Diuretics

Question 1

formulas for free H2O clearance,osmolar clearance and FE of X and filtered load of X

Answer 1

• CH2O= V - Cosm
• where Cosm = (Uosm x V)/Posm
• FEx = Cx/GFR (where GFR = Cin)
• Filtered load of X = GFR x plasma concentration of X

Question 2

potassium sparing diuretics

Answer 2

• spironolactone (aldo-dependent)
• **spironolactone is the only one that does not depend on GFR and tubular fluid concentration
• amiloride and triamterene (aldo-independent) –> block Na channels in luminal membrane –> lowers intracell Na –> slows down Na/K ATPase on BL membrane –> less K secretion
• act in late DT and CD

Question 3

SE of thiazides

Answer 3

• induce ECF volume contraction –> hyponatremia (higher risk), alkalosis, hyperuricemia, hypomagnesemia, azotemia
• increased lipids
• hypokalemia –> caution in PTs taking digitalis and quinidine (increased risk of arryhthmia)
• hypokalemia further increased when taking corticosteroids or amphotericin B
• diminshed activity with NSAIDs
• reduce absorption from gut with resins

Question 3

transcellular proximal tubule organic anion and cation secretion

Answer 3

• loops and thiazides = weak acids (anions)
• triamterence and amiloride= weak bases (cations)
• anions: active transport across BL and passive across luminal membrane
• cations: passive transport across BL membrane and active across lumenal
• with kidney disease, GFR decreases and the clearance of anionic metabolites decreases–> higher concentrations of anionic metabolites compete with anionic diuretics so you need to give a higher dose of diuretic

Question 4

loops

Answer 4

• furosemide, bumetanide, torsemide, ethacrynic acid
• acts in tALH (Na-2Cl-K transporter)
• also inhibits reabsorption of Mg and Ca indirectly by decreasing the (+) lumen potential
• when volume expanded, CH2O is decreased (blocks kidney’s ability to dilute the urine)
• when PT is volume contracted loops also prevent H20 from leaving CD (osmotic gradient isnt as steep) –> block kidney’s abilit to concentrate the urine

Question 4

uses and contraindications of K+ sparing diuretics

Answer 4

• in combo with loops or thiazides to prevent hypokalemia
• amiloride can tx Li-induced polyuria without increasing Li reabsorption
• can’t use in renal failure or with ACEI/ARBs

Question 7

aminophylline (theophylline)

Answer 7

• acts in proximal tubule
• PDE inhibitor –> increases levels of cAMP –> decreased Na reabsorption
• not really used as a diuretic but is used in PTs with asthma

Question 7

other uses of thiazides

Answer 7

• treat idiopathic hypercalciuria (increase the reabsorption of Ca – opp of loops!)
• nephrogenic diabetes insipidus(inability to respond to ADH) –> contract ECF volume –> decrease volume of tubular fluid and volume of urine
• tx Li-induced nephrogenic diabetes insipidus by same mechanism as above (but be careful of compensatory increase in solute and water reabsorption –> increased Li absorption and toxicity!)

Question 9

uses of loops

Answer 9

• edema
• hypercalcemia
• drug toxcities

Question 10

SE of loops

Answer 10

• hyponatremia
• hyperuricemia
• contraction alkalosis (further increases K+ secretion)
• azotemia
• hypokalemia
• possible onset of diabetes mellitus
• hypomagnesemia (lost in urine)
• ototoxicity
• NSAIDS decrease their effectiveness
• increased concentration of clotting factors

Question 11

osmotic diuretics

Answer 11

• mannitol, glucose, urea, isorbide
• greatest effect is on proximal tubule
• freely filtered, non-reabsorbeable solutes in tubular fluid increases osmotic pressure to oppose isotonic reabsorption of Na and H20
• administered IV (mannitol does not cross cell membrane so its volume of distribution is limited to ECF) –> increased ECF osmolarity –> increases renal medullary blood flow

Question 12

Thiazides

Answer 12

• chlorothiazide, hydrochlorothiazide, chlorthalidone, metolazone, indapamide
• act on early distal tubule (inhibit Na-Cl cotransporter)
• limit kidney’s ability to dilute the urine but not concentrate it –> greater risk of hyponatremia

Question 13

carbonic anhydrase inhibitors

Answer 13

• acetazolamide, methazolamide, dichlorphenamide (“-amide”)
• act in proximal tubule
• less CO2 diffusion ino the cell –> less bicarb available to couple with H+ –> slows H+/Na+ exchanger down –> less Na+ reabsorption
• SE: hypokalemia and metabolic acidosis (via increases loss of bicarb in urine)
• however, body compensates by becoming refractory to CAI and prevents greater loss of bicarb in urine when metabolic acidosis ensues decreases elimination of ammonia –> ammonia builds up in blood –> hepatic encephalopathy
• tx glaucoma and acute mtn sickness

Question 14

uses of osmotics and cautions

Answer 14

• induce diuresis for drug OD, shock (prevent renal failure), diff dx of oliguria
• reduce intraocular and intracranial pressure (induces absorption of water from intraocular and intracranial space into ECF)
• may induce pulmonary edema (IV infusion increases ECF volume –> transient increase in hydrostatic P)

Question 15

body fluid compartments

Answer 15

• TBW = 60% of person’s weight
• TBW = 1/3 ECF and 2/3 ICF
• ECF = 1/4 intravascular and 3/4 interstitial