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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)

Electrostatics The section of CBSE Class 12 Physics electrostatic potential and capacitance notes mainly deals with the in-depth analysis of electromagnetic phenomena when they are not performing any movements. Additionally, it is divided into ten further sub-topics to study the companion processes of reaching the state. These are - 1. Electric charge In this section of Physics ch 2 Class 12 notes, you get to learn about the basic features of electric charge and its expression in Physics. Along with its basics, the sections help to understand the full potential of charge. Different aspects of Charge included in Class 12 Physics Chapter 2 notes are - Definition Type: Positive and Negative Charge Unit and dimensional formula Point Charge Properties of Charge Comparison of Charge and Mass Methods of Charging Electroscope 2. Coulomb's Law Force is created when charges of opposite signs attract each other, and they repulse if the signs are the same. Coulomb's law tries to define this phenomenon through a mathematical formula, explicitly mentioned in Physics Class 12 notes Chapter 2. Moreover, there is key information about the variation of the constant k and its effect on a medium. Coulomb's law's vector form and the principle of superimposition are also explained in ch 2 Physics Class 12 notes. (Image will be uploaded soon) 3. Electric Field As stated in Class 12 Physics Chapter 2 notes, every positively or negatively charged particle has their respective electric fields. It feels a force at the time of interaction which might be attraction or repulsion. As it arises from electric charge, it is crucial to know about its different parts like - Electric field intensity Relation between electric force and electric field Super imposition of electric field Point charge Continuous charge distributions Properties of Electric Field Lines Motion of Charged Particles in an Electric field Learning more about the electric field from electric potential and capacitance notes Class 12 helps a student to get a grasp of upcoming chapters. 4. Electric Potential Energy When energy helps a charge to move from an electric field, it is known as the Electric Potential Energy. This section of electrostatic chapter Class 12 notes requires a student to study the Electron volt (eV), and the potential energy that an n number of charges can hold. 5. Electric Potential This section of Class 12 Physics Chapter 2 notes focuses on in-depth learning of Electric Potential or Voltage. Basically, it defines the potential movement of energy. 6. Relation between Electric Field and Potential Apart from knowing more about the relationship between the two values, Physics Class 12 Chapter 2 notes also discuss equipotential surfaces. 7. Electric Dipole Essentially, 'Dipoles' are two opposite points of charge represented with q and –q, with their distance between each other being 2a. Electric Dipoles are crucial in your study of Physics Class 12 Chapter 2 notes to learn more about electric fields and their potential. Additionally, Class 12 Physics Chapter 2 notes focus on the influence of electric dipoles on a uniform electric field mainly through Force and Torque, Work, and Potential Energy. In the last part of Electrostatics, further focus is on using the formulas to their fullest potential. It includes subsections of Electric Field, Electric Potential Energy, Electric Potential, and Electric Dipole. In the notes for electrostatic potential and capacitance, you will find proper solutions accompanied by clear and crisp diagrams for better understanding. 8. Gauss's Law Apart from just discussing the Gauss's Law, in Physics Class 12 ch 2 notes there is a thorough explanation of its properties and applications. The Gauss' Law states that net electric flux passing through a hypothetical closed surface is equal to the net electric charge present within the same closed surface. Being a broad part of the whole chapter, you may need to spend a little more time on it. Moving forward, it starts discussing the properties of conductors in relation to Gauss's Law. The Class 12 Physics notes Chapter 2 perfectly defines the journey to Gauss' Law from Coulomb's Law. Here is the Gauss's Law present in the Class 12 Physics ch 2 notes, (image will be uploaded soon) 9. Capacitors There is a dedicated section about Capacitors in the Class 12 Physics Chapter 2 notes elucidating its functions and importance as storage of potential electric energy. After explaining the structure of a capacitor, it points out the different types, parallel plate, spherical and cylindrical. The section of Chapter 2 notes of Physics Class 12 is further divided into subheads like: Properties of an ideal battery Grouping of capacitors Simple circuits (Series and Parallel) Dielectric Van de Graaff generator Combination of drops Charge distribution method Wheatstone Bridge-based circuit Extended Wheatstone Bridge Infinite network of capacitors Redistribution of charge between two capacitors Vedantu prepares the Class 12 Physics Chapter 2 notes with help from subject matter experts. In the PDF, you get a comprehensive idea of the topic along with potential answers to the most asked questions. Furthermore, the detailed explanation on each section and subsections are written in a simple language allows a student to ace their exams with wholesome knowledge. These Physics Chapter 2 Class 12 notes are going to be one of the best supplementary study materials besides a student’s textbooks. Visit the Vedantu website or download the app to get your hands on all important notes! Important Questions A charge of 4 × 10–8C is uniformly distributed on the surface of a spherical conductor, having a radius of 15 cm. Determine the electric field just outside this sphere at a point that is 15 cm from the centre of this sphere. Determine the capacitance given that the distance between the two plates has been reduced by half and the parallel plate capacitor holds a capacitance of 20 pF (where 1pF = 10-12 F) having air between the two plates. What will be the total capacitance of a combination where three capacitors, each having a capacitance of 20 pF, are connected in series. A square having a side of 10 cm has a 500 µC charge at its centre. Determine the work done to move a charge of 10 µC between two points that are diagonally opposite each other on the square. At an equatorial point, what will be the electrostatic potential because of an electric dipole? Calculate