Cardiac Medication Review Idaho Society of Health-Systems Pharmacists Cardiac Medication Review Lindsay Crawford, PharmD & Lindsey Hunt, PharmD PGY1 Pharmacy Residents Boise VA Medical Center March 6, 2016

Disclosures The presenters have no disclosures or conflicts of interest Medications discussed off label are identified throughout the presentation

Learning Objectives List various classes of medications used for various cardiac conditions Briefly explain basic pathophysiology of different cardiac conditions Recognize errors associated with dispensing cardiac medications Identify various formulations available and conversions made for cardiac medications

Cardiac Conditions Overview CARDIO = HEART Pressure abnormality  Hypertension Conduction abnormality  Arrhythmias Structural abnormality  Heart Failure VASCULAR = VESSELS Arterial Cerebrovascular disease (stroke, TIAs) Peripheral arterial disease Coronary artery disease (angina, myocardial infarction) Venous Thromboembolism (DVTs, PEs) OTHER Infections, autoimmune disorders, congenital disease Coronary artery disease is narrowing of coronary arteries which causes progressive thickening/plaque rupture of arterial wall leading to angina or myocardial infarction

Terminology Hypertension Arrhythmias Heart Failure Hypertension: >140/90 from 2+ BP measurements per visit at 2+ visits Hypertensive Crisis: severe elevations in blood pressure with or without signs of end organ dysfunction Caused by: genetics (~30%), age, gender, ethnicity, stress, environment, dietary factors, drugs, diseases Consequences: Coronary artery disease, heart failure, chronic kidney disease, stroke, intracerebral hemorrhage, transient ischemic attack (TIA), peripheral arterial disease (PAD), atrial flutter, mild cognitive impairment (MCI) Multifactorial Dietary factors- high salt, obesity, alcohol Drugs- cocaine, caffeine, adrenergics like pseudoephedrine, beta agonists, tobacco uses, NSAIDs Diseases: hyperaldosteronism, renal artery stenosis, pheochromocytoma, diabetes, sleep apnea Physiology: anxiety, pain, exercise

Pathophysiology Hypertension Arrhythmias Heart Failure Sites of BP control: In most cases, elevated blood pressure is associated with an overall increase in resistance to flow of blood through arterioles, whereas cardiac output is usually normal. Physiologically, in both normal and hypertensive individuals, blood pressure is maintained by moment-to-moment regulation of cardiac output and peripheral vascular resistance, exerted at three anatomic sites: arterioles, postcapillary venules (capacitance vessels) heart. the kidney, contributes to maintenance of blood pressure by regulating the volume of intravascular fluid. Baroreflexes, mediated by autonomic nerves, act in combination with humoral mechanisms, including the renin-angiotensin-aldosterone system, to coordinate function at these four control sites and to maintain normal blood pressure. Finally, local release of vasoactive substances from vascular endothelium may also be involved in the regulation of vascular resistance. For example, endothelin-1 constricts and nitric oxide dilates blood vessels.

Antiadrenergic agents Hypertension Arrhythmias Heart Failure Antiadrenergic agents Antiadrenergic agents CNS centrally acting alpha-2 agonists Clonidine Methyldopa Guanfacine Alpha & Beta Blockers Beta Selective B1: Metoprolol Esmolol Nebivolol Atenolol Bisoprolol Non-Selective: Propranolol Alpha 1 Doxazosin Terazosin Prazosin Non Selective Carvedilol Labetalol Vasodilators Angiotensin/ renin agents Diuretics

Alpha-2 Agonists Hypertension Arrhythmias Heart Failure Mechanism: Acts on CNS neurons to prevent the release of adrenergic molecules Medications: Clonidine Methyldopa Guanfacine Guanabenz

