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Pharmacology Block 2 > 11 Diuretics > Flashcards

11 Diuretics Flashcards

1
Q

Where is most sodium and chloride reabsorbed in the nephron?

A

Proximal Tubule

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2
Q

Function of proximal tubule

A

Reabsorption!

  • Na+ and Cl- (50-75%)
  • K+
  • HCO3- (80-90%)
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3
Q

On what part of the nephron is chloride actively reabsorbed?

A

Ascending Limb of Loop of Henle

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4
Q

On what part of the nephron is water impermeable?

A

Ascending Limb of Loop of Henle

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5
Q

Function of Ascending Limb of Loop of Henle

A
  • Na+ and Cl- reabsorbed (20-30%)
    • active chloride reabsorbed
  • impermeable to H2O: no reabsorption
  • compensates for inc Na+ delivery from proximal tubule by increasing reabsorption
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6
Q

On what part of the nephron is K+ secreted?

A

Distal Tubule and Collecting Duct

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7
Q

On what part of the nephron does regulation of Na+ and K+ exchange by aldosterone occur?

A

Distal Tubule and Collecting Duct

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8
Q

On what part of the nephron is water permeability regulated by ADH (Vasopressin)?

A

Distal Tubule and Collecting Duct

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9
Q

Function of Distal Tubule and Collecting Duct

A
  • Na+ reabsorbed (8-9%)
  • K+ secreted from blood to tubule lumen to urine
  • Aldosterone regulation of Na+/K+ exchange
  • Water permeability regulated by ADH
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10
Q

What drugs are renal vasodilators?

A

Dopamine
Fenoldapam
Atriopeptins

Work at glomerulus

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11
Q

Where do renal vasodilators such as dopamine, fenoldapam, and atriopeptins exert their action?

A

Glomerulus

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12
Q

What group of drugs selectively dilates the renal vasculature that modifies the proximal tubular function?

A

Renal Vasodilators: Dopamine, Fenoldapam, Atriopeptins

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13
Q

What group of drugs decrease filtration fraction?

A

Renal Vasodilators: Dopamine, Fenoldapam, Atriopeptins

Inc renal blood flow without changing GFR

FF = GFR / RBF

Dec FF reduces protein concentration and hydroosmotic forces in peritubular capillaries

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14
Q

Renal Vasodilator Characterisitcs

A

Dopamine, Fenoldapam, Atriopeptins

Mech:

  • inc RBF w/o reducing GFR, which dec FF, which reduces protein conc and hydroosmotic forces in the peritubular capillaries
  • Na+ and H2O leak back into tubule for excretion

Weak as diuretic due to compensatory Na+ reabsorption in distal nephron

Use:
- Limited clinically– hypertensive crisis and shock

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15
Q

What type of drug is mannitol?

A

Osmotic Diuretic

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16
Q

Where on the nephron does mannitol exert effect?

A

Whole nephron but mostly proximal tubule

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17
Q

What drug acts in the tubular lumen as a non-reabsorbable solute to increase urinary excretion of Na+, Cl+, K+, and H2O?

A

Mannitol

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18
Q

What is mannitol used for?

A

Edema
Glaucoma–reduce intraocular pressure
Acute renal failure

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19
Q

Characteristics of Mannitol

A
  • freely filtered at glomerulus
  • not reabsorbed by tubule
  • metabolically inert

Mech:
- act in tubular lumen as non-reabsorbable solute to limit reabsorption of water from tubule

  • urine volume and Na+ excretion proportional to osmotic load
  • increases urinary excretion of Na+, K+, Cl-, H2O, and mannitol

Tx:

  • edema
  • Glaucoma
  • Acute renal failure
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20
Q

What type of drug is acetazolamide?

A

Carbonic Anhydrase Inhibitor

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21
Q

What drug inhibits carbonic anhydrase in the proximal and distal tubule?

A

Acetazolamide–carbonic anhydrase inhibitor

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22
Q

What does acetazolamide do to the pH of urine?

A

Alkalinizes the urine

Prevents carbonic anhydrase from providing H+ ions to the lumen in exchange for Na+ for the reabsorption of HCO3-

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23
Q

What are the side effects of acetazolamide?

A

Metabolic acidosis

Hypokalemia

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24
Q

What drug can be used to alkalinize the urine (ex. to decrease drug toxicity)?

