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Renal > Diuretics and Aquaretics > Flashcards

Diuretics and Aquaretics Flashcards

1
Q

What is the MOA of Acetazolamide?

A
  •   Potent competitive inhibitor of carbonic anhydrase.
  •   Act in proximal tubule (90%) distal tubule (10%).
  •   Inhibit C.A. resulting in bicarbonate loss into urine.
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2
Q

What is the net effect of acetazolamide?

A

alkaline urine, enhanced chloride reabsorption (hyperchloremic systemic acidosis)

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3
Q

What are the clinical uses of acetazolamide?

A
  •   Glaucoma to reduce intraocular pressure.
  •   Cystinuria to alkalinize tubular urine.
  •   Management of seizures.
  •   Treat/Prophylaxis of mountain sickness.
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4
Q

What is the example of an osmotic diuretic?

A

mannitol

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5
Q

What is the MOA of osmotic diuretics?

A
  •   Osmotically inhibit Na+/H2O reabsorption in proximal convoluted tubule.
  •   Expand extracellular volume & increase renal medullary blood flow.
  •   Decrease medullary tonicity to impair ability of thin segments of loop of Henle to extract water and absorb NaCl.
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6
Q

What is the net effect of osmotic diuretics?

A
  •  Increase urine flow with small increments of Na+, K+ & Cl-.
  •  Initially increase plasma volume & B.P.
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7
Q

What are the clinical uses of osmotic diuretics?

A
  •   Treatment of dialysis disequilibrium syndrome.
  •   Reduce intracranial pressure.
  •   Reduce intraocular pressure.
  •   Drug overdose
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8
Q

What are the adverse effects of osmotic diuretics?

A

pulmonary edema, dehydration

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9
Q

What are the contraindications of osmotic diuretics?

A

anuria, CHF

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10
Q

List examples of loop diuretics.

A

Furosemide, Bumetanide, Torsemide

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11
Q

What is the MOA of loop diuretics?

A
  •   Inhibit Na+-K+-2Cl— symporter in TALH.
  •   Increase renal blood flow
  •   Increase renal prostaglandins
  •   Stimulate renin release and maintain GFR.
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12
Q

What is the effect on increasing renal prostaglandins?

A

vasodilation of afferent arteriole

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13
Q

What is the net effect of loop diuretics?

A
  •   Copious diuresis with significant Na loss
  •  Increase K+, Ca2+ and Mg2+ excretion
  •  Increase excretion of H+ resulting in mild metabolic alkalosis
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14
Q

What are the indications for loop diuretics?

A
  •  Given orally for edema of cardiac, hepatic & renal origin
  •  Acute pulmonary edema. (Given I.V. for rapid mobilization of edema fluid)
  •  Hypercalcemia
  •  Hypertension(with low GFR)
  •  Prevention of renal failure
  •  Wash out toxins
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15
Q

How do loop diuretics decrease pulmonary edema?

A
  •  Decrase pulmonary wedge pressure
  •  Venodilation resulting in decrease left ventricular filling pressure
  •  Increasecompliance of pulmonary vasculature that facilitates mobilization of fluid
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16
Q

What are the toxicities of loop diuretics (furosemide)?

A 
OH DANG!
Ototoxicity
Hypokalemia
Dehydration
Allergy (sulfa)
Nephritis (interstitial)
Gout (hyperuricemia)
(also leads to increased BUN and hyperglycemia)
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17
Q

When would you take bumetanide?

A

In cases when patient is on Warfarin (CANNOT TAKE FUROSEMIDE with NSAIDs or WARFARIN)

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18
Q

What is the specific extra action of torsemide that the other loop diuretics do not have?

A

vasodilator (so more commonly used to treat HTN)

19
Q

List examples of thiazide diuretics.

A

Hydrochlorothiazide, Chlorthalidone and Metolazone (potent), Quinothazone (potent)

20
Q

What is the MOA of thiazides?

