Unlocked Hypertension Final Presentation student version 5_8-2023.pptx

Hypertensi on Harleen Singh, PharmD, BCPS, BCACP Clinical Professor UTEP 1 Case 1 TY, a 43 y.o. female, is new to your clinic. BP mmHg Medications For Recently taken at a grocery store 160/88 Norethindrone-ethinyl estradiol 1mg/0.035mg Birth Control Today taken twice at clinic 138/88 Ib...

Hypertensi on Harleen Singh, PharmD, BCPS, BCACP Clinical Professor UTEP 1 Case 1 TY, a 43 y.o. female, is new to your clinic. BP mmHg Medications For Recently taken at a grocery store 160/88 Norethindrone-ethinyl estradiol 1mg/0.035mg Birth Control Today taken twice at clinic 138/88 Ibuprofen 400mg BID Headache Pseudoephedrine 30mg TID Congestion Lab BMI normal 31.2 kg/m2 SH Coffee ≥4 cups qam; beer ≈ 4 drinks qhs Questions 1. What are the key things to consider in this case? 3. What is her BP goal? 2. How would you classify her BP 4. What is the best intervention for her 2 Risks of HTN • Hypertension is a leading cause of death and disability • The 2019 age-adjusted death rate attributable primarily to high BP was 25.1 per 100 000 people • Risk is higher in non-Hispanic Black adults • > 50% of deaths from coronary heart disease and stroke occurred in individuals with HTN • Significance of BP-lowering: • Starting at 115/75 mm Hg, the risk of CVD doubles with every 20/10 mm Hg increase Circulation. 2022;145:e00–e00. 3 Damage from Uncontrolled Blood Pressure https://www.2minutemedicine.com/patient-basics-high-blood-pressure-hypertension/ 4 Anatomy of Heart/Blood SuperiorVessels vena cava Large/mediumsize artery Small size artery (1mm– 25mm) (0.01mm– 1mm) Inferior vena cava 5 Terminology What is Blood Pressure? Cardiac Output x Systemic Vascular Resistance CO is the amount of blood that is pumped by the heart per unit time, measured in liters per minute (l/min) SVR is resistance to the flow of blood determined by the tone of the vascular musculature and diameter of the blood vessels Stroke Volume is the amount of blood ejected from the heart with each beat 6 Determinants of Cardiac Output Pathophysiology Of Heart disease . Second edition Wolters Kluwer Health Lippincott Williams & Wilkins. If you increase cardiac output, what will happen to blood pressure? It will also increase BP = CO x SVR 7 Putting it all Together: Pressure, Flow & Resistance BP=CO×TPR ∆p=Q×R 5mmHg 10mmH g 95mm Hg 80 mmHg 15mmH g 20 30 mmHg ∆P=Pa – Pv = CO=SV×HR CO=Q Q=SV×HR 8 Mean Arterial Pressure •MAP= 2/3 diastolic pressure + 1/3 systolic pressure 9 What is Hypertension (HTN)? • When the force of blood flowing through blood vessels is consistently too high Cardiac Blood Pressure Output (CO) = (BP) (stroke volume x heart rate) X Peripheral Vascular Resistance (PVR) • Blood pressure (BP) is categorized based on average of ≥2 BP readings from 2 separate clinic visits • Signs and symptoms • Usually, asymptomatic • Headache Am Coll Cardiol. 2018;71(19):e127-e248. 10 HTN and CVD Risk Factors Modifiable Relatively-fixed Current or secondhand smoking Age Diabetes Mellitus Male sex Hyperlipidemia Family history Overweight/obesity CKD Physical inactivity Low socioeconomic/educational status Unhealthy diet Obstructive sleep apnea Psychosocial stress Whelton PK, et al. Hypertension. 2017. 11 Primary Hypertension (90-95%) • Idiopathic Secondary Hypertension (510%) • Chronic kidney disease • Cushing’s syndrome or excess glucocorticoid states • Drug-induced or drug-related • Obstructive uropathy • Pheochromocytoma • Primary aldosteronism or other mineralocorticoid excess • Renovascular disease • Sleep apnea • Thyroid or parathyroid disease Etiology 12 Causes of Primary Hypertension SNS NE Vasoconstriction TPR BP 1.↑SNS JGA Renin Angiotensin II BP 2.RAAA  Renin Angiotensin II BP 3. Low Renin Hypertension Na excretion [Na] in blood BV CO  BP [Na] vasoconstriction TPR BP SA HR CO BP Contractility ↑SV ↑CO ↑ BP 13 White Coat vs Masked HTN White Coat HTN Masked HTN • Elevated office BP but normal readings when measured with either ambulatory or home BP monitoring • Normal office BP despite elevated home or ambulatory BP monitoring • Utilize ambulatory BP monitoring or home BP monitoring J Am Coll Cardiol. 2018;71(19):e127-e248. 