Diuretics & Anti-Diuretics

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Hydrochlorothiazide

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Class: Thiazide diuretic
Use: A) edema of heart failure B) HTN (less effective w/ low GFR) C) prevent calcium nephrolithiasis & osteoporosis (by decreasing excretion of CA2+) D) nephrogenic diabetes insipidus (paradoxical effect) E) ascites associated w/ liver cirrhosis (give spironolactone 1st to avoid hypokalemic alkalosis)
MOA: A) inhibits Na+-Cl- symporter in distal convoluted tubule = NaCl excretion, water diuresis B) action independent of pt's acid-base balance C) ^ excretion of Na+, Cl- K+, H+; decreased excretion of Ca++
SFx: A) hypokalemia & metabolic alkalosis (increased excretion of K+ & H+ in late distal tubule & collecting duct) B) Gout C) sulfonamide allergy D) Stevens-Johnson syndrome E) hyperglycemia F) increase plasma LDL & total cholesterol, triglycerides G) fatal hyponatremia H) lithium toxicity
PK: A) secreted by organic acid secretory system in proximal tubule

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Chlorothiazide

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Class: Thiazide diuretic
Use: A) edema of heart failure B) HTN (less effective w/ low GFR) C) prevent calcium nephrolithiasis & osteoporosis (by decreasing excretion of CA2+) D) nephrogenic diabetes insipidus (paradoxical effect) E) ascites associated w/ liver cirrhosis (give spironolactone 1st to avoid hypokalemic alkalosis)
MOA: A) inhibits Na+-Cl- symporter in distal convoluted tubule = NaCl excretion, water diuresis B) action independent of pt's acid-base balance C) ^ excretion of Na+, Cl- K+, H+; decreased excretion of Ca++
SFx: A) hypokalemia & metabolic alkalosis (increased excretion of K+ & H+ in late distal tubule & collecting duct) B) Gout C) sulfonamide allergy D) Stevens-Johnson syndrome E) hyperglycemia F) increase plasma LDL & total cholesterol, triglycerides G) fatal hyponatremia H) lithium
PK: A) poor oral absorption B) secreted by organic acid secretory system in proximal tubule

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Chlorthalidone

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Class: Thiazide & thiazide-like diuretics
Use: A) edema of heart failure B) HTN (less effective w/ low GFR) C) prevent calcium nephrolithiasis & osteoporosis (by decreasing excretion of CA2+) D) nephrogenic diabetes insipidus (paradoxical effect) E) ascites associated w/ liver cirrhosis (give spironolactone 1st to avoid hypokalemic alkalosis)
MOA: A) inhibits Na+-Cl- symporter in distal convoluted tubule = NaCl excretion, water diuresis B) action independent of pt's acid-base balance C) ^ excretion of Na+, Cl- K+, H+; decreased excretion of Ca++
SFx: A) hypokalemia & metabolic alkalosis (increased excretion of K+ & H+ in late distal tubule & collecting duct) B) Gout C) sulfonamide allergy D) Stevens-Johnson syndrome E) hyperglycemia F) increase plasma LDL & total cholesterol, triglycerides G) fatal hyponatremia H) lithium
PK: A) secreted by organic acid secretory system in proximal tubule

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Indapamide

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Class: Thiazide & thiazide-like diuretics
Use: A) edema of heart failure B) HTN (still effective w/ low GFR) C) prevent calcium nephrolithiasis & osteoporosis (by decreasing excretion of CA2+) D) nephrogenic diabetes insipidus (paradoxical effect) E) ascites associated w/ liver cirrhosis (give spironolactone 1st to avoid hypokalemic alkalosis)
MOA: A) inhibits Na+-Cl- symporter in distal convoluted tubule = NaCl excretion, water diuresis B) action independent of pt's acid-base balance C) ^ excretion of Na+, Cl- K+, H+; decreased excretion of Ca++
SFx: A) hypokalemia & metabolic alkalosis (increased excretion of K+ & H+ in late distal tubule & collecting duct) B) Gout C) sulfonamide allergy D) Stevens-Johnson syndrome E) hyperglycemia F) unlike other thiazides, doesn't increase LDL, total cholesterol or triglycerides G) fatal hyponatremia H) lithium toxicity
PK: A) most potent thiazide diuretic, with greatest oral absorption B) secreted by organic acid secretory system in proximal tubule

