 Yeah, so we put a lei on the eagle to try and cheer you up, but let's face it, this is going to be depressing. 0:10 With slavery, every time you think, like, "Aw, it couldn't have been that bad," it turns out to have been much worse. 0:14 Mr. Green, Mr. Green! But what about – 0:15 Yeah, Me from the Past, I'm going to stop you right there, because you're going to embarrass yourself. Slavery was hugely important to America. 0:20 I mean, it led to a civil war and it also lasted what, at least in U.S. history, counts as a long-ass time, from 1619 to 1865. 0:29 And yes, I know there's a 1200-year-old church in your neighborhood in Denmark, but we're not talking about Denmark! 0:35 But slavery is most important because we still struggle with its legacy. 0:38 So, yes, today's episode will probably not be funny, but it will be important. 0:42 [Theme Music] North & South economic ties 0:51 So the slave-based economy in the South is sometimes characterized as having been separate from the Market Revolution, but that's not really the case. 0:57 Without southern cotton, the North wouldn't have been able to industrialize, at least not as quickly, because cotton textiles were one of the first industrially products. 1:04 And the most important commodity in world trade by the nineteenth century, and 3/4 of the world's cotton came from the American South. 1:11 And speaking of cotton, why has no one mentioned to me that my collar has been half popped this entire episode, like I'm trying to recreate the Flying Nun's hat. 1:18 And although there were increasingly fewer slaves in the North as northern states outlawed slavery, cotton shipments overseas made northern merchants rich. 1:26 Northern bankers financed the purchase of land for plantations. 1:29 Northern insurance companies insured slaves who were, after all, considered property, and very valuable property. 1:35 And in addition to turning cotton into cloth for sale overseas, northern manufacturers sold cloth back to the South, where it was used to clothe the very slaves who had cultivated it. 1:45 But certainly the most prominent effects of the slave-based economy were seen in the South. Slave-based agriculture in the South 1:49 The profitability of slaved-based agriculture, especially King Cotton, meant that the South would remain largely agricultural and rural. 1:56 Slave states were home to a few cities, like St. Louis and Baltimore, but with the exception of New Orleans, 2:00 almost all southern urbanization took place in the upper South, further away from the large cotton plantations. 2:06 And slave-based agriculture was so profitable that it siphoned money away from other economic endeavors. 2:11 Like, there was very little industry in the South. 2:13 It produced only 10% of the nation's manufactured goods. 2:16 And, as most of the capital was being plowed into the purchase of slaves, there was very little room for technological innovation, like, for instance, railroads. 2:23 This lack of industry and railroads would eventually make the South suck at the Civil War, thankfully. 2:27 In short, slavery dominated the South, shaping it both economically and culturally, and slavery wasn't a minor aspect of American society. Popular attitudes concerning slavery 2:35 By 1860, there were four million slaves in the U.S., and in the South, they made up one third of the total population. 2:42 Although in the popular imagination, most plantations were these sprawling affairs with hundreds of slaves, 2:47 in reality, the majority of slaveholders owned five or fewer slaves. 2:51 And, of course, most white people in the South owned no slaves at all, though, if they could afford to, they would sometimes rent slaves to help with their work. 2:57 These were the so-called yeoman farmers who lived self-sufficiently, raised their own food, and purchased very little in the Market Economy. 3:04 They worked the poorest land and, as a result, were mostly pretty poor themselves. 3:08 But even they largely supported slavery, partly, perhaps, for aspirational reasons, and partly because the racism inherent to the system gave even the poorest whites legal and social status. 3:18 And southern intellectuals worked hard to encourage these ideas of white solidarity and to make the case for slavery. 3:23 Many of the founders, a bunch of whom you'll remember, held slaves, saw slavery as a necessary evil. 3:29 Jefferson once wrote, quote, "As it is, we have the wolf by the ear, and we can neither hold him, nor safely let him go. 3:37 Justice is on one scale, and self-preservation in the other." 