#31 Diuretics, leg cramps, and resistant hypertension with The Salt Whisperer

March 20, 2017 | By Matthew Watto, MD

Dominate leg cramps, diuretic therapy, and resistant hypertension. Our guest, Dr. Joel Topf, is a clinical nephrologist, pioneer in the use of social media for medical education, and Assistant Clinical Professor at Oakland University William Beaumont School of Medicine, best known for his blog, Precious Bodily Fluids, and hilarious/informative Twitter feed @kidney_boy. We start with basic renal physiology and build up to the treatment of resistant hypertension.

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Clinical Pearls:

1. Renal physiology: Glomerulus = basket filter; Proximal tubule = “big dumb reabsorption”; loop of henle = “engine of the kidney” dilutes fluid, and concentrates medullary interstitium; distal convoluted tubule = “intelligent”, finely controlled reabsorption of sodium and water; cortical collecting duct = “brains of the kidney” for fine tuning, potassium and hydrogen secreted
2. Diuretics get secreted into proximal tubule before acting, thus if low renal blood flow, higher doses needed to achieve effect (thus the “lasix threshold” dose)
3. Diuretic resistance: Case 1: No response despite reasonable dose. Treat with higher dose or different route (e.g. IV)
4. Diuretic resistance: Case 2: Initial diuresis, then dose wears off and 24 hour urine output inadequate. Patient is sodium avid. Treat with more frequent dosing.
5. Chlorthalidone: Duration: Single dose: 24 to 48 hours; Long-term dosing: 48 to 72 hours; Half-life elimination: Single dose: 40 hours; Long-term dosing: 45 to 60 hours; may be prolonged with CKD
6. Hydrochlorothiazide: Duration: Adults: 6 to 12 hours; Half-life elimination: ~6 to 15 hours
7. Hyponatremia causes 1) weakness, falls 2) osteoporosis [sodium removed from bones to maintain serum sodium]
8. Thiazide diuretics lower urine calcium excretion and protect against fractures (see Cochrane Review and ALLHAT below)
9. DASH diet should be used for patients with hypertension (rich in potassium)
10. Leg cramps: try 1 tablespoon of pickle juice as needed for nocturnal leg cramps
11. Resistant HTN: If uncontrolled despite at least 3 drugs (including a diuretic), then add spironolactone next
12. Resistant HTN: Ratio of plasma aldosterone concentration:plasma renin activity >20, or an aldosterone level >15 suggests primary hyperaldosteronism [OKAY to check even if on ACEI/ARB/diuretic, but not if on aldosterone antagonist]
13. Lasix dose: Topf dosing = Cr times 20 (alternate method: House of God dosing = age + BUN)
14. Furosemide: Bioavailability 10-100% [Brater, NEJM 1998]; Onset of action: Diuresis: Oral, SL: 30 to 60 minutes; IM: 30 minutes; IV: ~5 minutes; Duration: Oral, SL: 6 to 8 hours; IV: 2 hours; Half-life elimination: Normal renal function: 0.5 to 2 hours; End-stage renal disease: 9 hours [values from UTDOL.com]
15. Bumetanide: Bioavailability 80-100% [Brater, NEJM 1998]; Onset of action: Oral, IM: 0.5 to 1 hour; IV: 2 to 3 minutes; Duration: Oral: 4 to 6 hours; IV: 2 to 3 hours; Half-life elimination: Adults: 1 to 1.5 hours [values from UTDOL.com]
16. Torsemide: Bioavailability 80-100% [Brater, NEJM 1998]; Onset of action: Diuresis: Oral: Within 1 hour; IV: 10 minutes; Onset Anti-HTN effect 4-6 weeks!; Duration: Diuresis: Oral, IV: ~6-8 hours; Half-life elimination: ~3.5 hours; Cirrhosis: 7-8 hours [values from UTDOL.com]

Goal: Listeners will describe the basics of renal physiology, and apply it to the use of diuretics for treating hypertension and resistant hypertension.

Learning objectives:
By the end of this podcast listeners will:

1. Recall the main parts of the nephron the functions they serve
2. Describe the mechanisms of diuretic resistance
3. Differentiate between the thiazide diuretics
4. Examine possible causes of resistant hypertension and employ appropriate diagnostic testing
5. Explain the risks of hyponatremia with diuretic therapy
6. Utilize pickle juice to treat nocturnal leg cramps
7. Calculate the starting dose of lasix
8. Differentiate between the three main loop diuretics

Disclosures:
Dr. Topf reports no relevant financial disclosures.

Time Stamps
00:00 Intro
01:52 Rapid fire questions
16:10 Intro to diuretics
16:54 Brief review of renal physiology
19:50 Diuretics: mechanism of action
22:35 Use of thiazide diuretics
24:47 Chlorthalidone versus hydrochlorothiazide
29:10 Diuretics and hyponatremia
32:10 Monitoring electrolytes and renal function on diuretics
33:33 Leg (muscle) cramps and pickle juice
37:25 Thiazides, osteoporosis and fracture prevention
40:00 Resistant hypertension
44:00 Working up secondary hypertension
48:04 Loop diuretics: how to choose an agent, dosing
56:21 Take home points

Links from the show:

1. Precious Bodily Fluids: Musing of a Salt Whisperer blog by Dr. Joel Topf
2. Check out @kidney_boy on Twitter Dr. Topf’s feed
3. Clinical Physiology of Electrolytes and Acid Base by Burton Rose, creator of UpToDate
4. The Fluid, Electrolyte And Acid-base Companion by Sarah Faubel and Joel Topf
5. Review article of diuretic therapy with table comparing pharmacology of each agent by D. Craig Brater, MD
6. Thiazide diuretics reduce risk of hip fracture (Cochrane Review 2011)
7. ALL-HAT trial showed thiazides reduce fracture risk JAMA Int Med 2017
8. ALLHAT Summary – https://www.nhlbi.nih.gov/health/allhat/qckref.htm
9. ALLHAT Citation – https://www.ncbi.nlm.nih.gov/pubmed/12479763
10. Pathway 2 Trial, Lancet 2015 – https://www.ncbi.nlm.nih.gov/pubmed/26414968
11. ASCEND-HF trial comparing torsemide and furosemide http://circ.ahajournals.org/content/130/Suppl_2/A14658