Alpha-2 Agonists: Clonidine Hypertension Arrhythmias Heart Failure Alpha-2 Agonists: Clonidine Usual total daily dose range 0.1 - 0.8 mg (BID dosing) Dose Conversions: Clonidine ER ≠ IR on mg:mg conversion Switching from oral to patch will require a 3 day taper of oral clonidine Other indications: pain management (Duraclon® - epidural solution), nicotine withdrawal symptoms [off label] Drug Names Generic Routes Dosage Forms Catapres® Yes Tablet IR 0.1, 0.2, 0.3 mg [scored] Kapvay® Tablet ER 0.1 mg Catapres-TTS® Transdermal patch (7d) 0.1, 0.2, 0.3 mg/24 hr clonidine Oral solution Compounded

Alpha-2 Agonists: Methyldopa Hypertension Arrhythmias Heart Failure Alpha-2 Agonists: Methyldopa Usual total daily dose range 250-1000mg (BID dosing) Special Administration: Dose increases should occur in the evening Notable adverse effects Same as clonidine Hepatic dysfunction (watch for fever/flu-like symptoms) Autoimmune disorders Drug Names Generic Routes Dosage forms methyldopa Yes Oral Tablet IR 250 mg, 500 mg IV solution 250mg/5mL Oral suspension compounded

Alpha-1 Blockers Hypertension Arrhythmias Heart Failure Mechanism: Blocks alpha 1 receptors to cause vasodilation of the arteries and veins Medications: Prazosin (Minipress®) Doxazosin (Cardura®) Terazosin (Hytrin®) Phentolamine Alpha 1 & Alpha 2

Alpha-1 Blockers - Doxazosin Hypertension Arrhythmias Heart Failure Alpha-1 Blockers - Doxazosin Usual total daily dose range Doxazosin IR 1-16mg (QDaily dosing) Other indications: BPH (ER form is FDA approved for BPH) Doses should be initiated in the evening Drug Names Generic Routes Dosage forms Cardura® Yes Oral Tablet IR [scored] 1, 2, 4, 8 mg Cardura XL® No Oral Tablet ER (24 hr) 4, 8 mg

Alpha-1 Blockers - Prazosin Hypertension Arrhythmias Heart Failure Alpha-1 Blockers - Prazosin Usual total daily dose range HTN: Prazosin 2-20mg (BID-TID dosing) PTSD: 1-15mg (QHS dosing) Other indications: PTSD-related nightmares and sleep disruption [off label] Drug Names Generic Routes Dosage forms Minipress® Yes Oral capsule IR 1, 2, 5 mg

Alpha Blocker - Phentolamine Hypertension Arrhythmias Heart Failure Alpha Blocker - Phentolamine Usual total daily dose range HTN Crisis [off label]: 5-15mg IV/IM 1-5mg bolus + continuous infusion of 1-40mg/hr Special indications: Cocaine overdose, pheochromocytoma Other Uses Extravasation of norepinephrine Drug Names Generic Routes Dosage forms phentolamine Yes IM, IV 5mg/mL

Beta Blockers Hypertension Arrhythmias Heart Failure Mechanism: Block cardiac contractility Decrease HR (Beta 1) Block secretion of renin Medications: Metoprolol (Lopressor®, Toprol®) Beta 1 selective Propranolol (Inderal®) Beta 1 & Beta 2 Esmolol (Brevibloc®) Many others

Beta Blockers - Metoprolol Hypertension Arrhythmias Heart Failure Beta Blockers - Metoprolol Usual total daily dose range IR: 100-200mg (BID) ER: 100-400mg (Qdaily) IV: 1.25-5mg+ Q6-12h Other uses: Heart failure (ER), A. Fib, post-MI, angina Dose conversions ER = IR mg:mg POIV = 2-2.5:1 total daily dose Drug Names Generic Routes Dosage forms Metoprolol tartrate (Lopressor®) Yes IV Oral IR tablets 1mg/mL, 5mg/5ml 25, 50, 100mg [scored] Metoprolol succinate (Toprol®) Oral ER tablets 25, 50, 100, 200 mg [scored]

