Diuretics, leg cramps, and resistant hypertension (Reboot)

March 4, 2019 | By Matthew Watto, MD

Classic episode with a fresh intro featuring Joel Topf MD

Listen to our first ever discussion with @kidney_boy, Joel Topf MD. It’s a classic diuretics episode with a fresh intro as we prepare for @NephMadness 2019 with our friends from Twitter and @AJKDonline

Dominate leg cramps, diuretic therapy, and resistant hypertension with tips from @kidney_boy, Joel Topf MD @kidney_boy, Chief of Nephrology Kashlak Memorial Hospital, co-creator @NephMadness. We start with basic renal physiology and build up to the treatment of resistant hypertension.

Corrections: Dr Topf posted the following corrections on his blog PBfluids.com 3/22/2017

I enjoyed the experience immensely, but in an hour of talking off the cuff I made some embarrassing mistakes:

Joel Topf MD

In describing water reabsorption I said it occured in the cortical collecting duct rather than the medullary collecting duct.

In describing my cure for cramps I tell the story of Gitelman’s and say it is like congenital loop diuretics rather than congenital thiazide diuretics

I mucked up the story about the MRFIT story and how it allowed a head to head comparison of HCTZ and chlorthalidone. I really oversold what happened.”

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Credits

Written by: Matthew Watto MD

Produced by: Stuart Brigham MD and Matthew Watto MD

Cohosts: Stuart Brigham MD and Matthew Watto MD

Guest: Joel Topf MD

Sponsor

Time Stamps

• 00:00 Sponsor – Become a member of the American College of Physicians
• 00:28 Disclaimer, Intro, Recap of upcoming shows, Corrections and Omissions
• 05:50 Guest one-liner, Discussion of social media in medical education, Joel’s book
• 12:45 Twitter for medical education including NephJC and NephMadness
• 19:50 Sponsor – Become a member of the American College of Physicians
• 21:30 Intro to diuretics, mechanism of action and a brief review of renal physiology
• 28:26 Use of thiazide diuretics
• 30:18 Chlorthalidone versus hydrochlorothiazide
• 34:47 Diuretics and hyponatremia, Monitoring electrolytes and renal function on diuretics
• 39:05 Leg (muscle) cramps and pickle juice
• 42:55 Thiazides, osteoporosis and fracture prevention
• 45:32 Resistant hypertension and  the workup for secondary hypertension
• 53:36 Loop diuretics: how to choose an agent, dosing
• 62:15 Take home points
• 67:00 Outro

Diuretic Clinical Pearls

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; medullary collecting duct = “brains of the kidney” for fine tuning, potassium and hydrogen secreted

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) —Se Won Oh Electrolyte Blood Press 2015 PMC4520883.

Diuretics

Diuretic Resistance

Case 1: No response despite reasonable dose. Treat with higher dose or different route (e.g. IV)

Case 2: Initial diuresis, then dose wears off and 24 hour urine output inadequate. Patient is sodium avid. Treat with more frequent dosing.

Thiazide and thiazide-like diuretics

1. 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 (Lexi-Drugs).
2. Hydrochlorothiazide: Duration: Adults: 6 to 12 hours; Half-life elimination: ~6 to 15 hours (Lexi-Drugs).

Loop Diuretics

Furosemide

Furosemide dosing: Topf dosing = Cr times 20 (alternate method: House of God dosing = age + BUN).

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]

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]

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]

Diuretics hyponatremia, legs cramps and fracture risk

Hyponatremia

Kashlak Pearl: Dr Topf notes that Hyponatremia causes 1) weakness, falls 2) osteoporosis [sodium removed from bones to maintain serum sodium]

Fractures

Thiazide diuretics lower urine calcium excretion and protect against fractures (see Cochrane Review and ALLHAT)

DASH diet should be used for patients with hypertension (rich in potassium).

Leg cramps

Kashlak Pearl: Try 1 tablespoon of pickle juice as needed for nocturnal leg cramps. Make sure to SELL IT!

Resistant Hypertension

Resistant hypertension is diagnosed when pressure is uncontrolled despite at least 3 drugs (including a diuretic). Add spironolactone in these cases —Pathway 2 Trial, Lancet 2015.

Look for a ratio of plasma aldosterone to plasma renin activity above 20 (with older assays). Additionally, an aldosterone level above 15 suggests primary hyperaldosteronism.

Kashlak Pearl: It is OKAY to check renin and aldosterone even if your patient is on an ACEI/ARB/diuretic. But, interpretation is more challenging if on an aldosterone antagonist.

Goals and Learning Objectives

Goals

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. The Curbsiders report no relevant financial disclosures.

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

Citation

Topf, Joel. “Reboot – Diuretics, leg cramps, and resistant hypertension”. The Curbsiders Internal Medicine Podcast http://thecurbsiders.com. March 4, 2018.