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Furosemide

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Class: Loop Diuretic
Use: A) CHF B) pulmonary edema C) HTN (thiazides better) D) hypercalcemia E) edema of nephrotic syndrome or liver cirrhosis F) used w/ hypertonic saline to treat hyponatremia
MOA: A) act in the thick ascending limb - block Na+-K+-2Cl- symporter in apical membrane (called high ceiling diuretics b/c of high reabsorptive capacity of thick ascending limb - strongest effect) B) blocking Na+ reabsorption inhibits kidney's ability to produce dilute urine and C) prevents generation of hyperosmotic medullary interstitium around collecting duct...so also inhibit kidneys ability to produce concentrated urine D) via prostaglandins - increase renal blood flow & systemic venous capacitance = decreases left ventricular filling pressure E) enhances excretion of Na+, Cl-, K+, H+, Ca++, Mg++, NH4, bicarb, phosphate F) drug overdose (rapidly increase renal excretion)
SFx: A) hypotension, hypovolemia, hyponatremia B) hypochloremic metabolic alkalosis & hypokalemia...may lead to cardiac arrhythmias C) Gout D) ototoxicity (more likely in pts. taking ototoxic aminoglycoside antibiotics...gentamycin) E) sulfonamide hypersensitivity rxns (use ethacrynic acid if pt. has allergy) F) (hyperglycemia, increased LDLs & triglycerides, hypomagnesemia...loss of lumen + potential, NSAIDS can decrease diuretic response, can increase plasma lithium...toxic)
PK: A) sulfonamide derivative B) bound to plasma proteins C) secreted by proximal tubule via organic acid secretion D) excreted unchanged in urine or metabolized by kidney

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Ethacrynic Acid

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Class: Loop Diuretic
Use: A) CHF B) pulmonary edema C) HTN (thiazides better) D) hypercalcemia E) edema of nephrotic syndrome or liver cirrhosis F) used w/ hypertonic saline to treat hyponatremia
MOA: A) act in the thick ascending limb - block Na+-K+-2Cl- symporter in apical membrane (called high ceiling diuretics b/c of high reabsorptive capacity of thick ascending limb- strongest effect) B) blocking Na+ reabsorption inhibits kidney's ability to produce dilute urine and C) prevents generation of hyperosmotic medullary interstitium around collecting duct...so also inhibit kidneys ability to produce concentrated urine D) via prostaglandins - increase renal blood flow & systemic venous capacitance = decreases left ventricular filling pressure E) enhances excretion of Na+, Cl-, K+, H+, Ca++, Mg++, NH4, bicarb, phosphate F) drug overdose (rapidly increase renal excretion
SFx: A) hypotension, hypovolemia, hyponatremia B) hypochloremic metabolic alkalosis & hypokalemia...may lead to cardiac arrhythmias C) Gout D) ototoxicity (more likely in pts. taking ototoxic aminoglycoside antibiotics...gentamycin) E) (hyperglycemia, increased LDLs & triglycerides, hypomagnesemia...loss of lumen + potential, NSAIDS can decrease diuretic response, can increase plasma lithium...toxic) F) no sulfonamide rxns
PK: A) phenoxyacetic acid derivative B) bound to plasma proteins C) secreted by proximal tubule via organic acid secretion D) excreted unchanged in urine or metabolized by kidney

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Mannitol

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Class: Osmotic Diuretic
Use: A) Prevent oliguric acute renal failure B) Reduction of intraocular & intracranial pressure (glaucoma attacks, eye/neuro- surgery) C) Induce urinary excretion of toxins/overdosed meds D) (treat edema or ascites of nephrotic, cirrhotic, cardiac origin)
MOA: A) increased osmotic pressure = decreased reabsorption of water in nephron segments permeable to water (proximal tubule, descending loop of Henle) B) (also increases ECF volume by pulling water from ICF...inhibits Renin release = ^ blood flow) C) (increases excretion of all electrolytes
SFx: A) pulmonary edema in pts. w/ heart failure or pulmonary congestion (b/c of moving fluid from ICF to ECF) B) hypernatremia & dehydration C) contraindicated in pts w/ severe renal dx, or w/ cranial bleeds (increase cerebral blood flow)
PK: administered IV, remains in extracellular compartment
- oral = osmotic diarrhea
- filtered by glomeruli w/ minimal tubular reabsorption

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Triamterene

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Class: K+ sparing Diuretics (inhibitors of renal Na+ channels)
Use: A) limited diuretic capacity B) combined w/ other diuretics to treat edema, HTN (counterbalance hypokalemia) C) Liddle's Syndrome (pseudohypoaldosteronism...excess Na+ reabsorption, K+ & H+ secretion)
MOA: A) block luminal Na+ channels in principal cells of late distal tubule & collecting duct - prevent K+ secretion B) decreased H+ secretion by intercalated cell (cortical collecting duct)
SFx: A) life-threatening hyperkalemia B) not used w/ spironolactone (risk of A above) C) nausea, vomiting, leg cramps, dizziness D) cautionary use w/ ACE inhibitors (hyperkalemia) & agents that block renin E) kidney stones (poorly soluble)
PK: A) secreted in proximal tubule by organic base secretory system B) orally administered C) metabolized in liver