14 Drug induced Hypertension Drug Mechanism Increase in SBP NSAIDs Reduces prostaglandins, which possess a vasodilatory and natriuretic effect. This reduction in natriuresis and kidney arterial blood flow increases sodium and water retention and activates RAAS. ~5 mm Hg Typically more pronounced in patients with hypertension and impaired blood flow to the kidney Pseudoephedrine Phenylephrine Activate the sympathomimetic ~1 mm Hg nervous system by stimulating α-1 ~20 mm Hg adrenergic receptors on vascular smooth muscle, causing vasoconstriction Oral Contraceptives Estrogen activates RAAS and ~8 mm Hg hepatic angiotensinogen production resulting in sodium Kassel LE. Our own worst enemy: pharmacologic mechanisms of hypertension. Adv Chronic Kidney Dis. 2015. retention and volume expansion. https://doi.org/10.1053/j.ackd.2014.10.002 15 Antihypertensive Medications Thiazide diuretics Beta blockers ACEI/ARBs CCB Aldosteron e Antagonist s Alpha 1 blockers Central alpha 2 agonists Direct Vasodilato rs 16 Physiologic Effects of Antihypertensive Medications Blood pressure Peripheral Resistance Cardiac Output HR • βblockers • Some CCB Circulati ng regulator s • SV CC • βblockers • CCB RAS blockers • α1-blockers • Central α2agonists VR Blood volum e Venous tone • diuretics • α1• RAS blockers blockers • CCB Pathophysiology Of Herat disease . Second • RAS edition Wolters Kluwer Health Lippincott Direct innervatio n • α1-blockers • Central α2agonists • CCB & direct vasodilato rs VR: Venous return CC: Cardiac contractility SV: Stroke Volume HR: Heart Rate 17 From the Old to the New JNC8 2014 ACC/AHA 2017 JAMA. 2014;311(5):507-520. Am Coll Cardiol. 2018;71(19):e127-e248. 18 BP Classification BP Category SBP (mm Hg) DBP (mm Hg) Normal <120 and <80 Elevated 120-129 and <80 Stage 1 130-139 or 80-90 Stage 2 ≥140 or ≥90 Hypertension J Am Coll Cardiol. 2018;71(19):e127-e248. 19 Accurate Measurement of BP Key Steps for Proper BP Measurements Step 1 Properly prepare the patient Step 2 Use proper technique for BP measurements Step 3 Take the proper measurements needed for diagnosis and treatment of elevated BP/HTN Step 4 Properly document accurate BP readings Step 5 Average the readings Step Provide BP readings to patient J Am Coll Cardiol. 2018;71(19):e127-e248. 6 20 Comparison of Guidelines BP Goals ACC/ AHA 2017 JNC8 HTN <130/80 < 140/90 DM <130/80 <140/90 <140/90 <130/80 <140/85 CVD CKD <130/80 -- ASH/ ISH CHEP 2017 ESH/ ESC 2013 <140/90 <140/90 <140/90 <140/90 SBP <120 <140/90 <130/80 <140/90 <140/90 <140/90 <140/90 Disease specific guidelin es -ADA 2018 <140/90 ACC/AHA 2015 <140/90 Age ≥80: <150/90 KDIGO 2012 <130/80 with proteinuria ASH/ISH: American Society of Hypertension/International Society of Hypertension. CHEP: Canadian Hypertension AgeSociety ≥65 of Hypertension/European Society of Cardiology. ADA: American Education Program. ESH/ESC: European Elderl Age ≥60 Age ≥80 Age ≥80 SBP -- Association. KDIGO: Kidney -Diabetes Association. ACC/AHA: American College of Cardiology/American Heart 21 BP Goals in Patients With Other Comorbidities Specific Comorbidities BP Goal mm Hg Diabetes mellitus Chronic kidney disease Chronic kidney disease after renal transplantation Heart failure Stable ischemic heart disease Secondary stroke prevention Secondary stroke prevention (lacunar) Peripheral arterial disease <130/80 Am Coll Cardiol. 2018;71(19):e127-e248. 22 2017 ACC/AHA HTN Treatment Algorithm BP thresholds and recommendations for treatment and follow-up Normal BP <120/80 mm Hg Promote optimal lifestyle habits Elevated BP 120-129/<80 mm Hg Stage 1 HTN 130-139/80-89 mm Hg Nonpharmacolog ic therapy Clinical ASCVD or est 10-y CVD risk ≥10% No Reassess in 1 year Class I Class IIa m Coll Cardiol. 2018;71(19):e127-e248. Reassess in 3-6 mo Stage 2 HTN ≥ 140/90 mm Hg Yes Nonpharm therapy Nonpharm therapy and BP-lowering medication Nonpharm therapy and BP-lowering medication Reassess in 36 mo Reassess in 1 mo Reassess in 1 mo 23 Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 Recommendations for the treatment of confirmed hypertension in people with diabetes. *An ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB) is suggested to treat hypertension for people with coronary artery disease (CAD) or urine albumin-to-creatinine ratio 30–299 mg/g creatinine and strongly recommended for individuals with urine albumin-to-creatinine ratio ≥300 mg/g creatinine. **Thiazide-like diuretic; long-acting agents shown to reduce cardiovascular events, such as chlorthalidone and indapamide, are preferred. ***Dihydropyridine calcium channel blocker (CCB). BP, blood pressure. Adapted from de Boer et al. . 