Pharmacotherapeutic Challenge Diuretic Resistance

Transcription

1 Pharmacotherapeutic Challenge Diuretic Resistance Barry E. Bleske, Pharm. D, FCCP Associate Professor University of Michigan, College of Pharmacy Learning Objectives Describe the causes for HF readmission. List key concepts related to diuretic effectiveness. List the reasons for diuretic resistance. Develop a therapeutic plan to overcome diuretic resistance. 1

2 Heart Failure Hospitalizations 1.0 Million Hospitalizations a Year and Rising 700 Discharges in Thousands Day Rehospitalization Rates in HF 24.8% (Medicare) Years Male Female The majority of patients hospitalized with HF were previously hospitalized with HF United States: Source: NHDS/NCHS, NHLBI. Hospital Compare Causes of Hospital Readmission for Heart Failure Over 2/3 of HF Hospitalizations Preventable Diet Noncompliance 24% Rx Noncompliance 24% 16% Inappropriate Rx Annals of Internal Medicine 122:415-21, % Failure to Seek Care 17% Other 14 2

3 Patient Case Mrs. HF comes to your clinic (or calls you) and after your assessment you find out that she has the following: 5lb weight gain Increase SOB Increase ankle edema Your assessment is that she is likely fluid overloaded. Patient Case Current Medications: Zestril 20 mg qd (no recent change) Toprol XL 100mg qd (no recent change) Furosemide 40 mg qd Crestor 10 mg qd Plavix 75 mg qd ASA 81 mg qd Next Step?? 3

4 Diuretic Therapy Key Concepts Diuretics Loop diuretics most often used most potent. Diuretic Threshold Diuretic Resistance 4

5 PD of Loop Diuretics 20 F e N a+ (% ) U rinary D iuretic C onc 5

6 PD of Loop Diuretics 20 F e N a + (% ) Diuretic Threshold 0 U rinary D iuretic C onc PD of Loop Diuretics 20 F e N a+ (% ) Diuretic Threshold 0 U rinary D iuretic C onc Furosemide 40 mg 80 mg 160 mg 6

7 Furosemide Bumetanide Torsemide Usual daily dose (po) mg/d mg/d mg/d Ceiling dose a Normal renal function CL CR ml/min CL CR <20 ml/min mg 160 mg 400 mg 1 2 mg 2 mg mg 40 mg 100 mg Bioavailability % Average: 50% 80 90% % Affected by food Yes Yes No Half-life h h 3 4 h (Bumex conv ~ 40:1 furosemide - bumex) (Torsemide conv ~ 2-4:1 furosemide - torsemide) Brater DC. Pharmacology of Diuretics. Am J Med Sci 2000;319: Key Concepts Diuretics Loop diuretics most often used most potent. Diuretic Threshold Diuretic Resistance 7

8 Diuretic Resistance Drug Compliance Dietary Compliance (sodium intake) Bioavailability, absorption absorption with furosemide as pts decompensate. Torsemide is better absorbed. May be preferred in sicker patients? Drug interactions (NSAID) Distal tubular hypertrophy PD of Loop Diuretics 20 S e r u m C o n c Diuretic Threshold 0 Dry Wet 8

9 Diuretic Resistance Drug Compliance Dietary Compliance (sodium intake) Bioavailability, absorption absorption with furosemide as pts decompensate Torsemide is better absorbed. May be preferred in sicker patients? Drug interactions (NSAID) Distal tubular hypertrophy 9

10 Distal Tubular Hypertrophy Enhanced sodium reabsorption at distal tubule Sequential blockade of loop of Henle and distal tubule Loop diuretic + thiazide diuretic Metolazone or HCTZ commonly used Metolazone 2.5mg to 10mg/day Delay in response, may take a few days for effect to stop, longer half-life. HCTZ 25mg to 100mg qd to bid. Faster onset, faster offset Patient Case Current Medications: Zestril 20 mg qd (no recent change) Toprol XL 100mg qd (no recent change) Furosemide 40 mg qd Crestor 10 mg qd Plavix 75 mg qd ASA 81 mg qd Next Step?? 10

11 Patient Case Next Step Additional background data to obtain? How is your water pill (name of drug) working? Assessing Diuretic Threshold Have you recently missed any doses of your water pill recently? Assessing Compliance Have you changed your diet recently have you been eating out more? Assessing Compliance Have you taken anything like ibuprofen or naproxen for anything recently? Assessing Drug Interactions Have you recently increased your dose of beta blocker or ACE-inhibitor? Assessing Dose Change Patient Case - Additional background data to obtain? How is your water pill (name of drug) working? Assessing Diuretic Threshold If urinating at threshold dose, may need to increase frequency to get more fluid off If not working well and compliant May need to increase dose to get to threshold (especially if patient is at a low dose) May need to switch to a better absorbed drug like torsemide. May need to add thiazide diuretic (especially if patient is already on a high dose of diuretic) 11

12 Patient Case - Additional background data to obtain? Have you recently missed any doses of your water pill recently? Assessing Compliance Improve compliance should help resolve fluid overload Have you changed your diet recently have you been eating out more? Assessing Compliance With dietary noncompliance, diuretic is likely working (ask patient) and if so just need to increase frequency of administration likely short term with improved dietary compliance. Patient Case Next Step Additional background data to obtain? How is your water pill (name of drug) working? Assessing Diuretic Threshold Have you recently missed any doses of your water pill recently? Assessing Compliance Have you changed your diet recently have you been eating out more? Assessing Compliance Have you taken anything like ibuprofen or naproxen for anything recently? Assessing Drug Interactions Have you recently increased your dose of beta blocker or ACE-inhibitor? Assessing Dose Change 12

13 Patient Case - Additional background data to obtain? Have you taken anything like ibuprofen or naproxen for anything recently? Assessing Drug Interactions D/C interacting drug - may need to increase diuretic dose or frequency short term (2-7 days?) until patient gets back to baseline. Patient Case - Additional background data to obtain? Have you recently increased your dose of beta blocker or ACE-inhibitor? Assessing Dose Change If recent dose change may need to return back to previous dose or increase diuretic frequency. 13

14 Overcoming Diuretic Resistance Improve drug and dietary compliance D/C interacting drugs Make sure at threshold dose Increase dose absorption? change to torsemide If at threshold and need to increase fluid lose - increase frequency of administration Add thiazide type diuretic distal tubular hypertrophy. Finally, don t forget to monitor (K, Mg, BP, etc) 14