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Pharm Block3
Diuretics
| Question | Answer |
|---|---|
| Hydrochlorothiazide; HCTZ (HydroDIURIL, Microzide) | thiazide; 1hr onset; 8-12hr halflife |
| Chlorthalidone (hygroton, hylidone) | thiazide |
| Indapamide (lozol) | thiazide-like diuretic; 1-2hr onset; 18-36hr halflife |
| Furosemide (lasix) | loop diuretic; 1hr onset; 6hr half-life |
| Bumetanide (bumex) | loop diuretic; 0.5-1hr onset; 4-6hr half-life |
| Torsemide (demadex) | loop diuretic |
| Ethacrynic acid (edecrin) | loop diuretic |
| Amiloride (midamor) | potassium-sparing diuretic |
| Triamterene (dyrenium) | potassium-sparing diuretic |
| Spironolactone (aldactone) | K-sparing diuretic/aldosterone receptor blocker; 1-2 day onset; 2-3d halflife; acts at collecting duct (inhibits Na/H2O reabs); directly prop to [aldosterone serum]; hyperaldosteronism adenoma, CHF, liver cirrhosis, nephrotic syndrome, HTN, hypokalemia |
| Acetazolamide (diamox) | carbonic anhydrase inhibitor; 1hr onset; 5hr half-life; inhibit membrane CA and interior of lumen cell to dec Na and HCO3 reabsorption by 80%; minor effect in descending loop and collecting ducts |
| Dorzolamide (trusopt) | carbonic anhydrase inhibitor; inhibit membrane CA and interior of lumen cell to dec Na and HCO3 reabsorption by 80%; minor effect in descending loop and collecting ducts |
| Mannitol (osmitrol) | osmotic diuretics; IV (poor oral absorption); not metabolized & freely filtered by glomerulus w/o absorption or secretion; *inc osmotic pressure w/in tubule and ECF* |
| Amiloride + HCTZ (moduretic) | combo therapy; 2hr onset; 24hr half-life |
| Triamtrene + HCTZ (maxzide, dyazide) | combo therapy |
| Spironolactone + HCTZ (aldactazide) | combo therapy |
| Diuretics defined | inc water and solute excretion |
| Natriuresis defined | increased excretion of Na in urine |
| Diuresis defined | increased urine outflow |
| Osmosis | net diffusion of water across selectively permeable membrane from region of high water conc. to region of lower water concen |
| Reabsorption of Na and Water | Proximal tubue (65% and 65%); Descending loop (15% water); Ascending loop (25% Na), Distal collecting duct (10% and 20%) |
| Proximal Tubule | highly permeable to H2O, Na reabsorption to interstitial fluid creates [ ] diff that results in osmosis of water in same direction in a 1:1 ratio; reabsorbes 65% of filtered Na, K, and H2O |
| Proximal Tubule: Early | Na is countertransported via Na-H exchange which is linked to HCO3 reabsorption |
| Proximal Tubule: Middle and Late | Na is reabsorbed w/Cl |
| Descending Limb | freely permeable to H2O; impermeable to Na and K |
| Ascending Limb | "diluting segment" - dec lumen osmolarity; impermeable to H2O; Na-K-2Cl cotransporter (25% filtered Na, 20% filtered K, NaCl reabsorbed w/o H2O); **good site for drug target** |
| Distal Tubule: Early | "cortical diluteing segment" - dec lumen osmolarity; reabsorbs 10% of filtered Na; impermeable to H2O, Na-Cl cotransporter, NaCl reabsorbed w/o H2O |
| Late Distal Tubule and Collecting Duct: Principal Cells | aldosterone increases reabsorption of Na and secretion of K; Antidiuretic hormone (ADH, AVP, vasopressin) increases reabsorption of H2O |
| Late Distal Tubule and Collecting Duct: Intercalated Cells | Aldosterone increases secretion of H by H-ATPase pump |
| Osmotic Diuretics: Proximal Tubule | limit osmosis of H2O from lumen to interstitial space |
| Osmotic Diuretics: Descending Loop | Cannot reabsorb increased load of H2O and Na |
