Non, je ne la prends pas

Est-ce que tu prends CETTE JUPE? (N)

Est-ce que tu as oublié TON SAC? (Y)

Non, je ne le prends pas

Est-ce que tu prends TON PORTABLE? (N)

Est-ce que tu aimes CES BOTTES? (Y)

Est-ce que tu aimes LES CHATS? (Y)

Non, je ne les aime pas

Est-ce que tu aimes LES RATS? (N)

Non, elle ne les prend pas

Est-ce qu'elle prend SES PANTOUFLES? (N)

Non, je ne les mets pas

Est-ce que tu mets TES LUNETTES DE SOLEIL? (N)

Non, je ne la mange pas

Est-ce que tu manges LA VIANDE? (N)

Est-ce que tu manges LE FROMAGE? (Y)

Est-ce que tu as vu LE NOUVEAU FILM? (Y)

Non, je ne les aime pas

Est-ce que tu aimes LES CROISSANTS? (N)

Est-ce que tu as fini LES DEVOIRS? (Y)

Answer with a DOP | Quizalize

Answer the questions with a DOP

Yaama I'm Jack Evans and you're watching BTN. Here's what's coming up. We uncover the story behind this famous photo, learn about First Nations seasons and find out the history of Book Week. What is Statehood? Reporter: Tatenda Chibika INTRO: But first, the Prime Minister Anthony Albanese has announced that Australia will join other countries in recognising Palestine as an independent state. So, what does that mean? Tatenda found out. Anthony Albanese, Prime Minister: Australia will recognise the state of Palestine. Australia will recognise the right of the Palestinian people to a state of their own. We will work with the international community to make this right a reality. Tatenda Chibika, Reporter: That's the moment our Prime Minister said Australia would recognise Palestine as an independent state at the upcoming United Nations General assembly next month. It's something other countries, including France and Canada, have said they'll be doing too. So, what does that mean exactly? To be considered an independent state under international law a place needs to have its own land or territories with defined borders, it needs to have people who permanently live there, have a working government and it has to be able to talk and make deals with other countries. Once a place meets all those rules, it can ask to be recognised by other independent states and countries. But a big step in becoming an independent state is being fully recognised by the United Nations. To do that you first need to get approval from at least nine members of the UN's Security Council. That's a group of countries responsible for maintaining international peace and security. But even then, that tick of approval can still be blocked by one of the Security Council's five permanent members Russia, China, the UK, the US and France. If the Security Council approves, the decision then goes to the UN's General Assembly where at least two thirds of the UN's 193 members have to agree to make it official. Yeah, it's a pretty complex process which is why we've only seen a handful of countries recognised by the UN in recent years like South Sudan and Montenegro. Others like Kosovo are only 'partially' recognised which means they have some recognition but not enough to become a full member state at the UN. Right now, Palestine is recognised by more than 140 countries — that's more than two thirds of the UN General Assembly. So, why hasn't it become a UN member state yet? Well, it came pretty close last year when 12 members of the Security Council voted in favour of it. VANESSA FRAZIER, AMBASSADOR OF MALTA, APRIL 2024 UNSC PRESIDENT: I shall now put the draft resolution to the vote. But the US, a close ally to Israel, used its special powers to block Palestine from becoming a member state. VANESSA FRAZIER: Those against? At the time, the U.S said Palestine and Israel needed to come to an agreement on their own first. Throughout the years, there have been attempts to figure out a way for both Palestine and Israel to exist peacefully alongside each other but that hasn't happened yet. And now Israel has said that recognising Palestine as an independent state would be rewarding Hamas the group in charge of Gaza which was responsible for the terror attacks on October 7th, 2023. But the Palestinian Authority which governs parts of the West Bank says Hamas won't have a role in any future state of Palestine which will exist peacefully alongside Israel. Australia, like the US, had previously said that it wanted Israel and Palestine to figure out things by themselves first but because of how the war has been going the Australian government is worried that if it continues to wait, there might not be a Palestinian state to recognise. ANTHONY ALBANESE, PRIME MINISTER: There has been too many lives lost, both Israeli's and Palestinians and the world is saying we need a solution to this conflict, we need to end the cycle of violence and the way to do that is to have a two-state solution. News Quiz Russia's President Vladimir Putin stepped foot on American Soil for the first time in a decade to meet with US President Donald Trump. What state did they meet in? Alabama, Alaska or Arizona?It's Alaska. The two leaders met to discuss a way to end the war in Ukraine but weren't able to make any final agreements. DONALD TRUMP, US PRESIDENT: There were many, many points that we agreed on. Most of them, I would say, a couple of big ones, that we haven't quite got there, but we've made some headway. There's no deal until there's a deal. A lot of people criticised the two world leaders for not including Ukraine's president Volodymyr Zelenskyy in the meeting. But that didn't seem to worry Mr Trump who said the meeting was a success and Mr