the work done to move a test charge, q, through a length of 1 cm along the equatorial axis of an electric dipole? Polarisation A capacitor has its plates enclosed in a medium that can be filled by insulating substances. A net dipole moment is then induced by an electric field in the dielectric. This event causes the field in an opposite direction. Equipotential Surface An equipotential surface is a type of surface where the potential always has a constant value. If considered as a point charge, the concentric spheres that are centred at a particular area of this charge are basically equipotential surfaces. Advantages of Vedantu's Revision Notes: A Comprehensive Resource for Effective Learning There are several reasons why one may refer to Vedantu's revision notes for studying a subject like Electrostatic Potential and Capacitance. Here are some key points: Comprehensive Coverage: Vedantu's revision notes provide a comprehensive coverage of the entire topic, ensuring that all important concepts and subtopics are included. Concise and Organized: The notes are designed to be concise, focusing on the key points and core ideas. They are organized in a structured manner, making it easy for students to navigate and revise the content. Simplified Explanation: The revision notes offer simplified explanations of complex concepts, making them more accessible and easier to understand. This helps students grasp the material more effectively. Key Formulas and Equations: The notes highlight the key formulas and equations relevant to the topic, ensuring that students have a clear understanding of the mathematical aspects of Electrostatic Potential and Capacitance. Examples and Illustrations: Vedantu's revision notes often include examples and illustrations that help clarify concepts and provide practical applications, enabling students to better relate theory to real-world scenarios. Quick Recap: The revision notes serve as a quick recap of the important points, allowing students to review the material efficiently before exams or assessments. Exam-Oriented Approach: Vedantu's revision notes are designed with an exam-oriented approach, focusing on the topics and concepts that are frequently asked in examinations. This helps students prepare effectively and increase their chances of scoring well. 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In many cases, cells must move materials from an area of lower concentration to an area of higher concentration, or “up” their concentration gradient. Such movement of materials is known as active transport. Unlike passive transport, active transport requires a cell to expend energy. CELL MEMBRANE PUMPS Ion channels and carrier proteins not only assist in passive trans- port but also help with some types of active transport. The car- rier proteins that serve in active transport are often called cell membrane “pumps” because they move substances from lower to higher concentrations. Carrier proteins involved in facilitated diffusion and those involved in active transport are very similar. In both, the molecule first binds to a specific kind of carrier protein on one side of the cell membrane. Once it is bound to the molecule, the protein changes shape, shielding the molecule from the hydrophobic interior of the phospholipid bilayer. The protein then transports the molecule through the membrane and releases it on the other side. However, cell membrane pumps require energy. Most often the energy needed for active transport is supplied directly or indirectly by ATP. Sodium-Potassium Pump One example of active transport in animal cells involves a carrier protein known as the sodium-potassium pump. As its name sug- gests, this protein transports Na ions and K ions up their con- centration gradients. To function normally, some animal cells must have a higher concentration of Na ions outside the cell and a higher concentration of K ions inside the cell. The sodium- potassium pump maintains these concentration differences. Follow the steps in Figure 5-6 on the next page to see how the sodium-potassium pump operates. First, three Na ions bind to the carrier protein on the cytosol side of the membrane, as shown in step . At the same time, the carrier protein removes a phosphate group from a molecule of ATP. As you can see in step , the phos- phate group from the ATP molecule binds to the carrier protein. Step shows how the removal of the phosphate group from ATP supplies the energy needed to change the shape of the carrier pro- tein. With its new shape, the protein carries the three Na ions through the membrane and then forces the Na ions outside the cell where the Na concentration must remain high. 3 2 1 SECTION 2 OBJECTIVES ● Distinguish between passive transport and active transport. ● Explain how the sodium-potassium pump operates. ● Compare endocytosis and exocytosis. VOCABULARY active transport sodium-potassium pump endocytosis vesicle pinocytosis phagocytosis phagocyte exocytosis www.scilinks.org Topic: Active Transport Keyword: HM60018 mb06se_homs02.qxd 5/18/07 11:02 AM Page 103 104 CHAPTER 5 K+ K+ K+ K+ K+ K+ INSIDE OF CELL OUTSIDE OF CELL Carrier protein Cell membrane P P P P Na+ Na+ Na+ ATP ADP Na+ Na+ Na+ Na+ Na+ Na+ 1 2 3 4 5 6 At this point, the carrier protein has the shape it needs to bind two K ions outside the cell, as step shows. When the K ions bind, the phosphate group is released, as indicated in step , and the carrier protein restores its original shape. As shown in step this time, the change in shape causes the carrier protein to release the two K ions inside the cell. At this point the carrier protein is ready to begin the process again. Thus, a complete cycle of the sodium-potassium pump transports three Na ions out of the cell and two K ions into the cell. At top speed, the sodium-potassium pump can transport about 450 Na ions and 300 K ions per second. The exchange of three Na ions for two K ions creates an electrical gradient across the cell membrane. That is, the outside of the membrane becomes positively charged relative to the inside of the membrane, which becomes relatively negative. In this way, the two sides of the cell membrane are like the positive and nega- tive terminals of a battery. This difference in charge is important for the conduction of electrical impulses along nerve cells. The sodium-potassium pump is only one example of a cell membrane pump. Other pumps work in similar ways to transport important metabolic materials across cell membranes.

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