HEART FAILURE WITH REDUCED EJECTION FRACTION School of Nursing and Health Sciences Advanced Pharmacology Amanda Cozza, Florence Redmond, Tuba Pak PATIENT PRESENTATION CHIEF COMPLAINT “I’ve been more short of breath lately. I can’t seem to walk as far as I used to, and either my feet are growing or my shoes are shrinking!” HISTORY OF PRESENT ILLNESS Rosemary Quincy is a 68-year-old African-American woman who presents to her family medicine clinic for evaluation of her shortness of breath and increased swelling in her lower extremities. She reports that her shortness of breath has been gradually increasing over the past 4 days. She has noticed that her shortness of breath is particularly worse when she is lying in bed at night, and she has to prop her head up with three pillows in order to sleep. She also reports exertional dyspnea that is usual for her, but especially worse over the past couple of days. 2 PAST MEDICAL HISTORY • Hypertension × 20 years • CHD with history of MI in 2005 (PCI performed and bare metal stents placed in LAD and RCA) • Heart failure (NYHA FC III) • Type 2 DM × 25 years • Atrial fibrillation • COPD (GOLD 3, group D) • CKD (stage 4) FAMILY HISTORY Father died of lung cancer at age 71, mother died of MI at age 73. SOCIAL HISTOTY Reports occasional alcohol intake. States she has been trying to follow her low-cholesterol and low-sodium diet. Former smoker (35 pack-year history; quit approximately 10 years ago). 3 MEDICATIONS Valsartan (Diovan) 160 mg PO BID Furosemide (Lasix) 40 mg PO BID Warfarin (Coumadin) 2.5 mg PO once daily Carvedilol (Coreg) 3.125 mg PO BID Pioglitazone (Actos) 30 mg PO once daily Glimepiride (Amaryl) 2 mg PO once daily Potassium chloride (Klor-Con) 20 mEq PO once daily Atorvastatin (Lipitor) 40 mg PO once daily Aspirin (Ecotrin) 81 mg PO once daily Albuterol (Proventil) MDI, two inhalations by mouth q 4–6 hours PRN shortness of breath • Tiotropium (Spiriva Handihaler) DPI 18 mcg, one inhalation by mouth daily • Fluticasone/salmeterol (Advair Diskus) DPI 250 mcg/50 mcg, one inhalation by mouth BID • • • • • • • • • • ALLERGIES Lisinopril (cough) REVIEW OF SYSTEMS Approximate 7-kg weight gain over the past week. No fever or chills. Denies any recent chest pain, palpitations, or dizziness. Reports worsening shortness of breath with exertion and three-pillow orthopnea. Describes a chronic, dry (nonproductive), hacking cough, which she describes as usual without recent worsening. No abdominal pain, nausea, constipation, or change in bowel habits. Denies joint pain or weakness. PHYSICAL EXAMINATION Gen African-American woman in moderate respiratory distress Vital Signs BP 134/76 (sitting; repeat 138/78), HR 65 (irreg irreg), RR 24, T 37°C, O2 sat 90% RA, Ht 5ʹ5ʺ, Wt 79 kg (Wt 1 week ago: 72 kg) Skin Color pale and diaphoretic; no unusual lesions noted HEENT PERRLA; lips mildly cyanotic; dentures Neck (+) JVD at 30° (7 cm); no lymphadenopathy or thyromegaly Lungs/Thorax Crackles bilaterally, 2/3 of the way up; no expiratory wheezing PHYSICAL EXAMINATION (CONT.) Heart Irregularly irregular; (+) S3; displaced PMI Abd Soft, mildly tender, nondistended; (+) HJR; no masses, mild hepatosplenomegaly; normal BS Genit/Rect Guaiac (–), genital examination not performed MS/Ext 3+ pitting pedal edema bilaterally; radial and pedal pulses are of poor intensity bilaterally Neuro A & O × 3, CNs intact. No motor deficits. LABS/ DIAGNOSTICS Labs Na 131 mEq/L Hgb 13 g/dL Mg 1.9 mEq/L INR 2.3 K 3.5 mEq/L Hct 40% Ca 9.3 mg/dL A1C 6.1% Cl 99 mEq/L Plt 192 × 103/mm3 Phos 4.3 mg/dL CO2 28 mEq/L WBC 9.1 × 103/mm3 AST 34 IU/L BUN 32 mg/dL ALT 27 IU/L SCr 2.3 mg/dL (baseline SCr 2.1 mg/dL) eGFR 20 mL/minute/1.73 m2 Glucose 124mg/dl BNP 776pg/mL (BNP drawn 2 months prior: 474 pg/mL) 8 LABS/ DIAGNOSTICS (CONT.) ECG Atrial fibrillation, LVH (left ventricular hypertropia) Echocardiogram LVH, reduced global left ventricular systolic function, estimated EF 20%; evidence of impaired ventricular relaxation, stage 1 diastolic dysfunction. Chest X-Ray PA and lateral views show evidence of congestive failure with cardiomegaly, interstitial edema, and some early alveolar edema. There is a small right pleural effusion. 