Unit 4- Diuretics Flashcards
Acetazolamide
Drug class
Carbonic anhydrase inhibitors
Acetazolamide
Mechanism
Inhibits luminal carbonic anhydrase at proximal tubule –> less activity of Na/H antiporter, decreased HCO3 and Na+ (and water) reabsorption
FeNa = 5%
Acetazolamide
Uses
Decrease intraocular volume/pressure and the prevention and treatment of mountain sickness
Acetazolamide
Side effects
Increased K+ excretion and metabolic acidosis
Hepatic encephalopathy, BM depression, skin toxicity, allergic reactions
Contraindicated in cirrhotic patients;
Methazolamide
Drug class
Carbonic anhydrase inhibitors
Methazolamide
Mechanism
Inhibits luminal carbonic anhydrase at proximal tubule –> less activity of Na/H antiporter, decreased HCO3 and Na+ (and water) reabsorption
FeNa = 5%
Methazolamide
Uses
Decrease intraocular volume/pressure and the prevention and treatment of mountain sickness
Methazolamide
Side effects
Increased K+ excretion and metabolic acidosis
Hepatic encephalopathy, BM depression, skin toxicity, allergic reactions
Contraindicated in cirrhotic patients;
Dichlorphenamide
Drug class
Carbonic anhydrase inhibitors
Dichlorphenamide
Mechanism
Inhibits luminal carbonic anhydrase at proximal tubule –> less activity of Na/H antiporter, decreased HCO3 and Na+ (and water) reabsorption
FeNa = 5%
Dichlorphenamide
Uses
Decrease intraocular volume/pressure and the prevention and treatment of mountain sickness
Dichlorphenamide
Side effects
Increased K+ excretion and metabolic acidosis
Hepatic encephalopathy, BM depression, skin toxicity, allergic reactions
Contraindicated in cirrhotic patients;
Aminophylline
Drug class
Bronchodilator (Methylxanthine)
Aminophylline
Mechanism
Phosphodiesterase inhibition and enhanced signalling via increased cAMP and cGMP; works at proximal tubule; decreased HCO3 and Na+ (and water) reabsorption
FeNa = 5%; aminophylline = theophylline + ethyelenediamine (solubility agent); metabolized by liver;
Aminophylline
Uses
Reduce inflammation and bronchospasm in moderate to severe asthma, night symptoms;
NOT as diuretic
Aminophylline
Side effects
Larger doses give nausea, vomiting, CNS stimulation or seizures, tachycardia/arrythmias
cimetidine and quinoline increase blood levels
Mannitol
Drug class
Osmotic diuretic
Mannitol
Mechanism
Opposes water and sodium reabsorption at proximal tubule –> increased osmolarity of tubular fluid
FeNa = 5%; must give IV; other osmotic diuretics include glucose, urea, isorbide
Mannitol
Uses
Increased clearance of drugs, minimize renal failure (shock or surgery), decrease intraocular or intracranial pressures, diagnose oliguria
Mannitol
Side effects
Risk of pulmonary edema
Furosemide
Drug class
Loop diuretic (- charge)
Furosemide
Mechanism
- 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
- FeNa = 25%; eventually causes increase in PT reabsorption,decreases positive & negative free water clearance; decreases cortex-medulla molarity gradient;
Furosemide
Uses
- Crisis edema (pulmonary, CHF, cirrhosis), hypercalcemia, drug toxicity/OD; severe hypertension in setting of CHF or cirrhosis
- take before salty meals, reduce salt intake; useful in patients with renal insufficiency (GFR < 30-40)
Furosemide
Side effects
- Hypokalemia/hypocalcemia/hypomagnesemia (–> arrhythmia), contraction alkalosis, increased BUN & creatinine, ototoxicity (esp. w/aminoglycoside)
- Hyper -glycemia, -lipidemia, -uricemia; hypo -magnesia, -natremia; gout, photosensitivity, nephrocalcinosis, drug interactions; erectile dysfunction
- Avoid NSAIDs
Bumetanide
Drug class
Loop diuretic (- charge)
Bumetanide
Mechanism
- 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
- FeNa = 25%; eventually causes increase in PT reabsorption,decreases positive & negative free water clearance; decreases cortex-medulla molarity gradient;
Bumetanide
Uses