3:41 The belief that justice and self-preservation couldn't sit on the same side of the scale was really opposed to the American idea, 3:47 and, in the end, it would make the Civil War inevitable. 3:50 But as slavery became more entrenched in these ideas of liberty and political equality were embraced by more people, 3:55 some southerners began to make the case that slavery wasn't just a necessary evil. 3:59 They argued, for instance, that slaves benefited from slavery. 4:03 Because, you know, because their masters fed them and clothed them and took care of them in their old age. 4:07 You still hear this argument today, astonishingly. 4:09 In fact, you'll probably see asshats in the comments saying that in the comments. 4:12 I will remind you, it's not cursing if you are referring to an actual ass. 4:15 This paternalism allowed masters to see themselves as benevolent and to contrast their family-oriented slavery with the cold, mercenary Capitalism of the free-labor North. 4:26 So yeah, in the face of rising criticism of slavery, some southerners began to argue that the institution was actually good for the social order. 4:33 One of the best-known proponents of this view was John C. Calhoun, who, in 1837, said this in a speech on the Senate floor: 4:40 "I hold that, in the present state of civilization, 4:43 where two races of different origin and distinguished by color and other physical differences as well as intellectual, are brought together, 4:51 the relation now existing in the slave-holding states between the two is, instead of an evil, a good. A positive good." 4:59 Now, of course, John C. Calhoun was a fringe politician, and nobody took his views particularly seriously. 5:04 Stan: Well, he was Secretary of State from 1844 to 1845. 5:07 John: Well, I mean, who really cares about the Secretary of State, Stan? 5:10 Danica: Eh, he was also Secretary of War from 1817 to 1825. 5:13 John: All right, but we don't even have a Secretary of War anymore, so... 5:16 Meredith: And he was Vice President from 1825 to 1832. 5:19 John: Oh my god, were we insane?! 5:21 We were, of course, but we justified the insanity with Biblical passages and with the examples of the Greeks and Romans, 5:28 and with outright racism, arguing that black people were inherently inferior to whites. 5:33 And that not to keep them in slavery would upset the natural order of things. 5:37 A worldview popularized millennia ago by my nemesis, Aristotle. God, I hate Aristotle. 5:42 You know what defenders of Aristotle always say? 5:44 "He was the first person to identify dolphins." 5:47 Well, ok, dolphin identifier. 5:50 Yes, that is what he should be remembered for, but he's a terrible philosopher! Lives & experiences of enslaved people 5:53 Here's the truth about slavery: 5:55 It was coerced labor that relied upon intimidation and brutality and dehumanization. 6:00 And this wasn't just a cultural system, it was a legal one. 6:03 I mean, Louisiana law proclaimed that a slave "owes his master... a respect without bounds, and an absolute obedience." 6:09 The signal feature of slaves' lives was work. 6:12 I mean, conditions and tasks varied, but all slaves labored, usually from sunup to sundown, and almost always without any pay. 6:20 Most slaves worked in agriculture on plantations, and conditions were different, depending on which crops are grown. 6:25 Like, slaves on the rice plantations of South Carolina had terrible working conditions, 6:29 but they labored under the task system, which meant that once they had completed their allotted daily work, they would have time to do other things. 6:36 But lest you imagine this is like how we have work and leisure time, bear in mind that they were owned and treated as property. 6:42 On cotton plantations, most slaves worked in gangs, usually under the control of an overseer, or another slave who was called a "driver." 6:49 This was back-breaking work done in the southern sun and humidity, and so it's not surprising that whippings – or the threat of them – were often necessary to get slaves to work. 6:58 It's easy enough to talk about the brutality of slave discipline, but it can be difficult to internalize it. 7:03 Like, you look at these pictures, but because you've seen them over and over again, they don't have the power they once might have. 7:09 The pictures can tell a story about cruelty, but they don't necessarily communicate how arbitrary it all was. 7:14 As, for example, in this story, told by a woman who was a slave as a young girl: 7:18 "[The] overseer... went to my father one morning and said, "Bob, I'm gonna whip you this morning." 