Putin even invited the US President to meet up again in Russia. DONALD TRUMP: We'll see you again very soon. Thank you very much, Vladimir. VLADIMIR PUTIN, RUSSIAN PRESIDENT: Next time in Moscow. DONALD TRUMP: Oh, that's an interesting one. No, no, no. I'll get a little heat on that one. Last week thousands of people marked the 80th anniversary of VJ Day. What does VJ Day commemorate? The victory of Allied forces in Europe, the surrender of Japan and the end of World War II or the dropping of the first atomic bomb? VJ Day or Victory over Japan day commemorates the surrender of Japan and the end of World War II on the 15th of August 1945. Around the world, and here in Australia, people marked the anniversary with ceremonies remembering those who fought in the war. REPORTER: Who will you be remembering today? VETERAN: Oh, a lot of fellows that I knew that never made it home. Scientists in the UK have created toothpaste that includes which of these ingredients? Hair, eye lashes or fingernails? Yeah, they're all a bit random and gross but the answer is hair. According to scientists from King's College in London, hair could be the key to good oral health because it contains a protein called Keratin which they say when mixed with saliva forms a crystal-like protective coating similar to enamel. And Swifties rejoice because Taylor Swift has announced her 12th Studio album. It's called life of a show what? Is it show pony, show girl or show bag? It's Life of a Showgirl and it'll be released October 3rd. Vincent Lingiari Reporter: Joseph Baronio INTRO: Now to this very famous photograph. It was taken 50 years ago and depicts a really significant moment in Australian history. Joe found out about the story behind it. On the 16th of August 1975, this famous photo was taken. It shows the former Prime Minister Gough Whitlam pouring sand into the hand of Aboriginal leader Vincent Lingiari. A simple gesture that symbolised handing the land at Wave Hill in the Northern Territory back to the Gurindji people. But the journey to get there was far from simple. It started back in the 1960s. At the time, Wave Hill was the biggest cattle station in the world, controlled by British landowner Lord Vestey. The Gurindji people, who had lived on the land for generations, worked for Vestey, but they weren't paid fairly, and conditions were tough. NEWS REPORTER: The station's 100 aboriginal stockmen, with their 100 dependents, are camped in the dry bed of the Victoria River with little shade from 90-degree heat, dust and flies. Eventually, Gurindji leader Vincent Lingiari said it was time to act. VINCENT LINGIARI: I said, "What was it before Lord Vestey born and I was born?" It was blackfella country. So, on August 23rd, 1966, Mr Lingiari and his fellow Aboriginal workers went on strike. It became known as the Wave Hill Walk Off. They moved their camp away from the Wave Hill station to a sacred site called Daguragu on Wattie Creek. They wanted to set up their own cattle station, and said they wouldn't move until their land was returned to them. For years, petitions and negotiations went on between the Gurindji people, the NT Administration, and the Australian Government in Canberra. CLAPPERS: 31. 32. 33. DAVID QUINN, ABSCOL: Well, it's basic justice that their land is recognised. PROTESTORS: Equal rights! As the news spread across the country, thousands of Aussies joined the campaign, including the leader of the Labor Party, Gough Whitlam, who made this promise during his 1972 election campaign. GOUGH WHITLAM: We will legislate to give Aborigines land rights. Not just because their case is beyond argument, but because all of us as Australians are diminished, while the Aborigines are denied their rightful place in this nation. Later that year, Gough Whitlam became Prime Minister. (Song From Little Things Big Things Grow, Song by Kev Carmody and Paul Kelly, 1993) From little things big things grow,from little things big things grow… But it wasn't until 1975, 9 years after the Wave Hill Walk Off started, that he followed through with his promise. Eight years went by, eight long years of waiting'Til one day a tall stranger appeared in the landAnd he came with lawyers and he came with great ceremony GOUGH WHITLAM: I solemnly hand to you these deeds as proof in Australian law that these lands belong to the Gurindji people. And through Vincent's fingers poured a handful of sandFrom little things big things grow 50 years on, and The Wave Hill Walk Off is seen as a pivotal moment in Australia's history. It led to significant legal and social changes for First Nations people, which is something many agree is worth celebrating. First Nations Seasons Reporter: Saskia Mortarotti INTRO: Recently, Melbourne's Lord Mayor suggested ditching the four-season calendar that most of us are familiar with and adopting a six-season Wurundjeri calendar instead saying it gives a better description of what the weather's actually like there. Sas found out more about the different seasonal calendars used by First Nations people. SASKIA MORTAROTTI, REPORTER: Right now, in most of the country, it's pretty cold. COLD GIRL: Think of somewhere warm. What? It's 32 degrees in Darwin in the middle of winter? But ah, yeah. There are some places where it's, well, quite warm. Which makes you wonder whether the weather actually matches the seasons. You see, Australia is pretty big, and we have lots of different weather patterns. Which is something First Nations people have