4/3/2018 PHARMACOLOGICAL MANAGEMENT OF HYPERTENSION IN THE PATIENT WITH CKD TONI A. HARPS, APRN-CNS, MSN NEPHROLOGY WHY THIS TOPIC/OBJECTIVES

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1 PHARMACOLOGICAL MANAGEMENT OF HYPERTENSION IN THE PATIENT WITH CKD TONI A. HARPS, APRN-CNS, MSN NEPHROLOGY WHY THIS TOPIC/OBJECTIVES To identify Blood pressure (BP) medications which are used to manage Hypertension (HTN) in the adult patient with chronic kidney disease (CKD) Identify common and not so common issues associated with these medications, such as monitoring, adverse reactions, side effects, interactions, etc To identify primary systems which impact blood pressure Determine how to choose add on BP medications for CKD patients with co-morbidities Apply knowledge to everyday practice 2 WHAT IS HYPERTENSION Definition of Hypertension (HTN) Systolic Blood Pressure (SBP) > 140 and Diastolic Blood Pressure > 90 Classified as Essential HTN Commonly starting in the 5 th or 6 th decade of life Associated with increased salt intake, obesity, and some familiar components Secondary HTN is associated with Renal Artery Stenosis, Chronic Kidney Disease, Sleep Apnea and Adrenal diseases This Photo by Unknown Author is licensed under CC BY-NC-ND 3 1

2 WHAT IS HYPERTENSION Prevalence It is a global problem Major risk factor for Cardiovascular Disease (CVD) Impacts > 60% of adults older than 60 y.o. Responsible for 7.5million deaths per year globally In the United States HTN is associated with > $45million plus bill related to cost such as medication, health care services, workforce absentees it estimated over 1.5 billion adults will be diagnosed with HTN This Photo by Unknown Author is licensed under CC BY-NC-SA 4 PRIMARY SYSTEMS WHICH IMPACT BLOOD PRESSURE Sympathetic Nervous System (SNS) utilizes Alpha- adrenergic receptor impact blood vessels causing vasoconstriction Beta Adrenergic receptors impact the heart and blood vessels causing vasodilatation Of note, the Renal SNS is a key player in BP management This Photo by Unknown Author is licensed under CC BY-NC-SA The efferent pathway of the Kidney is a highway which moves signals between the SNS and the Kidneys activating the Renin-angiotensin-aldosterone system (RAAS) 5 PRIMARY SYSTEMS WHICH IMPACT BLOOD PRESSURE Renin-angiotensin-aldosterone system Stimulates renin which initiates a process which causes vasoconstriction Which works to retain sodium and water to increase blood pressure Endothelial (form the lining of the blood cells) Endothelial Dysfunction causes decreased nitric oxide (Nitric oxide causes vasodilatation) which plays a major role in regulating the tone of blood vessels This Photoby Unknown Author is licensed under CC BY-SA 6 2

3 WHAT IS CHRONIC KIDNEY DISEASE (CKD) CKD Decline in Glomerular Filtration Rate (GFR) <60 Presence of Kidney Damage for more than 3 months. CKD is staged according to Glomerular Filtration Rate (the rate of blood flow through the kidneys) Stage 1 > 90, Stage 2 (60-89), Stage 3 (30-59), Stage 4 (15-29), Stage 5 (< 15 or dialysis) Stage 1 and 2 have to be associated with some form of renal injury such as proteinuria to be considered CKD Albuminuria (Albumin or protein in the urine) Primary causes include HTN and Diabetes 7 This Photoby Unknown Author is licensed under CC BY-NC-SA WHAT IS CHRONIC KIDNEY DISEASE Chronic Kidney Disease (CKD) is on the rise Effecting > 25 million American Adults With > 600,000 progressing to End Stage Renal Disease Many will transition to dialysis or transplantation Patients with CKD are at increased risk for Cardio Vascular Disease (CVD) and death The diagnoses (Dx) responsible for the increased risk include uncontrolled HTN and Diabetes The risk increases with the declining function of the kidney 8 WHAT S THE CONNECTION So, which came first CKD or HTN? Hypertension can be the etiology or the result CKD Hypertension is major risk factor for CVD and CKD Patients with CKD are higher risk for HTN HTN is more common in pt s with CKD Strong relationship between HTN and Renal Artery Stenosis, Polycystic Disease, and Diabetic Nephropathy A primary goal of HTN management is to decrease progression of CKD 9 3