7:22 Daddy said, "I ain't done nothing," and he said, "I know it, I'm going to whip you to keep you from doing nothing," 7:28 and he hit him with that cowhide – you know it would cut the blood out of you with every lick if they hit you hard." 7:33 That brutality – the whippings, the brandings, the rape – was real, and it was intentional, because, in order for slavery to function, slaves had to be dehumanized. 7:43 This enabled slaveholders to rationalize what they were doing, and it was hoped to reduce slaves to the animal property that is implied by the term "chattel slavery." 7:51 So the idea was that slaveholders wouldn't think of their slaves as human, and slaves wouldn't think of themselves as human. 7:57 But it didn't work. Let's go to the Thought Bubble. 7:59 Slaves' resistance to their dehumanization took many forms, but the primary way was by forming families. Family, love, & religion of enslaved people 8:05 Family was a refuge for slaves and a source of dignity that masters recognized and sought to stifle. 8:10 A paternalistic slave owner named Bennet H. Barrow wrote in his rules for the Highland Plantation: 8:15 "No rule that I have stated is of more importance than that relating to Negroes marrying outside of the plantation... It creates a feeling of independence." 8:23 Most slaves did marry, usually for life, and, when possible, slaves grew up in two-parent households. 8:28 Single-parent households were common, though, as a result of one parent being sold. 8:32 In the upper South, where the economy was shifting from tobacco to different, less labor-intensive cash crops, the sale of slaves was common. 8:40 Perhaps one-third of slave marriages in states like Virginia were broken up by sale. 8:45 Religion was also an important part of life in slavery. 8:47 While masters wanted their slaves to learn the parts of the Bible that talked about being happy in bondage, 8:52 slave worship tended to focus on the stories of Exodus, where Moses brought the slaves out of bondage, 8:57 or Biblical heroes, who overcame great odds, like Daniel and David. 9:01 And, although most slaves were forbidden to learn to read and write, many did anyway. And some became preachers. 9:07 Slave preachers were often very charismatic leaders, and they roused the suspicion of slave owners, and not without reason. 9:13 Two of the most important slave uprisings in the South were led by preachers. 9:16 Thanks, Thought Bubble. 9:17 Oh, it's time for the Mystery Document? Mystery Document 9:19 We're doing two set pieces in a row? All right. [buzzing noise] [music] 9:24 The rules here are simple. 9:26 I wanted to re-shoot that, but Stan said no. 9:29 I guess the author of the Mystery Document. 9:30 If I am wrong, I get shocked with the shock pen. 9:33 "Since I have been in the Queen's dominions I have been well contented, yes well contented for sure, man is as God intended he should be. 9:40 That is, all are born free and equal. 9:43 This is a wholesome law, not like the southern laws which puts man made in the image of God on level with brutes. 9:49 O, what will become of the people, and where will they stand in the day of judgment. 9:53 Would that the 5th verse of the 3rd chapter of Malachi were written as with a bar of iron, 9:59 and the point of a diamond upon every oppressor's heart that they might repent of this evil, and let the oppressed go free..." 10:06 All right, it's definitely a preacher, because only preachers have read Malachi. 10:10 Probably African American, probably not someone from the South. 10:13 I'm going to guess that it is Richard Allen, the founder of the African Methodist Episcopal Church? 10:18 [buzzing noise] DAAAH, DANG IT! 10:19 It's Joseph Taper, and Stan just pointed out to me that I should have known it was Joseph Taper because it starts out, 10:24 "Since I have been in the Queen's dominions..." 10:27 He was in Canada. He escaped slavery to Canada. The Queen's dominions! 10:31 All right, Canadians, I blame you for this, although, thank you for abolishing slavery decades before we did. 10:36 [electric sounds] AHHH! How people resisted & escaped slavery 10:37 So, the Mystery Document shows one of the primary ways that slaves resisted their oppression: by running away. 10:42 Although some slaves like Joseph Taper escaped for good by running away to northern free states, 10:47 or even to Canada, where they wouldn't have to worry about fugitive slave laws, even more slaves ran away temporarily, hiding out in the woods or the swamps, and eventually returning. 