05.12 - Diuretics, Aquaretics (Bahouth) Flashcards Preview

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Flashcards in 05.12 - Diuretics, Aquaretics (Bahouth) Deck (145):
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CA Inhibitor

Acetazolamide

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___ may be effective in patients w/ impaired renal function when class 1 thiazides are not

Metolazone, Indapamide (class 2 thiazides)

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2 main conditions that cause ADH release

Elevation in plasma osmolarity >280; Depletion of ECV

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2 Organic Base K-Sparing Diuretics

Triametrene, Amiloride

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2 Types of Na Channels in IMCD

(1) CNG: Amiloride-sensitive, cyclic nucleotide gated cation channel; (2) Low-conductance highly-selective Na ENaC channel

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3 Clinical uses of Osmotic Diuretics

Intra-cranial pressure, Intra-ocular pressure, Dialysis disequilibrium syndrome

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3 Drugs classes associated with SIADH

Psychotropics, Sulfonylureas, Vinca Alkyloids

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3 Net Effects of Loop Diuretics

(1) Significant NaCl loss; (2) Increase excretion of K, H; (3) Increase excretion of Ca, Mg

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4 Clinical uses of CA inhibitors

Cysteinurea, Intra-ocular pressure, Seizures, Mountain sickness

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4 Therapeutic Uses of Loop Diuretics

(1) Edema of cardiac, hepatic, or renal origin; (2) Pulmonary edema; (3) Hypercalcemia; (4) Protect against renal failure

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A poor response to Thiazides may reflect

Either an overwhelming load of dietary Na, or impairted renal capacity to excrete Na

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Action of ANP

Binds NP receptor-A, activates GC and increases cGMP

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Action of BNP

Binds NP receptor-A, activates GC and increases cGMP

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Action of CNP

Binds NPR-B in vascular SM cells --> Relaxation

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Action of Demeclocycline

Antagonizes ADH at V2R's

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Activation of V1 receptor activates

Gq-PLC-IP3 pathway --> Mobilizes Ca --> Vasoconstriction

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Advantages of Torsemide

Also lowers BP; Longer Half Life

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Best tolerated drug classes for monotherapy in HTN

Diuretics, ACEi's

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Bindin of ADH to V2 receptor activates

Gs-cAMP, PKA --> Insertion of AP-2, p-lation of urea transporter

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Bumetanide vs Furosemide

Bum is 40x more potent

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Class 2 Thiazides

Metolazone, Indapamide

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Clinical effects of Nesiritide

(1) Increase Na excretion; (2) Useful in CHF

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Clinical Uses of Spironolactone

Diuretic in combo with HCTZ; CHF, Cirrhosis

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Clinical Uses of Triametrene, Amiloride

Combined with HCTZ to decrease K excretion

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Common preventable cause of diuretic resistance

Co-administration of NSAID with Loop

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Concentration of urine in Mannitol use

Hypoosmotic (losing free water)

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DDAVP is also used in

Bleeding disorders, Nocturnal Enurisis

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Desmopressin

Highly selective V2R agonist

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Difference between Loop and Osmotic

Loop have high [Na] in urine

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Diuretic of choice in Cirrhosis

Spironolactone

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Diuretic to use in Chronic Renal Failure

Loop

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Diuretic to use in Mild CHF

Thiazide, Loop

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Diuretic to use in Moderate or Severe CHF

Loop

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Diuretic to use in Nephrotic Syndrome

Loop

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Do PG's increase or decrease with Loop Diuretics?

Increase

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Drug interactions of Furosemide

Li, Indomethacin, Probenecid, Warfarin

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Effect of ADH on urea transport

V2 --> PKA p-lates urea transporter --> inc. permeability of CD to urea

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Effect of Furosemide on K, H, Ca, Mg

Increases secretion of all

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Effect of Furosemide on Renal PG's and Venous capacitance

Increases both

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Effect of Osmotic Diuretics on PCT

Osmotically inhibit Na/H2O reabsorption

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Effect of Thiazides on Ca, Mg

Decrease excretion of Ca, Increase secretion of Mg

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Effect of Thiazides on Na, K, Cl

Loss of all three --> Hypokalemia

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Effect of Triametrene, Amiloride on Na, K, H

Weak excretion of Na; Inhibit secretion of K, H

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Eplerenone vs Spironolactone