30 and 300 mg/24h Diabetes Care. 2022;46(Supplement_1):S158-S190. doi:10.2337/dc23-S010 24 Treatment Considerations BP response to attain goal adherence to lifestyle modifications and pharmacotherapy progression to hypertensionassociated complications and Drug-related toxicity. 25 Non-pharmacological Interventions Recommendations for Nonpharmacological Interventions Weight loss 1 mm Hg for every 1 kg reduction A heart-healthy diet, such as the DASH (Dietary Approaches to Stop Hypertension) diet Sodium reduction <1500mg/d, but aim for a 1000mg COR: I reduction LOE: A Potassium supplementation unless contraindicated by the presence of CKD or use of drugs that reduce potassium excretion. Increased physical activity with a structured exercise program no more than 2 (men) and 1 (women) standard drinks per day Am Coll Cardiol. 2018;71(19):e127-e248. Approx. Impact on SBP -5 mm Hg -11 mm Hg -5/6 mm Hg -4/5 mm Hg -5/8 mm Hg -4 mm Hg 26 General Principles of Drug Therapy COR LOE Recommendations I ASR First-line agents include thiazide diuretics, CCBs, and ACE-i/ARBs. III: Harm A Simultaneous use of an ACE-i, ARB, and/or renin inhibitor is potentially harmful and is not recommended. J Am Coll Cardiol. 2018;71(19):e127-e248. 27 First-line Options for Uncomplicated HTN ACE-i Thiazide Diuretics Dihydropirid ine CCB Firstline ARB Which of these options would we consider for JP? 28 Thiazides: Site of Action 1 4 5 2 3 at. Rev. Cardiol. doi:10.1038/nrcardio.2014.215 https://www.cvpharmacology.com/diuretic/diur 29 Thiazide/Thiazide-like Diuretics MOA: Inhibit Na+ reabsorption in the distal convoluted tubules of the nephron leading to an increase in sodium and water excretion. Generic/Brand Hydrochlorothiazide (HCTZ) / Microzide Chlorthalidone/ Thalitone Metolazone / Zaroxolyn/ Indapamide / Lozol 12.5 mg, 25 mg, 50 25 mg, 50 mg mg Daily Daily Contraindicatio • Anuria • Severe electrolyte imbalance ns/ • Renal dysfunction (CrCl < 30 precautions ml/min) • Gout 2.5 mg, 5 mg, 10 mg Daily 1.25 mg, 2.5 mg Daily Common Side Effects Pregnancy Category: B Dosing Rash, sun sensitivity, hypokalemia, hypercholesterolemia hyponatremia, hypomagnesemia, hyperuricemia, hypercalcemia Place in Therapy • 1st line hypertension drug (uncomplicated HTN) therapy alone or in combination • Reduction in cardiovascular events and mortality benefits • Enhances the efficacy of other antihypertensive drugs when used in combination Potassium Sparing Diuretics MOA: Mineralocorticoid antagonists. Competes to inhibit interaction of aldosterone with mineralocorticoid receptor. Generic / Brand Spironolactone / Aldactone Eplerenone / Inspra Triamterene / Dyrenium Dosing 25 mg, 50 mg, 100 mg Daily to BID 25mg, 50 mg Daily to BID 50 mg, 100 mg Daily to BID Monitor SCr and K monthly for the first 2 months of therapy and after dose titrations when used solely for HTN indication. When used with concomitant HFrEF, monitor SCr and K on day 3, day 7, and monthly for the first 3 months after initiation or titration and periodically thereafter. Contraindication • eGFR <30ml/min Place in Therapy: • K ≥5.0 mEq/L( aldosterone • Resistant HTN s • Patients with HTN and HFrEF or HFpEF antagonists) • Anuria Common Side Effects Hyperkalemia, Hyponatremia, Hypotension, gynecomastia (more in spironolactone) Pregnancy Category: C Monitoring Parameters BP, Electrolytes Drug Interactions: NSAIDs Loop Diuretics MOA: In thick ascending loop of Henle these medications inhibit the Na+/K+/2CL- pump cotransporter leading to decreased sodium and chloride reabsorption. The decreased retention of sodium and chloride leads to a decrease in water reabsorption Generic/Brand Furosemide/Lasix Torsemide/Bumex Bumetanide/Demadex Dosing 20 mg, 40 mg, 80 mg BID 2.5 mg, 5 mg, 10 mg Daily 0.5 mg,1 mg, 2 mg BID Differences shorter duration of action Bioavailability variable Available both IV and PO Longer duration of action Better