10:55 No one knows exactly how many slaves escaped to freedom, but the best estimate is that a thousand or so a year made the journey northward. 11:01 Most fugitive slaves were young men, but the most famous runaway has been hanging out behind me all day long: Harriet Tubman. 11:07 Harriet Tubman escaped to Philadelphia at the age of 29, and over the course of her life, she made about 20 trips back to Maryland to help friends and relatives make the journey north on the Underground Railroad. 11:17 But a more dramatic form of resistance to slavery was actual, armed rebellion, which was attempted. 11:22 Now, individuals sometimes took matters into their own hands and beat or even killed their white overseers or masters. 11:27 Like Bob, the guy who received the arbitrary beating, responded to it by killing his overseer with a hoe. 11:33 But that said, large-scale slave uprisings were relatively rare. 11:36 The four most famous ones all took place in a 35-year period at the beginning of the 19th century. Slave rebellions 11:41 Gabriel's Rebellion in 1800 – which we've talked about before – was discovered before he was able to carry out his plot. 11:45 Then, in 1811, a group of slaves upriver from New Orleans seized cane, knives, and guns, and marched on the city before militia stopped them. 11:52 And in 1822, Denmark Vesey, a former slave who had purchased his freedom, may have organized a plot to destroy Charleston, South Carolina. 11:59 I say "may have" because the evidence against him is disputed and comes from a trial that was not fair. 12:05 But regardless, the end result of that trial was that he was executed, as were 34 slaves. Nat Turner's Rebellion 12:09 But the most successful slave rebellion, at least in the sense that they actually killed some people, was Nat Turner's in August 1831. 12:15 Turner was a preacher, and with a group of about 80 slaves, he marched from farm to farm in South Hampton County, Virginia, 12:21 killing the inhabitants, most of whom were women and children, because the men were attending a religious revival meeting in North Carolina. 12:27 Turner and 17 other rebels were captured and executed, but not before they struck terror into the hearts of whites all across the American South. 12:34 Virginia's response was to make slavery worse, passing even harsher laws that forbade slaves from preaching, and prohibited teaching them to read. 12:42 Other slave states followed Virginia's lead and, by the 1830s, slavery had grown, if anything, more harsh. 12:47 So, this shows that large-scaled armed resistance was – Django Unchained aside – not just suicidal, but also a threat to loved ones and, really, to all slaves. How enslaved people resisted their oppression & why it matters 12:55 But, it is hugely important to emphasize that slaves did resist their oppression. 12:59 Sometimes this meant taking up arms, but usually it meant more subtle forms of resistance, 13:03 like intentional work slowdowns or sabotaging equipment, or pretending not to understand instructions. 13:08 And, most importantly, in the face of systematic legal and cultural degradation, they re-affirmed their humanity through family and through faith. 13:16 Why is this so important? 13:17 Because too often in America, we still talk about slaves as if they failed to rise up, 13:21 when, in fact, rising up would not have made life better for them or for their families. 13:26 The truth is, sometimes carving out an identity as a human being in a social order that is constantly seeking to dehumanize you, is the most powerful form of resistance. 13:34 Refusing to become the chattel that their masters believed them to be is what made slavery untenable and the Civil War inevitable, so make no mistake, slaves fought back. 13:45 And in the end, they won. I'll see you next week. Credits 13:48 Crash Course is produced and directed by Stan Muller. 13:50 The script supervisor is Meredith Danko. 13:52 Our associate producer is Danica Johnson. 13:54 The show is written by my high school history teacher Raoul Meyer and myself. 13:57 And our graphics team is Thought Cafe. 13:58 Every week, there's a new caption to the Libertage, but today's episode was so sad that we couldn't fit a Libertage in... 14:04 UNTIL NOW! [Libertage Rock Music] 14:08 Suggest Libertage caption in comments, where you can also ask questions about today's video that will be answered by our team of historians. 14:13 Thanks for watching Crash Course, and as we say in my home town, don't forget to be abolitionist.

