EXAM 2 - LOOP DIURETICS

Location And Mechanism Of Action

"Thick Ascending Limb" - Loop Of Henle ***Blocks Na+/K+/2CL- Cotransport w/in Tubules Luminal Membrane = ↓ reabsorption of electrolytes ↑Secretion/↑Excretion: Na+, K+, CL-, Mg2+, Ca2+ "loops Lose Ca2+" ↑Dilute Urine Excretion ↑Prostaglandin Synthesis = ↑Renal Blood Flow = ↑Solute Delivery to Nephron

A 57-year-old man with a history of heavy alcohol use is being admitted for a first episode of congestive heart failure (CHF), which likely resulted from untreated alcoholic cardiomyopathy. The cardiologist decides to start the patient on diuretic therapy. Which class of diuretics is preferred in this scenario? (A) Loop diuretics, because they exert their action at the distal convoluted tubule (B) Loop diuretics, because the thick ascending limb is an area of high capacity for NaCl reabsorption (C) Thiazide diuretics, because they exert their action at the thick ascending limb of the loop of Henle (D) Thiazide diuretics, because they increase cardiac output (E) Thiazide diuretics, because they increase peripheral vascular resistance

B. Loop diuretics are used in cases of congestive heart failure (CHF) and pulmonary edema because they result in fast and significant diuresis. These agents exert their action at the thick ascending limb of the loop of Henle, which is the area of highest capacity for NaCl reabsorption. Thiazide diuretics actually decrease cardiac output initially, because of decrease blood volume. As well, thiazides decrease peripheral vascular resistance, because they relax arteriolar smooth muscle.

SC is a 75-year-old white male who has HF. He is seen in clinic today, reporting shortness of breath, increased pitting edema, and a 5-pound weight gain over the last 2 days. His current medication regimen includes losartan and metoprolol succinate. SC has no chest pain and is deemed stable for outpatient treatment. Which of the following is the best recommendation? A. Increase the dose of metoprolol succinate. B. Start hydrochlorothiazide. C. Start furosemide. D. Discontinue losartan.

C. As it is possible that SC is having a HF exacerbation, increasing the dose of the β-blocker is not indicated at this time. There is no reason to stop losartan, based on the information we have. Loop diuretics are preferred over thiazide diuretics when patients require diuresis immediately.

A 54-year-old man develops congestive heart failure (CHF) after suffering his second myocardial infarction. His physician puts him on a regimen of several medications, including furosemide. On follow-up, the patient is found to have hypokalemia, likely secondary to furosemide use. The addition of which medication would likely resolve the problem of hypokalemia, while helping to treat the underlying condition, CHF? (A) Allopurinol (B) Hydrochlorothiazide (C) Spironolactone (D) Acetazolamide (E) Ethacrynic acid

C. Spironolactone is commonly added to the regimen of anti-congestive heart failure (CHF) medications, since it counteracts the loss of potassium caused by the loop diuretics such as furosemide. This agent is also effective in reducing the symptoms of refractory edema. Allopurinol is not used to treat CHF. Hydrochlorothiazide will exacerbate hypokalemia caused by the loop diuretics. Acetozolomide will not counteract hypokalemia. Ethacrynic acid is an example of another loop diuretic.

6. An 87-year-old woman who is taking multiple medications for her "heart disease" is prescribed gentamicin for diverticulitis. After a few days of taking the antibiotic, she complains of dizziness and tinnitus. What "heart medication" might she be on? (A) Spironolactone (B) Hydrochlorothiazide (C) Mannitol (D) Ethacrynic acid (E) Urea

D. Ototoxicity, as demonstrated by tinnitus and dizziness, is a common side effect of loop diuretics, especially ethacrynic acid. This effect is magnified when aminoglycoside antibiotics are added to the regimen. Spironolactone is not associated with tinnitus. Hydrochlorothiazide can cause gout in susceptible individuals. Mannitol and urea are osmotic diuretics and are not indicated in patients with heart disease, especially congestive heart failure (CHF).

Which drug may exacerbate HF? A. Acetaminophen. B. Cetirizine. C. Chlorthalidone. D. Ibuprofen.

D. NSAIDs, such as ibuprofen, lead to increased fluid retention and increased blood pressure. If possible, NSAIDs should be avoided in HF patients in order to avoid exacerbations of HF.

A 66-year-old woman suffers a myocardial infarction while in the hospital and immediately goes into respiratory distress. On examination, you realize the patient has flash pulmonary edema as a result of her infarction. Along with the management of the myocardial infarction, you start the patient on furosemide therapy to treat pulmonary edema. What is the mechanism of action of this agent? (A) Inhibition of action of aldosterone by binding to its receptor in principal cells of the collecting duct (B) Reduction of bicarbonate reabsorption and concomitant sodium uptake (C) Inhibition of active reabsorption of sodium chloride at the distal convoluted tubule (D) Alteration of the diffusion of water relative to sodium, thereby reducing sodium reabsorption (E) Inhibition of active reabsorption of sodium chloride at the thick ascending limb of the loop of Henle

E. Loop diuretics inhibit active NaCl reabsorption in the thick ascending limb of the loop of Henle by inhibiting a specific Na1/K1/2Cl2 cotransporter. Inhibition of action of aldosterone by binding to its receptor in principal cells of the collecting duct describes the mechanism of action of potassium-sparing diuretics. Reduction of bicarbonate reabsorption and concomitant sodium uptake refers to carbonic anhydrase inhibitors. Inhibition of active reabsorption of sodium chloride at the distal convoluted tubule describes thiazide diuretics. Finally, alteration of the diffusion of water relative to sodium, thereby reducing sodium reabsorption, refers to osmotic diuretics.

Loop Diuretics (Name Them)

Furosemide (Lasix) Torsemide (Demadex) Bumetanide Ethacrynic Acid (Edecrin) - "The Weirdo" Non-Sulfa + ↑ Ototoxic

Side Effects

OTOTOXICITY and/or Deafness Reversible - Furosimide (Lasix) End Trx Irreversible - Ethacrynic Acid (Edecrin) Hypo: Kalemia = Alkalosis, Calcemia, Magnesemia, Chloremia = Metabolic Acidosis Hyper: Glycemia (Caution: Diabetes Mellitus) Uricemia (Caution: Gout) Dehydration

Indications

Strongest Diuretic 1st Line Agent: ***CHF = Acute Decompensated Heart Failure = EDEMA aka "fluid overload", Dyspnea (Secondary to P. Edema), Orthopnea, SOB etc. Pulmonary Edema = Cyanosis, Digital Clubbing, JVD, etc. Nephrotic Syndrome = Edema Cirrhosis = Portal Hypertension = Ascites, peripheral edema, Varicosity of Veins etc. Combined Trx = Loop + Sporanolactone HTN - In Combo w/ Other Agent ***ETHACRINIC ACID - All of the above + Sulfa-Allergy Dx

Contraindications

Sulfa Allergy Dx: EXCEPTION - Non-Sulfa: Ethacrynic Acid NSAIDS - Decrease Prostaglandin Synth = Decrease Renal Blood Flow = Decrease Drug Efficacy