tracked for thousands of years with their own seasonal calendars. KARL WINDA TELFER, CULTURAL CREATIVE KANYANYAPILLA: Why have we got four seasons when you know that don't make any sense here. It doesn't relate to the country here. This is Karl Telfer. He's an artist and storyteller who produced the Kuri Kurru exhibition at the Museum of Discovery in Adelaide that explores the 6 different seasons of the Kaurna Meyunna. SASKIA MORTAROTTI: So, how do you know when you're in one of those six seasons? KARL WINDA TELFER: Well, there are stars that rise. So, you know, there are certain stars, like in Parnatti, for example. There's a star called Parna, and we know what that star is. So, that talks to us about, okay, the time now is going to be cold on the ground. First Nations calendars like the Kaurna one don't just tell us what's happening with the weather; they're also used to track when certain plants and animals are around. KARL WINDA TELFER: It teaches you about what plants you can, you know, what you can eat what you can't and all that what is ready certain times a year and fruit everything, bird shows you the right time to eat the fruit, perfect time, if you try and go get them the next week they're gone. Karl says we can also use these calendars to see how the environment has changed over time. KARL WINDA TELFER: Kudlilla is the season we're in now and Kudlilla that talks about like the rain but we're not having enough rain these days, well, these times. And this is due to climate and the climate changing. There are many different First Nations seasonal calendars around the country. Like Ngan'gi calendar from the Northern Territory which has 13 seasons that follow the life cycle of the native spear grass. Or the Wurundjeri Calendar in Victoria which has 6 seasons. And recently, Melbourne's Lord Mayor, Nicholas Reece, said Melbourne, or Naarm, would be better off adopting the Wurundjeri calendar because it's more in tune to what's happening with the weather. Something many, including Karl, think we should be doing right across the country. KARL WINDA TELFER: I'm talking about the English four seasons. So, this is totally different systems that we're talking about and weather patterns and currents and all sorts of different things, because it's the sea country too. So, my question is, well, why do we have that? If that doesn't work, you know? Quiz How many seasons are there in the Tiwi Island Calendar? 1, 2 or 3? It's 3, although they also have 13 minor seasons. Book Week Reporter: Wren Gillett INTRO: This week, kids across Australia have been dressing up as their favourite characters to celebrate Book Week. Wren finds out why Book Week began 80 years ago and why it's still important today for getting young Aussies into reading. STUDENT: I read an hour every night, maybe even two hours some nights. STUDENT: My favourite book series are the Harry Potter series and the Keeper of the Lost City series. STUDENT: Probably Bad Guys and Weirdo. STUDENT: I like the Amulet, I've been reading that. STUDENT: I love reading Dork Diaries and Exploding Endings. Whether it's Fantasy, mystery, history — whatever you're into. Book week is a time to celebrate, well, books. STUDENT: Me and my friends are dressing up as Inside Out. STUDENT: I was thinking SpongeBob. STUDENT: I'm dressing up as Winnie the Pooh and it's just a fun way to express what kind of books you like. And guess what, book week has actually been a thing for many, many years. WREN GILLETT, REPORTER: Once upon a time, in a land not so far away, literacy lovers noticed a problem. The year was 1945. The second World War had just ended, and kids were mainly reading books from overseas, in particular the UK. Because, at the time, there weren't many Aussie authors writing books for children. WREN GILLETT: So, a group of passionate teachers, librarians, booksellers, publishers, and book-loving volunteers, decided to create what we now know as The Children's Book Council of Australia. Familiar logo, right? Together, they launched book week, all in an effort to get Aussie kids' reading more. And it seemed to work. The 1960s saw a boom in Australian children's books being published. REPORTER: How many books do you read a week? STUDENT: Well, it really depends on the week. If there's exams, I might read only one or two. But if there's no exams and if I've got plenty of time, I might read up to five or six. WREN GILLETT: But today, it's a slightly different story. Studies show that less than one in five eight to 18-year-olds are reading in their free time, and that only one in three actually enjoy reading for fun. WREN GILLETT: Why do you reckon we're seeing this trend? STUDENT: People are getting sucked into screens and they're like spending hours just scrolling through TikTok and stuff, and they're getting so attached to it that they don't feel the need to pick up books and read them. Yeah, there's a lot of different things competing for our attention these days, but many think books are still worth our time. PETER HELLIER, AUSSIE COMEDIAN AND AUTHOR: Books are the exact opposite of boring. And if you think they're boring, I'm sorry, but you're wrong. This is Peter Hellier, he's a pretty famous Aussie comedian, actor, and the author behind these books. And he's just released another one called Detective Galileo, about a trail horse who dreams of solving crimes. PETER HELLIER: He joins the police force and quickly finds out that the horses don't actually solve the crimes, it's