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59 Cards in this Set
- Front
- Back
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Mechanism of Action
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Inhibit the renal ion transporters, decreasing re-absorption of ions (Na, Cl) that enter urine in greater amounts along with water
Can change volume, pH, ion composition in urine and blood |
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Which diuretics excrete most Na
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K+ sparing 2%
>> 20% for Loop |
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prevent absorption of water, aldosterone antagonists, carbonic anhydrase inhibitors
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osmotic diuretics
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Major clinical indications
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1. Edema
2. HTN---by decreasing plasma volume |
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Filters 16-20% blood plasma
Filtrate is FREE of proteins, blood Contains glucose, sodium bicarbonate, amino acids, Na, Cl, K |
Glomerular Filtration
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Located in cortex
Glucose, sodium bicarbonate, amino acids, lipid soluble metabolites reabsorbed 66% Na reabsorbed (Water follows) Na transported actively by Na/K ATPase |
Proximal Convoluted Tubule
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what regulates absorption of bicarbonate
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carbonic anhydrase
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Location of Acid-base secretory system
Diuretics compete for secretion by this system with endogenous organic acids (uric acid) Results in HYPERURCEMIA when furosemide or hydrochlorothiazide are administered Bases....creatinine, cholineare secreted in middle and upper segments |
proximal convoluted tubule
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Filtrate entering is ISOTONIC....enters medulla....permeable to H2O bu not Na
Osmolarity INCREASES as water diffuses out into interstitial fluid due to countercurrent mechanism created by ascending loop Filtrate is 4X more hyperosmotic!!!! |
Descending Loop
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Cells are impermeable in H2O
Na is actively transported out of the lumen into interstitial fluid by Na/K/2Cl transporter Mg and Ca enter the interstitial fluid via paracellular pathway |
Ascending Loop
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Diluting region of nephron
Principle location of NaCl reabsorption (25-30%) pumped out, increases osmolarity of interstitial fluid Site where diuretics are MOST effective |
Ascending Loop
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Impermeable to H2O
10% NaCl absorbed by Na/Cl transporter, responds to THIAZIDES Ca reabsorbed through Ca channels and then transported by Na/Ca transporter into interstitial fluid Excretion of Ca controlled by parathyroid hormone |
Distal Convoluted Tubule
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Transport Na, K, and H2O
The Na passes thru ion channels but depends on Na/K ATPase pump to be transported into blood Aldosterone receptors responsible for Na and K excretion ADH: Vasopressin promote re-absorption of H2O Mediated by cyclic AMP |
Collecting Tubule and Duct
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Overall Pathway
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1. Proximal Convoluted Tubule
2. Descending Loop 3. Ascending Loop 4. Distal Convoluted Tubule 5. Collecting Tubule and Duct |
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Good way to remember
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COLT K
1. Carbonic Anhydrase Inhibitors--Proximal Tubule 2. Osmotic--Descending Loop 3. Loop---Ascending Loop 4. Thiazides--Distal Tubule 5. K sparing---Collecting Tubule |
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Causes of Edema
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Heart Failure---Decreased CO, kidneys retain Na and H2O to increase blood volume-----heart can't increase CO results in edema
TX: Loop |
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Causes of Edema
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Hepatic Ascites---Fluid accumulates in abdominal cavity due to cirrhosis of liver
Causes..... 1. Increase portal BP leads to decrease osmolarity of blood, fluid accumulates 2. Secondary Hyperaldosteronism--elevated aldosterone due to decrease in blood volume, liver can't metabolize aldosternone....Na and H2O reabsorption results in edema K sparing drugs |
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Causes of Edema
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Nephrotic Syndrome
Glomerulus membranes are damaged, proteins leak into glomerular filtrate Decreases colloidal osmotic pressure resulting in edema |
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Causes of Edema
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Premenstrual Edema
Imbalance hormones, excess estrogen which causes movement of fluid into extracellular space |
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Non-Edematous Cause
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HTN--diuretics decrease blood volume and cause arteriolar dilation
