(2) CV & Renal: Diuretics (2.1-2.4) Flashcards
What part of the nephron do Acetazolamide and Mannitol act on?
PCT
Is the renal tubule Na+/K+ ATPase located on the apical or basolateral membrane?
Basolateral
(Yellow tract is tubular lumen, gray track is intracellular compartment)
Is the renal tubule Na+/H+ exchanger located on the apical or basolateral membrane?
Apical
What reaction does carbonic anhydrase in the renal tubule catalyze?
HCO3- + H+ → H2O + CO2
What reaction does intracellular carbonic anhydrase catalyze in the renal tubule?
H2O + CO2 → H+ + HCO3-
MOA: Acetazolamide
Inhibits carbonic anhydrase
Name 3 effects Acetazolamide has on renal electrolyte concentrations
(1) ↑ HCO3-
(2) ↑ Na+
(3) ↑ K+
* (↓ CA ⇒ ↓ Intracellular H+ ⇒ Inhibition of Na+/H+ exchanger ⇒ ↑ lumenal [Na+])*
What acid/base disorder does Acetazolamide cause?
Normal anion gap metabolic acidosis
(Remember, anion gap acidosis is due to the production of volatile organic acids such as in diabetic ketoacidosis)
Indications - Non-diuretic (3) : Acetazolamide
(1) Glaucoma
(2) Idiopathic intracranial hypertension
(3) Mountain sickness
* (Alkalinization of urine also treats gout and cystinuria by ↑ crystal solubility)*
What type of renal tubular acidosis does Acetazolamide cause?
Type II
Acetazolamide promotes the precipitation of what type of kidney stone?
Calcium phosphate
(Tubular alkalinization shifts the HPO42- ↔ PO43- + H+ to the right ∴ ↑ [PO43-] ∴ ↑ Ca3(PO4)2 solubility product ⇒ Precipitation)
Which diuretics are Sulfa drugs?
(1) Acetazolamide
(2) Loop diuretics
(3) Thiazide diuretics
* (Note: Ethacrynic acid is a loop diuretic but NOT a Sulfa drug)*
MOA: Mannitol
Osmotic diuretic
Indications (2) : Mannitol
(1) ↑ Intracranial pressure
(2) ↑ Intraocular pressure
Adverse Effects (3) : Mannitol
(1) Pulmonary edema
(2) Exacerbate heart failure
(3) Altered Na+ levels
* (↑ Serum osmolarity draws fluid from CSF/eyes, but this can dilute serum sodium and increase cardiac afterload)*
Does Mannitol cause hyper or hyponatremia?
Either, depending on the situation
- (↑ Solute in serum ⇒ ↑ Osmotic draw from ECF ⇒ Dilution and hyponatremia)*
- (↑ Solute in urine ⇒ ↑ Osmotic draw in tubular fluid ⇒ ↑ Water excretion ⇒ Concentration and hypernatremia)*
Which segment of the nephron is most impermeable to water?
Thick ascending loop of Henle
(Note: DCT is relatively impermeable to water as well)
What transporter do loop diuretics inhibit?
Na+/K+/2Cl- Cotransporter
(On the lumenal membrane)
MOA: Furosemide
Inhibits Na+/K+/2Cl- Cotransporter
MOA: Ethacrynic acid
Inhibits Na+/K+/2Cl- Cotransporter
What ions do loop diuretics promote excretion of indirectly?
(1) Mg2+
(2) Ca2+
Do loop diuretics have a larger effect on serum Mg2+ or Ca2+?
Mg2+
(Ca2+ levels are corrected by ↑ intestinal absorption due to Vitamin D, ↑ renal absorption due to PTH)
Which class of diuretics induce the expression of COX-2?
Loop diuretics
Which class of pain medication can interfere with loop diuretics?
NSAIDs
Indications (3) : Loop diuretics
(1) Pulmonary edema/CHF
(2) Ascites
(3) Hypertension
* (Also useful in hypercalcemia)*
Which class of diuretics are the first-line treatment for pulmonary edema secondary to heart failure?
