Pharmacology Review of Renal Physiology & Diuretics - III and IV - Grassl Flashcards
What drugs decrease the ability of ADH to increase the water permeability of the late distal tubule and the collecting duct?
Aquaretics
What drugs decrease the solute reabsorption in one or more segments of the nephron?
Saluretics
Loop diuretics, thiazide diuretics and potassium-sparing diuretics are what kinds of drugs?
Saluretics
decrease the solute reabsorption in one or more segments of the nephron
Lithium is what kind of drug with respect to the kidney?
Aquaretic
decrease the ability of ADH to increase the water permeability of the late distal tubule and the collecting duct
Fluoride is what kind of drug with respect to the kidney?
Aquaretic
decrease the ability of ADH to increase the water permeability of the late distal tubule and the collecting duct
Demeclocycline is what kind of drug with respect to the kidney?
Aquaretic
decrease the ability of ADH to increase the water permeability of the late distal tubule and the collecting duct
Use: Demeclocycline
Aquaretic
To reverse the effect of inappropriate ADH secretion arising from ADH-secreting oat-cell carcinomas of the lung
Use: vaptan family of ADH receptot antagonists, ie Lixivaptan
Treat euvolemic hyponatremia
In what segment of the nephron do carbonic anhydrase inhibitors act?
Carbonic anhydrase inhibitors act in the proximal tubule by decreasing sodium and bicarbonate reabsorption –> decrease tubular reabsorption
Why do carbonic anhydrase inhibitors yield urine that has increased amounts of potassium?
Because the increase in sodium reabsorption in the late distal tubule and collecting duct is coupled to potassium secretion
Where do high-ceiling or loop diuretics exert their effects?
thick ascending limb of the loop of Henle (medullary portion)
Where do thiazide diuretics exert their effects?
thick ascending limb of the loop of Henle (cortical portion), (early distal tubule)
T/F: High-ceiling, loop and thiazide diuretics all significantly increase the amount of potassium in the urine.
True, because of the sodium reabsorption in the late distal tubule.
MOA: Potassium-sparing diuretics
Act in the late distal tubule and collecting duct to decrease sodium reabsorption (and potassium secretion)
Which diuretics induce the smallest diuresis?
Potassium-sparing diuretics
Which diuretics induce the largest diuresis?
Loop diuretics
T/F: When a patient is volume CONTRACTED, loop diuretics increase free water clearance by causing a decrease in osmotic clearance.
True
The result is a less negative free water clearance than in the absence of diuretic and an impaired ability to defend against dehydration and ECF volume contraction
T/F: When a patient is volume EXPANDED, loop diuretics decrease free water clearance (C-H2O) by causing an increase in osmolar clearance (C-osm)
True
The result is less positive free water clearance and an increase in the time necessary to return ECF volume to normal.
Where a patient is volume expanded, thiazide diuretics decrease the magnitude of positive free water clearance by causing:
Where a patient is volume expanded, thiazide diuretics decrease the magnitude of positive free water clearance by causing an increase in osmolar clearance –> increases the time necessary for the kidney to correct ECF volume expansion –> risk of hyponatremia
Class: Acetazolamide
Carbonic anhydrase inhibitor
Sulfonamide
Class: Methazolamide
Carbonic anhydrase inhibitor
Sulfonamide
Class: Dichlorphenamide
Carbonic anhydrase inhibitor
Sulfonamide
Class: Hydrochlorothiazide
Thiazide
Class: Dihydrochlorothiazide
Thiazide
Class: Ethacrynic acid
High-ceiling diuretic
Class: Furosemide
High-ceiling diuretic
Class: Torsemide
High-ceiling diuretic
Class: Bumetanide
Loop diuretic
Class: Spironolactone
Potassium-sparing diuretic
Class: Triamterene
Potassium-sparing diuretic
Class: Amiloride
Potassium-sparing diuretic
What diuretics are inhibitors of Na/Cl symport?
Thiazide diuretics
Act in the Early distal tubule
What diuretics are inhibitors of Na/K/2Cl symport?