the police officers who solve the crime. So he promptly gets thrown out of the force and begins his own detective agency, which I'm reliably told is the only detective agency in the world run by a horse. Peter actually started writing books when he was a kid. PETER HELLIER: I started writing when I was six, seven, eight years old. In fact, I started my own publishing company called Better Books. And I would write these books, and then I would get a parent or one of my parents or teachers to type them up. And I would read them in front of the class. And, you see, each has the logo, the Better Books logo, there it is — the famous Better Books logo. WREN GILLETT: You weren't mucking around. PETER HELLIER: There all on all of them. There we go. There we go. Many, Including Peter, say there's plenty to get from a good book. They help us learn new words and phrases, get a better understanding of the world around us, and strengthen our imaginations. PETER HELLIER: Books can take you absolutely anywhere. They can take you to countries that you never dreamed about going. Countries that exist, countries that don't exist. Reading just makes the world a much bigger place. It's why for the past 80 years, schools around the country have been taking part in book week. STUDENT: Reading is a place where you can have your own world just to yourself. STUDENT: It's like watching a movie inside your head, but you can choose how it goes. STUDENT: Picking up a book is a good idea, maybe you should start with something that you're interested with and then you can start exploring from there. Quiz What is the title of the book that took out this year's Book of the year Award for younger readers? It's Laughter is the Best Endingby Maryam Master. Some other winners included I'm not really here by Gary Loneborough which took out book of the year for older readers and best picture book went to The Truck Cat, by Deborah Frenkel. Sport Australia's men's national basketball team — the Boomers — have won their third Asia Cup in a row, with an epically narrow victory over China. COMMENTATOR: It is Australia who are celebrating! China started strong, leading 25-17 at quarter time. But Aussie Xavier Cooks led a fierce comeback, shooting 30 points and collecting nine rebounds, earning him the title of MVP. And there seriously couldn't have been a tighter finish. Just as the final buzzer went off, China missed a shot that would have won them the game, leaving Australia with a 90-89 victory. COMMENTATOR: An unbelievable finish. The 2025 AFLW season kicked off last week, and so did a new trick. Yeah, 19-year-old Ash Centra from Collingwood, pulled out this move in the warm-up before their season-opener to Carlton, and since then, a lot of people have been trying to do it, with some success, kind of? FOOTY PLAYER: No, I'm not doing it on camera. But despite the epic warmup, Carlton did end up beating Collingwood by 24 points. Now, the moves from these athletes in China weren't quite so graceful but give 'em a break, okay, they're robots. For the first time ever, humanoid robots from all over the world, competed in their very own games, which featured, soccer, boxing, running, and ahh, lots of falling over. Lots. Luckily though, they did bring their own cheer squad. Young Rapper Reporter: Rylie INTRO: Finally, we're going to meet another winner of this year's Heywire competition — which asks young people in regional areas to share their stories. Rylie's going to tell us how music helped to transform his life. Check it out. Mum and I were homeless. We lived at a caravan park, in motels and tents around Warrnambool. It wasn't pretty. I'm First Nations, and I remember feeling like, my own country is failing me right now. So, we camped right along here. I remember pitching a tent right here and this was actually around the same time I started to get into music which was a good way for me to have something to look forward to. I was raised by the SoundCloud era, listening to a lot of trap music. When I was in school, I'd rap along to songs by Juice World, then I started to make my own. My first track was recorded on my phone. It was bad but a lot of fun to make. Some kids in my school heard it and shamed me. That put me off music for the next couple of years, until a friend of mine bought a microphone and encouraged me to give it another go. There was something about that mic and the energy of the crew around me that gave me confidence. It lit a fire in me. Over time, I was able to focus my flow. My songs are about escapism, living the life, being a success. I rap about stuff that takes me to a better place in my head. I'm manifesting my future. My stage name is Hundo Milli, it's short for hundreds of millions. Money's not really the end goal; it's more about having the freedom to dream big. Mum taught me to never stop believing. Even when times were tough, she kept pushing for us to get housing and eventually we did. We're some of the lucky ones. Today, I'm in a Melbourne studio recording my next single. I remember living in my tent dreaming about this very moment and now I'm here, doing what I love. Ain't nothing going to stop me. Closer Well, that's all we've got for you today, but we'll be back before you know it. In the meantime, you can head to our website, there's plenty to see and do. You can also catch Newsbreak every weeknight and there's BTN High for all you highschoolers out there. Have an awesome week and I'll see you next time. Bye.