bioavailability (90%) Better bioavailability (90%) Available both IV and PO Contraindications • Anuria • History of hypersensitivity( or Sulfonamides) Place in therapy: • Heart failure • Severe CKD (eGFR <30 mL/min/1.73 m2) Common Side Effects Hypokalemia, Ototoxicity, Hyperuricemia hyponatremia, hypochloremic alkalosis, Ototoxicity Pregnancy Category: C Monitoring Parameters BP, potassium, SCr, BUN, Uric Acid, sodium Drug Interactions: NSAID’s, Lithium, Aminoglycosides Renin Angiotensin Aldosterone System (RAAS) Low renal volume/pressu re Angiotensinogen Angiotensin I Bradykinin ANP BNP Substance P Angiotensin II Inactive peptides Renin ACEInhib itor Vasodilation ↓Sympathetic tone ↓ Aldosterone ↓BP ↓Fibrosis ↓Hypertrophy Diuresis/ natriuresis ARB AT1 receptor AT2 receptor Vasoconstriction Vasodilation Aldosterone Stimulate NO production + Na retention LV remodeling Catecholamine release Adapted from Applied Therapeutics: the Clinical Use of Drugs 11th Edition 33 ACE Inhibitors (-pril) MOA: Competes with angiotensin I for its binding site on the angiotensin-converting enzyme (ACE). As a result, the drug blocks the conversion of angiotensin I to angiotensin II. Generic/Brand Lisinopril/Zestril Dosing 2.5 mg, 5 mg, 10 5 mg, 10 mg 2.5 mg, 5 mg 12.5 mg, 25 mg mg, 20 mg, 40 mg 10 mg, 20 mg 50 mg, 100 mg 20 mg, 30 mg, 40 Once Daily Once Daily Once Daily mg Once Daily • Reduce cardiovascular morbidity and mortality in patients with left ventricular dysfunction • Nephroprotective and can reduce proteinuria • HF LVEF of 40% or less • CAD, Post-MI, recurrent stroke prevention • Concomitant ARB therapy Place in Therapy: • Bilateral renal artery stenosis • 1st line hypertension drug therapy • Chronic Kidney Disease • H/O angioedema Advantages Contraindication s Benazepril/Lotensin Enalapril/Vasotec Captopril/Capoten Common Side Effects Dry cough, hypotension, hyperkalemia, angioedema, increased serum creatine Pregnancy Category: D BBW: Fetal Toxicity Monitoring SCr, BUN, K, Na, BP Drug Interactions: NSAIDs, Angioedema 35 http://www.pharmacytimes.com/publications/issue/2011/october Albuminuria • Urine albumin-to-creatine ratio (UACR) is most frequently applied to diagnose albuminuria. In spot urine specimens, normal level of UACR is below 30 mg/g. Catego ry ACR (mg/g) Meaning A1 < 30 Normal to mildly increased A2 30-300 Moderately increased A3 > 300 Severely increased 36 Comparison of Angiotensin converting enzyme inhibitors AGENT DOSE (mg) ONSET (hrs) PEAK EFFECT (hrs) DURATION (hrs) Captopril (Capoten) 6.25-150 in 2 or 3 doses 0.25 1-2 4-6 Enalapril (Vasotec) 2.5 - 20 qd - bid 1-4 4-8 12 -24 Lisinopril (Zestril, Prinivil) 2.5 - 20 qd 1 7 24 Quinapril (Accupril) 5-40 mg qd-bid 1/2 - 1 2-4 12-24 Fosinopril (Monopril) 10-40 mg in 1 or 2 doses 1 2-6 24 Benazepril (Lotensin) 10 - 40 mg in 1-2 doses 1 2-4 24 Moexipril (Univasc) 7.5-30 mg in 1-2 doses 1-2 3-6 24 Trandolapril (Mavik) 1-4 mg qd 4 24 Ramipril (Altace) 2.5 to 20 mg qd2 6-8 24 *FDA approved indications vary. Refer to individual product prescribing information 37 AT1 Antagonists (-sartan) MOA: Inhibit angiotensin receptors (AT1) and interferes with the binding of formed angiotensin II to its endogenous receptor. Generic/Brand Losartan/ Cozaar Olmesartan/ Benicar Candesartan/ Telmisartan/ Atacand Micardis Valsartan/ Diovan Dosing Irbesartan/ Avapro 25 mg, 5 mg, 20 mg 4 mg, 8 mg 20 mg, 40 40 mg, 80 75 mg, 150 50 mg 40 mg 16 mg, 32 mg mg mg 100 mg Once Daily mg 80 mg 160 mg, 320 300 mg Once Once Daily Once Daily mg Once Daily Daily Once Daily • Less to no risk of dry cough Advantages • Nephroprotective and can reduce proteinuria • Decrease progression of nephropathy in patients with Type 2 Diabetes Mellitus Contraindicatio • Prior angioedema Place in Therapy: • Pregnancy (Teratogenic) • 1st line hypertension drug therapy ns • Concomitant ACEi therapy Common Side Effects Hypotension, headache, hyperkalemia, increased serum creatine, angioedema (rare) Pregnancy Category: D BBW: Fetal Toxicity Monitoring Parameters SCr, BUN, K, Na, BP Drug Interactions: NSAIDs, Pseudoephedrine Angiotensin II Receptor Inhibitors DRUG BRAND NAME DAILY DOSE Losartan Cozaar 25 - 100 mg in 1-2 doses Valsartan Diovan 80 - 320 mg QD Telmisartan Micardis 40 - 80 mg QD