Beta Blockers - Propranolol Hypertension Arrhythmias Heart Failure Beta Blockers - Propranolol Usual total daily dose range IR: 40-160mg IR BID ER: 120-160mg QD Other Uses Essential tremor, migraine prophylaxis, pheochromocytoma, post MI, stable angina, arrhythmias, akathisia [off-label], performance anxiety [off label], thyroid storm [off label], tremor [off label], variceal hemorrhage prophylaxis [off label] Drug Names Generic Routes Dosage forms Propranolol Yes IV 1mg/ml Oral solution 20mg/5mL, 40mg/5mL Oral IR tablets 10, 20, 40, 60, 80 mg Propranolol (Inderal LA®) Oral ER capsules (24 hr) 60, 80, 120, 160 mg

Beta Blockers - Esmolol Hypertension Arrhythmias Heart Failure Beta Blockers - Esmolol Usual total daily dose range HTN Crisis: Min 1: IV 250-500 mcg/kg Min 2-5: IV 50-100 mcg/kg/min Other uses Tachycardia, arrhythmias Special indications During surgery, aortic dissection Dosing varies, but this is an example If extravasation occurs stop infusion immediately and disconnect with needle in place; gently aspirate extravasated solution (DO NOT FLUSH THE LINE) remove needle elevate extremity Drug Names Generic Routes Dosage forms Esmolol Yes IV 10mg/mL [PF] 10mg/mL, 100mg/10mL Esmolol HCl in NaCl (Brevibloc®) No 2000mg (100mL); 2500mg (250mL)

Alpha & Beta Blockers Hypertension Arrhythmias Heart Failure Mechanism: Block cardiac contractility Decrease HR (Beta 1) Block secretion of renin Vasodilation of veins Medications: Labetalol Carvedilol (Coreg®)

Alpha & Beta Blockers - Labetalol Hypertension Arrhythmias Heart Failure Alpha & Beta Blockers - Labetalol Usual total daily dose range HTN crisis: IV- bolus & infusion 20-80mg at 10 min intervals (MAX 300mg) 0.5-2 mg/min IV infusion Hypertension: PO - 100-300 mg BID Drug Names Generic Routes Dosage forms Labetalol Yes IV 5 mg/mL Oral tabs Oral suspension 100, 200, 300 mg Compounded

Alpha & Beta Blockers- Carvedilol Hypertension Arrhythmias Heart Failure Alpha & Beta Blockers- Carvedilol Usual dosing ranges HTN doses: 6.25 mg BID Heart failure target: 25-50mg IR BID Other Uses Heart failure, angina [off label], A fib [off label] Drug Names Generic Routes Usual total dose range Carvedilol Yes Oral IR tab- 3.125, 6.25, 12.5, 25mg 3.125-50mg BID Carvedilol (Coreg CR®) No Oral ER tab- 10, 20, 40,80mg 10-80 mg Qdaily

Vasodilators Hypertension Arrhythmias Heart Failure Antiadrenergic agents Vasodilators Arterial Hydralazine Minoxidil Arterial and Venous Calcium Channel Blockers Nitroprusside Nitroglycerin Angiotensin/ renin agents Diuretics

Vasodilators Hypertension Arrhythmias Heart Failure Mechanism: Many; dilates arteries and/or veins Medications: Arterial Hydralazine Minoxidil Arterial & Venous Nitroprusside Nitroglycerin Calcium Channel blockers (CCBs) DHP Nicardipine Non-DHP

Vasodilators - Hydralazine Hypertension Arrhythmias Heart Failure Vasodilators - Hydralazine Usual total daily dose range HTN Crisis: 10-20 mg slow IVP HTN: 10-50mg QID (Max 300) Max rate 5mg/min IV push Drug Names Generic Routes Dosage forms Hydralazine Yes Oral tab Oral suspension 10, 25, 50, 100mg compounded IV 20 mg/mL

