Exam 2 - Diuretics Flashcards
The following medications belong to what class of diuretics?
- Acetazolamide
- Dorzolamide
- Brinzolamide
Carbonic Anhydrase Inhibitors
What is the MOA of Carbonic Anhydrase Inhibitors?
- Inhibits CA enzyme in the proximal tubule
- Blocks the production of H2CO3
- Decreases the amount of H+ available (due to no H2CO3) to exchange with Na+, resulting in increased Na+ and H2O loss
What are some indications for use of Carbonic Anhydrase Inhibitors?
- Glaucoma
- Alkalinization of urine
- Alkalosis
What are some adverse effects of Carbonic Anhydrase Inhibitors?
- Hyperchloremic metabolic acidosis (Na+ loss is in the form of NaHCO3, not NaCl)
- Hypokalemia (more Na+ in lumen –> increased Na+/K+ exchange)
- Hyperuricemia (compete for uric acid excretion)
What are some contraindications for Carbonic Anhydrase Inhibitors?
- Hepatic cirrhosis
- Sulfa hypersensitivity
What are examples of Loop Diuretics?
- Furosemide (Lasix)
- Ethacrynic Acid
What is the MOA of Loop Diuretics?
- Block the NKCC2 transporter which reduces the renal medulla concentration gradient and leads to impaired function in concentrating/diluting (Na+, K+, and Cl- remain outside the cell and in the lumen)
- Induces kidney PGs which decreases salt transport and cause vasodilation
What is the most powerful class of diuretics?
Loop Diuretics
What are indications for using a Loop Diuretic?
- HF
- Pulmonary edema (relieves congestion by increasing systemic venous capacitance)
- Hypercalcemia (loops decrease the reabsorption of Mg and Ca by reducing K+ gradient which is needed to drive Mg/Ca reabsorption)
- Low GFR
What are some adverse effects from Loop Diuretics?
- Hypokalemic metabolic acidosis (K+ still being exchanged/loss for Na+ via the Na-K+ pump, but no K+ is coming back into the cell due to the inhibited NKCC2)
- Hypocalcemia and hypomagnesemia (Mg/Ca reabsorption are reduced as this is driven by an increased K+ concentration)
- Hyperuricemia
- Irreversible ototoxicity (ethacrynic acid is worse; all worse when given with aminoglycosides)
What are some contraindications to Loop Diuretics?
- Sulfa hypersensitivity (except ethacrynic acid)
- Drug interactions with aminoglycosides, Lithium, Digoxin
- Overuse in those with cirrhosis, borderline renal failure, HF
Which loop diuretic has the highest risk of ototoxicity?
Ethacrynic acid
When would you give Ethacrynic acid over Furosemide?
If patient has a sulfa allergy
The following medications belong to what class of diuretics?
- Hydrochlorothiazide
- Metolazone
- Indapamide
Thiazide Diuretics
What is the MOA of Thiazide Diuretics?
- Inhibition of sodium reabsorption at the early distal tubule via inhibiting the Na+, Cl- co-transporter
What are some indications/therapeutic effects of Thiazide Diuretics?
- HTN (one of recommended initial drugs)
- HF
- Lower BP and enhance antihypertensive action of other drugs
- Nephrolithiasis (removes calcium from the tubules)
What makes Indapamide different from the other Thiazide Diuretics?
Excreted by biliary system and is therefore useful is patients with renal insufficiency
What are adverse effects of Thiazide Diuretics? (there are a lot)
- Hypokalemic metabolic alkalosis (induce K+ and H+ loss at distal exchange sites for Na+; causes plasma volume contraction which stimulates aldosterone, further encouraging K+ loss)
- Dizziness, leg cramps, weakness
- Hyperuricemia (compete for uric acid excretion and may induce gouty attacks)
- Hypomagnesemia (enhances Mg excretion)
- Hyperglycemia (may decrease release of insulin and increase glucose intolerance)
- Elevated serum lipid levels (due to decreased insulin levels - except Indapamide)
- Lithium toxicity (clearance is reduced)
What are some contraindications/precautions of Thiazide Diuretics?
- Sulfa allergy
- Diabetics
- Hypokalemia may precipitate digitalis toxicity in cirrhotic patients
- Caution in those with hx of gout
What are three major differences associated with Indapamide compared to other Thiazide drugs?
- Causes pronounced vasodilation
- Does not increase plasma lipids
- Metabolized in liver and kidney
What are the two classes of Potassium sparing diuretics?
- Aldosterone antagonists (Spironolactone, Eplerenone)
- Direct inhibitors of Na+ flux (Amiloride, Triamterene)
What is the MOA of Spironolactone and Eplerenone (Potassium sparing diuretics)?
1) Competitive inhibitor of aldosterone which causes the promotion of Na+ excretion and retention of K+
2) Less Na+ channels
3) Blocked Na+ conductance –> hyperpolarized cell –> decreased K+ excretion
4) Decreased Na+-K+-ATPase activity –> decreased K+ secretion and excretion
What are indications/therapeutic effects of Spironolactone?
- Edema associated wit HF, cirrhosis, and nephrotic syndrome
- Hyperaldosteronism
- Hirsutism (at high doses, can become an adrogen receptor antagonist)
What are some adverse effects associated with Spironolactone?
- GI upset, cramps, dizziness
- Gynecomastia
- Occasional hyperkalemia