A
  •  Inhibit Na-CL symporter in early distal tubule
  •  Net effect: mild loss of sodium and water
  •  Increase K+ excretion…..Hypokalemia
21
Q

What is the therapeutic utility of thiazides?

A
  •  Treatment of mild to moderate edema
  •  Essential hypertension
  •  Diabetes insipidus (nephrogenic)
  •  Hypercalciurea/osteoporosis
22
Q

What are the side effects of thiazides?

A 
"HyperGLUC"
HyperGlycemia
HyperLipidemia
HyperUricemia
HyperCalcemia
(along with hyponatremia, hypomagnesemia, hypokalemia metabolic alkalosis)
23
Q

List examples of aldosterone antagonists.

A

Spironolactone and Eplenorone

24
Q

What is the MOA of aldosterone antagonists?

A

Competitive inhibitors to aldosterone in late D.T. and collecting ducts.

25
Q

What is interesting about the pharmacokinetics of spironolactone?

A
  •   Spironolactone extensively metabolized

*   active metabolite “Canrenone”

26
Q

What is the net effect of aldosterone antagonists?

A

Increased Na+ excretion, reduces K+ secretion

Acts as mild diuretic with thiazides!

27
Q

What are the adverse effects of spironolactone?

A
  •   Gynecomastia (in males)

*   Hirsutism and uterine bleeding (in females

28
Q

List the K+ sparing diuretics.

A

Triamterene and amiloride

29
Q

What is the MOA of K+ sparing diuretics?

A
  •  Inhibits Na+ reabsorption and K+ secretion in late distal tubule and collecting ducts
  •   Combined with thiazides [Dyazide]
30
Q

What adverse effect do aldosterone antagonists and K+ sparing diuretics have in common?

A

hyperkalemia that could lead to arrhythmias

31
Q

What drugs is used to treat ADH-sensitive (central) diabetes insipidus?

A

Desmopressin

32
Q

What is the MOA of desmopressin?

A

Agonist of V2R receptors that stimulates the Gs-cAMP-PKA pathway to increase rate of insert and phosphorylate aquaporin-2 containing vesicles into the apical membrane—which increases permeability of collecting duct to water.

33
Q

What is the MOA of 8-arginine vasopressin?

A

Agonist of V1R that stimulates the Gq-PLC-IP3 pathway gets stimulated→ mobilizes Ca2+ to cause vasoconstriciton of vascular smooth muscle

34
Q

What is the indication for 8-arginine vasopressin?

A

Post operative ileus

Decrase bleeding in esophageal varices and acute hemorrhagic gastritis

35
Q

What is the treatment for Nephrogenic diabetes insipidus?

A

maintaining adequate water intake

thiazides

36
Q

What drugs can cause SIADH?

A
  • Psychotropics: SSRI, tricyclic anti-depressants
  • Sulfonylureas: chloropropaide
  • Vinca Alkaloids
37
Q

What drugs can be used to treat SIADH?

A

Demeclocycline

Vaptans

38
Q

What is the MOA of Demeclocycline?

A

antagonist of ADH at V2R

39
Q

What is the other use for demeclocycline and sartans?

A

can also be used in patients with hyponatremia due to CHF, cirrhosis, and nephrotic syndrome.

40
Q

List the vaptans.

A

Tolvaptan (very selective, oral)

Conivaptan (IV)

41
Q

What is the MOA of vaptans?

A

Antagonist of V2R receptors that prevents the Gs-cAMP-PKA pathway to decrease rate of insert and phosphorylate aquaporin-2 containing vesicles into the apical membrane—which decreases permeability of collecting duct to water.

42
Q

What are the adverse effects of tolvaptan?

A

CYP3 DDIs, hyperglycemia, GI problems, clotting problems

43
Q

What are the adverse effects of conivaptan?

A

CYP3A4 metabolized, numerous AE, infusion site reaction

Renal (12 decks)

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