4 PHARMACOLOGICAL TREATMENT RECOMMENDATIONS Usually, pts with CKD require more than one BP medication to control HTN Pharmacological treatment recommendations for HTN in CKD include initiation with an Angiotensin Converting Enzyme Inhibitor (ACE I), Angiotensin Receptor Blockers (ARBs) Calcium Channel Blocker (CCB) or a diuretic Additional HTN medications are chosen according to the patient s other co-morbidities These BP medications include Calcium Channel Blocker, Beta Blockers, Aldosterone, Alpha-blockers, Vasodilators, Centrally Acting adrenergic inhibitors BP Goals for pts with CKD per JNC 8 is < 140/90 This Photoby Unknown Author is licensed under CC BY-NC- ND 10 PHARMACOLOGY OF ACE AND ARBS AND ITS IMPACT ON HTN Renin Angiotensin-aldosterone system (RAAS) is one of several primary systems which regulate HTN 4 Categories of medications which are used to regulate HTN in this system Angiotensin converting enzyme (ACE) Inhibitors, Angiotensin II Receptor Blockers (ARBs), Aldosterone Agonist, Direct Renin inhibitors 11 PHARMACOLOGY OF ARBS AND ITS IMPACT ON HTN ACE I and ARBs work on the RAA system to inhibit or limit Angiotensin II development Angiotensin II impacts the vascular system causing vasoconstriction, increased aldosterone levels resulting in sodium and fluid retention Although these 2 classes of medications work on the same system, each class impacts at a separate target point ARBs work to block angiotensin II to angiotensin II type one ACE I work to Inhibit the conversion of angiotensin I into angiotensin II 12 This Photoby Unknown Author is licensed under CC BY 4

5 ARBS ARBS are not only efficacious in blood pressure management ( Candesartan, Irbesartan, Losartan, Olmesartan, Telmisartan, valsartan) ARBS are also a treatment recommendation to decrease left ventricular remodeling after myocardial infarction (MI), hinder development of diabetic neuropathy, decrease the risk for strokes, and decrease proteinuria etc. ARBs do not have the same coughing side effect associated with an ACE I ARBs start working in about 3-6 hours 13 ARBS Monitor K+ levels in these pts Avoid taking Lithium and ARBs together as ARBs cause increase renal reabsorption of Lithium Digoxin and Telmisartan taken together increase dig levels and may result in dig toxicity Telmisartan is the longest acting in the group with a 24 hr half-life Can be used with other BP meds and diuretics Usually well tolerated Beneficial in CKD with proteinuria 14 ACE INHIBITORS Decreases renal excretion of protein in the urine slowing progression to ESRD Can be used with other BP meds and diuretics Usually well tolerated Associated side effect non-dose dependent coughing and angio-edema minimally seen in Asian and African Americans (AA) More effective in Caucasians as RAA system is less pronounced in the AA Beneficial in CKD with proteinuria, Left Ventricular systolic dysfunction and post MI 15 5

6 CALCIUM CHANNEL BLOCKERS Non-dihydropyridines (1 st generation) work by decreasing heart rate and force of heart contraction Verapamil, Diltiazem (has more vasodilator action, and works better for management of HTN) Short acting Peripheral edema Reflex tachycardia Skin reactions Also Beneficial in decreasing the risk of stroke in pts with HTN 16 CALCIUM CHANNEL BLOCKERS Dihydropyridine (2 nd generation) CCBS decrease BP primarily through direct vasodilatation and are more suited for HTN management Contraindicated in pt with Congestive Heart Failure (CCBs may cause bradycardia) Amlodipine, Felodipine, Nicardipine, Nifedipine, More favorable profile such as absorption, distribution, and impact on the body For example amlodipine has a half life of hrs and takes about 8-10 hrs to peak effect 17 CALCIUM CHANNEL BLOCKERS Can be used with ACE or ARBs Recommended by the European guidelines for AA and elderly patients with isolated systolic hypertension Caution when combining Non-dihydropyridines with Beta Blocker in pt with heart failure CCBs may cause bradycardia 18 6