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)

All living things are made up of one or more cells. A cell is the smallest unit that can carry on all of the processes of life. Beginning in the 17th century, curious naturalists were able to use microscopes to study objects too small to be seen with the unaided eye. Their studies led them to propose the cellular basis of life. Hooke In 1665, English scientist Robert Hooke studied nature by using an early light microscope, such as the one in Figure 4-1a. A light micro- scope is an instrument that uses optical lenses to magnify objects by bending light rays. Hooke looked at a thin slice of cork from the bark of a cork oak tree. “I could exceedingly plainly perceive it to be all perforated and porous,” Hooke wrote. He described “a great many little boxes” that reminded him of the cubicles or “cells” where monks live. When Hooke focused his microscope on the cells of tree stems, roots, and ferns, he found that each had similar little boxes. The drawings that Hooke made of the cells he saw are shown in Figure 4-1b. The “little boxes” that Hooke observed were the remains of dead plant cells, such as the cork cells shown in Figure 4-1c. SECTION 1 OBJECTIVES ● Name the scientists who first observed living and nonliving cells. ● Summarize the research that led to the development of the cell theory. ● State the three principles of the cell theory. ● Explain why the cell is considered to be the basic unit of life. VOCABULARY cell cell theory Robert Hooke used an early microscope (a) to see cells in thin slices of cork. His drawings of what he saw (b) indicate that he had clearly observed the remains of cork cells (300) (c). FIGURE 4-1 (a) (b) (c) Copyright © by Holt, Rinehart and Winston. All rights reserved. 70 CHAPTER 4 Leeuwenhoek The first person to observe living cells was a Dutch trader named Anton van Leeuwenhoek. Leeuwenhoek made microscopes that were simple and tiny, but he ground lenses so precisely that the magnification was 10 times that of Hooke’s instruments. In 1673, Leeuwenhoek, shown in Figure 4-2a, was able to observe a previ- ously unseen world of microorganisms. He observed cells with green stripes from an alga of the genus Spirogyra, as shown in Figure 4-2b, and bell-shaped cells on stalks of a protist of the genus Vorticella, as shown in Figure 4-2c. Leeuwenhoek called these organisms animalcules. We now call them protists. THE CELL THEORY Although Hooke and Leeuwenhoek were the first to report observ- ing cells, the importance of this observation was not realized until about 150 years later. At this time, biologists began to organize information about cells into a unified understanding. In 1838, the German botanist Matthias Schleiden concluded that all plants were composed of cells. The next year, the German zoologist Theodor Schwann concluded the same thing for animals. And finally, in his study of human diseases, the German physician Rudolf Virchow (1821–1902) noted that all cells come from other cells. These three observations were combined to form a basic theory about the cel- lular nature of life. The cell theory has three essential parts, which are summarized in Table 4-1. Anton van Leeuwenhoek (1632–1723) is shown here with one of his hand-held lenses (a). Leeuwenhoek observed an alga of the genus Spirogyra (b) and a protist of the genus Vorticella (c). FIGURE 4-2 TABLE 4-1 The Cell Theory All living organisms are composed of one or more cells. Cells are the basic units of structure and function in an organism. Cells come only from the reproduction of existing cells. (a) (b) (c) www.scilinks.org Topic: Cell Theory Keyword: HM60241 mb06se_csfs01.qxd 5/18/07 10:54 AM Page 70