Vasodilators - Nitroprusside Hypertension Arrhythmias Heart Failure Vasodilators - Nitroprusside Usual total daily dose range HTN Crisis: 0.25-10 mcg/kg/min IV infusion Other uses Acute decompensated HF Special Administration: protect from light Cyanide intoxication- Drug Names Generic Routes Dosage forms Nitropress® No IV 25 mg/mL

Vasodilators - Nitroglycerin Hypertension Arrhythmias Heart Failure Vasodilators - Nitroglycerin Usual total daily dose range HTN Crisis: 5-100 mcg/min IV infusion Special indications Myocardial infarction, ischemia Other uses Chest pain, anal fissure, variceal hemorrhage (off label) Drug Names Generic Routes Dosage forms Nitronal® Yes IV solution NitroStat® No SL tab 0.3, 0.4, 0.6 mg Other forms: Translingual spray, ER cap, rectal ointment, transdermal ointment, patch

CCBs – Dihydropyridines (DHP) Hypertension Arrhythmias Heart Failure CCBs – Dihydropyridines (DHP) Amlodipine is a first line hypertension agent Other uses Migraine prophylaxis, angina, pulmonary hypertension (off label) Avoid in Acute heart failure Drug Names Generic Routes/Dosage Form Usual dosage range Amlodipine (Norvasc®) Yes Oral tab- 2.5, 5, 10mg 2.5-10mg (Qdaily) Nicardipine IV, Oral cap- 20, 30mg 60-120mg (Qdaily) Nifedipine (Procardia XL®) Oral IR cap- 10,20mg Oral ER cap- 30,60,90mg 30-60mg (Qdaily)

CCBs-Nicardipine Hypertension Arrhythmias Heart Failure Usual total daily dose range HTN Crisis: 5-15mg/hr IV Special indications BP lowering for ischemic stroke Avoid in Acute heart failure Drug Names Generic Routes Dosage forms Nicardipine Yes IV- central line preferred 2.5mg/mL

CCBs- Non-DHPs Hypertension Arrhythmias Heart Failure Mechanism Dose conversions Affects contractility of heart Diltiazem (IR=ER) Other uses Diltiazem (IV:PO) A Fib – rate control, Angina, migraine prophylaxis (off label) [(Rate) x 3 +3] x 10 = PO dose 3mg/hr = 120mg Qdaily Notable adverse effects Avoid in drug interactions, heart block, edema, headache Heart failure Drug Names Generic Routes/Dosage Form Diltiazem Yes IV – for arrhythmias  0.25mg/kg IVP over 2 minutes Oral IR Cap – 30, 60, 90, 120mg (given Q6h) Oral ER Cap 12h- 60, 90, 120mg 24h- 120, 180, 240, 300, 360, 420mg Oral ER Tab 24h- 180, 240, 300, 360, 420mg Verapamil IV – for arrhythmias 2.5-5mg IVP over 2 minutes Oral IR Tab – 40, 80, 120mg (given BID-TID) Oral ER Cap-100, 120, 180, 200, 240, 300, 360mg Oral ER Tab- 120, 180, 240 mg less potent vasodilators Avoid IR for long term use Capsules may be sprinkled on applesauce do not chew

Medications Overview Hypertension Arrhythmias Heart Failure Antiadrenergic agents Vasodilators Angiotensin/ renin agents ACE Inhibitors Lisinopril Enalapril Captopril Angiotensin Receptor Antagonists Losartan Valsartan Irbesartan Diuretics

Angiotensin/Renin Agents Mechanism: Vasodilation by blocking angiotensin II effects Reduces aldosterone to inhibit volume increase Medications: ACE Inhibitors “-prils” Lisinopril Enaloprilat Many ARBs “-sartans” Losartan http://www.nature.com/ki/journal/v81/n7/images/ki2011460f1.jpg