Loop diuretics
(∵ They are the most efficacious. Also note the #1 on the balloon)
Are loop diuretics potassium wasting?
Yes
(Inhibition of Na+/K+/2Cl- cotransporter ⇒ ↑ lumenal Na+ concentration and ∴ increased activity of Na+/K+ ATPase)
Adverse Effects (5) : Loop diuretics
(1) Ototoxicity
(2) Sulfa allergy
(3) Interstitial nephritis
(4) Hyperuricemia
(5) Contraction alkalosis
Name a loop diuretic that is NOT a Sulfa drug
Ethacrynic acid
Where do thiazide diuretics act?
Distal convoluted tubule
MOA: Thiazide diuretics
Inhibits NaCl cotransporter
(In DCT)
What is the difference in the mechanism of Ca2+ reabsorption in DCT vs. TAL?
(1) DCT: Active transport
(2) TAL: Driven by (+) lumenal voltage
What effect do thiazide diuretics have on Ca2+ reabsorption?
Increase
(Contrast with loop diuretics)
Indications (5) : Thiazides
(1) Hypertension
(2) Heart failure
(3) Nephrogenic diabetes insipidus
(4) Ca2+ stones
(5) Osteoporosis
Adverse Effects (7) : Thiazides
(1) Hypercalcemia
(2) Hyperglycemia
(3) Hyperlipidemia
(4) Hyperuricemia
(5) ↑ Serum Li+
(6) Hyponatremia
(7) Hypokalemia
* (“Hydrochlorothiazide at the high dive makes a lot of labs high!”)*
Which part of the renal tubule do K+ sparing diuretics act on?
Collecting duct
What part of the renal tubule does Aldosterone act on?
Collecting duct
Which cell regulates Na+/K+/H2O reabsorption in the collecting duct?
Principal cell
Where is ENaC located?
Apical collecting duct membrane
What drives K+ secretion in the collecting duct?
(-) Lumenal voltage
(Na+ reabsorption ⇒ (-) Lumenal voltage ⇒ Pulls K+ through channels)
What cell is responsible for H+ secretion in the collecting duct?
α-intercalated cells
(α for αcid)
Name 4 ion transporters in the collecting duct upregulated by Aldosterone
(1) K+ channels
(2) ENaC
(3) Na+/K+ ATPase
(4) H+ ATPase
Which K+ sparing diuretics directly inhibit Na+ channels?
(1) Amiloride
(2) Triamterene
MOA (2) : K+ sparing diuretics
(1) Inhibit ENaC
(2) Antagonize aldosterone receptor
* (∴ Prevents generation of negative lumenal potential and ∴ K+ wasting)*
What ENZYME does Spironolactone inhibit?
17α-hydroxylase
Name 2 mineralcorticoid receptor antagonists
(1) Eplerenone
(2) Spironolactone
Other than Spironolactone, what can be used to treat the symptoms of Conn’s syndrome?
Eplerenone
What are two classes of diuretics which prevent cardiac remodeling and improve outcomes in heart failure?
(1) Aldosterone receptor antagonists
(2) ACE Inhibitors
* (Theme: ↓ Aldosterone Fx ⇒ ↑ Survival)*
Which class of antidiuretics are useful in Liddle’s syndrome?
K+ sparing diuretics
- (Specifically, ones that target ENaC)*
- Recall: Liddle’s syndrome is overactive ENaCs*
Adverse Effects (2) : K+ sparing diuretics
(1) Hyperkalemia
(2) Normal anion gap metabolic acidosis
What type of renal tubular acidosis do K+ sparing diuretics cause?
Type 4
What is the only cause of type 4 renal tubular acidosis associated with hyperkalemia?
K+ sparing diuretics
Name 4 side effects of Spironolactone which distinguish it from other K+ sparing diuretics
(1) Inhibits 17α-hydroxylase
(2) Inhibits androgen receptor
(3) ⇒ Gynecomastia
(4) ⇒ Impotence
What diuretic can be used to treat polycystic ovarian syndrome (PCOS)?
Spironolactone
