Diuretics Flashcards
What are the Thiazides diuretics?
hydrochlorothiazide Metolazone Chlorthalidone
What are the loop diuretics (edema, hypertension)?
-semide
- Furosemide (biggy)
- Torsemide
- Bumetanide
- Ethacrynic Acid (only one that isn’t a sulfa drug)
What are the K+ sparing diuretics (edema, hypertension). Specifically, Na+ channel blockers?
Amiloride Triamterene
What are the K+ sparing diuretics (edema, hypertension), specifically aldosterone antagonists?
(Also as antifibrotic in heart failure)
- Spironolactone
- Eplerenone
What are the aquaretics (hyponatremia)
-vaptan Conivaptan Tolvaptan MOA: Inhibit ADH receptors
What are the Carbonic Anhydrase inhibitors? What are the used to treat?
Acetazolamide
- urinary alkalinization (ex. ASA overdose trapping in lumen)
- Mountain sickness (you blow off CO2 because of altitude, acetazolamide gets ride of bicarbonate to balance things out)
- Glaucoma
Osmotic diuretics maintain urine flow by pulling water from cells for excretion. What are their names?
Mannitol
What’s the difference between a natriuretic and an aquaretic?
Natriuretic: diuretic that promotes renal excretion of sodium Aquaretic: diuretic that promotes free water clearance
Where do osmotic diuretics act within the nephron?
Proximal tubule Thin descending limb of Henle
Where do carbonic Anhydrase inhibitors act within the nephron?
Proximal tubule
Where do loop diuretics act on in the nephron?
Thick ascending limb of Henle
Where do thiazide diuretics act in the nephron?
Distal convoluted tubule
Where do Na+-channel blockers act on the nephron?
Cortical collecting duct
Where do vaptans act on the nephron?
Collecting duct:
- Prevents ADH-mediated insertion of aquaporins into the membranes of principle cells
The majority of diuretics are of what type?
Natriuretics
What are common clinical reasons for administering diuretics?
- Essential hypertension
- Edema (CHF, liver failure, kidney failure)
What are the K+ sparing diuretics?
- Triamterene (Na+ channel blocker)
- Amiloride (Na+ channel blocker)
- Spironolactone (aldosterone antagonist)
What are the K+ losing diuretics?
- Thiazides (Na+ Cl- cotransporter blockers)
- Loop diuretics (Na+ K+ 2Cl- cotransporter blockers)
- Carbonic Anhydrase inhibitors (seldom used)
- Osmotic diuretics (non reabsorbable solutes)
What are two concerns of hyperkalemia?
Tall T waves
Arrhythmias:
- Bradycardia
- Ventricular tachycardia Fibrillation
Gives the greatest amount of diuresis. Sulfa type drugs.
Loop diuretics
What is the mechanism of action of loop diuretics?
MOA: Blocks the Na+-K+-2Cl- cotransporter in the thick ascending limb of Henles’s Loop
Diuretic that causes the greatest HCO3- loss?
Thiazide diuretics
What are the therapeutic uses of Thiazides?
Hypercalcemia:
- osteoporosis tx
- recurrent calcium kidney stone tx
- Primary hypertension (combined w/ other drugs)
- Paradoxically treats nephrogenic diabetes insipidus
- Synergistic effects w/ loop diuretics
What type of urine do Loop Diuretics (Furosemide) produce regardless if the patient is excreting concentrated or already dilute urine?
Large volumes of isotonic urine
max doses produce profound diuresis
What is another common name for Furosemide a loop diuretic?
Lasix
What are the indications for Loop Diuretics?
- Edema of hepatic, cardiac, or renal origin
- Acute pulmonary edema (removes EC fluid <30 min)
- Furosemide produces a prostaglandin effect (venodilation —> reduced preload)
When rapid and massive fluid removal is needed
What is an additional benefit of Furosemide aside from its actions as a diuretic?
Thought to mediate prostaglandin-mediated venodilation reducing preload
Pt presents hypertensive and a thiazide diuretic is indicated, but GFR is too low (< 30mL/min) and a thiazide diuretic won’t work. What can you use instead?
Loop Diuretic (Furosemide)
Still works when RBF and GFR are low
What are the adverse effects of Loop Diuretics?