| Osmotic Diuretics: Ascending Loop | Increased load of H2O and Na reduces efficiency of Na-K-2Cl cotransporter |
| Osmotic Diuretics: Distal Tubule and Collecting Ducts | cannot reabsorb increased load of H2O and Na |
| Collecting Tubule | reabsorbs 2-5% of filtered Na; final site of NaCl reabsorption; determines final urine [Na]; regulated blood vol; |
| Collecting Tubule: Principal Cells - Distinct Na and K Channels | Na reabsorption > K reabsorption; Lumen negative potential (+75 to +60mV) inc K secretion; Inc Na delivery to collecting tubule inc K secretion into lumen |
| General characteristics of diuretics | inhibit absorption of Na & H2O; ptn-bound, not freely filtered at glomerulus, secreted into prox tubule & subject to compet inhib; Dec ECF vol (d/t Na & H2O excretion; limited d/t breaking phenomena: Na/H2O reaborption inc in segments not inhibited |
| Relative Naturetic Potency of Various Diuretics | Loop (20-25%) > Osmotic (>10%); > Thiazide (5%) > K+ Sparing (1-3%) > Carbonic Anhydrase Inhibitor (1-3%) |
| Mechanism of Action for Osmotic Diuretics - Descending Limb | proximal tubule is secondary site; Rx reduces Na and H2O reabsorption; inc osmotic pressure w/in lumen opposes H2O reabsorption, continued Na reabsorption dec [Na] in lumen causing backflux of interstitial Na into lumen |
| Osmotic Diuretics: MOA - Expanded ECF | decreases renin release (less vasoconstriction), inc renal blood flow, inc NaCL reabsorption from medulla; hypotonic medulla = less reabsorption of H2O from descending limb; Result: dilute NaCL entering ascending limb |
| Summary of Osmotic Diuretics: Ascending limb, distal tubule and collecting duct | Ascending limb (reduced NaCl reabsorption d/t dilute filtrate); Distal Tubule + Collecting Duct (cannot reabsorb inc Na and H2O load) |
| Osmotic Diuretics: Indications | Dec intraocular pressure prior to ocular surgery; Reduce cerebral edema (used to extract H2O d/t inc osmotic pressure of plasma); Maintain renal blood flow during surgery |
| Osmotic Diuretics: Adverse Drug Reactions | ECF expansion: worsening CHF and pulm edema; reversible acute renal dysfxn; N &V, headache, dehydration |
| Carbonic Anhydrase Inhibitors: metabolic effects and indications | Urinary alkalization (enhance excretion of weak acids which are ionized in alk pH (aspirin, uric acid); Open angle glaucoma (dec aq humor synth 50% ); Acute mountain sickness (dec synth of CSF, pulm/cerebral edema); Use as diuretic for metabolic acidosis |
| Thiazides: MOA - Proximal Tubule | 2* site; binds to Cl site of NaCl; dec Na reabsorption; inc flow of Na & H2O to ascending limb; diuresis limited b/c most Na is absorbed prior to DCT |
| Thiazides: MOA - Early Distal Tubule | 1* site; inc flow of Na & H2O to downstream segments of distal tubule; Na reabsorption is 10% |
| Thiazide Indications: Hypertension | 80% efficacy, dec BP; more effective than loops; acutely dec plasma vol, chronically dec periph vasc resistance; 1st therapy w/ClCr >30%; enhances efficacy of other antihypertensives! |
| Thiazide Indications: Mild and Severe CHF | Mild: infreq monotherapy (effective if ClCr >50%); Severe: combo therapy (CHF dec renal blood flow & allows more time for Na reabsorption in prox tubule; minimal efficacy for action in distal tubule) |
| Thiazide Indications: Acute renal failure | management of hypervolemia w/NaCL and H2O restriction |
| Thiazide Indications: Hyperkalemia w/normal renal function | may be used w/loop diuretics |
| Thiazide Indications: Other | Edema |
| Thiazides: Metabolic Effects - Hyperuricemia | compets w/uric acid for secretion from blood into tubules; increases serum uric acid and can cause gouty arthritis |