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Non-Edematous Cause
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Hypercalcemia----LOOP b/c the promote excretion of Ca
May also get decrease in blood volume so saline is infused to maintain blood volume |
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Non-Edematous Cause
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DM---Polyuria and polydipsia
THIAZIDE decreases blood volume, decrease GFR which causes retention of Na and H2O Results in reduction urine entering diluting segment and urine flow |
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Inhibits carbonic anhydrase on apical membrane of epithelium in proximal tubule
CA catalyzes the reaction of H2O and CO2----> carbonic acid which then splits into bicarbonate and H+ The decrease in ability to exchange H+ for Na, results in diuresis HCO3 remains in lumen increasing pH of urine Loss of HCO3 causes hyperchloremic metabolic acidosis LESS efficacy than other diuretics DOSE: 250 mg qd to qid 500mg bid SR |
CAIs
Acetazolamide |
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1. Urinary Excretion
2. Na excretion 3. HCO3 excretion 4. Phosphate excretion |
CAIs
Acetazolamide |
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1. POAG: Decreases IOP
Decreases aqueous formation by inhibiting carbonic anhydrase in ciliary processes in eye Important as an adjunct in acute angle closure with pilocarpine 2. Mountain Sickness: Administered as prophylaxis for those who climb above 10,000ft Dose qhs 5 days prior Prevents weakness, breathlessness, dizziness, nausea, cerebral/pulmonary edema |
CAIs
Acetazolamide USES |
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1. Metabolic Acidosis
2. HYPOkalemia 3. Renal calculi 4. Drowsiness 5. METALLIC TASTE 6. PARASTHESIA 7. THROMBOCYTOPENIA |
CAIs
Acetazolamide Side Effects |
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Cirrhosis of liver b/c leads to decreased excretion of NH4
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CAIs
Acetazolamide Contraindications |
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Filtered by glomeruli, with little or no re-absorption and attracts H2O with them, results in diuresis
Increase urinary output Maintaining urine flow preserves kidney and may postpone dialysis Little effect on Na |
Osmotic Diuretics
Mannitol, Urea |
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1. Acute ingestion of toxic substances that cause renal failure
2. ICP 3. Renal failure due to shock 4. Drug toxicities 5. Trauma |
Osmotic Diuretics
Indications |
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NOT absorbed orally.....must give IV
Draws water from the cells into extracellular fluid HYPOnatremia until dialysis occurs Dehydration if H2O is not adequately replaced |
Mannitol
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Act on Ascending Loop of Henle
Greatest excretion of Na and Cl Increase excretion of Ca and Mg Produce large volume of urine |
LOOP
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Inhibit co-transport of Na/K/2Cl....reduced absorption of these ions
Ascending loop responsible for 25-30% of normal filtered Na The more distal sites do not have the capability to re-absorb the increased Na Flow--dependent enhancement of ion secretion at collecting duct NON-osmotic vasopressin release Activation of Renin-Angiotensin-Aldosterone axis Small vasodilator effect on arterioles |
LOOP Mechanism
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1. Hypercalcemia
2. Hyperkalemia 3. Acute pulmonary edema admin. IV 4. Edema from CHF 5. Edema associated with chronic renal insifficiency |
Loop Indications
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Derivative of Sulfonamide
More potent vs Furosemide |
Bumentanide
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Steeper dose response curve vs furosemide BUT GREATER SE
Higher incidence of ototoxicity |
Ethacrynic Acid
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Derivative of Sulfonamide
Weak inhibitor of carbonic anhydrase which increases excretion of HCO3 UNLIKE bumentanide |
Furosemide---Lasix
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1. Ototoxicity (tinnitus, deafness, vertigo, vestibular function)
2. Hyperuricemia--leads to gout, hyperglycemia 3. Hypovolemia 4. Hypo Mg 5. May increase LDL and triglycerides and decrease HDL 6. Significant decrease in blood volume 7. Hypo K--may need supplements 8. Hypo Na Can adversely affect hearing especially when used with aminoglycosides Rahes, Photosensitivity, Paresthesia, bone marrow depression, GI |
Loop Side Effects
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1. Aminoglycosides---ototoxicity
2. Anticoagulant 3. Cardiac Glycosides and anti-arrhythmic agents that prolong repolarization 4. Lithium 5. Propranolol 6. Sulfonylureas---Hyperglycemia 7. Cisplatin 8. Probenecid 9. Thiazide 10. Amphotericin B |
Loop Drug Interactions
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1. Severe Na volume depletion
2. Hypersensitivity to sulfonamide 3. Anuria unresponsiveness to trial dose of loop 4. Postmenopausal women who are osteopenic |
Loop Contraindications
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Which increase excretion of Ca?? Which decrease??