ACE Inhibitors Hypertension Arrhythmias Heart Failure First line hypertension agent Uses Heart failure, after MI, renal protection for diabetics Contraindicated pregnancy Drug Names Generic Routes/Dosage Form Usual dosage range Benazepril (Lotensin®) Yes Oral tab-5,10,20,40mg 10-40mg (QD-BID) Captopril (Capoten®) Oral tab-12.5,25,50,100mg 25-100mg (BID-TID) Fosinopril (Monopril®) Oral tab- 10,20,40mg Lisinopril (Zestril®) Oral tab- 2.5,5,10,20,30,40mg 10-40mg (Qdaily) Ramipril (Altace®) Oral cap- 1.25,2.5,5,10mg 1.25-20mg (Qdaily) Interactions- lithium (HCTZ decreases lithium clearance, also lithium blocks thiazides effects)

ACE Inhibitors - Enalaprilat Hypertension Arrhythmias Heart Failure ACE Inhibitors - Enalaprilat Usual total daily dose range HTN Crisis: 1.25-5mg IV Q6h Contraindicated teratogenic Avoid in Myocardial infarction Acute heart failure Interactions- lithium (HCTZ decreases lithium clearance, also lithium blocks thiazides effects) S/S of angioedema Drug Names Generic Routes/Dosage Form Usual dosage range Enalapril (Vasotec®, Epaned®) Tab-Yes Sol-No Oral tab- 2.5,5,10,20mg Oral solution- 1mg/ml 2.5-40 (QD-BID) Enalaprilat Yes IVP or infusion 1.25-5mg IV Q6h

ARBs Hypertension Arrhythmias Heart Failure First line hypertension agent Other uses Heart failure, post MI Administration: No benefit to use with ACE-Inhibitors Contraindicated Pregnancy Interactions- lithium (HCTZ decreases lithium clearance, also lithium blocks thiazides effects) S/S of hyperkalemia - Drug Names Generic Routes/Dosage Form Usual dosage range Candesartan (Atacand®) Yes Oral tab- 4,8,16,32mg 8-32 mg (Qdaily) Irbesartan (Avapro®) Oral tab- 75,150,300mg 150-300mg (Qdaily) Losartan (Cozaar®) Oral tab- 25,50,100mg 25-100mg (QD-BID) Olmesartan (Benicar®) No Oral tab- 5, 20, 40mg 20mg (Qdaily) Valsartan (Diovan®) Oral tab- 40,80,160,360mg 80-320mg (Qdaily)

Diuretics Hypertension Arrhythmias Heart Failure Antiadrenergic agents Vasodilators Angiotensin/ renin agents Diuretics Thiazides HCTZ Chlorthalidone Metolazone Loops Furosemide Bumetanide Torsemide K+ Sparing Spironolactone Triamterene

Hypertension Arrhythmias Heart Failure Diuretics

Thiazides & Thiazide Like Hypertension Arrhythmias Heart Failure Thiazides & Thiazide Like First line hypertension agent Other Uses Edema (heart failure/renal disease) Dose conversions Chlorthalidone is 1.5-2x more potent than HCTZ Special Administration: Dose should occur in AM Drug Names Generic Routes/Dosage Form Usual dosage range Chlorothiazide (Diuril®) IV-No PO-Yes IV- susp, solution Oral tab- 250, 500mg 125-500 mg (Qdaily) Hydrochlorothiazide Yes Oral tab-12.5,25,50mg Oral cap-12.5mg 12.5-50mg (Qdaily) Chlorthalidone Oral tab-25, 50, 100mg 12.5-25mg (Qdaily) Metolazone Oral tab- 2.5, 5, 10 mg 2.5-10mg (Qdaily) Interactions- lithium (HCTZ decreases lithium clearance, also lithium blocks thiazides effects)