Loop diuretics and high-ceiling diuretics
Act in loop of Henle
What diuretics are inhibitors of renal epithelial sodium channels OR antagonists of mineralcorticoid receptors?
Potassium-sparing diuretics
Act in the late distal tubule and collecting duct
Main uses: carbonic anhydrase inhibitors
Decrease intraocular volume and pressure;
Prevention and treatment of acute mountain sickness
Complications: Carbonic anhydrase inhibitors
Hypokalemia resulting from loss of potassium in the urine;
Toxicity can be caused by metabolic acidosis, bone marrow depression, skin toxicity, allergic reactions
Use: Aminophylline
To prevent and relieve inflammation and bronchospasm in patients with asthma
MOA: Aminophylline
Aminophylline = methylxanthine theophylline + ethylene diamine
Increases GFR;
Inhibits phosphodiesterase –> increases intracellular cAMP –> decreased sodium reabsorption in the proximal tubule
What is osmotic diuresis?
An increase in the rate and volume of urine elimination due to the filtration and presence of a nonreabsorbable solute in the tubular fluid.
ie Mannitol, excess glucose
Class: Mannitol
Osmotic diuretic
Use: Mannitol
Treatment of drug overdoses ie barbituates, to hasten the clearance of the drug;
Used in shock or major surgery to minimize acute renal failure;
To reduce intraocular and intracranial pressure
Risk: Mannitol
Pulmonary edema, because of transient increase in ECF volume and intravascular pressure
MOA: Mannitol
Opposes water and sodium reabsorption at proximal tubule –> increased osmolarity of tubular fluid
MOA:
Acetazolamide
Methazolamide
Dichlorphenamide
Inhibits luminal carbonic anhydrase at proximal tubule –> less activity of Na/H antiporter, decreased HCO3 and Na+ (and water) reabsorption
Are carbonic anhydrase inhibitors contraindicated for some patients?
Yes, cirrhotics
MOA: Furosemide Bumetanide Torsemide Ethacrynic acid
Loop diuretics
Inhibits Cl portion of Na-K-2Cl cotransporter in luminal membrane at medullary and cortical (proximal) talH –> decreased K+, Ca++ and Na+ reabsorption, resultant K+ loss
Use: Furosemide Bumetanide Torsemide Ethacrynic acid
Loop diuretics
Crisis edema (pulmonary, CHF, cirrhosis),
hypercalcemia,
drug toxicity/OD;
severe hypertension in setting of CHF or cirrhosis
Side effects: Furosemide Bumetanide Torsemide Ethacrynic acid
Hypokalemia/hypocalcemia/hypomagnesemia (–> arrhythmia),
contraction alkalosis,
increased BUN & creatinine,
ototoxicity (esp. w/aminoglycoside)
Other side effects: Hyper -glycemia, -lipidemia, -uricemia; hypo -magnesia, -natremia; gout, photosensitivity, nephrocalcinosis, drug interactions; erectile dysfunction
MOA:
Chlorothiazide
Hydrochlorothiazide
Thiazide diuretics
Inhibits the Cl portion of the Na-Cl cotransporter in the luminal membrane at the early distal tubule –> decreased Na+ (and water) reabsorption, increased Ca++ reabsorption, resultant K+ loss
Uses:
Chlorothiazide
Hydrochlorothiazide
Thiazide diuretics HTN (intravascular contraction), chronic edema (cardiac insufficiency), idiopathic hypercalciuria (stones), nephrogenic diabetes insipidus
Side Effects:
Chlorothiazide
Hydrochlorothiazide
Thiazide diuretics
Hypokalemia/hypercalcemia,
contraction alkalosis,
increased BUN & creatinine
READ: Contraindications for thiazide AND thiazide like diuretics: Chlorothiazide Hydrochlorothiazide Chlothalidone Quinethazone Metolazone Indapamide
FeNa = 8%; lethal interaction w/quinidine (v. tach –> fib, may be due to hyperkalemia);
avoid NSAIDs, bile sequestrants;
increased risk of hypokalemia w/anti-inflammatory steroids or Amphotericin B;
decreases positive free water clearance