CARBOHYDRATES Carbohydrates are organic compounds composed of carbon, hydrogen, and oxygen in a ratio of about one carbon atom to two hydrogen atoms to one oxygen atom. The number of carbon atoms in a carbohydrate varies. Some carbohydrates serve as a source of energy. Other carbohydrates are used as structural materials. Carbohydrates can exist as monosaccharides, disaccharides, or polysaccharides. Monosaccharides A monomer of a carbohydrate is called a monosaccharide (MAHN-oh-SAK-uh-RIED). A monosaccharide—or simple sugar— contains carbon, hydrogen, and oxygen in a ratio of 1:2:1. The gen- eral formula for a monosaccharide is written as (CH2O)n, where n is any whole number from 3 to 8. For example, a six-carbon mono- saccharide, (CH2O)6, would have the formula C6H12O6. The most common monosaccharides are glucose, fructose, and galactose, as shown in Figure 3-6. Glucose is a main source of energy for cells. Fructose is found in fruits and is the sweetest of the monosaccharides. Galactose is found in milk. Notice in Figure 3-6 that glucose, fructose, and galactose have the same molecular formula, C6H12O6, but differing structures. The different structures determine the slightly different properties of the three compounds. Compounds like these sugars, with a single chemical formula but different structural forms, are called isomers (IE-soh-muhrz). SECTION 2 OBJECTIVES ● Distinguish between monosaccharides, disaccharides, and polysaccharides. ● Explain the relationship between amino acids and protein structure. ● Describe the induced fit model of enzyme action. ● Compare the structure and function of each of the different types of lipids. ● Compare the nucleic acids DNA and RNA. VOCABULARY carbohydrate monosaccharide disaccharide polysaccharide protein amino acid peptide bond polypeptide enzyme substrate active site lipid fatty acid phospholipid wax steroid nucleic acid deoxyribonucleic acid (DNA) ribonucleic acid (RNA) nucleotide C HO H C H OH C OH H C CH2OH H C H OH O Glucose C OH C O H OH C OH H CH2OH C H CH2OH Fructose C H HO C OH H C OH H C CH2OH H C H OH O Galactose Glucose, fructose, and galactose have the same chemical formula, but their structural differences result in different properties among the three compounds. FIGURE 3-6 Copyright © by Holt, Rinehart and Winston. All rights reserved. 56 CHAPTER 3 Disaccharides and Polysaccharides In living things, two monosaccharides can combine in a condensa- tion reaction to form a double sugar, or disaccharide (die-SAK-e-RIED). For example in Figure 3-4, the monosaccharides fructose and glu- cose can combine to form the disaccharide sucrose. A polysaccharide is a complex molecule composed of three or more monosaccharides. Animals store glucose in the form of the polysaccharide glycogen. Glycogen consists of hundreds of glucose molecules strung together in a highly branched chain. Much of the glucose that comes from food is ultimately stored in your liver and muscles as glycogen and is ready to be used for quick energy. Plants store glucose molecules in the form of the polysaccha- ride starch. Starch molecules have two basic forms—highly branched chains that are similar to glycogen and long, coiled, unbranched chains. Plants also make a large polysaccharide called cellulose. Cellulose, which gives strength and rigidity to plant cells, makes up about 50 percent of wood. In a single cellu- lose molecule, thousands of glucose monomers are linked in long, straight chains. These chains tend to form hydrogen bonds with each other. The resulting structure is strong and can be broken down by hydrolysis only under certain conditions. PROTEINS Proteins are organic compounds composed mainly of carbon, hydrogen, oxygen, and nitrogen. Like most of the other biological macromolecules, proteins are formed from the linkage of monomers called amino acids. Hair and horns, as shown in Figure 3-7a, are made mostly of proteins, as are skin, muscles and many biological catalysts (enzymes). Amino Acids There are 20 different amino acids, and all share a basic structure. As Figure 3-7b shows, each amino acid contains a central carbon atom covalently bonded to four other atoms or functional groups. A single hydrogen atom, highlighted in blue in the illustration, bonds at one site. A carboxyl group, —COOH, highlighted in green, bonds at a second site. An amino