| Thiazides: Metabolic Effects - Hypokalemia | onset w/in hrs of first dose; lowest pt ~1mo; it takes several wks to restore normal serum K after stopping drug |
| Thiazides: Hypokalemia normal mechanism | late distal + collecting ducts: basolat lumen membrane (Na-K-ATPase establishes Na/K gradient); Lumen Surface Membrane (Na diffuses thru Na channels to cell interior; relative neg charge of lumen inc K diffusion into lumen) |
| Thiazides: Metabolic Effects - Hyponatremia | reduced blood flow vol increases secretion of ADH; increases absorption of H2O dilutes plasma Na |
| Thiazides: Adverse Drug Reactions | Impaired CHO tolerance (impairs insulin release, dec tissue utilization of glucose); Impotence; Hyponatremia; Hemolytic anemia; Thrombocytopenia |
| Loop Diuretics: Ascending loop | 1* site; Inhibits Na-K-2Cl cotransporter; inc delivery of Na and Cl to distal tubule; distal tubule & collecting ducts do not reabsorb extra Na and Cl |
| Loop Diuretics: Descending Loop | 2* site; inhibits Na reabsorption into interstitial fluid surrounding loop of henle; reduces osmolarlity of interstitial fluid; there is less reabsorption or H2O from descending loop |
| Loop Diuretics: Proximal Tubule | 3* site; weak inhibition of carbonic anhydrase |
| Loop Diuretics: "Ceiling effect" - Indications | dose above which additional effect is not likely; edema, HTN (pts w/impaired renal fxn); CHF; Pts w/renal dysfxn |
| Loop Diuretics: Adverse Drug Reactions | hyponatremia, hypokalemia, metabolic acidosis, ototoxicity (reverses if drug is stopped); severe dehydration; hypomagnesemia |
| Potassium Sparing Diuretics: MOA | Distal tubule + Collecting Duct; blocks Na channels in lumen membrane; dec development of relative negative charge at lumen membrane (less diffusion of K into lumen); limited diuretic effect |
| Potassium Sparing Diuretics: Indications - HTN or CHF | adjunct with HCTZ (minor enhanced anti-HTN or diuretic effect in combo); |
| Potassium Sparing Diuretics: Indications - Hypokalemia | only when persistent hypokalemia is documented (titrate dose and monitor serum electrolytes) |
| Potassium Sparing Diuretics: Indications - HTN or Edema | for pts who develop hypokalemia on HCTZ or pts who cannot risk hypokalemia (Hx of cardiac arrhythmias or concomitant digitalis glycosides); enhances effect of antihypertensives |
| Potassium Sparing Diuretics: Adverse Drug Reactions | Hyperkalemia, dec glucose tolerance, photosensitivity, N&V, headache |
| Potassium Sparing Diuretics: WARNING | Hyperkalemia (>5.5mEq/L); Amiloride (10% occurance; risk d/t renal impairment, DM, & elderly); Amiloride + HCTZ (risk drops to 1-2%) |
| Potassium Sparing Diuretics: Contraindications | Potassium supplements; Other K+ sparing drugs (angiotensin-converting enzyme ACE-inhibitors) |
| Potassium Sparing Diuretics: Spironolactone - Adverse Drug Reactions, Warnings, Contraindications | reversible gynecomastia; similar to other K sparing diuretics |
| Combo Diuretic Therapy | loop resistance; NSAIDs block prostaglandin-ind release of renal blood flow; chronic renal failure (dec RBF dec diuretic delivery to kidney; inc organic acids compete w/diuretics for secretion into prox tubule); Inc lumen Na d/t block reab by DCT |
| Combined Rx: Loop + Thiazide Diuretic | may result in large diuresis (requires close hemodynamic monitoring); K loss may be significant (monitor); few pts are refractory at start; 2 drugs acting at diff sites may be synergistic |
Created by:
bscaryp