A

Acetazolamide

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25
What drug can be used to treat mountain or altitude sickness?
Acetazolamide
26
What can acetazolamide be used to treat?
Glaucoma Akalinize the urine Mountain or altitude sickness Anticonvulsant
27
Characteristics of Acetazolamide
Carbonic Anhydrase Inhibitor - weak diuretic - inhibited by acidosis (limited clinical use) Mech: - filtered and secreted by OAT on tubular lumen - inhibit CA in proximal and distal tubule - - CA provides H+ ions for bicarb reabsorption - increases excretion of Na+, K+, HCO3-, and H2O (less excretion of Cl-) AEs: - metabolic acidosis (reduces renal response to drug) - hypokalemia Tx: - glaucoma - alkaline the urine - mountain or altitude sickness - anticonvulsant
28
What type of drugs are furosemide, bumetanide, and ethacrynic acid?
Loop Diuretics
29
What drug inhibits the Na+/K+/2Cl- symporter?
Loop Diuretics: furosemide, bumetanide, ethacrynic acid
30
Where on the nephron do furosemide, bumetanide, and ethacrynic acid exert action?
Cortical and medullary segments of ascending limb of Loop of Henle
31
What are disadvantages to using loop diuretics such as furosemide, bumetanide, ethacrynic acid?
``` Hypokalemia Alkalosis Hypovolemia Hyperuricemia Hyperglycemia (furosemide only) Ototoxicity ```
32
Characteristics of furosemide, bumetanide, and ethacrynic acid
Loop Diuretics - high efficacy (20-30% filtered Na+ load excreted) - rapid onset/short duration Mech: - filtered and secreted by OAT - inhibits Na+/K+/2Cl- symporter - act on cortical and medullary segments of ascending limb of loop of Henle - increases excretion of Na+, K+, Cl-, and H2O (also Ca2+) - inc RBF and GFR - large urine volume AEs: - hypokalemia - alkalosis - hypovolemia - hyperuricemia (inc urate reabsorption @PT) - hyperglycemia (furosemide only) - ototoxicity Tx: - edema of cardiac, hepatic, or renal origin - acute pulmonary edema - hypertension
33
What type of drugs are hydrochlorothiazide and metolazone?
Thiazide and Thiazide-like Diuretics
34
Where do thiazide and thiazide-like diuretics exert action on the nephron?
Cortical segments of distal tubule
35
What drugs inhibit the Na+/Cl- symporter?
Hydrochlorothiazide and Metolazone: Thiazide and Thiazide-like Diuretics
36
What drug exerts effect on cortical segment of the distal tubule to create a hypertonic urine?
Hydrochlorothiazide and Metolazone: Thiazide and Thiazide-like Diuretics
37
What are the disadvantages to using hydrochlorothiazide or metolazone?
``` Hypokalemia Alkalosis Hyperuricemia Hyperglycemia Dec in GFR ```
38
What can hydrochlorothiazide or metolazone be used to treat?
Edema due to CHF Hypertension Hypercalciuria
39
Characteristics of Hydrochlorothiazide and Metolazone
Thiazide or Thiazide-like - intermediate efficacy (8-10% of filtered Na+ load excreted) - moderate onset/long duration Mech: - filtered and secreted by OAT - inhibits Na+/Cl- symporter - acts on cortical segment of distal tubule - increases excretion of Na+, K+, Cl-, and H2O - urine is hypertonic - enhances urate reabsorption (PT) - dec renal Ca2+ excretion AEs: - hypokalemia - alkalosis - hyperuricemia - hyperglycemia - dec in GFR Tx: - edema due to CHF (chronic disease) - hypertension - hypercalciuria
40
What is used for hypercalciuria?
Hydrochlorothiazide or Metolazone
41
What are the 2 classes of K+ sparing diuretics?
Aldosterone Antagonists: Spironolactone, Eplerenone Sodium Channel Inhibitors: Amiloride, Triamterene
42
What drugs are Na+ channel inhibitors?
Amiloride and Triamterene
43
What drugs are aldosterone antagonists?
Spirinolactone and Eplerenone
44
What drugs can be used to increase Na+ excretion without K+ loss?
K+ sparing diuretics: Aldosterone antagonists: Spirinolactone, Eplerenone Sodium channel inhibitors: amiloride and triamterene
45
Why are K+ sparking drugs used in combination with loop diuretics?
K+ sparing can cause hyperkalemia Loop diuretics can result in hypokalemia
46
Where on the nephron do K+ sparing diuretics exert its effect?