7 DIURETICS -LOOP Furosemide (Oral) Used to manage edema through excretion of Na and water from the kidneys BID dosing Bioavailability is extremely variable (10 90%) Take before meals to increase bioavailability Peaks in about 1 1.5hrs 19 This Photo by Unknown Author is licensed under CC BY-SA DIURETICS -LOOP Pt with renal dysfunction have a decreased response and increased plasma half-life r/t decreased urinary excretion It is recommended to use loop diuretics in pts with egfr < 30 or stage 4 CKD Torsemide effects of low doses improve with nighttime dosing -really!!!!! Daily dosing Half-life is 3-4 hrs 20 DIURETICS -LOOP Major Adverse Events associated with Furosemide Hypovolemia Electrolyte imbalance r/t to diuresis hypokalemia, hypomagnesemia, hypocalcemia, hyponatremia, hyperuricemia Hypersensitivity Furosemide is a sulfur based medication and cause allergic or hypersensitivity reactions (rash or acute interstitial nephritis) 21 7

8 DIURETICS -LOOP An alternative to furosemide is ethacrynic acid (a loop diuretic) w/o sulfur but has shown to be more ototoxic Furosemide can displace warfarin, meaning a lower dose of warfarin maybe needed Furosemide induced hypokalemia increases the risk of digitalis-induced arrhythmia Furosemide can increase risk of gout when given with cyclosporine which decreases renal urine excretion Ototoxicity 22 DIURETICS -THIAZIDES Thiazides Chlorothiazide, Hydrochlorothiazide (HCTZ), Metolazone, Chlorthalidone and indapamide Work to increase Na excretion in the urine Resulting in decreased extracellular volume, venous return and in the end decreased cardiac output Inexpensive 23 DIURETICS -THIAZIDES Keep in mind volume overload is a major contributor to HTN in the pt with CKD With declining GFR, less sodium (Na) is filtered resulting in fluid retention JNC7 recommended changing from thiazide to a loop diuretic when egfr is <30, JNC8 made no recommendations Many providers change to a loop diuretic when the pt reaches stage 4 of CKD 24 8

9 DIURETICS MINERALOCORTICOID RECEPTOR ANTAGONIST Spironolactone/Aldactone (mineralocorticoid receptor antagonist family) Very helpful when used in combination with and ACE, ARB, CCB or Diuretic Especially in the management of Heart Failure (blocks Aldosterone which causes fluid and Na retention) Works by inhibiting sodium potassium exchange and inhibits aldosterone-induced vasoconstriction Spironolactone is also known to reduce proteinuria by 61% in proteinuric kidney disease and decrease albuminuria by 60% Common problems associated with its use include gynecomastia, electrolyte imbalances such as hyperkalemia Electrolyte imbalances and hyperkalemia are more common in the pt who already has CKD and are on an ACE or ARB 25 BETA BLOCKERS Beta Blockers (BB) are the go to when treating history of MI and heart failure Carvedilol bid dosing and Metoprolol daily, Bisoprolol daily BB work to decrease cardiac output and decrease renal renin secretion BB alter glucose metabolism and mask hypoglycemia BB are also associated with depression, fatigue and sexual dysfunction 26 ALPHA-BLOCKER Are usually used as an add on or maybe used for the pt who cannot tolerate other first line BP meds Doxazosin (Cardura), Prazosin (Minipress), Terazosin Alpha-Blockers work to cause vasodilatation Primary problems associated with AB include first dose syncope and vasovagal syncope please caution pt Using with a diuretic increases the total impact on BP Very helpful when treating HTN in the older male with benign prostate hypertrophy (BPH) 27 9