Class: Chlothalidone Quinethazone Metolazone Indapamide
Thiazide-like diuretic
MOA: Chlothalidone Quinethazone Metolazone Indapamide
Thiazide-like diuretic
Inhibits the Cl portion of the Na-Cl cotransporter in the luminal membrane at the early distal tubule –> decreased Na+ (and water) reabsorption, increased Ca++ reabsorption, resultant K+ loss
Use: Chlothalidone Quinethazone Metolazone Indapamide
Thiazide-like diuretic HTN (intravascular contraction), chronic edema (cardiac insufficiency), idiopathic hypercalciuria (stones), nephrogenic diabetes insipidus
Side Effects: Chlothalidone Quinethazone Metolazone Indapamide
Thiazide-like diuretic
Hypokalemia/hypercalcemia,
contraction alkalosis,
increased BUN & creatinine
Class:
Amiloride
Triamterene
K+-sparing diuretic; renal ENaC inhibitor (+ charge)
MOA:
Amiloride
Triamterene
K+-sparing diuretic; renal ENaC inhibitor (+ charge)
Blocks Na channel and Na/H antiporter in lumenal membrane at the late distal tubule and collecting duct –> decreased K+ secretion and distal tubule acid secretion, increased Ca++ absorption
Use: Amiloride
Combination with other diuretics to prevent hypokalemia;
edema,
idiopathic hypercalciuria (stones);
lithium-induced polyuria & toxicity,
Liddle syndrome,
mucocilliary clearance
Use: Triamterene
Combination with other diuretics to prevent hypokalemia;
edema
Side effects: Amiloride and Triamterene
Hyperkalemia in patients with renal failure or on ACE inhibitors
Important side effect: Triamterene
Megaloblastic anemia in patients with liver cirrhosis
Amiloride and Triamterene are contraindicated in what patient population?
Renal failure
Spironolactone is contraindicated in what patient population?
Renal failure
Contraindicated in patients with renal failure (hyperkalemia); FeNa = 2%; requires a salt-restricted diet; only drug not requiring tubular lumen access
Use: Spironolactone
K+-sparing diuretic; aldosterone receptor antagonist
Reduction in CHF mortality (30% in NYHA class III and IV);
combination with other diuretics to prevent hypokalemia;
edema;
primary and secondary aldosteronism;
hypertension;
anti-testosterone agent
MOA: Sprionolactone
Competes for aldosterone receptor, inhibiting mRNA transcription and translation –> decreased Na and K channels, decreased number and activity of Na-K-ATPase pumps in the late distal tubule and collecting duct –> decreased K+ secretion, distal tubule acid secretion
Class:
Conivaptan
Tolvaptan
Aquaretic
Use:
Conivaptan
Tolvaptan
Hyponatremia (SIADH, CHF)
MOA:
Conivaptan
Tolvaptan
Vasopressin (ADH) receptor antagonist working at collecting duct –> increased free water excretion
Aldosterone-dependent regulation of Na+ reabsorption occurs in the:
Aldosterone-dependent regulation of Na+ reabsorption occurs in the late distal tubule.
T/F: the hypocalciuric effect of the thiazide and thiazide-like diuretics is greater than the hypocalciuric effect of amiloride
True
Thiazide diuretics may be used to control the polyuria resulting from nephrogenic diabetes insipidus by an indirect effect on:
Glomerular filtration
Thiazide diuretics may be used to control the polyuria resulting from nephrogenic diabetes insipidus by further decreasing the ECF volume which induces a decrease in GFR. Any reduction in GFR, when dehydrated, will decrease urine excretion.
How does hydrochlorothiazide work?
Hydrochlorothiazide inhibits solute reabsorption in the diluting segment of the nephron which raises the osmolality of the tubular fluid and urine. This effect decreases the positive free water clearance in response to ECF volume expansion which puts the patient at risk for hyponatremia.