Lower affinity for AR's so less side effects

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Found in urine, paracrine regulator of Na transport

Urodilantin

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Furosemide vs Indomethacin

NSAIDs inhibit PG effect of Furosemide

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Furosemide vs Probenecid

Compete for secretion by Organic Acid Transporter

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Furosemide vs Warfarin

Compete for protein binding

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General MOA Acetazolamide

CA Inhibitor

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General MOA Mannitol

Osmotic Diuretic

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General MOA of AVP, DDVAP

V2R Agonism, Collecting Duct

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General MOA of Conivaptan, Tolvaptan

V2R Antagonism, Collecting Duct

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Given in large doses, Osmotic Diuretics

increase osmolarity of plasma

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Highly selective V2R agonist

Desmopressin

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How are Loop diuretics administered

IV in hypertensive crisis or in Acute Pulmonary Edema

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How are Thiazides unlike Loops

Thiazides decrease secretion of Ca

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How do Load-Dependent Principal cells work

The more Na is delivered, the more is absorbed in exchange for K secretion

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How do Loop Diuretics affect Macula Densa

MD thinks very little Na, so it secretes PG's --> Increase RBF and FF

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How do PG's affect actions of Loops

Reduce Na re-absorption in distal nephron, antagonize ADH, distribute renal blood from cortex to JG

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How does Furosemide reach the luminal symporter

Secreted by Organic Acid Transporter

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How does Furosemide travel in blood

Extensively protein bound

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How does Hypovolemia lead to Hyponatremia

Hypovolemia stimulates ADH-mediate retention of H20

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How does Nesiritide increase Na excretion

Inhibits CNG_nonspecific cation channel in IMCD; Inhibits RAAS

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How will V2R agonist affect Central vs Nephrogenic DI

Increase urine osmolarity in central by not nephrogenic

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In CHF, Cirrhosis, or Nephrotic Syndrome, hypovolemia is exacerbated by

Diuretics

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In what condition is Mannitol contraindicated

CHF

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Indications for Vaptans

Significant Hypervolemic and Euvolemic Hyponatremia (including patients with HF, Cirrhosis, SIADH)

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Inhibiting CA results in loss of what in urine

Bicarbonate

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K-Sparing Diuretics are useful in what patients

At risk of K depletion; Hyperuricemia

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Late DCT, CD Principal cells are involved in __ re-absorption and __ secretion

Na reabsorption, K secretion

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Like Loops, Thiazides require

secretion into tubular fluid to exert effect

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Loop Diuretics

Furosemide, Bumetanide, Torsemide

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Loop that also lowers BP

Torsemide

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MOA of Loop Diuretics

Inhibit Na-K-2Cl symporter in TALH

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MOA of Thiazide Diuretics

Inhibit NaCl reabsorption in the Na-K Aldosterone-independent sement of distal tubule

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MOA of Triametrene, Amiloride

Inhibit Na re-absorption in late distal tubule (sodium load segment)

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MOA of Vaptans

Selective V2R antagonists

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Most popular drug for HTN

HCTZ

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Most potent class of diuretics in mobilizing NaCl

Loop

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Most Thiazides are ineffective when

GFR < 30-40 mL/minute

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Net Effect of Aldosterone Antagonists

Increase excretion of Na; Inhibit secretion of K, H

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Net effect of Osmotic Diuretics

Significantly increase urine

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On which part of nephron do Triametrene, Amiloride act

Late Distal Tubule, Sodium Load segment

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On which part of nephron does Furosemide act

TALH

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Osmolarity of urine with ADH present

1200

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Osmolarity of urine without ADH

50

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Osmotic Diuretic

Mannitol

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Patients with what type of HTN show better responses to Thiazides

Volume-dependent HTN (low renin)

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Pharmacokinetics of Furosemide

Short half-life; Extensively protein-bound

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Pharmacokinetics of Vaptans

CYP3

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Physiological effects of Aldosterone

NaCl transport enhanced; Increased secretion of K, H+

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Retention phenomena of Thiazides

Hyperuricemia, Hypercalcemia

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Role of Renin in Loop Diuretic use

Potently increased

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Route of Acetazolamide

Oral

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Route of HCTZ

Oral

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Route of Mannitol

Injection

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Selective V2R antagonists

MOA of Vaptans

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SIADH Tx:

Water restriction, Loops, Demeclocycline, Vaptans

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Side effects of Acetazolamide

Metabolic Acidosis, K loss (hypokalemia)

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Side effects of Furosemide

Hypokalemia, Ototoxicity; Elevated BUN, Hyperglycemia, Hyperuricemia

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Side effects of Mannitol

Volume overload (don't use in CHF)

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Side effects of Nesiritide are related to

its narrow therapeutic index

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Side effects of Spironolactone

Hyperkalemia; AR: Gynecomastia, Hirsutism, Uterine Bleeding

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Side effects of Triametrene, Amiloride

Hyperkalemia, Megaloblastic Anemia in cirrhosis

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Side effects of Vaptans

Hyperglycemia, GI disturbances, Clotting probs

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Sodium loss in Thiazides results in chronic

Reduced GFR

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Spironolactone vs Canrenone

Sp is a pro-drug that is extensively metabolized; Can is active metabolite with longer half-life

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T/F: Diuretics only reduce mortality from HTN when used with BB's

False, effective alone or in combo

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T/F: Nesiritide reduces mortality in CHF

FALSE

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Therapeutic Uses of Thiazides

Edema, Hypercalciurea, Essential HTN, Osteoporosis, Nephrogenic Diabetes Insipidus

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Thiazides are widely used to treat

Mild or Moderate HTN

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Tx of Central DI

Selective V2R agonists

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Tx of Nephrogenic DI

Thiazide Diuretics

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Type A Principal cells are regulated by

Hormone: Aldosterone

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Type B Principal cells are regulated by

Load dependent

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Type of channel in Aldosterone Sensitive Channel

Aldosterone-Sensitive ENaC Channel: Na-K/H

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Type of channel in Na-K Aldosterone-independent segment

Na-Cl symporter

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Type of Channel in Sodium Load Segment

ENaC Channel: Na-K/H

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Type of channels affected by Aldosterone in DCT

Epithelial Sodium Channels (ENaC) are increased

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Urine with Acetazolamide use

Alkaline, bicarbonate loss into it

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Urodilatin arises from same precursor as

ANP

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Use of Loop Diuretics for Non-Pulmonary edema

Oral use in Cardiac, Hepatic, or renal origin edema (GFR<30)

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Uses of V1R agonists

Post-op Ileus; Esophageal varices; Acute Hem Gastritis

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V2R agonism

Arginine Vasopressin, Desmopressin (DDAVP)

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V2R Ant-agonism

Conivaptan, Tolvaptan

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What causes acidosis with CA inhibitors

Enhanced chloride reabsorption

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What is substituted for Furosemide in patients receiving Warfarin

Bumetanide

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When are class 1 Thiazides perferably used

When GFR >50

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When are class 2 Thiazides used

More potent, so when GFR<50 but greater than 30

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When are K-Sparing Diuretics contraindicated

Significant Renal Insufficiency (GFR<75); Other K-retaining conditions

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When are Loop used over Thiazides

Severe Htn unresponsive to Thiazides, especially w/ renal insufficiency, cardiac failure, cirrhosis

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Where do CA inhibitors mostly act

Proximal Tubule (90%), Distal (10%)

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Where do CNP's originate

Endothelium and Kidneys

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Where do Loop Diuretics act

Inhibit Na-K-2Cl symporter in TALH

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Where do Vasopressin and Desmopressin act

Collecting duct, V2R agoism

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Where is V1 receptor found

Vascular SM

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Where is V2 receptor found

Principal Cells in Renal CD

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Which are more potent anti-hypertensives: Thiazides or K-Sparing

Equipotent

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Which class of drugs creates largest volume of urine

Osmotic Diuretics

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Which is preferred: Terlipressin or 8-arg vasopressin

Terlipressin has less side effects

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Which parts of nephron have Aquaporin-1

Proximal Convoluted Tubule, Descending Limb

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Which parts of nephron have Aquaporin-2

Collecting Duct

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Why are Thiazides only mild diuretics

Act on distal tubule, which only absorbs 5% of Na

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Why is Nesiritide useful in CHF

Decreases SVR, Decreases LVP, Increases CO

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Wide margin of safety; Dose-response curve influence by renal disease

Furosemide