- Crisis edema (pulmonary, CHF, cirrhosis), hypercalcemia, drug toxicity/OD; severe hypertension in setting of CHF or cirrhosis
- take before salty meals, reduce salt intake; useful in patients with renal insufficiency (GFR < 30-40)
Bumetanide
Side effects
- Hypokalemia/hypocalcemia/hypomagnesemia (–> arrhythmia), contraction alkalosis, increased BUN & creatinine, ototoxicity (esp. w/aminoglycoside)
- Hyper -glycemia, -lipidemia, -uricemia; hypo -magnesia, -natremia; gout, photosensitivity, nephrocalcinosis, drug interactions; erectile dysfunction
- Avoid NSAIDs
Ethacrynic acid
Drug class
Loop diuretic (- charge)
Ethacrynic acid
Mechanism
- 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
- FeNa = 25%; eventually causes increase in PT reabsorption,decreases positive & negative free water clearance; decreases cortex-medulla molarity gradient;
Ethacrynic acid
Uses
- Crisis edema (pulmonary, CHF, cirrhosis), hypercalcemia, drug toxicity/OD; severe hypertension in setting of CHF or cirrhosis; sulfa-free
- useful in patients with renal insufficiency (GFR < 30-40)
Ethacrynic acid
Side effects
- Hypokalemia/hypocalcemia/hypomagnesemia (–> arrhythmia), contraction alkalosis, increased BUN & creatinine, ototoxicity (esp. w/aminoglycoside)
- Hyper -glycemia, -lipidemia, -uricemia; hypo -magnesia, -natremia; gout, photosensitivity, nephrocalcinosis, drug interactions; erectile dysfunction
- Avoid NSAIDs
Chlorthiazide
Drug class
Thiazide diuretic (- charge)
Chlorthiazide
Mechanism
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
Chlorthiazide
Uses
HTN (intravascular contraction), chronic edema (cardiac insufficiency), idiopathic hypercalciuria (stones), nephrogenic diabetes insipidus
Chlorthiazide
Side effects
Hypokalemia/hypercalcemia, contraction alkalosis, increased BUN & creatinine
Hyper -glycemia, -lipidemia, -uricemia, -calcemia; hypo -magnesia, -natremia; gout, photosensitivity, impotence, drug interactions
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
Hydrochlorothiazide
Drug class
Thiazide diuretic (- charge)
Hydrochlorothiazide
Mechanism
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
Hydrochlorothiazide
Uses
HTN (intravascular contraction), chronic edema (cardiac insufficiency), idiopathic hypercalciuria (stones), nephrogenic diabetes insipidus
Hydrochlorothiazide
Side effects
Hypokalemia/hypercalcemia, contraction alkalosis, increased BUN & creatinine
Hyper -glycemia, -lipidemia, -uricemia, -calcemia; hypo -magnesia, -natremia; gout, photosensitivity, impotence, drug interactions
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
Chlorthalidone
Drug class
Thiazide-like diuretic
Chlorthalidone
Mechanism
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
Chlorthalidone
Uses
Reduce stroke risk, CHF events; HTN (intravascular contraction), chronic edema (cardiac insufficiency), idiopathic hypercalciuria (stones), nephrogenic diabetes insipidus
Chlorthalidone
Side effects
Hypokalemia/hypercalcemia, contraction alkalosis, increased BUN & creatinine
Hyper -glycemia, -lipidemia, -uricemia, -calcemia; hypo -magnesia, -natremia; gout, photosensitivity, impotence, drug interactions
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
Quinethazone
Drug class
Thiazide-like diuretic
Quinethazone
Mechanism
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
Quinethazone
Uses
HTN (intravascular contraction), chronic edema (cardiac insufficiency), idiopathic hypercalciuria (stones), nephrogenic diabetes insipidus
Quinethazone
Side effects
Hypokalemia/hypercalcemia, contraction alkalosis, increased BUN & creatinine
Hyper -glycemia, -lipidemia, -uricemia, -calcemia; hypo -magnesia, -natremia; gout, photosensitivity, impotence, drug interactions
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
Metolazone
Drug class
Thiazide-like diuretic
Metolazone
Mechanism
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
Metolazone
Uses