Candesartan Atacand 8 - 32 mg QD Irbesartan Avapro 150 - 300 mg QD Olmesartan Benicar 20 - 40 mg QD Eprosartan Teveten 400 – 800 mg 1-2 doses *FDA approved indications vary. Refer to individual product prescribing information 39 Calcium Channel Blockers • MOA: Bind to L-type voltagegated channels located on the vascular smooth muscle, cardiac myocytes, and cardiac nodal tissue (sinoatrial and atrioventricular nodes) to inhibit Ca2+ influx. • Effects: dilation of coronary and peripheral arteries, decreased myocardial force generation (negative inotropy), decreased heart rate (negative chronotropy), and decreased conduction velocity within the heart (negative dromotropy), particularly at the atrioventricular node. Binding 1 Activates 2 MLCK Enhanced Phosphorylation 3 4 Promotes Myosin-Actin interaction 40 Calcium Channel Blockers (Dihydropyridines) (dipine) MOA: Block L-type calcium channels in the smooth muscle of blood vessels. Act by relaxing the smooth muscle in the arterial wall, decreasing total peripheral resistance, and hence reducing blood pressure Generic/Brand Amlodipine/ Norvasc Nifedipine/ Procardia Felodipine ER/ Plendil Nicardipine SR/ Cardene Dosing 2.5 mg, 5 mg, 10 mg Once Daily • Concomitant use 30 mg, 60 mg, 90 mg Once Daily 2.5 mg, 5 mg, 10 mg Once Daily 45 mg, 60 mg, 120 mg BID Contraindication s of beta blockers Common Side Effects Peripheral edema, orthostasis, reflex tachycardia Monitoring Parameters BP Place in Therapy: • Option as first-line therapy for most patients with HTN • Recommended in African American patients • Potent blood pressure lowering • Improve anginal symptoms Drug Interactions: May increase serum concentrations of other CYP3A4 substrates. (Simvastatin, Lovastatin, Carbamazepine, Cyclosporine, Calcium Channel Blockers (Non-Dihydropyridines) MOA: Act as a potent vasodilator of coronary vessels, increasing blood flow and decreasing the heart rate by strong depression of atrioventricular (AV) node conduction. In addition, act as a potent vasodilator of peripheral vessels, reducing peripheral resistance and afterload. They have negative inotropic effects. Generic/Brand Verapamil/Verelan SR, ER Diltiazem/Cardizem SR, ER Dosing 40 mg, 80 mg, 120 mg, 180mg, 240 mg Once Daily • Non-DHPs are moderate CYP3A4 inhibitors • Heart failure with reduced EF • Hypotension (SBP <90) • Second- or third-degree AV block • Sick sinus syndrome 120 mg, 180 mg, 240 mg, 300 mg Once Daily Common Side Effects Peripheral edema, dizziness, bradycardia, constipation (More common with verapamil) Use with caution in patients receiving concomitant β-blocker therapy Pregnancy Category: C Monitoring Parameters BP, HR Drug Interactions: May increase serum concentrations of other CYP3A4 substrates. Contraindicatio ns Place in therapy: • 1st line hypertension drug therapy • in patients with concomitant conditions (e.g., atrial fibrillation/tachycardia) who would benefit from these medications Effects of Calcium Channel Blocking Agents VERAPAMIL DILTIAZEM DHPS* SVR ¯¯ ¯ ¯¯¯ CORONARY VASODILATION ­↑­↑ ­↑ ­↑↑↑ CONTRACTILITY ¯¯ ¯ 0 HR ¯ ¯ ­0, ↑ AV NODAL CONDUCTION ¯¯ ¯ 0 *NOTE: Short acting dihydropyridines generally not used to treat angina because their powerful systemic vasodilator and pressure lowering effects can lead to reflex cardiac stimulation (tachycardia and increased inotropy), which can dramatically increase myocardial oxygen demand 43 Calcium Channel Blockers DRUG BRAND NAME USUAL DOSE MAXIMUM DAILY DOSE Verapamil Calan, Isoptin, Veralan (all RR, SR) 80 - 120MG TID 120 - 240 mg qd bid 480 mg Diltiazem Cardizem Cardizem SR Cardizem CD Dilacor XR Tiazac Er 30-120 mg tid/ qid 60-180 mg bid 120-360 mg qd 120-480 mg qd 120-480 mg qd 480 mg Nifedipine Procardia Procardia XL Adalat 10 - 30 mg tid 30 - 90 mg qd 120 mg Nicardipine Cardene 20 mg tid 120 mg Amlodipine Norvasc 2.5-10 mg qd 15 mg Felodipine Plendil 2.5-10 mg qd 15 mg Isradipine DynaCirc 2.5 mg bid 20 mg Nisoldipine Sular 20-40 mg qd 60 mg Dihydropyridin es 44 Case 1 TY, a 43 y.o. female, is new to your clinic. BP mmHg Medications For Recently taken at a grocery store 160/88 Norethindrone-ethinyl estradiol 1mg/0.035mg Birth Control Today taken twice at clinic 138/88 Ibuprofen 400mg BID Headache Pseudoephedrine 30mg TID Congestion Lab BMI normal 31.2 kg/m2 SH Coffee ≥4 cups qam; beer ≈ 4 drinks qhs Questions 1. What are the key things to consider in this case? 3. What is her BP goal? 2. How would you classify her BP 4. What is the best intervention for her45 Patient Case 1 • What are the key things to consider in this case? • What additional information would you need at this visit? 