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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 Drug Alpha1 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 Drugs Alpha 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 Inhibitors aka 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 ïƒ 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 HTN Treatment 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)Generate all of these 25 questions Part A: Each correct answer is worth 5. 1. The regular pentagon shown has a side length of 2 cm. The perimeter of the pentagon is (A) 2 cm (B) 4 cm (C) 6 cm (D) 8 cm (E) 10 cm 2 cm 2. The faces of a cube are labelled with 1, 2, 3, 4, 5, and 6 dots. Three of the faces are shown. What is the total number of dots on the other three faces? (A) 6 (B) 8 (C) 10 (D) 12 (E) 15 3. The equation that best represents \a number increased by _ve equals 15" is (A) n ô€€€ 5 = 15 (B) n _ 5 = 15 (C) n + 5 = 15 (D) n + 15 = 5 (E) n _ 5 = 15 4. The line graph shows the number of bobbleheads sold at a store each year. The sale of bobbleheads increased the most between (A) 2016 and 2017 (B) 2017 and 2018 (C) 2018 and 2019 (D) 2019 and 2020 (E) 2020 and 2021 Number of 2016 2017 2018 2019 2020 Year Sale of Bobbleheads 2021 Bobbleheads 20 40 60 80 5. Starting at 72, Aryana counts down by 11s: 72; 61; 50; : : : . What is the last number greater than 0 that Aryana will count? (A) 4 (B) 5 (C) 6 (D) 7 (E) 8 6. In the diagram, \ABC = 90_. The value of x is (A) 68 (B) 23 (C) 56 (D) 28 (E) 26 Day of the Week 44° x° A B C x° 7. Which of the following values is closest to zero? (A) ô€€€1 (B) 5 4 (C) 12 (D) ô€€€4 5 (E) 0:9 Grade 8 8. A jar contains 267 quarters. One quarter is worth $0.25. How many quarters must be added to the jar so that the total value of the quarters is $100.00? (A) 33 (B) 53 (C) 103 (D) 133 (E) 153 9. A package of 8 greeting cards comes with 10 envelopes. Kirra has 7 cards but no envelopes. What is the smallest number of packages that Kirra needs to buy to have more envelopes than cards? (A) 3 (B) 4 (C) 5 (D) 6 (E) 7 10. For the points in the diagram, which statement is true? (A) e > c (B) b < d (C) f > b (D) a < e (E) a > c y x (e, f ) (a, b) (c, d ) Part B: Each correct answer is worth 6. 11. The 26 letters of the English alphabet are listed in an in_nite, repeating loop: ABCDEFGHIJKLMNOPQRSTUVWXY ZABC : : : What is the 258th letter in this sequence? (A) V (B) W (C) X (D) Y (E) Z 12. A public holiday is always celebrated on the third Wednesday of a certain month. In that month, the holiday cannot occur on which of the following days? (A) 16th (B) 22nd (C) 18th (D) 19th (E) 21st 13. A circular spinner is divided into three sections. An arrow is attached to the centre of the spinner. The arrow is spun once. The probability that the arrow stops on the largest section is 50%. The probability it stops on the next largest section is 1 in 3. The probability it stops on the smallest section is (A) 1 4 (B) 2 5 (C) 1 6 (D) 2 7 (E) 3 10 14. A positive number is divisible by both 3 and 4. The tens digit is greater than the ones digit. How many positive two-digit numbers have this property? (A) 4 (B) 5 (C) 6 (D) 7 (E) 8 15. A rectangular pool measures 20 m by 8 m. There is a 1 m wide walkway around the outside of the pool, as shown by the shaded region. The area of the walkway is (A) 56 m2 (B) 60 m2 (C) 29 m2 (D) 52 m2 (E) 50 m2 20 m 8 m 1 m Grade 8 16. The results of asking 50 students if they participate in music or sports are shown in the Venn diagram. What percentage of the 50 students do not participate in music and do not participate in sports? (A) 0% (B) 80% (C) 20% (D) 70% (E) 40% Music Sports 15 5 20 17. There are 2 3 as many golf balls in Bin F as in Bin G. If there are a total of 150 golf balls, how many fewer golf balls are in Bin F than in Bin G? (A) 15 (B) 30 (C) 50 (D) 60 (E) 90 18. In the sequence shown, Figure 1 is formed using 7 squares. Each _gure after Figure 1 has 5 more squares than the previous _gure. What _gure has 2022 squares? (A) Figure 400 (B) Figure 402 (C) Figure 404 (D) Figure 406 (E) Figure 408 Figure 1 Figure 2 Figure 3 19. Mateo's 300 km trip from Edmonton to Calgary passed through Red Deer. Mateo started in Edmonton at 7 a.m. and drove until stopping for a 40 minute break in Red Deer. Mateo arrived in Calgary at 11 a.m. Not including the break, what was his average speed for the trip? (A) 83 km/h (B) 94 km/h (C) 90 km/h (D) 95 km/h (E) 64 km/h 20. Equilateral triangle ABC has sides of length 4. The midpoint of BC is D, and the midpoint of AD is E. The value of EC2 is (A) 7 (B) 6 (C) 6:25 (D) 8 (E) 10 Part C: Each correct answer is worth 8. 21. The positive factors of 6 are 1, 2, 3, and 6. There are two perfect squares less than 100 that have exactly _ve positive factors. What is the sum of these two perfect squares? (A) 177 (B) 80 (C) 145 (D) 52 (E) 97 22. In the list p; q; r; s; t; u; v, each letter represents a positive integer. The sum of the values of each group of three consecutive letters in the list is 35. If q + u = 15, then p + q + r + s + t + u + v is (A) 85 (B) 70 (C) 80 (D) 90 (E) 75 Grade 8 23. The net shown is folded to form a cube. An ant walks from face to face on the cube, visiting each face exactly once. For example, ABCFED and ABCEFD are two possible orders of faces the ant visits. If the ant starts at A, how many possible orders are there? (A) 24 (B) 48 (C) 32 (D) 30 (E) 40 A D B C E F 24. The number 385 is an example of a three-digit number for which one of the digits is the sum of the other two digits. How many numbers between 100 and 999 have this property? (A) 144 (B) 126 (C) 108 (D) 234 (E) 64 25. Student A, Student B, and Student C have been hired to help scientists develop a new avour of juice. There are 4200 samples to test. Each sample either contains blueberry or does not. Each student is asked to taste each sample and report whether or not they think it contains blueberry. Student A reports correctly on exactly 90% of the samples containing blueberry and reports correctly on exactly 88% of the samples that do not contain blueberry. The results for all three students are shown below. Student A Student B Student C Percentage correct on samples 90% 98% (2m)% containing blueberry Percentage correct on samples 88% 86% (4m)% not containing blueberry Student B reports 315 more samples as containing blueberry than Student A. For some positive integers m, the total number of samples that the three students report as containing blueberry is equal to a multiple of 5 between 8000 and 9000. The sum of all such values of m is (A) 45 (B) 36 (C) 24 (D) 27 (E) 29A1A1 (3)A1 "TO ASK AND GIVE DIRECTIONS"a1 dictee arthur et lilou 2 couleurs A1 "TO LEARN MORE IRREGULAR VERBS IN THE PRESENT TENSE"A1.1 scegli il verbo