Distal tubule Cortical Collecting Duct
47
Characteristics of Spironolactone and Eplerenone
K+ sparing: Aldosterone Antagonist - weak diuretic (2-3%) - act on distal tubule as competitive antagonist of aldosterone - urine volume inc - inc Na+ / dec K+ excretion AEs: - hyperkalemia - gynecomastia (spirinolactone is weak progesterone agonist) Uses: - hypertension - refractory edema - primary aldosteronism - use with thiazide or loop diuretic to enhance diuretic effect and reduce potassium loss
48
Characteristics of amiloride and triamterene
K+ sparing: Na+ channel inhibitor - weak diuretic (2-3%) - inhibit entry of Na+ into principal cells (prevents Na+/K+ exchange on basolateral membrane) - urine volume inc - inc Na+/ dec K+ excretion AEs: - hyperkalemia - mild azotemia (high Nitrogen levels) - Triamterene dec RBF and GFR (high dose) Tx: - edema or hypertension - use with thiazide or loop diuretic to enhance diuretic effect and reduce potassium loss
49
Which what drugs can mild azotemia (high levels of Nitrogen) occur?
Potassium sparing diuretic: - Sodium channel inhibitors: amiloride and triamterene
50
What is often the cause of edema?
Edema is often secondary to cardiac or hepatic disease. Treat primary condition
51
Which diuretic has greatest intrinsic activity?
loop > thiazides > potassium-sparing
52
Which diuretic is cheapest to prescribe?
thiazides < loop < potassium sparing
53
Which diuretic has a faster onset of action?
Loop > Thiazide
54
Diuresis derives fluid from what fluid compartments first?
Intravascular Space Edematous tissue (ECF) Body compartments (peritoneal or pleural space)
55
Which diuretic has the greatest ceiling effect? Diseased conditions that exhibit ceiling effect?
Loop > Thiazide > K+ sparing Diminished nephron response in nephrotic syndrome, cirrhosis, and heart failure Exceeding ceiling dose yields possible adverse effects
56
What does K+ loss parallel? How can this be corrected? Is this fatal?
- K+ loss parallels Na+ excretion - can inc intake of K+ supplements or dec output with K+ sparing diuretics - hyperkalemia = fatal; hypokalemia is rarely life-threatening
57
Foundation of Diuretic Antihypertensive therapy
Reduce renal tubular Na+ and H2O reabsorption 1. Lower BP 2. Prevent Na+ and H2O retention and enhance BP lowering by other antihypertensive drugs Drugs: hydrochlorothiazide, furosemide
58
How do diuretics decrease BP?
=> Deceases vascular volume => Decreases venous return (preload) => Decreases Cardiac output => Decreases BP Also relaxes arteriolar smooth muscle
59
Diuretics in Chronic Heart Failure
- inc salt and water excretion. reduce ECF volume and preload - reduce symptoms of CHF and improve exercise capacity Furosemide and thiazides: - reduce symptoms of CHF - do not improve survival from CHF so used in combo with ACE inhibitors, etc. Spironolactone and Eplerenone: - inhibit renal and cardiac effects of aldosterone - weak diuretics so small effect on salt and water excretion and CHF symptoms - act on heart to inhibit hypertrophy and fibrosis caused by aldosterone - proven to improve survival from CHF
60
Drugs used in chronic heart failure target compensatory reflexes. What types of drugs are these?
Sympathetic nervous system: - Beta blockers Renin/angiotensin/aldosterone activation: - ACE inhibitors - ARBs - Spironolactone, Eplerenone
61
What Starling Forces are imbalanced by disease that results in edema?
Edema = fluid entering interstitial space Decreased oncotic pressure due to: - malabsorption - nephrotic syndrome - liver failure - malnutrition Increased capillary hydrostatic pressure due to: - venous obstruction - cirrhosis - CHF - constriction/restriction - renal failure - pregnancy
62
Foundation of diuretic edema therapy
Increase salt and water excretion by reducing renal tubular sodium and water reabsorption 1. Reduce intravascular volume 2. Reduce ECF and edema Drugs: hydrochlorothiazide, furosemide

Pharmacology Block 2 (12 decks)

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