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

“There’s No Such Thing as Sound Science” by By Christie Aschwanden was a lead science writer for FiveThirtyEight. FiveThirtyEight, Science, Dec. 6, 2017 Science is being turned against itself. For decades, its twin ideals of transparency and rigor have been weaponized by those who disagree with results produced by the scientific method. Under the Trump administration, that fight has ramped up again. In a move ostensibly meant to reduce conflicts of interest, Environmental Protection Agency Administrator Scott Pruitt has removed a number of scientists from advisory panels and replaced some of them with representatives from industries that the agency regulates. Like many in the Trump administration, Pruitt has also cast doubt on the reliability of climate science. For instance, in an interview with CNBC, Pruitt said that “measuring with precision human activity on the climate is something very challenging to do.” Similarly, Trump’s pick to head NASA, an agency that oversees a large portion the nation’s climate research, has insisted that research into human influence on climate lacks certainty, and he falsely claimed that “global temperatures stopped rising 10 years ago.” Kathleen Hartnett White, Trump’s nominee to head the White House Council on Environmental Quality, said in a Senate hearing last month that she thinks we “need to have more precise explanations of the human role and the natural role” in climate change. The same entreaties crop up again and again: We need to root out conflicts. We need more precise evidence. What makes these arguments so powerful is that they sound quite similar to the points raised by proponents of a very different call for change that’s coming from within science. This other movement strives to produce more robust, reproducible findings. Despite having dissimilar goals, the two forces espouse principles that look surprisingly alike: Science needs to be transparent. Results and methods should be openly shared so that outside researchers can independently reproduce and validate them. The methods used to collect and analyze data should be rigorous and clear, and conclusions must be supported by evidence. These are the arguments underlying an “open science” reform movement that was created, in part, as a response to a “reproducibility crisis” that has struck some fields of science.1 But they’re also used as talking points by politicians who are working to make it more difficult for the EPA and other federal agencies to use science in their regulatory decision-making, under the guise of basing policy on “sound science.” Science’s virtues are being wielded against it. What distinguishes the two calls for transparency is intent: Whereas the “open science” movement aims to make science more reliable, reproducible and robust, proponents of “sound science” have historically worked to amplify uncertainty, create doubt and undermine scientific discoveries that threaten their interests. “Our criticisms are founded in a confidence in science,” said Steven Goodman, co-director of the Meta-Research Innovation Center at Stanford and a proponent of open science. “That’s a fundamental difference — we’re critiquing science to make it better. Others are critiquing it to devalue the approach itself.” Calls to base public policy on “sound science” seem unassailable if you don’t know the term’s history. The phrase was adopted by the tobacco industry in the 1990s to counteract mounting evidence linking secondhand smoke to cancer. A 1992 Environmental Protection Agency report identified secondhand smoke as a human carcinogen, and Philip Morris responded by launching an initiative to promote what it called “sound science.” In an internal memo, Philip Morris vice president of corporate affairs Ellen Merlo wrote that the program was designed to “discredit the EPA report,” “prevent states and cities, as well as businesses from passing smoking bans” and “proactively” pass legislation to help their cause. The sound science tactic exploits a fundamental feature of the scientific process: Science does not produce absolute certainty. Contrary to how it’s sometimes represented to the public, science is not a magic wand that turns everything it touches to truth. Instead, it’s a process of uncertainty reduction, much like a game of 20 Questions. Any given study can rarely answer more than one question at a time, and each study usually raises a bunch of new questions in the process of answering old ones. “Science is a process rather than an answer,” said psychologist Alison Ledgerwood of the University of California, Davis. Every answer is provisional and subject to change in the face of new evidence. It’s not entirely correct to say that “this study proves this fact,” Ledgerwood said. “We should be talking instead about how science increases or decreases our confidence in something.” The tobacco industry’s brilliant tactic was to turn this baked-in uncertainty against the scientific enterprise itself. While insisting that they merely wanted to ensure that public policy was based on sound science, tobacco companies defined the term in a way that ensured that no science could ever be sound enough. The only sound science was certain science, which is an impossible standard to achieve. “Doubt is our product,” wrote one employee of the Brown & Williamson tobacco company in a 1969 internal memo. The note went on to say that doubt “is the best means of competing with the ‘body of fact’” and “establishing a controversy.” These strategies for undermining inconvenient science were so effective that they’ve served as a sort of playbook for industry interests ever since, said Stanford University science historian Robert Proctor. The sound science push is no longer just Philip Morris sowing doubt about the links between cigarettes and cancer. It’s also a 1998 action plan by the American Petroleum Institute, Chevron and Exxon Mobil to “install uncertainty” about the link between greenhouse gas emissions and climate change. It’s industry-funded groups’ late-1990s effort to question the science the EPA was using to set fine-particle-pollution air-quality standards that the industry didn’t want. And then there was the more recent effort by Dow Chemical to insist on more scientific certainty before banning a pesticide that the EPA’s scientists had deemed risky to children. Now comes a move by the Trump administration’s EPA to repeal a 2015 rule on wetlands protection by disregarding particular studies. (To name just a few examples.) Doubt merchants aren’t pushing for knowledge, they’re practicing what Proctor has dubbed “agnogenesis” — the intentional manufacture of ignorance. This ignorance isn’t simply the absence of knowing something; it’s a lack of comprehension deliberately created by agents who don’t want you to know, Proctor said.2 In the hands of doubt-makers, transparency becomes a rhetorical move. “It’s really difficult as a scientist or policy maker to make a stand against transparency and openness, because well, who would be against it?” said Karen Levy, researcher on information science at Cornell University. But at the same time, “you can couch everything in the language of transparency and it becomes a powerful weapon.” For instance, when