9 LABS/ DIAGNOSTICS (CONT.) PA CXR demonstrates increased vascular markings representative of interstitial edema, with some early alveolar edema. The arrow points out fluid lying in the fissure of the right lung. Note the presence of cardiomegaly. No evidence of infiltrates; evidence of pulmonary edema suggestive of congestive heart failure; enlarged cardiac silhouette. Lateral view of CXR. Arrow points out the presence of pulmonary effusion. 10 ASSESSMENT AND DIAGNOSIS 1. 2. 3. 4. 5. 6. 7. HFrEF, Stage C AHA, Class III NYHA, Chronic heart failure with acute exacerbation requiring drugs and other treatment. Hypertension, notably in the presence of HF, CHD, and diabetes with blood pressure (BP) currently not at goal; adjustment of HF regimen could help achieve BP goal. CHD with history of MI, currently on statin but lipids not at goal. Type 2 DM, on pioglitazone regimen, potential to worsen HF and is contraindicated in NYHA Class III and IV. Atrial fibrillation with rate control, appropriately anticoagulated with warfarin (therapeutic INR). COPD, currently stable on regimen, but receiving carvedilol, potential to worsen the patient’s COPD, HR is also low. CKD stable on lisinopril, with SCr slightly increased above baseline on presentation but likely secondary to HF exacerbation leading to decreased renal perfusion. 11 CLINICAL COURSE & PHARMACOTHERAPY Initially- The patient is diagnosed with an acute exacerbation of HF and is admitted to the hospital for intravenous (IV) diuretic therapy and adjustment of her chronic medications for heart failure with a reduced ejection fraction (HFrEF). • Furosemide (Lasix) 40 mg PO BID ~ D/C (may keep during 36h washout) 3 days later, the patient is eventually stable- Upon discharge the following order(s) will be transmitted to the pharmacy via e-scribe: • • • • • • Furosemide (Lasix) 20mg 1 tab PO BID - DISCONTINUE, no longer needed as per Entresto Valsartan (Diovan) 160mg 1 tab PO BID - DISCONTINUE, do not use while on Entresto Potassium chloride (Klor-Con) 20 mEq 1 tab PO BID - DISCONTINUE, do not use while on Entresto Carvedilol (Coreg) 3.125mg 1 tab PO BID - DISCONTINUE, replaced w/ metoprolol XL Pioglitazone (Actos) 30mg 1 tab PO QD – DISCONTINUE Glimepiride (Amaryl) 2mg 1 tab PO QD – DISCONTINUE (cont. next page) 12 CLINICAL COURSE & PHARMACOTHERAPY (CONT.) 13 QUESTION 1 Based on the pharmacotherapeutic plan, (including any med that will be discontinued) discuss: a. Pharmacodynamics b. Pertinent pharmacokinetics Furosemide “Lasix” (loop diuretic) D/C Furosemide is a potent loop diuretic that works to increase the excretion of Na+ and water by the kidneys by inhibiting their reabsorption from the proximal and distal tubules, as well as the loop of Henle. Loop diuretics also induce a prostaglandinmediated increase in renal blood flow, which contributes to their natriuretic effect. Potassium Chloride “Klor-Con” D/C Potassium ions participate in a number of essential physiological processes including the maintenance of intracellular tonicity, the transmission of nerve impulses, the contraction of cardiac, skeletal and smooth muscle, and the maintenance of normal renal function. Valsartan “Diovan” (angiotensin II receptor blocker) D/C ARB drugs selectively bind to angiotensin receptor 1 (AT1) and prevent angiotensin II from binding and exerting its hypertensive effects. These include vasoconstriction, stimulation and synthesis of aldosterone and ADH, cardiac stimulation, and renal reabsorption of sodium among others. Overall, valsartan's physiologic effects lead to reduced blood pressure, lower aldosterone levels, reduced cardiac activity, and increased excretion of sodium. Caution: hypotension, hyperkalemia, impaired renal function 14 Question 1 (cont) Sacubitril and Valsartan “Entresto” (angiotensin receptor neprilysin inhibitor) Sacubitril/valsartan is a combination product. Sacubitril is a prodrug that, upon activation, acts as a neprilysin inhibitor. Valsartan is an angiotensin receptor blocker, and it works on blocking the RAAS system. However, because neprilysin breaks down angiotensin II, inhibiting neprilysin will accumulate angiotensin II. For this reason, a neprilysin inhibitor cannot be used alone; it must always be combined with an ARB to block the effect of the excess angiotensin II. Sacubitril is converted to its active metabolite, LBQ657, by plasma esterases and not further metabolized. Valsartan is minimally metabolized; approximately 20% of the dose is recovered as metabolites. After oral administration, 52% to 68% of sacubitril (primarily as metabolite) and approximately 13% of valsartan and its metabolites are excreted in urine. The remaining drug and metabolites are excreted in feces. 