Loop Diuretics Hypertension Arrhythmias Heart Failure Special Administration: Doses should occur earlier in the day Other uses Edema (d/t heart failure), hepatic cirrhosis Dose conversions Furosemide POIV = 2:1 Furosemide IV  Bumetanide IV = 20:1 Furosemide PO  Bumetanide PO  Torsemide PO = 40:1:20 Furosemide Oral tab may be used sublingual (under tongue x 5min) Furosemide – 20-40mg/min Drug Names Generic Routes/Dosage Form Usual dosage range Bumetanide (Bumex®) IV, IM, oral-tab 0.5-2mg+ (QD-BID) Furosemide (Lasix®) Yes IV [PF], oral-tab, solution 20-80mg+ (QD-BID) Torsemide (Demadex®) oral-tab [scored] 2.5-10mg (Qdaily)

Dose Conversions H.S. is a 58 y/o male admitted to hospital and unable to take oral medications On furosemide 40mg po QAM for edema at home You are asked to deliver furosemide 40mg IV to the floor Is this an equivalent dose? Team decides to convert H.S. to IV torsemide (Demadex®) from furosemide 20mg IV What is the equivalent dose? H.S. is discharged from hospital and would like to pick up his bumetanide (Bumex®) 3mg po QAM for edema. Is this an equivalent dose to what he was taking at home?

K+ Sparing Diuretics Hypertension Arrhythmias Heart Failure Other uses Spironolactone Edema, hypokalemia, hyperaldosteronism, hirsutism in women [off label], acne in women [off label], ascites from cirrhosis [off label] Eplerenone Heart Failure Contraindicated Pregnancy Drug Names Generic Routes/Dosage Form Usual dosage range Spironolactone Yes Oral tab- 25, 50, 100mg 25-50mg+ (QD-BID) Eplerenone (Inspra®) Oral tab- 25, 50mg 50-100mg (QD-BIDD) Triamterene (Direnium®) PO 2.5-10mg (Qdaily)

Arrhythmias Hypertension Arrhythmias Heart Failure Definition: cardiac condition caused by abnormalities in the formation and/or conduction of electrical impulses controlling the rate of the heart Causes Myocardial ischemia/infarction Conditions damaging heart tissue Heart valve disorders, hypertension, heart failure Electrolyte imbalances Elevated sympathetic states Hyperthyroidism, infection Drugs Antiarrhythmics. In: Shapiro K, Brown SA, eds. 2015

Pathophysiology Hypertension Arrhythmias Heart Failure Cardiac Conduction Pathway

Pathophysiology Hypertension Arrhythmias Heart Failure Cardiac Muscle Cell Action Potential https://www.khanacademy.org/science/health-and-medicine/circulatory-system/heart-depolarization/v/action-potentials-in-cardiac-myocytes

Types of Arrhythmias Hypertension Arrhythmias Heart Failure Supraventricular (above AV node) Sinus tachycardia Atrial fibrillation Atrial flutter Ventricular (below AV node) Premature ventricular contractions Ventricular tachycardia Ventricular fibrillation Antiarrhythmics. In: Shapiro K, Brown SA, eds. 2015

Atrial Fibrillation Hypertension Arrhythmias Heart Failure Definition: the result of the heart’s two upper chambers (atria) beating chaotically and out of coordination with the two lower chambers (ventricles), leading to an irregular and usually rapid heart rate Antiarrhythmics. In: Shapiro K, Brown SA, eds. 2015

Medication Overview Hypertension Arrhythmias Heart Failure Sodium channel blockers Class IA Procainamide Class IB Lidocaine Class IC Flecainide Propafenone Beta-blockers (Class II) Potassium channel blockers (Class III) Amiodarone Sotalol Dofetilide Dronedarone Calcium channel blockers (Class IV) Verapamil Diltiazem Digoxin