46 Patient Case 1 • How would you classify her blood pressure category? • What is her blood pressure goal? • How do you evaluate the patients risk to determine treatment options? 47 2017 ACC/AHA HTN Treatment Algorithm BP thresholds and recommendations for treatment and follow-up Normal BP <120/80 mm Hg Promote optimal lifestyle habits Elevated BP 120-129/<80 mm Hg Stage 1 HTN 130-139/80-89 mm Hg Nonpharmacolog ic therapy Clinical ASCVD or est 10-y CVD risk ≥10% No Reassess in 1 year Class I Class IIa m Coll Cardiol. 2018;71(19):e127-e248. Reassess in 3-6 mo Stage 2 HTN ≥ 140/90 mm Hg Yes Nonpharm therapy Nonpharm therapy and BP-lowering medication Nonpharm therapy and BP-lowering medication Reassess in 36 mo Reassess in 1 mo Reassess in 1 mo 48 Hydralazine/Apresoline MOA: Direct vasodilation of arterioles: inhibit inositol trisphosphate (IP3)-induced release of calcium from the smooth muscle cells This reduces peripheral vascular resistance and leads to a compensatory baroreceptor-mediated release of epinephrine and norepinephrine. Act as a vasodilator primarily in arteries and arterioles Dosing 10 mg, 25 mg, 50 mg, 100 mg TID to QID Contraindications • Dissecting aortic aneurysm, hypersensitivity to hydralazine Place in therapy: • Usually viewed as fourth or fifth-line agent for HTN • May be useful for resistant HTN • Acute hypertensive emergencies (IM/IV) • Preeclampsia • CHF • In combination with nitrates Common Side Effects headache, flushing, reflex tachycardia, angina, druginduced lupus-like syndrome Pregnancy Category: C Monitoring Parameters BP, HR, LFT's, signs of SLE (systemic lupus erythematosus) Beta -Blockers https://www.cvpharmacology.com/cardioinhibitory/beta-blockers 50 β Blockers: (-lol) β1-Selective MOA: Cardio selective (beta1-selective) beta-blocker that results in negative chronotropic and inotropic effects that decrease heart rate and cardiac output, reduction of sympathetic outflow to the periphery, and suppression of renin activity. Generic/Brand Metoprolol tartrate/ Atenolol/Tenormin Lopressor Metoprolol Succinate ER / Toprol Bisoprolol/Zebeta Nebivolol/Bystolic Dosing 25 mg, 50 mg 25 mg, 50 mg 100 mg, 200 mg 100 mg • Cardiogenic shock • Bradycardia • Second- or third-degree AV block • Avoid in patients with an active asthma exacerbation or COPD 5 mg 10 mg 2.5 mg, 5 mg 10 mg, 20 mg Common Side Effects Bradycardia, , CNS effects (insomnia, fatigue Taper shorter-acting agents rather than abruptly discontinuing them to avoid rebound anginal and hypertensive effects. Pregnancy Category: C Monitoring BP, HR, glucose Drug Interactions: Clonidine, CCB’s, Contraindication s Place in therapy: • Third to fourth line for HTN • First line with CV comorbidities(HF, MI) β Blockers: (-lol) Non-Selective MOA: Nonselective beta-adrenergic blocker (class II antiarrhythmic); competitively blocks response to beta1- and beta2-adrenergic stimulation which results in decreases in heart rate, myocardial contractility, blood pressure, and myocardial oxygen demand. Generic/Brand Propranolol/ Inderal Nadolol/Corgard Carvedilol/Coreg Labetalol/Trandate Dosing 10 mg, 20 mg, 40 mg, 60 mg, 80 mg 20 mg 40 mg 3.125 mg, 6.25 mg 12.5 mg, 25 mg 100 mg, 200 mg 300 mg Advantages Anxiety management Hyperthyroidism Hyperthyroidism Liver disease Activity at α1, β1, β2 PLUS antioxidant, antiinflammatory. Used in pregnancy Contraindication s • Contraindicated in cardiogenic shock • Bradycardia • Second- or third-degree AV block • Avoid in patients with an active asthma exacerbation Common Side Effects Bradycardia, arrythmias, CNS effects Pregnancy Category: C (insomnia, fatigue), headache, dizziness, nausea, hypotension Place in therapy: • Labetalol in pregnancy • Carvedilol in HFrEF Alpha-adrenoceptor Antagonists (alpha-blockers) α1 blockade = prevention of compensatory vasoconstriction of systemic vasculature leading to decreased