group, —NH2, highlighted in yel- low, bonds at a third site. A side chain called the R group, high- lighted in red, bonds at the fourth site. The main difference among the different amino acids is in their R groups. The R group can be complex or it can be simple, such as the CH3 group shown in the amino acid alanine in Figure 3-7b. The differences among the amino acid R groups gives different proteins very different shapes. The different shapes allow pro- teins to carry out many different activities in living things. Amino acids are commonly shown in a simplified way such as balls, as shown in Figure 3-7c. (a) Many structures, such as hair and horns are made of proteins. (b) Proteins are made up of amino acids. Amino acids differ only in the type of R group (shown in red) they carry. Polar R groups can dissolve in water, but nonpolar R groups cannot. (c) Amino acids have complex structures, so, in this and other textbooks, they are often simplified into balls. FIGURE 3-7 (b) Alanine (an amino acid) (c) Simplified version of amino acid CH3 H N OH C C H O H (a) Copyright © by Holt, Rinehart and Winston. All rights reserved. BIOCHEMISTRY 57 H H N C C OH H O H CH3 H2O Glycine Alanine H N OH C C H O H H H N C C H O H CH3 N OH C C H O H (a) (b) (a) The peptide bond (shaded blue) that binds amino acids together to form a polypeptide results from a condensation reaction that produces water. (b) Poly- peptides are commonly shown as a string of balls in this textbook and elsewhere. Each ball represents an amino acid. FIGURE 3-8 Substrate Products Enzyme 1 2 3 In the induced fit model of enzyme action, the enzyme can attach only to a substrate (reactant) with a specific shape. The enzyme then changes and reduces the activation energy of the reaction so reactants can become products. The enzyme is unchanged and is available to be used again. 3 2 1 FIGURE 3-9 Dipeptides and Polypeptides Figure 3-8a shows how two amino acids bond to form a dipeptide (die-PEP-TIED). In this condensation reaction, the two amino acids form a covalent bond, called a peptide bond (shaded in blue in Figure 3-8a) and release a water molecule. Amino acids often form very long chains called polypeptides (PAHL-i-PEP-TIEDZ). Proteins are composed of one or more polypep- tides. Some proteins are very large molecules, containing hun- dreds of amino acids. Often, these long proteins are bent and folded upon themselves as a result of interactions—such as hydrogen bonding—between individual amino acids. Protein shape can also be influenced by conditions such as temperature and the type of solvent in which a protein is dissolved. For exam- ple, cooking an egg changes the shape of proteins in the egg white. The firm, opaque result is very different from the initial clear, runny material. Enzymes Enzymes—RNA or protein molecules that act as biological catalysts—are essential for the functioning of any cell. Many enzymes are proteins. Figure 3-9 shows an induced fit model of enzyme action. Enzyme reactions depend on a physical fit between the enzyme molecule and its specific substrate, the reactant being catalyzed. Notice that the enzyme has folds, or an active site, with a shape that allows the substrate to fit into the active site. An enzyme acts only on a specific substrate because only that substrate fits into its active site. The linkage of the enzyme and substrate causes a slight change in the enzyme’s shape. The change in the enzyme’s shape weakens some chemical bonds in the substrate, which is one way that enzymes reduce activation energy, the energy needed to start the reaction. After the reaction, the enzyme releases the products. Like any catalyst, the enzyme itself is unchanged, so it can be used many times. An enzyme may not work if its environment is changed. For example, change in temperature or pH can cause a change in the shape of the enzyme or the substrate. If such a change happens, the reaction that the enzyme would have catalyzed cannot occur.

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