Class I Antiarrhythmics Hypertension Arrhythmias Heart Failure Class I Antiarrhythmics Sodium channel blockers Sub-classified based on duration of time they bind to sodium channel 1A: intermediate; also block potassium channels 1B: fast 1C: long-acting Black Box Warning: increased risk of mortality Class IA Class IB Class IC disopyramide PO mexiletine moricizine quinidine IV, PO lidocaine IV, IM (off-label) flecainide procainamide IV tocainide propafenone phenytoin Antiarrhythmics. In: Shapiro K, Brown SA, eds. 2015

Class I Antiarrhythmic Acronym Double (disopyramide) Quarter (quinidine) Pounder (procainamide) 1B: Mayo (mexiletine) Lettuce (lidocaine) Tomato (tocainide) Pickles (phenytoin) IC: More (moricizine) Fries (flecainide) Please (propafenone)

Class II Antiarrhythmics Hypertension Arrhythmias Heart Failure Class II Antiarrhythmics Beta-blockers Esmolol Propranolol Antiarrhythmics. In: Shapiro K, Brown SA, eds. 2015

Class III Antiarrhythmics Hypertension Arrhythmias Heart Failure Class III Antiarrhythmics Potassium Channel Blockers Amiodarone dosing dependent on arrhythmia type Special Administration: Amiodarone infusions longer than 2 hours must be administered in non-PVC container Inline 0.22 micron filter should be used Dofetilide requires REMS program Drug Names Generic Routes/Dosage Form Amiodarone (Pacerone®) Yes IV, PO (tablet) Sotalol (Betapace®) IV, PO (tablet & solution) Dofetilide (Tikosyn®) No PO (capsule) Dronedarone (Multaq®) PO (tablet) To minimize risk of induced arrhythmia, pts initiated or re-initiated on tikosyn are placed for a minimum of 3 days in facility that can provide CrCl, continuous ECG and cardiac resuscitation Antiarrhythmics. In: Shapiro K, Brown SA, eds. 2015

Class IV Antiarrhythmics Hypertension Arrhythmias Heart Failure Class IV Antiarrhythmics Non-dihydropyridine calcium channel blockers Verapamil Diltiazem Talk about difference– non dihydro vs. dihydro Ca channel blockers Antiarrhythmics. In: Shapiro K, Brown SA, eds. 2015

Digoxin Hypertension Arrhythmias Heart Failure Dose adjusted to fall between a therapeutic range (0.5-2ng/mL) Not given alone– usually in combination with a calcium channel blocker or beta-blocker Increased risk of toxicity Toxicity: greater than 2 Antiarrhythmics. In: Shapiro K, Brown SA, eds. 2015

Heart Failure Hypertension Arrhythmias Heart Failure Definition: clinical syndrome caused by any structural or functional cardiac disorder that impairs the ability of the ventricle to fill or eject blood Causes: Coronary artery disease/heart attack High blood pressure Heart defects Damage to heart muscle Arrhythmias Heart Failure. In: Shapiro K, Brown SA, eds. 2015

Pathophysiology Hypertension Arrhythmias Heart Failure Source: Pharmacotherapy © 2003 Pharmacotherapy Publications

Presentation Hypertension Arrhythmias Heart Failure Chronic vs. Acute (“decompensated”) Image from: www.heart.org

Types of Heart Failure Hypertension Arrhythmias Heart Failure “Reduced Ejection Fraction” “Preserved Ejection Fraction” Wiggins BS. In: ACCP Updates in Therapeutics 2015. 169-181.

Most often used for decompensated heart failure Hypertension Arrhythmias Heart Failure Medication Overview Vasodilators ACE inhibitors ARBs Beta-blockers Diuretics Potassium-sparing Loop Positive Inotropes Digoxin Sympathomimetics Dobutamine Dopamine Most often used for decompensated heart failure

ACE-inhibitors Hypertension Arrhythmias Heart Failure Shown to significantly decrease cardiovascular mortality, heart attacks and hospitalizations for heart failure patients with reduced ejection fraction Image from: Do AN, et al. Front. Pharmacol. 2014. .

