Renal Drugs

Question 1

Carbonic acid anhydrase inhibitors

Answer 1

Acetazolamide
inhibits carbonic anhydrase in the PT; prevents breakdown of carbonic acid and subsequent reabsorption of bicarbonate, and relatedly NaCl reabsorption (via NaH antiporter); result is increased excretion of water, bicarb, and mild increased Na and K excretion

Question 2

Osmotic diuretics

Answer 2

Mannitol; Glucose (when SGLT is saturated)
molecules that are freely filtered but not reabsorbed, take water out with it; this also prevents NaCl reabsorption so they are potent

Question 3

Loop diuretics

Answer 3

Furosemide
block NKCC and thereby 20% of NaCl reabsorption; increase Na, K, Cl, and H2O excretion; but must be secreted into the tubule to act on the luminal transporter

Question 4

Thiazide diuretics

Answer 4

Class I: Hydrochlorothiazide; use when GFR is adequate
Class II: Metolazone, Indapamide; newer and more potent, use when GFR is 30
block NaCl (electroneutral transporter) in early DCT, thereby preventing about 5% of Na reabsorption; increase Na, K, Cl, and H2O excretion - risk of hypo-electrolytes and dilutional hypoNa

Question 5

ANP

Answer 5

binds receptors in medullary CD and increases IC cGMP which decreases Na reabsorption, and water follows Na out; no change in K excretion

Question 6

Diuretics acting in CD

Answer 6

block ENaC: Amiloride, Triamterene
ALD-R antagonist: Spironolactone/Eplerenone
These all increase Na excretion, and lumen is less negative so both K and H secretion are reduced; thus these are K-sparing diuretics

Question 7

Which diuretics increase potassium excretion?

Answer 7

PT - acetezolamide
LOH - furosemide
DCT - thiazide
Osmotic diuretics
Because they all increase the Na delivered to the CD, and attempts to reabsorb more means more K secretion (recall that hypoK is also related to alkalosis when protons are secreted to try and reabsorb the secreted K)

Question 8

Vasopressin

Answer 8

aka AVP/ADH; an anti-diuretic
Binds both V1 and V2 receptors - V1 causes vascular smooth muscle contraction; V2 (in PCs in CD) causes more AQPs and urea transporters to be put into the membrane

Question 9

Selective V2R agonists

Answer 9

Desmopressin (DDAVP)
Used to treat central DI (kidneys waste water) because it will stimulate the V2R which says to put more AQPs into membrane

Question 10

Selective V1R agonists

Answer 10

Terlipressin

Increase constriction of GI and vascular smooth muscle; used to treat bleeding

Question 11

Vaptans

Answer 11

[highly selective] V2R antagonists (so also vasopressin/ADH antagonists)
used to treat hypervolemia, SIADH, and hyponatremia; CYP3 metabolism

Question 12

Aquaretic

Answer 12

a class of drugs that increases blood flow to the kidney without increasing reabsorption of NaCl reabsorption; result is water loss without loss of electrolyte concentration; Examples: vasopressin antagonists (vaptans)