15 Question 1 (cont) Carvedilol “Coreg” (non-selective Beta-Blocker) D/C Pioglitazone “Actos” (thiazolidinediones) D/C Carvedilol reduces tachycardia through beta adrenergic antagonism and lowers blood pressure through alpha-1 adrenergic antagonism. Pioglitazone enhances cellular responsiveness to insulin, increases insulin-dependent glucose disposal, and improves impaired glucose homeostasis. In patients with type 2 diabetes mellitus, these effects result in lower plasma glucose concentrations, lower plasma insulin concentrations, and lower HbA1c values. Metoprolol ER “Toporol” (Beta-1-adrenergic receptor inhibitor) Decreases cardiac excitability, cardiac output, and myocardial oxygen demand. In the case of arrhythmias, metoprolol produces its effect by reducing the slope of the pacemaker potential as well as suppressing the rate of atrioventricular conduction. Metoprolol is widely distributed throughout the body. It is moderately lipid-soluble, is concentrated in breast milk, and crosses the blood brain barrier and placenta. It is metabolized by the liver via CYP2D6. It is excreted mainly via the urine. Caution: Patients taking beta-blockers should not abruptly stop taking this medication as this may exacerbate coronary artery disease. Caution: Significant fluid retention leading to the development/exacerbation of heart failure has been reported with pioglitazone. Glimepiride “Amaryl” (sulfonylurea) D/C Glimepiride stimulates the secretion of insulin granules from the pancreatic beta cells and improves the sensitivity of peripheral tissues to insulin to increase peripheral glucose uptake, thus reducing plasma blood glucose levels and glycated hemoglobin (HbA1C) levels. 16 Question 1 (cont) Dapagliflozin “Farixiga” (sodium-glucose cotransporter 2 inhibitor) Dapagliflozin inhibits the sodium-glucose cotransporter 2(SGLT2) which is primarily located in the proximal tubule of the nephron. SGLT2 facilitates 90% of glucose reabsorption in the kidneys and so its inhibition allows for glucose to be excreted in the urine. This excretion allows for better glycemic control and potentially weight loss in patients with type 2 diabetes mellitus. Dapagliflozin is approximately 91% protein bound. Dapagliflozin is mainly metabolized via Oglucuronidation by UGT1A9; CYP3A4-mediated metabolism is a minor clearance pathway in humans, Dapagliflozin is extensively metabolized, primarily to yield dapagliflozin 3-O-glucuronide, which is an inactive metabolite. Elimination of dapagliflozin and its metabolites occurs primarily via the renal pathway. After oral administration, 75% and 21% of the dose is excreted in urine and feces. Among individuals with HFrEF, with or without DM, the addition of dapagliflozin has been associated with decreased rates of CV death or worsening HF, as well as all-cause mortality. Renal effects Reduction in albuminuria Reduction in tubular inflammation due to lower RAAS activation Reduction in intraglomerular pressure and tubular hypertrophy Cardiovascular effects Weight loss BP reduction Decrease in epicardial fat thickness - empagliflozin Reduction in the serum uric acid Favorable effect on the lipid profile Lesser surges of insulin secondary to hypoglycemia as the glycemic actions of the class are non-insulin dependent Warfarin “Coumadin” (anticoagulant) Warfarin is an anticoagulant, as such it disrupts the coagulation cascade to reduce frequency and extent of thrombus formation. Warfarin inhibits the synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S. Specifically, warfarin inhibits the