the EPA was preparing to set new limits on particulate pollution in the 1990s, industry groups pushed back against the research and demanded access to primary data (including records that researchers had promised participants would remain confidential) and a reanalysis of the evidence. Their calls succeeded and a new analysis was performed. The reanalysis essentially confirmed the original conclusions, but the process of conducting it delayed the implementation of regulations and cost researchers time and money. Delay is a time-tested strategy. “Gridlock is the greatest friend a global warming skeptic has,” said Marc Morano, a prominent critic of global warming research and the executive director of ClimateDepot.com, in the documentary “Merchants of Doubt” (based on the book by the same name). Morano’s site is a project of the Committee for a Constructive Tomorrow, which has received funding from the oil and gas industry. “We’re the negative force. We’re just trying to stop stuff.” Some of these ploys are getting a fresh boost from Congress. The Data Quality Act (also known as the Information Quality Act) was reportedly written by an industry lobbyist and quietly passed as part of an appropriations bill in 2000. The rule mandates that federal agencies ensure the “quality, objectivity, utility, and integrity of information” that they disseminate, though it does little to define what these terms mean. The law also provides a mechanism for citizens and groups to challenge information that they deem inaccurate, including science that they disagree with. “It was passed in this very quiet way with no explicit debate about it — that should tell you a lot about the real goals,” Levy said. But what’s most telling about the Data Quality Act is how it’s been used, Levy said. A 2004 Washington Post analysis found that in the 20 months following its implementation, the act was repeatedly used by industry groups to push back against proposed regulations and bog down the decision-making process. Instead of deploying transparency as a fundamental principle that applies to all science, these interests have used transparency as a weapon to attack very particular findings that they would like to eradicate. Now Congress is considering another way to legislate how science is used. The Honest Act, a bill sponsored by Rep. Lamar Smith of Texas,3 is another example of what Levy calls a “Trojan horse” law that uses the language of transparency as a cover to achieve other political goals. Smith’s legislation would severely limit the kind of evidence the EPA could use for decision-making. Only studies whose raw data and computer codes were publicly available would be allowed for consideration. That might sound perfectly reasonable, and in many cases it is, Goodman said. But sometimes there are good reasons why researchers can’t conform to these rules, like when the data contains confidential or sensitive medical information.4 Critics, which include more than a dozen scientific organizations, argue that, in practice, the rules would prevent many studies from being considered in EPA reviews.5 It might seem like an easy task to sort good science from bad, but in reality it’s not so simple. “There’s a misplaced idea that we can definitively distinguish the good from the not-good science, but it’s all a matter of degree,” said Brian Nosek, executive director of the Center for Open Science. “There is no perfect study.” Requiring regulators to wait until they have (nonexistent) perfect evidence is essentially “a way of saying, ‘We don’t want to use evidence for our decision-making,’” Nosek said. Most scientific controversies aren’t about science at all, and once the sides are drawn, more data is unlikely to bring opponents into agreement. Michael Carolan, who researches the sociology of technology and scientific knowledge at Colorado State University, wrote in a 2008 paper about why objective knowledge is not enough to resolve environmental controversies. “While these controversies may appear on the surface to rest on disputed questions of fact, beneath often reside differing positions of value; values that can give shape to differing understandings of what ‘the facts’ are.” What’s needed in these cases isn’t more or better science, but mechanisms to bring those hidden values to the forefront of the discussion so that they can be debated transparently. “As long as we continue down this unabashedly naive road about what science is, and what it is capable of doing, we will continue to fail to reach any sort of meaningful consensus on these matters,” Carolan writes. The dispute over tobacco was never about the science of cigarettes’ link to cancer. It was about whether companies have the right to sell dangerous products and, if so, what obligations they have to the consumers who purchased them. Similarly, the debate over climate change isn’t about whether our planet is heating, but about how much responsibility each country and person bears for stopping it. While researching her book “Merchants of Doubt,” science historian Naomi Oreskes found that some of the same people who were defending the tobacco industry as scientific experts were also receiving industry money to deny the role of human activity in global warming. What these issues had in common, she realized, was that they all involved the need for government action. “None of this is about the science. All of this is a political debate about the role of government,” she said in the documentary. These controversies are really about values, not scientific facts, and acknowledging that would allow us to have more truthful and productive debates. What would that look like in practice? Instead of cherry-picking evidence to support a particular view (and insisting that the science points to a desired action), the various sides could lay out the values they are using to assess the evidence. For instance, in Europe, many decisions are guided by the precautionary principle — a system that values caution in the face of uncertainty and says that when the risks are unclear, it should be up to industries to show that their products and processes are not harmful, rather than requiring the government to prove that they are harmful before they can be regulated. By contrast, U.S. agencies tend to wait for strong evidence of harm before issuing regulations. Both approaches have critics, but the difference between them comes down to priorities: Is it better to exercise caution at the risk of burdening companies and perhaps the economy, or is it more important to avoid potential economic downsides even if it means that sometimes a harmful product or industrial process goes unregulated? In other words, under what circumstances do we agree to act on a risk? How certain do we need to be that the risk is real, and how many people would need to be at risk, and how costly is it to reduce that risk? Those are moral questions, not scientific ones, and openly discussing and identifying these kinds of judgment calls would lead to a more honest debate. Science matters, and we need to do it as rigorously as possible. But science can’t tell us how risky is too risky to allow products like cigarettes or potentially harmful pesticides to be sold — those are value judgements that only humans can make.

