Renal Pharmacology

Question 1

what are diuretics

Answer 1

drugs that increase water excretion

Question 2

which diuretic agents exert their effects on specific membrane transport proteins in renal tubular epithelial cells.

Answer 2

loop diuretics, thiazides, amiloride, and triamterene

Question 3

diuretics that exert osmotic effects that prevent water reabsorption

Answer 3

osmotic agents (mannitol)

Question 4

diuretics that act by inhibiting enzymes

Answer 4

acetazolamide

Question 5

diuretics that acts by interfering with hormone receptors in renal epithelial cells

Answer 5

spironolactone

Question 6

Sodium bicarbonate reabsorption by the proximal tubule is initiated by the action of ?

Answer 6

Na+/H+ exchanger

Question 7

Na+/H+ exchanger allows?

Answer 7

allows sodium to enter the cell from the tubular lumen in exchange for a proton from inside the cell

Question 8

why is water is reabsorbed in direct proportion to salt reabsorption in the PCT

Answer 8

Because of the high water permeability of the proximal tubule

Question 9

where are Organic acid secretory systems located

Answer 9

in the middle third of the proximal tubule (S2 segment).

Question 10

Organic base secretory systems (creatinine, choline, etc) are also present

Answer 10

in the early and middle segments of the proximal tubule.

Question 11

where does the thin limb of Henle’s loop begins

Answer 11

At the boundary between the inner and outer stripes of the outer medulla

Question 12

Water is extracted from where in the loop of henle and by what?

Answer 12

from the thin descending limb of the loop of Henle by osmotic forces created in the hypertonic medullary interstitium.

Question 13

in the proximal tubule what oppose water extraction

Answer 13

impermeant luminal solutes such as mannitol

Question 14

where in the loop of henle is NaCl actively reabsorbed from the lumen

Answer 14

The thick ascending limb of the loop of Henle (about 35% of the filtered sodium) and its nearly impermeable to water.

Question 15

why is the thick ascending limb designated as a “diluting segment”

Answer 15

Salt reabsorption in the thick ascending limb therefore dilutes the tubular fluid

Question 16

The NaCl transport system in the luminal membrane of the thick ascending limb is what transporter

Answer 16

Na+/K+/2Cl cotransporter .

Question 17

Na+/K+/2Cl cotransporter is blocked by what diuretic agents?

Answer 17

loop diuretics

Question 18

the action of the Na+/K+/2Cl- transporter contributes to excess K+ accumulation within the cell.
This results in?

Answer 18

in back diffusion of K+ into the tubular lumen and development of positive electrical potential in the lumen

Question 19

how many percentage of filtered NaCl is reabsorbed in the distal convoluted tubule.

Answer 19

Only about 10% of the filtered NaCl, this segment is relatively impermeable to water, and the NaCl reabsorption therefore further dilutes the tubular fluid.

Question 20

the NaCl transporter in the DCT is blocked by diuretics of what class?

Answer 20

thiazide class.

Question 21

The collecting tubule is responsible for how many percentage of NaCl reabsorption

Answer 21

only 2–5% of NaCl reabsorption, responsible for volume regulation and for determining the final Na+ concentration of the urine

Question 22

at what site in the kidney do mineralocorticoids exert a significant influence.

Answer 22

, the collecting tubule

Question 23

the major site of potassium secretion by the kidney and the site at which virtually all diuretic-induced changes in potassium balance occur?

Answer 23

the collecting tubule

Question 24

The principal cells of collecting duct are the major sites of

Answer 24

Na+, K+, and H2O transport

Question 25

intercalated cells of collecting duct are the primary sites of

Answer 25

proton (H+) secretion.

Question 26

Reabsorption of Na+ via the epithelial Na channel and its coupled secretion of K+ in the collecting duct is regulated by

Answer 26

aldosterone. This steroid hormone, through its actions on gene transcription, increases the activity of both apical membrane channels and the basolateral N+/K+ ATPase.

Question 27

In the absence of ADH what happens to the collecting tubule

Answer 27

it is impermeable to water, and dilute urine is produced

Question 28

where is Carbonic anhydrase predominantly located and catalyses what reaction

Answer 28

is present in many nephron sites, but the predominantly located luminal membrane of the PCT cells. it catalyzes the breakdown of H2CO3, a critical step in the reabsorption of bicarbonate.

Question 29

list the classes of diuretics

Answer 29

Carbonic Anhydrase Inhibitors Loop Diuretics Thiazides Potassium-Sparing Diuretics Osmotic agents

Question 30

PK of carbonic anhydrase inhibitors ADME

Answer 30

The carbonic anhydrase inhibitors are well absorbed after oral administration. An increase in urine pH from the bicarbonate diuresis is apparent within 30 minutes, maximal at 2 hours, and persists for 12 hours after a single dose. Excretion of the drug is by the kidney Therefore, dosing must be reduced in renal insufficiency