C1 subunit of the vitamin K epoxide reductase (VKORC1) enzyme, which reduces the regeneration of vitamin K epoxide. In patients with deep vein thrombosis or atrial fibrillation, there is an increased risk of thrombus formation due to the reduced movement of blood. Warfarin when administered via the oral route is absorbed in the GI tract. Warfarin is highly bound (about 97%) to plasma protein, mainly albumin. The high degree of protein binding is one of several mechanisms whereby other drugs interact with it. Warfarin is distributed to the liver, lungs, spleen, and kidneys but does not appear to be distributed into breast milk in significant amounts. It crosses the placenta and is a known teratogen. It is metabolized by hepatic cytochrome CYPP450 isoenzymes to inactive hydroxylated metabolites (predominant route) and by reductases to reduced metabolites (warfarin alcohols). Caution: Anticoagulation appears to mediate warfarin-related nephropathy, a seemingly spontaneous kidney injury or worsening of chronic kidney disease associated with warfarin therapy. 17 QUESTION 2 Based on the pharmacotherapeutic plan, for EACH medication, discuss the monitoring parameter(s). Include monitoring for BOTH: a. Therapeutic effectiveness b. Adverse drug effects (address ways to prevent/minimize/manage) Furosemide (Lasix) 40 mg (IV) Mix N.C cons. 2mg/ml ( D/C) and 20 mg (PO) BID (D/C) ◼ a- Furosemide is given to help treat fluid retention (edema) we should Check patient : Electrolyte (BUN) levels, (hypomagnesemia, hyponatremia, hypokalemia, serum creatinine and blood urea nitrogen normal level of electrolytes: K+: 3.6- 5.2 mEq/L Na +: 135-145 mEq/L Mg+: 1.7 -2.2 m/dL BUN: 6-20 mg/dL creatinine: 0.7-1.3 mg/dL b- monitor for: ototoxicity, orthostatic hypotension dehydration. weight daily. intake and output Drugs.com, 2023 AtraZeneca, 2010 18 Question 2 cont • Carvedilol (Coreg) 3.125mg 1 tab PO BID - (D/C) a- Low heart rate and Lower blood pressure. b-Monitor for: patient blood pressure, heart rate and shortness of breath , fluid retention and hyperglycemia. weight gain, BUN level. • Pioglitazone (Actos) 30mg 1 tab PO QD (D/C) a- Pioglitazone is used together with diet and exercise to improve blood sugar control in adults with type 2 DM. b- Monitor for signs and symptoms of heart failure (dyspnea,, rapid and excessive weight gain, edema) and patient’s blood sugar. Metoprolol ER ( Toprol XL) 25 mg 1 Tab PO QD (replace carvedilol) a- Metoprolol is used to treat angina and hypertension. Metoprolol is also used to lower your risk of death or needing to be hospitalized for heart failure. b- Monitor patient heart rate (bradycardia) and hypotension. Drugs.com, 2023 19 Question 2 cont • Potassium chloride (Klor-Con) 20 mEq 1 tab PO BID ( D/C) a- prevent or treat low potassium levels in the body. b- monitoring potassium levels, (Hyperkalemia and hypokalemia) Electrolyte imbalances( sodium and magnesium) Gastrointestinal disturbances: nausea, vomiting, diarrhea, and abdominal discomfort. • Valsartan (Diovan) 160mg 1 tab PO BID - (D/C) a- Relaxes the blood vessels and lowers blood pressure; risk for hypotension Monitor for: Angioedema (allergic reaction) Liver dysfunction, Kidney dysfunction Dizziness, potassium level and blood pressure. Warfarin ( Coumadin) 2.5 mg 1 tab PO QD a- Reduce the risk of blood clots and prevent thromboembolic events. b--monitor for patient: INR level: 2.0-3.0 .checked monthly and closely monitored for any signs of bleeding or clotting complications, like bloody stool, Drugs.com, 2023 20 Question 2 cont • Glimepiride (Amaryl) 2mg 1 tab PO QD – D/C Sacubitril and Valsartan(Entresto) 24 mg/26 mg tab PO QD- (Do not initiate until Diovan washout for 36hr.) a-Sacubitril and valsartan are blood pressure medicines. b- monitor for patient: hyperkalemia, hypotension, and increased serum creatinine level, acute kidney injury, and renal failure syndrome. a- Treats DM type 2 b - Monitor for patient: Hypoglycemia and sodium level for hyponatremia. Dapagliflozin (farixiga) 10 mg 1 tab PO QD . a- Dapagliflozin is used to lower the risk of hospitalization for heart failure in patients with type 2 diabetes b -monitor for patient: weight gain, bloody or cloudy urine and swelling of the face, fingers, or lower legs. Drugs.com, 2023 21 Drug-Drug Interaction Based on the pharmacotherapeutic plan, discuss pertinent potential drug interaction(s). Include BOTH drug-drug and drug-food interaction(s), (when applicable). DRUG-DRUG INTERACTION Major Drug-Drug Interaction Coumadin (warfarin), Ecotrin (aspirin) GENERALLY AVOID: even low-dose aspirin are noted to increase bleeding when combined with an anticoagulant by inhibiting platelet aggregation, prolonging bleeding time, and inducing gastrointestinal lesions. Avoid unless the potential benefit outweighs the risk of bleeding. Moderate Drug-Drug Interaction Toprol-XL (metoprolol), Proventil (albuterol) Toprol-XL (metoprolol), Advair Diskus (fluticasone / salmeterol) GENERALLY AVOID: Although cardioselective beta-blockers do not generally inhibit the bronchodilating effect of beta-2 adrenergic agonists, they may worsen pulmonary function in patients with asthma or other obstructive airway diseases. However, little data exist regarding their safety during chronic use or use in patients with severe respiratory disease. Beta-blockers, including those with relative cardioselectivity, should generally be avoided in patients with bronchospastic diseases. However, given their demonstrated benefit in such conditions as heart failure, myocardial infarction, cardiac arrhythmias and hypertension, cardioselective beta-blockers may be administered with caution to those who do not respond to or tolerate alternative treatment. The benefits generally outweigh the risks in patients with mild or moderate reactive airway disease that is well controlled on inhaled corticosteroids and beta-2 agonists, provided they have no prior history suggesting a predisposition to severe exacerbations. Drugs.com, 2023 22 Drug-Drug Interaction (cont…) Proventil (albuterol), Advair Diskus (fluticasone / salmeterol) MONITOR: Coadministration of beta-2 adrenergic agonists with other adrenergic agents may potentiate the risk of cardiovascular side effects. Beta-2 adrenergic agonists can produce clinically significant cardiovascular effects including increases in pulse rate and systolic or diastolic blood pressure as well as ECG changes such as flattening of the T wave, prolongation of the QTc interval, and ST segment depression. The risk is lower when beta-2 adrenergic agonists are inhaled at normally recommended dosages. However, these effects may be more common when the drugs are administered systemically or when recommended dosages are exceeded. Toprol-XL (metoprolol), Entresto (sacubitril / valsartan) GENERALLY AVOID: In the Valsartan Heart Failure Trial, the combination of valsartan with a beta-blocker and an ACE inhibitor was associated with unfavorable outcomes on morbidity and mortality in heart failure patients. The mechanism is unknown. The manufacturer recommends that the triple combination of valsartan with a beta-blocker and an ACE inhibitor be avoided in heart failure patients. Drugs.com, 2023 23 Drug-Drug Interaction (cont…) Ecotrin (aspirin), Entresto (sacubitril / valsartan) MONITOR: Nonsteroidal anti-inflammatory drugs (NSAIDs) may attenuate the antihypertensive effects of angiotensin II receptor antagonists. The proposed mechanism is NSAID-induced inhibition of renal prostaglandin synthesis, which results in unopposed pressor activity producing hypertension. In addition, NSAIDs can cause fluid retention, which also affects blood pressure. Clinical data is limited. Toprol-XL (metoprolol), Farxiga (dapagliflozin) MONITOR: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors may potentiate the hypotensive effects of diuretics and other antihypertensive agents or vasodilators. Inhibition of glucose and sodium co-transport produces mild diuresis and transient natriuresis, resulting in intravascular volume contraction. Volume depletion-related adverse reactions including hypotension, postural dizziness, orthostatic hypotension, syncope, and dehydration can occur after initiating treatment with SGLT-2 inhibitors, and the risk may be increased with concomitant use of other agents