Covalent Molecules and Compounds Just as an atom is the simplest unit that has the fundamental chemical properties of an element, a molecule is the simplest unit that has the fundamental chemical properties of a covalent compound. Some pure elements exist as covalent molecules. Hydrogen, nitrogen, oxygen, and the halogens occur naturally as the diatomic (“two atoms”) molecules H2, N2, O2, F2, Cl2, Br2, and I2 (part (a) in Figure 3.1.1). Similarly, a few pure elements exist as polyatomic (“many atoms”) molecules, such as elemental phosphorus and sulfur, which occur as P4 and S8 (part (b) in Figure 3.1.1). Each covalent compound is represented by a molecular formula, which gives the atomic symbol for each component element, in a prescribed order, accompanied by a subscript indicating the number of atoms of that element in the molecule. The subscript is written only if the number of atoms is greater than 1. For example, water, with two hydrogen atoms and one oxygen atom per molecule, is written as H2O. Similarly, carbon dioxide, which contains one carbon atom and two oxygen atoms in each molecule, is written as CO2. Covalent compounds that predominantly contain carbon and hydrogen are called organic compounds. The convention for representing the formulas of organic compounds is to write carbon first, followed by hydrogen and then any other elements in alphabetical order (e.g., CH4O is methyl alcohol, a fuel). Compounds that consist primarily of elements other than carbon and hydrogen are called inorganic compounds; they include both covalent and ionic compounds. In inorganic compounds, the component elements are listed beginning with the one farthest to the left in the periodic table, as in CO2 or SF6. Those in the same group are listed beginning with the lower element and working up, as in ClF. By convention, however, when an inorganic compound contains both hydrogen and an element from groups 13–15, hydrogen is usually listed last in the formula. Examples are ammonia (NH3) and silane (SiH4). Compounds such as water, whose compositions were established long before this convention was adopted, are always written with hydrogen first: Water is always written as H2O, not OH2. The conventions for inorganic acids, such as hydrochloric acid (HCl) and sulfuric acid (H2SO4), are described elswhere. Note! For organic compounds: write C first, then H, and then the other elements in alphabetical order. For molecular inorganic compounds: start with the element at far left in the periodic table; list elements in same group beginning with the lower element and working up. Write the molecular formula of each compound. a. The phosphorus-sulfur compound that is responsible for the ignition of so-called strike anywhere matches has 4 phosphorus atoms and 3 sulfur atoms per molecule. b. Ethyl alcohol, the alcohol of alcoholic beverages, has 1 oxygen atom, 2 carbon atoms, and 6 hydrogen atoms per molecule. c. Freon-11, once widely used in automobile air conditioners and implicated in damage to the ozone layer, has 1 carbon atom, 3 chlorine atoms, and 1 fluorine atom per molecule. Solution: a. • A The molecule has 4 phosphorus atoms and 3 sulfur atoms. Because the compound does not contain mostly carbon and hydrogen, it is inorganic. • B Phosphorus is in group 15, and sulfur is in group 16. Because phosphorus is to the left of sulfur, it is written first. • C Writing the number of each kind of atom as a right-hand subscript gives P4S3 as the molecular formula. b. • A Ethyl alcohol contains predominantly carbon and hydrogen, so it is an organic compound. • B The formula for an organic compound is written with the number of carbon atoms first, the number of hydrogen atoms next, and the other atoms in alphabetical order: CHO. • C Adding subscripts gives the molecular formula C2H6O. c. • A Freon-11 contains carbon, chlorine, and fluorine. It can be viewed as either an inorganic compound or an organic compound (in which fluorine has replaced hydrogen). The formula for Freon-11 can therefore be written using either of the two conventions. • B According to the convention for inorganic compounds, carbon is written first because it is farther left in the periodic table. Fluorine and chlorine are in the same group, so they are listed beginning with the lower element and working up: CClF. Adding subscripts gives the molecular formula CCl3F. • C We obtain the same formula for Freon-11 using the convention for organic compounds. The number of carbon atoms is written first, followed by the number of hydrogen atoms (zero) and then the other elements in alphabetical order, also giving CCl3F. Write the molecular formula for each compound. a. Nitrous oxide, also called “laughing gas,” has 2 nitrogen atoms and 1 oxygen atom per molecule. Nitrous oxide is used as a mild anesthetic for minor surgery and as the propellant in cans of whipped cream. b. Sucrose, also known as cane sugar, has 12 carbon atoms, 11 oxygen atoms, and 22 hydrogen atoms. c. Sulfur hexafluoride, a gas used to pressurize “unpressurized” tennis balls and as a coolant in nuclear reactors, has 6 fluorine atoms and 1 sulfur atom per molecule. Answer: a. N2O b. C12H22O11 c. SF6. Ionic Compounds The substances described in the preceding discussion are composed of molecules that are electrically neutral; that is, the number of positively-charged protons in the nucleus is equal to the number of negatively-charged electrons. In contrast, ions are atoms or assemblies of atoms that have a net electrical charge. Ions that contain fewer electrons than protons have a net positive charge and are called cations. Conversely, ions that contain more electrons than protons have a net negative charge and are called anions. Ionic compounds contain both cations and anions in a ratio that results in no net electrical charge. Note! Ionic compounds contain both cations and