Question 31

PD of carbonic anhydrase inhibitors MOA

Answer 31

By blocking carbonic anhydrase, inhibitors block sodium bicarbonate reabsorption in the PCT and cause diuresis. 85% of the bicarbonate reabsorptive capacity of the PCT is inhibited, when it is maximally safely administered. Some bicarbonate can still be absorbed at other nephron sites by carbonic anhydrase–independent mechanisms, so therefore the overall effect is about 45% inhibition of whole kidney bicarbonate reabsorption carbonic anhydrase inhibition causes hyperchloremic metabolic acidosis, cuz HCO3 - depletion leads to enhanced NaCl reabsorption by the remainder of the nephron. As NaCl is reabsorbed, it retains water in the body which reduces the efficacy of diuretic significantly with use over several days,

Question 32

examples of Carbonic Anhydrase Inhibitors

Answer 32

Acetazolamide Methazolamide Dichlorphenamide

Question 33

Indication for CA inhibitors

Answer 33

Glaucoma Urinary Alkalinization Metabolic Alkalosis Acute Mountain Sickness Renal Potassium Wasting

Question 34

Contraindications for CA inhibitors

Answer 34

The drug should be avoided in patients with hepatic cirrhosis ,because it could lead to a decreased excretion of NH4, may contribute to the development of hyperammonemia and hepatic encephalopathy

Question 35

Loop Diuretics MOA

Answer 35

Loop diuretics inhibit the cotransport of Na+/K+/2Cl− in the thick ascending limb of the loop of Henle. Therefore, reabsorption of these ions is decreased. These agents have the greatest diuretic effect of all the diuretic drugs, since the ascending limb accounts for reabsorption of 35% of filtered NaCl and the fact that diuresis is not limited by development of acidosis.

Question 36

examples of loop diuretics(3)

Answer 36

Furosemide Torsemide Ethacrynic acid Bumetanide

Question 37

PK of Loop diuretics

Answer 37

Loop diuretics are administered orally or parenterally. Their duration of action is relatively brief (2 to 4 hours), allowing patients to predict the window of diuresis. They are secreted into urine.

Question 38

Indications for Loop diuretics

Answer 38

Hyperkalemia acute pulmonary edema acute/chronic peripheral edema hypercalcemia Hint: loop has hope for home Hypercalcemia Hypertension Odema PE-pulmonary and peripheral edema

Question 39

Contraindications for loop diuretics

Answer 39

Furosemide, bumetanide, and torsemide may demonstrate cross-reactivity in patients who are sensitive to other sulfonamides. Overzealous use of any diuretic is dangerous in hepatic cirrhosis, borderline renal failure heart failure

Question 40

ADR's for loop diuretics

Answer 40

Acute Renal Failure Anion Overdose Hypokalemic Metabolic Alkalosis Ototoxicity Hyperuricemia Allergic Reactions Acute hypovolemia Hypomagnesemia

Question 41

ADR'S FOR CA inhibitors

Answer 41

Metabolic acidosis (mild), potassium depletion, renal stone formation Hint; GEM Made a Small DP with zola(acetazolamide) Glaucoma Edema Mountain sickness Metabolic acidosis Stone( renal) Depletion of k Paresthesia

Question 42

Thiazide MOA

Answer 42

thiazides inhibit NaCl transport predominantly in the DCT, by inhibition of a Na+/Cl− cotransporter

Question 43

The prototypical thiazide is

Answer 43

hydrochlorothiazide

Question 44

examples of thiazide

Answer 44

Benzthiazide Chlorothiazide Hydrochlorothiazide Hydroflumethiazide Polythiazide

Question 45

indications of thiazide

Answer 45

hypertension heart failure hypercalcuria Diabetes insupidus Hint;HARD Hypertension inappropriate ADH secretions Renal impairment Diabetes insupidus

Question 46

PK for thiazides

Answer 46

The drugs are effective orally. Most thiazides take 1 to 3 weeks to produce a stable reduction in blood pressure, and they exhibit a prolonged half-life. All thiazides are secreted by the organic acid secretory system of the kidney

Question 47

ADR of thiazides

Answer 47

volume depletion hyponatremia hyperglycemia hyperuricemia

Question 48

Potassium-Sparing Diuretics MOA PD

Answer 48

antagonize the effects of aldosterone at the DCT and collecting tubule. Inhibition may occur by direct pharmacologic antagonism of mineralocorticoid receptors (spironolactone) or by inhibition of Na+ influx through ion channels in the luminal membrane (amiloride, triamterene)

Question 49

PK of Potassium-Sparing Diuretics

Answer 49

spironolactone- Its onset and duration of action depends on the kinetics of the aldosterone response in the target tissue. its substantial inactivation occurs in the liver. It has a rather slow onset of action, Eplerenone, a spironolactone analog has greater selectivity for the aldosterone receptor. Amiloride is excreted unchanged in the urine. Triamterene is metabolized in the liver, but renal excretion is a major route of elimination for the active form and the metabolites. Because triamterene is extensively metabolized, it has a shorter half-life and must be given more frequently than amiloride.

Question 50

Indication /therapeutic uses of potassium sparing diuretics

Answer 50

Hypertension PCOS Diuretic Secondary hyperaldosteronism

Question 51

examples of PSD

Answer 51

spironolactone, eplerenone amiloride, triamterene