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Amiloride

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Class: K+ sparing Diuretics (inhibitors of renal Na+ channels)
Use: A) limited diuretic capacity B) combined w/ other diuretics to treat edema, HTN (counterbalance hypokalemia) C) Liddle's Syndrome (pseudohypoaldosteronism...excess Na+ reabsorption, K+ & H+ secretion)
D) Cystic Fibrosis
MOA: A) A) block luminal Na+ channels in principal cells of late distal tubule & collecting duct - prevent K+ secretion B) decreased H+ secretion by intercalated cell (cortical collecting duct)
SFx: A) life-threatening hyperkalemia B) not used w/ spironolactone (risk of A above) C) nausea, vomiting, diarrhea, headache D) cautionary use w/ ACE inhibitors (hyperkalemia) & agents that block renin E) megaloblastic anemia in alcohol-induced cirrhosis
PK: orally administered

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Spironolactone

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Class: K+ sparing Diuretics (Aldosterone antagonists)
Use: A) edema & HTN (given w/ loop/thiazide diuretic)...prevents hypokalemia B) hyperaldosteronism
MOA: A) antagonist at mineralocorticoid (aldosterone) receptors (prevents aldosterone-induced gene transcription) B) blocks effects of aldosterone in cortical collecting duct (aldo. ^ luminal Na+ conductance, ^ basolateral Na+/K+ ATPase activity, ^ secretion of K+ & H+)
SFx: A) life threatening hyperkalemia B) never combined w/ other K+ sparing diuretics C) antiandrogen fx (by interactions w/ androgen, progesterone & other receptors) D) not combined w/ ACE inhibitors
PK: A) synthetic steroid, metabolized in liver to canrenone
B) efficacy depends on endogenous aldosterone levels
C) intracellular site of action (not lumen)

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Eplerenone

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Class: K+ sparing Diuretics (Aldosterone antagonists)
Use: A) edema & HTN (given w/ loop/thiazide diuretic)...prevents hypokalemia B) hyperaldosteronism
MOA: A) antagonist at mineralocorticoid (aldosterone) receptors (prevents aldosterone-induced gene transcription) B) blocks effects of aldosterone in cortical collecting duct (aldo. ^ luminal Na+ conductance, ^ basolateral Na+/K+ ATPase activity, ^ secretion of K+ & H+)
SFx: A) life threatening hyperkalemia B) never combined w/ other K+ sparing diuretics C) antiandrogen fx (by interactions w/ androgen, progesterone & other receptors) D) not combined w/ ACE inhibitors PK: A) synthetic steroid

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Acetazolamide

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Class: Carbonic Anhydrase Inhibitor
Use: A) Glaucoma - inhibition of CA...decreased intraocular pressure by less aqueous humor formation. B) Urinary alkalization C) epilepsy D) Mountain sickness E) Metabolic alkalosis F) Edema (effectiveness as diuretic is limited b/c of NaCl reabsorption by later segments & decreased filtered bicarb as result of met. acid.)
MOA: A) Primarily act on proximal tubule (also in eye & choroid plexus - aqueous humor & CSF production) B) Inhibit NaHCO3 reabsorption by action on membrane-bound & cytoplasmic carbonic anhydrase = hypochloremia & metabolic acidosis
SFx: A) Bicarb wasting - hyperchloremic metabolic acidosis B) Urinary alkalization can precipitate Ca++ salts to form kidney stone C) Hypokalemia - increased K+ excretion from increased lumen electronegativity D) Sulfonamide allergy E) (also paresthesias, somnolence; contraindicated in hepatic cirrhosis & pts. who are Na+ or K+ depleted)
PK: sulfonamide derivative

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Desmopressin acetate

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Class: Anti-diuretic drug
Use: A) nocturnal enuresis B) Central Diabetes Insipidus C) Hemophilia A, von Willebrand's dx
MOA: A) increases water reabsorption in collecting ducts (principal cells) B) greater antidiuretic activity than vasopressin, but much less cardiovascular vasopressor activity C) increases levels of procoagulant factor VIII & von Willebrand factor
SFx: A) water intoxication B) cautionary use in pts. w/ angina, HTN, CHF
PK: similar structure to vasopressin (ADH)