blood pressure Selective 2nd generation (Bind to IP3 Sensitive Ca2+ Channels on ER → ↑Cytosolic Ca++) IP3 = Inositol trisphosphate http://cvpharmacology.com/vasodilator/vasodilators.htm 53 Alpha Blockers MOA: These drugs block the effect of sympathetic nerves on blood vessels by binding to alpha1-adrenoceptors located on the vascular smooth muscle, decrease total peripheral resistance and venous return. Generic/Brand Prazosin/Minipress Terazosin/Hydrin Doxazosin/Cardura Dosing 1-15 mg BID to TID 1-10 mg QD to BID 1-4 mg daily Contraindication s • Alpha blockers have not been shown to be beneficial in heart failure or angina and should not be used in these conditions. Common Side Effects • Sodium and fluid retention • Dizziness, orthostatic hypotension or “1st dose syncope” (due to loss of reflex vasoconstriction upon standing) • Start with a very low dose. The patient should consider taking the first dose at night while in bed. Titrate slowly over time as needed. Monitoring Parameters • BP Place in therapy: • In general, reserved for hypertensive male patients with concomitant benign prostatic hyperplasia • Usually viewed as fourth- or fifth-line agent for HTN Centrally Acting Sympatholytic http://cvpharmacology.com/vasodilator/ vasodilators.htm 55 Centrally Acting Sympatholytic MOA: Block sympathetic activity by binding to and activating alpha-2 (α2)-adrenoceptors within the brain. which decreases sympathetic outflow, cardiac output, and peripheral vascular resistance, lowering blood pressure and heart rate Generic/Brand Clonidine (tablets and transdermal patch) / Catapres α-methyldopa/Aldomet Guanfacine/Intuniv Dosing * Initial Dose : 0.1 mg tablet twice daily 250mg, 500mg BID or TID 1mg - 2mg daily Advantages • Clonidine – most often used for resistant hypertension • Methyldopa – hypertension in pregnancy Contraindications/ precautions • Methyldopa is contraindicated in patients with active hepatic disease, such as acute hepatitis and active cirrhosis. • Clonidine: Rebound HTN possible if withdrawn too quickly, especially if taking concomitant β-blocker (except for carvedilol and labetalol, because of unopposed α-stimulation) • Drowsiness, dizziness, headache, dry mouth, bradycardia(clonidine) • Anemia, liver disorders – (α-methyldopa) • HR, BP, CBC Common Side Effects Monitoring Parameters Clonidine Dosing* (cont.) Clonidine • Initial Dose : 0.1 mg tablet twice daily • Maintenance Dose : further increments of 0.1 mg per day may be made at weekly intervals. Most commonly doses range from 0.2 mg to 0.6 mg per day given in divided doses. However, doses greater than 2.4 mg are rarely employed. Clonidine patch • Initial Dose : Start with #1 patch. If after one or two weeks the desired reduction in blood pressure is not achieved, increase the dosage by adding another #1 patch or changing to a larger system. • Maintenance Dose: An increase in dosage above two #3 patches is usually not associated with additional efficacy. 57 Clonidine Dosing (cont.) 58 Patient Case 1 • What are the key things to consider in this case? • Lifestyle • Diet • What additional information would you need at this visit? 59 Patient Case 1 • How would you classify her blood pressure category? • What is her blood pressure goal? • How do you evaluate the patient's risk to determine treatment options? 60 2017 ACC/AHA HTN Treatment Algorithm BP thresholds and recommendations for treatment and follow-up Normal BP <120/80 mm Hg Promote optimal lifestyle habits Elevated BP 120-129/<80 mm Hg Stage 1 HTN 130-139/80-89 mm Hg Nonpharmacolog ic therapy Clinical ASCVD or est 10-y CVD risk ≥10% No Reassess in 1 year Class I Class IIa m Coll Cardiol. 2018;71(19):e127-e248. Reassess in 3-6 mo Stage 2 HTN ≥ 140/90 mm Hg Yes Nonpharm therapy Nonpharm therapy and BP-lowering medication Nonpharm therapy and BP-lowering medication Reassess in 36 mo Reassess in 1 mo Reassess in 1 mo 61 Patient Case What is the best intervention for this patients HTN today? 