anions in a ratio that results in zero electrical charge.An ionic compound that contains only two elements, one present as a cation and one as an anion, is called a binary ionic compound. One example is MgCl2, a coagulant used in the preparation of tofu from soybeans. For binary ionic compounds, the subscripts in the empirical formula can also be obtained by crossing charges: use the absolute value of the charge on one ion as the subscript for the other ion. This method is shown schematically as follows: Crossing charges. One method for obtaining subscripts in the empirical formula is by crossing charges. When crossing charges, it is sometimes necessary to reduce the subscripts to their simplest ratio to write the empirical formula. Consider, for example, the compound formed by Mg2+ and O2−. Using the absolute values of the charges on the ions as subscripts gives the formula Mg2O2:Polyatomic Ions Polyatomic ions are groups of atoms that bear net electrical charges, although the atoms in a polyatomic ion are held together by the same covalent bonds that hold atoms together in molecules. Just as there are many more kinds of molecules than simple elements, there are many more kinds of polyatomic ions than monatomic ions. Two examples of polyatomic cations are the ammonium (NH4+) and the methylammonium (CH3NH3+) ions. P. The method used to predict the empirical formulas for ionic compounds that contain monatomic ions can also be used for compounds that contain polyatomic ions. The overall charge on the cations must balance the overall charge on the anions in the formula unit. Thus, K+ and NO3− ions combine in a 1:1 ratio to form KNO3 (potassium nitrate or saltpeter), a major ingredient in black gunpowder. Similarly, Ca2+ and SO42− form CaSO4 (calcium sulfate), which combines with varying amounts of water to form gypsum and plaster of Paris. The polyatomic ions NH4+ and NO3− form NH4NO3 (ammonium nitrate), a widely used fertilizer and, in the wrong hands, an explosive. One example of a compound in which the ions have charges of different magnitudes is calcium phosphate, which is composed of Ca2+ and PO43− ions; it is a major component of bones. The compound is electrically neutral because the ions combine in a ratio of three Ca2+ ions [3(+2) = +6] for every two ions [2(−3) = −6], giving an empirical formula of Ca3(PO4)2; the parentheses around PO4 in the empirical formula indicate that it is a polyatomic ion. Writing the formula for calcium phosphate as Ca3P2O8 gives the correct number of each atom in the formula unit, but it obscures the fact that the compound contains readily identifiable PO43− ions.Summary • There are two fundamentally different kinds of chemical bonds (covalent and ionic) that cause substances to have very different properties. • The composition of a compound is represented by an empirical or molecular formula, each consisting of at least one formula unit.Contributors The atoms in chemical compounds are held together by attractive electrostatic interactions known as chemical bonds. Ionic compounds contain positively and negatively charged ions in a ratio that results in an overall charge of zero. The ions are held together in a regular spatial arrangement by electrostatic forces. Most covalent compounds consist of molecules, groups of atoms in which one or more pairs of electrons are shared by at least two atoms to form a covalent bond. The atoms in molecules are held together by the electrostatic attraction between the positively charged nuclei of the bonded atoms and the negatively charged electrons shared by the nuclei. The molecular formula of a covalent compound gives the types and numbers of atoms present. Compounds that contain predominantly carbon and hydrogen are called organic compounds, whereas compounds that consist primarily of elements other than carbon and hydrogen are inorganic compounds. Diatomic molecules contain two atoms, and polyatomic molecules contain more than two. A structural formula indicates the composition and approximate structure and shape of a molecule. Single bonds, double bonds, and triple bonds are covalent bonds in which one, two, and three pairs of electrons, respectively, are shared between two bonded atoms. Atoms or groups of atoms that possess a net electrical charge are called ions; they can have either a positive charge (cations) or a negative charge (anions). Ions can consist of one atom (monatomic ions) or several (polyatomic ions). The charges on monatomic ions of most main group elements can be predicted from the location of the element in the periodic table. Ionic compounds usually form hard crystalline solids with high melting points. Covalent molecular compounds, in contrast, consist of discrete molecules held together by weak intermolecular forces and can be gases, liquids, or solids at room temperature and pressure. An empirical formula gives the relative numbers of atoms of the elements in a compound, reduced to the lowest whole numbers. The formula unit is the absolute grouping represented by the empirical formula of a compound, either ionic or covalent. Empirical formulas are particularly useful for describing the composition of ionic compounds, which do not contain readily identifiable molecules. Some ionic compounds occur as hydrates, which contain specific ratios of loosely bound water molecules called waters of hydration.

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)

Create a quiz with 15 multiple choice questions with answer that assesses students' understanding of Oscillator which objective are 1.Understand sinusoidal oscillator circuits and their characteristics 2.Apply the theory of sinusoidal oscillator to various oscillator circuits such as hartley, colpitt, amstrong,phase shift and crystal. 3.Calculate the oscillation frequency.

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