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Pharmacology > Renal Pharmacology > Flashcards

Renal Pharmacology Flashcards

1
Q

what are diuretics

A

drugs that increase water excretion

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2
Q

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

A

loop diuretics, thiazides, amiloride, and triamterene

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3
Q

diuretics that exert osmotic effects that prevent water reabsorption

A

osmotic agents (mannitol)

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4
Q

diuretics that act by inhibiting enzymes

A

acetazolamide

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5
Q

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

A

spironolactone

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6
Q

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

A

Na+/H+ exchanger

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7
Q

Na+/H+ exchanger allows?

A

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

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8
Q

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

A

Because of the high water permeability of the proximal tubule

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9
Q

where are Organic acid secretory systems located

A

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

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10
Q

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

A

in the early and middle segments of the proximal tubule.

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11
Q

where does the thin limb of Henle’s loop begins

A

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

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12
Q

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

A

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

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13
Q

in the proximal tubule what oppose water extraction

A

impermeant luminal solutes such as mannitol

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14
Q

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

A

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

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15
Q

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

A

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

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16
Q

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

A

Na+/K+/2Cl cotransporter .

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17
Q

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

A

loop diuretics

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18
Q

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

A

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

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19
Q

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

A

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

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20
Q

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

A

thiazide class.

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21
Q

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

A

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

22
Q

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

A

, the collecting tubule

23
Q

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

A

the collecting tubule

24
Q

The principal cells of collecting duct are the major sites of

A

Na+, K+, and H2O transport

25
Q

intercalated cells of collecting duct are the primary sites of

A

proton (H+) secretion.

26
Q

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

A

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

27
Q

In the absence of ADH what happens to the collecting tubule

A

it is impermeable to water, and dilute urine is produced

28
Q

where is Carbonic anhydrase predominantly located and catalyses what reaction

A

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.

29
Q

list the classes of diuretics

A

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

30
Q

PK of carbonic anhydrase inhibitors ADME

A

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

31
Q

PD of carbonic anhydrase inhibitors MOA

A

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,

32
Q

examples of Carbonic Anhydrase Inhibitors

A

Acetazolamide
Methazolamide
Dichlorphenamide

33
Q

Indication for CA inhibitors

A

Glaucoma
Urinary Alkalinization
Metabolic Alkalosis
Acute Mountain Sickness
Renal Potassium Wasting

34
Q

Contraindications for CA inhibitors

A

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

35
Q

Loop Diuretics MOA

A

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.

36
Q

examples of loop diuretics(3)

A

Furosemide
Torsemide
Ethacrynic acid
Bumetanide

37
Q

PK of Loop diuretics

A

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.

38
Q

Indications for Loop diuretics

A

Hyperkalemia
acute pulmonary edema
acute/chronic peripheral edema
hypercalcemia

Hint: loop has hope for home
Hypercalcemia
Hypertension
Odema
PE-pulmonary and peripheral edema

39
Q

Contraindications for loop diuretics

A

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

40
Q

ADR’s for loop diuretics

A

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

41
Q

ADR’S FOR CA inhibitors

A

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

42
Q

Thiazide MOA

A

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

43
Q

The prototypical thiazide is

A

hydrochlorothiazide

44
Q

examples of thiazide

A

Benzthiazide
Chlorothiazide
Hydrochlorothiazide
Hydroflumethiazide
Polythiazide

45
Q

indications of thiazide

A

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

46
Q

PK for thiazides

A

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

47
Q

ADR of thiazides

A

volume depletion
hyponatremia
hyperglycemia
hyperuricemia

48
Q

Potassium-Sparing Diuretics MOA PD

A

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)

49
Q

PK of Potassium-Sparing Diuretics

A

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.

50
Q

Indication /therapeutic uses of potassium sparing diuretics

A

Hypertension
PCOS
Diuretic
Secondary hyperaldosteronism

51
Q

examples of PSD

A

spironolactone, eplerenone
amiloride, triamterene

Pharmacology (11 decks)

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