62 HTN and Pregnancy Hypertensive disease occurs in 5% to 8% of all pregnancies and is a major cause of maternal and perinatal morbidity and mortality Hypertension in pregnancy is defined as a systolic BP of at least 140 mm Hg or a diastolic BP of at least 90 mm Hg on two separate occasions at least 6 hours apart Zeind, Caroline, S. et al. Applied Therapeutics. Available from: VitalSource Bookshelf, (12th Edition). Wolters 63 HTN and Pregnancy • Chronic hypertension is defined as hypertension diagnosed before conception or before the 20th week of gestation, or hypertension persisting beyond 12 weeks postpartum • Preeclampsia is a pregnancy-specific condition usually occurring after 20 weeks’ gestation and consisting of hypertension with proteinuria • Preeclampsia superimposed on chronic hypertension • Gestational hypertension 64 Antihypertensive Agents in Pregnancy Drug Methyldopa Dose 750-1000mg/day start twice a day, increase up to 2-3g/day, divided in three to four doses if needed Labetalol 200-400mg/day start, increase up to 2400mg/day, divided into two or sometimes three doses Other βblockers Various Nifedipine, long- 30 mg/day start, increase to up to acting 120 mg/day, once daily Comments Longest safety record in pregnancy. Considered a first-line drug. Dizziness, sedation, and lack of energy are common symptoms, which tend to resolve. Can cause liver toxicity. Low breast milk concentrations, so considered safe in breast-feeding. Combined α- and β- receptor antagonist properties. Considered a first-line drug. Increasingly preferred to methyldopa owing to fewer side effects. Neonatal effects could include bradycardia and hypotension. Low concentration in breast milk and generally considered safe in breast-feeding. Atenolol, in particular, associated with decreased placental weight and IUGR. IUGR thought to be related to β- blocker- induced increase. Limited pregnancy data on nifedipine or other calcium channel blockers such as verapamil, diltiazem, and amlodipine. Concentrations of nifedipine in breast milk are low and considered compatible with breast-feeding Zeind, Caroline, S. et al. Hypertension Applied Therapeutics. Available from: VitalSource Bookshelf, (12th Edition). Wolters Kluwer Health, 2023. 65 Test your knowledge! Condition Drug of Choice for HTN HFrEF Angina Proteinuria African American CAD Migraine Uncomplicated HTN Pregnancy DM 66 Management of risk factors Accurate measurement of BP Summary Identifying other caused of HTN Establishing realistic goals Removing offending agents Appropriate therapy based on patient specific factors 67 68 Case 2 Patient C.S. was recently diagnosed with hypertension and was prescribed Lisinopril 20 mg once daily. Soon after the patient reports experiencing a dry, persistent cough. Current BP log of past three days: 120/72 mmHg, 116/68 mmHg, 122/74 mmHg. Which of the following options are possible next steps? (Select all that apply) A. Rule out all other causes of cough B. Switch to Losartan 50 mg daily C. Decrease Lisinopril to 10 mg daily D. Do nothing, continue to monitor 69 Case 2 (cont.) C.S. was switched to Losartan 50 mg daily. What are the key monitoring parameters for Losartan? A. Potassium, SCr, BP, angioedema B. Potassium, uric acid, HR, weight C. Potassium, SCr, HR, angioedema D. Potassium, SCr, INR, weight 70 Recall Question! Which of the following is a main difference between ACEis and ARBs? A. ACEis cause less hypokalemia than ARBs B. ACEis are preferred for proteinuria over ARBs C. ARBs cause an acute bump in serum creatinine after initiation, compared to ACEis D. ARBs can potentially cause less angioedema compared to ACEis 71 Case 3 Patient J.M. 40-year-old male with a PMH of hypertension for 2 years and is currently on Amlodipine 10 mg daily. He has been adherent to their medication regimen; however, his blood pressure remains elevated at 150/95 mmHg, HR 70 BMP. Which of the following would be best? A. Start HCTZ 25 mg daily and monitor potassium and serum creatinine B. Start Metoprolol Succinate 25 mg daily and monitor HR C. Increase Amlodipine to 15 mg daily and monitor BP D. Start Verapamil 80 mg daily and monitor BP and HR 72 Recall Question! Which of the following statement/s are true? (Select all that apply) A. Spironolactone is contraindicated in eGFR < 30 ml/min and K ≥ 5 mEq/L B. Spironolactone can be used for resistant hypertension. C. Electrolytes should be monitored within 3 day of initiation. D. Spironolactone causes more gynecomastia compared to eplerenone. 73 Questions? 74