Angiotensin II Receptor Blockers Hypertension Arrhythmias Heart Failure Angiotensin II Receptor Blockers Shown to significantly decrease cardiovascular mortality, heart attacks and hospitalizations for heart failure patients with reduced ejection fraction Angiotensin II Receptor Blockers Image from: Do AN, et al. Front. Pharmacol. 2014. .

Beta-blockers Hypertension Arrhythmias Heart Failure Shown to improve survival and reduce hospitalization in heart failure patients with reduced ejection fraction Heart failure beta-blockers: Carvedilol Metoprolol Bisoprolol

Diuretics Hypertension Arrhythmias Heart Failure Reduces symptoms of heart failure Image from: Do AN, et al. Front. Pharmacol. 2014. .

Potassium Sparing Diuretics Hypertension Arrhythmias Heart Failure Potassium Sparing Diuretics Shown to improve survival and reduce morbidity and mortality in heart failure patients with reduced ejection fraction NYHA class II-IV, CrCl >30, K <5.0 “Aldosterone antagonists” Spironolactone Eplerenone

Positive Inotropes Hypertension Arrhythmias Heart Failure Increase cardiac contractility during heart failure exacerbations Used as emergency medications (dobutamine, dopamine) Warning: arrhythmias! Digoxin Dobutamine Dopamine Heart Failure. In: Shapiro K, Brown SA, eds. 2015

Drug Update: Entresto™ (sacubitril/valsartan) Hypertension Arrhythmias Heart Failure Drug Update: Entresto™ (sacubitril/valsartan) Inactive fragments Damaged Heart with CHF Natriuretic Peptide System Renin-Angiotensin-Aldosterone System Natriuretic Peptides Angiotensin-II Beneficial Physiological Response Pathophysiological Response AT1 receptor ↑ BP ↑ Sympathetic tone ↑ Fibrosis ↑ Aldosterone ↑ Hypertrophy Vasoconstriction Vasodilation ↓ BP Natriuresis/Diuresis ↓ Sympathetic tone ↓ Fibrosis ↓ Aldosterone ↓ Hypertrophy NEPRILYSIN Sacubitril Valsartan Tablets; $450/month Adapted from : Langenickel TH, Dole WP. Drug Discovery Today: Therapeutic Strategies. 2013; 9 (4): 131-139

Assessment Question #1 Which of the following classes of medications is NOT indicated for the treatment of cardiac conditions? Anti-arrhythmics Beta-agonists Angiotensin II receptor blockers Thiazide diuretics Correct Answer: B

Assessment Question #2 “The result of the heart’s two upper chambers (the atria) beating chaotically and out of coordination with the two lower chambers (the ventricles), leading to an irregular and usually rapid heart rate” is the clinical definition of what cardiac disease state? Heart failure Transient Ischemic Attack Angina Atrial fibrillation Correct Answer: D

Assessment Question #3 Which of the following prescription order(s) may be wrong and should be brought to the attention of the pharmacist? Metoprolol succinate 100mg po BID for heart failure #60 Hydralazine 25mg po Qdaily for hypertension #30 Diltiazem SA 240mg po BID for atrial fibrillation #60 All of the above Correct Answer: D

Assessment Question #4 Patient is currently receiving furosemide 40 mg po Qdaily for heart failure. Provider wants to switch to bumetanide. What is the equivalent dose of bumetanide? Bumetanide 40mg Bumetanide 20mg Bumetanide 10mg Bumetanide 1mg Correct Answer: D

References Chyka PA, Boucher BA, Franks AS, eds. The APhA Complete Review for Pharmacy. 11th ed. Amer Pharmacists Assn. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Hudson, OH. Available at: http://online.lexi.com. Accessed January 17, 2016. Katzung B, Trevor A. Basic & Clinical Pharmacology. 13th ed. McGraw-Hill Education. 2015. Shapiro K, Brown SA, eds. RxPrep CourseBook. 2015 ed. Manhattan Beach, CA; RxPrep, Inc.

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