10 MISCELLANEOUS Vasodilators -Hydralazine / TID dosing/2 nd line of medication/used along with other medications Central Agonist Clonidine/use with other meds/works in the central nervous system/may cause drowsiness Nitrate Isosorbide/used for chest pain and can be used for HTN/dizziness with position change 28 CASE SCENARIO JD a 75 y.o. AA male was referred to CKD clinic for SCr of 2.2 and HTN Dx include CKD, HLD, OA, OSA, HTN, Diab Exam findings: 20 yr hx of Diab, and HTN, CKD 5yrs, with egfr of 29, and +2 LE edema Home sys bp 140s- 170s, C/o difficulty starting stream, A1c ave.6.5% No proteinuria, Electrolytes within normal range Current BP meds include Amlodipine (Norvasc) 10mg every morning, HTCZ 25mg qd What BP medications would be most helpful considering pt s co-morbidities? 29 RECOMMENDATIONS Terazosin for BPH and it BP lowering properties Change HCTZ to Furosemide 20mg as pt with egfr <

11 CASE SCENARIO DJ a 75 y.o. male was referred to CKD clinic for SCr of 1.7 and uncontrolled HTN Dx include CKD, HLD, OA, OSA, HTN, Diab Exam findings: 20 yr hx of Diab, and HTN, CKD 10yrs, with egfr of 38, and +3 LE edema, No hx of MI Home sys bp 140s- 170s, Heart Rate , A1C ave.9.5%, Moderate proteinuria 1.5 grams for 2 years Electrolytes within normal range, K+ is 5.0 Current BP meds include Amlodipine 10mg every morning, Spironolactone (Aldactone) 50mg qd, Carvedilol 6.25mg daily, Lisinopril 20mg qd What BP medications would be most helpful considering pt s co-morbidities? 31 RECOMMENDATIONS Increase carvedilol to bid as dosing recommendation is bid to address tachycardia Keep lisinopril to address proteinuria Change Spironolactone to Furosemide as pt s CKD is at stage 3 and this will also address slightly elevated K+ level and edema 32 CASE SCENARIO TH a 75 y.o. male was referred to CKD clinic for SCr of 1.8 and HTN Dx include CKD, HLD, OA, OSA, HTN, Diab, Exam findings: 20 yr hx of Diab, and HTN, CKD 10yrs, with egfr of 38, and +3 LE edema Home sys bp 140s- 170s, A1C ave. 6.5%, Moderate proteinuria 1.5 grams for 2 years, MI 3 weeks ago Persistent cough for last few months Electrolytes within normal range Current BP meds include Lisinopril 30 mg daily, Carvedilol 6.25mg bid, Furosemide 40mg daily What BP medications would be most helpful considering pt s co-morbidities? 33 11

12 RECOMMENDATIONS Increase Furosemide Immediately stop Lisinopril r/t persistent cough Start Losartan as it does not have the side effects of coughing and possible angioedema 34 OVERVIEW Cornerstone for BP management for the pt with CKD is an ACE I or an ARB with a diuretic There are settings in which a ACE I or ARB may not be used Evaluation of pt s other co-morbidities should be used in the equation identifying add on bp meds 35 Abraham, H. M. A., White, C. M., & White, W. B. (2015). The Comparative Efficacy and Safety of the Angiotensin Receptor Blockers in the Management of Hypertension and Other Cardiovascular Diseases.Drug Safety,38(1), Arjun, S. & Agarwa;.R. (2015). Thiazide diuretics in Chronic Kidney Disease. Curr Hypertension Rep. 17, Doi: /s x Delacroix, et al., J (2014), Hypertension: Pathophysiology and Treatement. Neurol Neurophysiol, 5: Dézsi, C. A. (2014). Differences in the Clinical Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers: A Critical Review of the Evidence.American Journal of Cardiovascular Drugs,14(3), Frohlich, H., Nelges, C., Tager, t., Schwenger, V., Schnorbach, J., Cebola, r., Schnorbach, J.,... Frankenstein, L. (2016). Longterm changes of renal function in relation to ace inhibitor/angiotensin receptor blocker dosing in patients with heart failure and chronic kidney disease, http//dx.doi.org/ /j.ahj

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