that can lower blood pressure. Drugs.com, 2023 24 Drug-Drug Interaction (cont…) Proventil (albuterol), Farxiga (dapagliflozin) Advair Diskus (fluticasone / salmeterol), Farxiga (dapagliflozin) MONITOR: The efficacy of insulin and other antidiabetic agents may be diminished by certain drugs, including atypical antipsychotics, corticosteroids, diuretics, estrogens, gonadotropin-releasing hormone agonists, human growth hormone, phenothiazines, progestins, protease inhibitors, sympathomimetic amines, thyroid hormones, L-asparaginase, alpelisib, copanlisib, danazol, diazoxide, isoniazid, megestrol, omacetaxine, phenytoin, sirolimus, tagraxofusp, temsirolimus, as well as pharmacologic dosages of nicotinic acid and adrenocorticotropic agents. These drugs may interfere with blood glucose control because they can cause hyperglycemia, glucose intolerance, new-onset diabetes mellitus, and/or exacerbation of preexisting diabetes. Entresto (sacubitril / valsartan), Farxiga (dapagliflozin) MONITOR: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors may potentiate the hypotensive effects of diuretics and other antihypertensive agents or vasodilators. Inhibition of glucose and sodium co-transport produces mild diuresis and transient natriuresis, resulting in intravascular volume contraction. Volume depletion-related adverse reactions including hypotension, postural dizziness, orthostatic hypotension, syncope, and dehydration can occur after initiating treatment with SGLT-2 inhibitors, and the risk may be increased with concomitant use of other agents that can lower blood pressure. Drugs.com, 2023 25 Drug-Drug Interaction (cont…) Lipitor (atorvastatin), Entresto (sacubitril / valsartan) MONITOR: Coadministration with sacubitril may increase the plasma concentrations of drugs that are substrates of organic anion transporting polypeptides (OATP) 1B1 and 1B3, such as some HMG-CoA reductase inhibitors (i.e., statins). The proposed mechanism is sacubitril-mediated inhibition of hepatic uptake transporters OATP1B1 and/or OATP1B3. Coadministration of sacubitril-valsartan with atorvastatin increased the Cmax and AUC of atorvastatin by up to 2-fold and 1.3 fold, respectively. High levels of HMG-CoA reductase inhibitory activity in plasma are associated with an increased risk of musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death. All patients receiving statin therapy should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise and/or dark colored urine. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed. Drugs.com, 2023 26 Drug-Drug Interaction (cont…) Minor Drug-Drug Interactions Toprol-XL (metoprolol), Ecotrin (aspirin) High doses of salicylates may blunt the antihypertensive effects of beta-blockers. The proposed mechanism is inhibition of prostaglandin synthesis. Low-dose aspirin does not appear to affect blood pressure. In addition, beta-blockers may exert an antiplatelet effect, which may be additive with the effects of some salicylates. Metoprolol may also increase aspirin absorption and/or plasma concentrations of salicylates; however, the clinical significance of this effect is unknown. Proventil (albuterol), Advair Diskus (fluticasone / salmeterol) Advair Diskus (fluticasone / salmeterol), Advair Diskus (fluticasone / salmeterol) Although they are often combined in clinical practice, the concomitant use of beta-2 adrenergic agonists and corticosteroids may result in additive hypokalemic effects. Since beta-2 agonists can sometimes cause QT interval prolongation, the development of hypokalemia may potentiate the risk of ventricular arrhythmias including torsade de pointes. However, clinical data are limited, and the potential significance is unknown. Coumadin (warfarin), Lipitor (atorvastatin) Theoretically, no interaction should occur with other oral anticoagulants and atorvastatin, although data is lacking. Drugs.com, 2023 27 Drug-Food Interaction Moderate Drug-Food Interactions Coumadin (warfarin) Vitamin K may antagonize the hypoprothrombinemic effect of oral anticoagulants. Resistance to oral anticoagulants has been associated with consumption of foods or enteral feedings high