- Hyponatremia
- hypochloremia
- Hypovolemia & hypotension
- Hypocalcemia (result of hypokalemia) —> kidney stone formation
- Hypomagnesemia (result of hypokalemia)
- hyperglycemia
Hypokalemia (potassium losing diuretic):
- Na+ reabsorbed using a K+/H+ exchanger leading to hypochloremic metabolic alkalosis
What are drug interactions to loop diuretics?
- Digoxin (Digoxin and LDs lower K+) digoxin is a competitive inhibitor of K+ in the heart
- ototoxic drugs - risk of hearing loss
- potassium-sparing diuretics
What is the MOA of thiazides?
Blocks the Na-Cl cotransporter in the distal convoluted tubule
- Thiazides result in severe magnesium wasting
What diuretic doesn’t function well with a low GFR (< 30 mL/ ) and low RBF?
Thiazide diuretics
What are the adverse effects of Thiazide diuretics?
- hypochloremic metabolic alkalosis
- hypomagnesia
What are the drug interactions to be conscious of with Thiazide diuretics?
increases risk of digoxin and lithium toxicity
in terms of ion excretion what are the major differences between thiazides and loop diuretics?
Thiazides as compared to loop diuretics:
- less Na+ excretion
- less K+ excretion
- more bicarbonate excretion
What is the MOA of amiloride and triamterene?
K+ sparing diuretics (Na+ channel blockers)
blocks luminal Na+ channels (ENaC) in the collecting duct
What is the MOA of spirinolactone and eplerenome?
K+ sparing diuretic (aldosterone receptor blocker)
blocks aldosterone receptors in the colleting duct
What is the therapeutic use of triamterene?
K+ sparing diuretic (Na+ channel blocker)
- tx: hypertension
- tx: edema
What are the adverse effects of triamterene?
K+ sparing diuretic (Na+ channel blocker)
- hyperkalemia
- nausea, vomiting, leg cramps, and dizziness
What’s the key difference between K+ sparing diuretics: Na+ channel blockers vs aldosterone antagonists?
aldosterone antagonisits such as spironolactone is a steroid and can take 48 hours to work.
Na+ channel blockers are much more immediate
Known to greatly reduce mortality rate in patients with severe heart failure due to decreasing myocardial fibrosis and reducing early morning rises in heart rate
Spironolactone
What are adverse effects of the K+ sparing diuretic Spironolactone?
- Hyperkalemia
Endocrine effects:
- Gynecomastia - major differentiation from Eplerenone (not seen w/ eplerenone use)
- Impotence
- menstrual irregularities
- hirsutism (abnormal hair growth)
- deepening voice
What are drug interactions of K+ sparing diuretics, Spironolactone?
- DO NOT give w/ drugs increasing plasma potassium
- use cautiously w/ ACE (-) in heart failure
- combined w/ thiazides & loop diuretics to counteract their potassium loss
What are the therapeutic uses of Spironolactone?
K+ sparing diuretic (aldosterone antagonist)
- Primary hyperaldosteronism
- severe heart failure (anti-fibrotic agent)
- Combined with K+ losing diuretics to counteract potassium loss
What is the MOA of aquaretics? What’s the goal of their use?
-vaptans (Conivaptan, Tolvaptan)
Increase free water clearance by selective V2 receptor antagonism
the purpose being to correct for a proper Na+:free water
What is a major consideration with the oral administration of aquaretics such as Tolvaptan?
can cause hyponatremia and should be used for less than 30 days or the patient runs the risk of developing hepatotoxicity
Non-peptide arginine vasopressin receptor antagonists w/ affinity for receptor subtype V1A and V2
Aquaretics: Conivaptan, Tolvaptan
Which aquaretic is given orally and which is administered by IV?
Tolvaptan - oral
Conivaptan - Intravenously
What are the clinical applications of Aquaretics (Conivaptan, Tolvaptan)
- Euvolemic/hypervolemic hyponatremia (correcting Na+:free water)
- slows progression of adult polycystic kidney disease (must monitor liver)
What is the typical dose for an osmotic diuretic (mannitol)?
50-200 grams over 24 hours
If you’re presented with a patient with: renal insufficiency, nephrotic syndrome, or severe congestive heart failure what is your first choice diuretic?
Loop diuretic (Furosemide)
then add thiazide if you need to
(these are acute patients that need to lose fluid fast)
What is a major difference between Spironolactone and Eplereonone?
Both K+ Sparing (Aldosterone antagonists)
Eplerenone - does not cause gynecomastia
Spironolactone - has been correlated w/ gynecomastia