HTN (intravascular contraction), chronic edema (cardiac insufficiency), idiopathic hypercalciuria (stones), nephrogenic diabetes insipidus
Metolazone
Side effects
Hypokalemia/hypercalcemia, contraction alkalosis, increased BUN & creatinine
Hyper -glycemia, -lipidemia, -uricemia, -calcemia; hypo -magnesia, -natremia; gout, photosensitivity, impotence, drug interactions
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
Indapamide
Drug class
Thiazide-like diuretic
Indapamide
Mechanism
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
Indapamide
Uses
HTN (intravascular contraction), chronic edema (cardiac insufficiency), idiopathic hypercalciuria (stones), nephrogenic diabetes insipidus
Indapamide
Side effects
Hypokalemia/hypercalcemia, contraction alkalosis, increased BUN & creatinine
Hyper -glycemia, -lipidemia, -uricemia, -calcemia; hypo -magnesia, -natremia; gout, photosensitivity, impotence, drug interactions
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
Amiloride
Drug class
K+-sparing diuretic; renal ENaC inhibitor (+ charge)
Amiloride
Mechanism
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
Amiloride
Uses
Combination with other diuretics to prevent hypokalemia; edema, idiopathic hypercalciuria (stones); lithium-induced polyuria & toxicity, Liddle syndrome, mucocilliary clearance
Amiloride
Side effects
Hyperkalemia in patients with renal failure or on ACE inhibitors
Contraindicated in patients with renal failure (hyperkalemia), ACEi/ARB use; FeNa = 2%
Torsemide
Drug class
Loop diuretic (- charge)
Torsemide
Mechanism
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
Torsemide
Uses
Crisis edema (pulmonary, CHF, cirrhosis), hypercalcemia, drug toxicity/OD; severe hypertension in setting of CHF or cirrhosis
Torsemide
Side effects
Hypokalemia/hypocalcemia/hypomagnesemia (–> arrhythmia), contraction alkalosis, increased BUN & creatinine, ototoxicity (esp. w/aminoglycoside)
Hyper -glycemia, -lipidemia, -uricemia; hypo -magnesia, -natremia; gout, photosensitivity, nephrocalcinosis, drug interactions; erectile dysfunction
FeNa = 25%; eventually causes increase in PT reabsorption,decreases positive & negative free water clearance; decreases cortex-medulla molarity gradient; avoid NSAIDs, take before salty meals, reduce salt intake; useful in patients with renal insufficiency (GFR < 30-40)
Triamterene
Drug class
K+-sparing diuretic; renal ENaC inhibitor (+ charge)
Triamterene
Mechanism
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
Triamterene
Uses
Combination with other diuretics to prevent hypokalemia; edema
Triamterene
Side effects
Hyperkalemia in patients with renal failure or on ACE inhibitors
Megaloblastic anemia in patients with liver cirrhosis
Contraindicated in patients with renal failure (hyperkalemia); FeNa = 2%
Spironolactone
Drug class
K+-sparing diuretic; aldosterone receptor antagonist
Spironolactone
Mechanism
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
Spironolactone
Uses
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
Spironolactone
Side effects
Hyperkalemia in patients with renal failure or on ACE inhibitors; male patients may have gynecomastia, erectile dysfunction, and loss of libido; female patients may have amenorrhea, breast soreness, and oligomenorrhea
Contraindicated in patients with renal failure (hyperkalemia); FeNa = 2%; requires a salt-restricted diet; only drug not requiring tubular lumen access
Conivaptan
Drug class
Aquaretic
Conivaptan
Mechanism
Vasopressin (ADH) receptor antagonist working at collecting duct –> increased free water excretion
Conivaptan
Uses
Hyponatremia (SIADH, CHF)
New drug class with unproven clinical benefit
Tolvaptan
Drug class
Aquaretic
Tolvaptan
Mechanism
Vasopressin (ADH) receptor antagonist working at collecting duct –> increased free water excretion
Tolvaptan
Uses
Hyponatremia (SIADH, CHF)
New drug class with unproven clinical benefit