in vitamin K content. Likewise, a reduction of vitamin K intake following stabilization of anticoagulant therapy may result in elevation of the INR and bleeding complications. Foods rich in vitamin K include beef liver, broccoli, Brussels sprouts, cabbage, collard greens, endive, kale, lettuce, mustard greens, parsley, soybeans, spinach, Swiss chard, turnip greens, watercress, and other green leafy vegetables. Intake of vitamin K through supplements or diet should not vary significantly during oral anticoagulant therapy. The diet in general should remain consistent, as other foods containing little or no vitamin K such as mangos and soy milk have been reported to interact with warfarin. Toprol-XL (metoprolol) The bioavailability of metoprolol may be enhanced by food. Lipitor (atorvastatin) Coadministration with grapefruit juice may increase the plasma concentrations of atorvastatin. Fibers such as oat bran and pectin may diminish the pharmacologic effects of HMG-CoA reductase inhibitors by interfering with their absorption from the gastrointestinal tract. Drugs.com, 2023 28 Drug-Food Interaction (cont…) Entresto (sacubitril / valsartan) Moderate-to-high dietary intake of potassium, especially salt substitutes, may increase the risk of hyperkalemia in some patients who are using angiotensin II receptor blockers (ARBs). Farxiga (dapagliflozin) Alcohol may cause in patients with diabetes. Hypoglycemia most frequently occurs during acute consumption of alcohol. Even modest amounts can lower blood sugar significantly, especially when the alcohol is ingested on an empty stomach or following exercise. Drugs.com, 2023 29 HF PATIENT COUNSELING Based on the pharmacotherapeutic plan, describe how you would counsel the patient. You can also include lifestyle modifications in your response. HF Management Explain to the patient the pathophysiology of HF, the prognosis of HF and the long-term effects on the organs Discuss lifestyle modifications, including diet and exercise, fluid and sodium restriction. Educate on rising slowly from supine to standing to avoid orthostatic hypotension Discuss importance of treatment plan and importance of adherence to treatment plan Educate on self-monitoring of symptoms of worsening HF, include daily weight Discuss what to do when symptoms worsen Instruct on importance of regular f/u with PCP Discuss on for drug therapy and its action for HF Discuss dosing and schedule of meds Discuss adverse effects of medications and what to do if they occur Discuss interactions with drug-drug and drug-food medications for treatment other than HF Woo & Robinson, 2020 30 References: AstraZeneca (2010) Highlights of Prescribing Information. Retrieved June 22, 2023, from https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020297s036lbl.pdf Drug Interaction Report: Advair Diskus, Coumadin, Ecotrin, Entresto, Farxiga, Lipitor, Proventil, Spiriva, Toprol-XL (drugs.com). (2023). Drugs.com. Retrieved June 23, 2023, from https://www.drugs.com/interactions-check.php?drug_list=1126-657,2311-1529,243-2548,3637-17453,3506-16379,276-128,109-41,2202-10791,16153128&types%5B%5D=major&types%5B%5D=minor&types%5B%5D=moderate&types%5B%5D=food&types%5B%5D=therapeutic_duplication&professional=1 Ferri, F. F. (2023). Ferri's Best Test: A Practical Guide to Clinical Laboratory Medicine and Diagnostic Imaging (5th ed.). Elsevier. Merck Manuals Professional Edition (2023). Entresto. Elsevier. Retrieved June 23, 2023, from Search results for: entresto - Merck Manuals Professional Edition Merck Manuals Professional Edition (2023). Farxiga. Elsevier. Retrieved June 23, 2023, from Search results for: farxiga - Merck Manuals Professional Edition Merck Manuals Professional Edition (2023). Toprol XL. Elsevier. Retrieved June 23, 2023, from Search results for: toprol xl - Merck Manuals Professional Edition Merck Manuals Professional Edition (2023). Warfarin. Elsevier. Retrieved June 23, 2023, from Search results for: warfarin - Merck Manuals Professional Edition Woo, T. M. & Robinson M.V. (2020). Pharmacotherapeutics for Advanced Practice Nurse Prescribers (5th ed). Philadelphia, PN: F.A. Davis. 31 THANK YOU!
