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24 Cards in this Set
- Front
- Back
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Name the portions of the Nephron in order of entrance to exit via ureter.
State what percentage of Na and Cl are reabsorbed in each portion |
Glomerulus
PCT - 65% TAL - 25% DCT - 10% CD - 1-5% Na, K moves into tubules |
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What is a consequence of inhibit Na reabsorption in one of these spots?
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The nephron will attempt to compensate in another area, possibly resulting in increased K lose.
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What effect would hypokalemia have on the heart?
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Deceased K could lead to an early after depolarization
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Where do osmotic agents work?
Carbonic Anhydrase Inhibitors? |
Throughout the nephron
Proximal Tubule |
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Loop Diuretics?
Thiazides? K-sparing Diuretics? |
TAL
DCT CD |
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What is the mechanism of action of osmotic agents?
Give an example. |
They increase the osmolarity of tubular fluid. They undergo glomerular filtration but are not reabsorbed.
Mannitol |
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What are osmotic diuretics used for?
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Renal Failure - maintain GFR
They decrease the concentration of toxic compounds in renal tubule They decrease the CSF pressure and volume They decrease intra-ocular pressure |
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What is their side effect?
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Dehydration with hypernatremia
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What is the MOA for carbonic anhydrase inhibitors?
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Non-competitive/reversible inhibition of PCT cell carbonic anhydrases
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Name the transporters/describe the general process that carbonic anhydrase inhibits block.
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In the PCT lumen, H2CO3 is broken down to CO2 and H2O by CA IV. They cross into the cytosol where CA II reassembles it to H2CO3. CA inhibitors block these two reactions.
H2CO3 then loses an H that goes through a Na/H exchanger on the Apical side into the lumen. This brings in Na that then leaves with HCO3 via a Na/HCO3 cotransporter The overall result is decreased Bicarb reabsorbed and decrease Na reabsorbed. |
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What are the therapeutic uses of CA inhibitors?
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Diuresis - low in monotherapy but works well to augment other diuretics
Glaucoma Altitude Sickness- stimulates breathing to increase O2 intake Metabolic Alkalosis - Decreased H secretion Heart Failure - Deceased edema |
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What are 2 side effects?
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Metabolic acidosis - H secretion decreased
Hypersensitivity to sulfonamides - many CA inhibitors are sulfa drugs |
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What is the MOA for Loop Diuretics?
Example? |
Competitive inhibition of TAL cell Na/K/2Cl (NKCC2) transporter which leads to decreased Na reabsorption and loss of transepithelial potential.
Furosemide |
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Describe the process that Loop Diuretics block.
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On the Apical Membrane of the TAL there exists a Na/2Cl/K co transporter. If blocked, Na, K, and Cl cannot be reabsorbed. This disrupts the positive transthelial potential on the apical side of the membrane and prevents Calcium and Magnesium from being reabsorbed. So in addition to inhibition of Na reabsorption, these drugs can cause hypocalcemia and hypomagnesemia
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Name the 3 therapeutic uses of Loop Diuretics.
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- HF associated edema (pulmonary or peripheral)
- Acute renal failure (to increase urine volume) - Hypercalcemia, hyperkalemia |
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What are the side effects of Loop Diuretics?
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- Hypokalemia and metabolic alkalosis (increased secretion of K and H in the CD due to increased tubular Na load)
- Hypocalcemia and hypomagnesemia - Hypersensitivity to sulfonamides (many loop diuretics are sulfa drugs) |
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What is the primary site of action of Thiazides?
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DCT
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What is the mechanism of action?
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They competitively inhibit the Na/Cl co-transporter (NCC1)
This leads to a modest decrease in Na reabsorption (only 10% of Na reabsorption occurs here) as well as increased Calcium reabsorption |
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What is an example of a prominent Thiazide drug?
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Hydrochlorothiazide
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What is the mechanism by which Thiazides increase Calcium reabsorption?
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Thiazide treatment causes increased expression of TRPV5 and NCX1 channels. TRPV5 is located on the apical membrane and NCX1 is located on the Basolateral membrane.
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Name the 4 therapeutic uses of Thiazides?
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- Hypertension (via decreased blood volume)
- HF associated edema - Ca nephrolithiasis (stones) - Osteoporosis (increased Ca absorption) |
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What class of diuretics are Thiazides synergistic with?
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Loop Diuretics (Furosemide)
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Name the 3 side effects of Thiazides.
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- Hypokalemia and metabolic alkalosis (increased secretion of K and H due to increase tubular Na load)
- Erectile Dysfunction (possibly due to effects of Na depletion in CNS) - Hypersensitivity to sulfonamides - thiazides are sulfa drugs |
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What are the important DDI's for Thiazides?
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Class 1A anti-arrhythmics (Quinidine)
- Hypokalemia plus prolonged QT interval = torsades de pointes Loop Diuretics - synergistic block of Na reabsorption in TAL and DCT. Can cause hypokalemia. Be careful with dosing. |