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Loop
Thiazide |
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Compete with uric acid for renal tubular and biliary secretion...inhibiting secretion of uric acid....may exacerbate attacks of Gout
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Ethacrynic Acid and Furosemide
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Sulfonamide Derivatives
More potent than CAIs Act at Distal Tubule Decrease re-absorption of Na by inhibiting Na/Cl co-transporter on luminal side Na and Cl increased in tubular fluid Hyperosmolar urine NOT seen with other diuretics Loss Mg, Na, Cl, K NOT Ca Decreases peripheral vascular resistance No effect on pH "Ceiling Diuretics" b/c there is a max dose when NO more effect can occur Mechanism dependent on prostaglandin synthesis Decreases Ca excretion---preserve bone density Decreases peripheral resistance--decreases BP |
Thiazides
Chlorothiazide, Hydrochlorothiazide |
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Decreased edema of cirrhosis and CHF
Minimal SE |
Chlorothiazide
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More potent vs Chlorothiazide
Less ability to inhibit carbonic anhydrase |
Hydrochlorothiazide---Esidrix, Hydrodiuril
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1. Hypo K--MOST COMMON
2. Hypo Mg 3. Hypo Na 4. Hyperuricemia--Gout 5. Hypovolemia 6. Hypercalcemia 7. Hyperglycemia 8. Hypersensitivity 9. Hyperlipidemia |
Thiazide SE
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1. HTN--preferred in AA, decreases systolic and diastolic
2. Heart Failure--decrease extracellular volume but LOOP PREFERED 3. HypercalcURIA 4. DM---produce hyperosmolar urine |
Thiazide Indications
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Takes 1-3 wks to stable decrease in BP
Hydrochlorothiazide: T1/2 6 Hrs, 25mg or less qd Indapamide: T1/2 25 Hrs Chlorothalidone: T1/2 48-72 Hrs |
Thiazide Dose
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Thiazide Analogs
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Chlothalidone, Indapamide, Metolazone
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NON Thiazide Derivative
T1/2 LONGER Administered qd USES: HTN |
Chlorthalidone
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More potent than Thiazides
Causes excretion of Na in advanced renal failure UNLIKE the Thiazides |
Metolazone
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Lipid soluble, LONG duration of action
Significant HTN reduction w/ low diuretic effect at low doses Metabolized by GI; excreted by kidneys USES: Advanced renal failure, less likely to accumulate in these pts |
Indapamide
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In edema, levels of aldosterone are high promoting absorption of Na
K+ sparing: inhibit aldosterone resulting in excretion of Na and retention of K As with LOOP and THIAZIDE, K+ Sparing is dependent of prostaglandin synthesis Main indication is in combo with Thiazide for HTN Can be used alone for Hyperaldosteronism |
K+ Sparing
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1. Diuretic
2. Hyperaldosteronism 3. Heart Failure Diuretic of Choice in pts with cirrhosis of liver |
Spironolactone Indications
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Blocks intracellular aldosterone receptor, cell DNA can't synthesize proteins in response to aldosterone
Prevents Na reabsorption and prevents excretion of K NO DIURETIC EFFECT OCCURS IN ADDISON'S (primary adrenal insufficiency) In secondary Hyperaldosteronism, induces a negative salt balance |
Spironolactone
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1. GI upset/Peptic ulcers
2. Gynecomastia in males and menstrual irregularities in females 3. Hyper K 4. Nausea, lethargy, mental confusion |
Spironolactone SE
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Highly bound to plasma proteins
Absorbed 65% T1/2: 1.6 Hr Metabolized to canrenone which has a T1/2 of 16.5 Hr Undergoes enterohepatic circulation Most effective administed a few days at a time |
Spironolactone Dose
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Inhibits Na transport channels resulting in decrease Na/K exchange
Independent of presence of aldosterone UNLIKE Spironolactone Can be used in ADDISIONS Normally used in combo with other diuretics, mainly used for K sparing ability |
Triamterene and Amiloride
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Leg Cramps
Increase in blood urea nitrogen Retention of K and uric acid |
Triamterene SE
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Aldosterone receptor antagonist, same mechanism as spironolactone but LESS endocrine effects
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Eplerenone
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