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Pharmacology > Diuretics > Flashcards

Diuretics Flashcards

1
Q

Diuretics

-goal

A

increase urine volume

increase excretion of sodium and water

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2
Q

“Natriuretic” vs. “Aquaretic”

A

“Natriuretic” - increase renal sodium excretion
-directly act on the cells of the nephron by blocking enzymes and carriers

“Aquaretic” - increase water excretion
-modify the content of the filtrate

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3
Q

Where does Mannitol acts on? Which parts of the nephron?

A

proximal convoluted tubule
thin descending limb
collecting duct

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4
Q

Where do Thiazides acts on? Which parts of the nephron?

A

Proximal straight tubule

Distal convoluted tubule

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5
Q

Where does Adenosine acts on? Which parts of the nephron?

A

glomerulus
proximal convoluted tubule
thick ascending limb
collecting duct

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6
Q

In which part of the nephron water easily crosses the membrane (urine –> interstitium)?

A

proximal convoluted tubule
thin descending limb
collecting duct

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7
Q

Juxtaglomerular apparatus

  • main parts
  • macula densa cells - mechanism of action
A
  • afferent arteriole (contains granular cells), distal tubule (contains macula densa cells) and efferent arteriole
  • macula densa cells recognize the amount of sodium in the ruine and based on the level of it, they are capable of activating granular cells and either increase or decrease the release of renin
    ex: too much sodium in the urine –> macula densa cells detect it –> granular cells are activated –> granular cells release renin –> deactivation of the RAAS
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8
Q

Medullary counter-current

A

-brings electrolytes into the interstitium

  • Ascending limb –> impermeable to water, electrolytes co-transporter
  • Descending limb –> permeable to water, no electrolytes transporter
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9
Q

Proximal convoluted tubule (6)

A
  • sodium and bicarbonate re-absorption from urine
  • Carbonic anhydrase plates an imp. role in the exchange of hydrogen and bicarbonate
  • Chlorine is exchanged with a base
  • Na+/K+ in the membrane maintains intracellular sodium and potassium levels
  • Na+/H+ exchange via NHE3
  • uric acid is mainly secreted here as well as ammonia and some other drugs
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10
Q

Carbonic anhydrase inhibitor

  • name
  • mechanism
A

-Acetozalomide

  • activated when urine pH is alkaline –> decrease formation of aqueous humor in eyes, CSF in brain
  • when carbonic anhydrase is inhibited –> bicarbonate levels in the urine will increase
  • no indication as a diuretic agents because they are weak drugs –> effect wouldnt last long because increase levels of sodium will cause other parts of the nephron to compensate
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11
Q

Carbonic anhydrase inhibitor

  • indications
  • unwanted effects
A
  • glaucoma, infantile epilepsy, metabolic alkalosis

- metabolic acidosis, hypoK+, kidney stones

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12
Q

Why is hypokalemia a side effect of many diuretics?

A
  • sodium levels would reach the collecting tubules and lead to a increased reabsorption in exchange of potassium
  • increase sodium reabsorption in collecting tubules = loss of potassium and hydrogen
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13
Q

Which diuretic drug is the strongest?

A

Loop diuretics - Furosemide

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14
Q

Thick ascending limb (3)

A
  • NKCC2 is the primary transporter in the luminal membrane - sodium, potassium and chlorine are actively reabsorbed
  • reabsorption –> NaCl, Mg, Ca
  • intracellularly is more negative and the lumen is more positive –> movement of magnesium and calcium to negative side
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15
Q

Loop diuretics

  • name
  • mechanism of action
A

-Furosemide

  • secretion of many electrolytes - most powerful
  • increase PG production –> vasodilation –> increase blood supply to kindeys –> hypotensive effect!
  • inhibit NKCC12 receptor
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16
Q

Loop diuretics

  • indications
  • unwanted effects
A
  • hyperK+, pulmonary edema, heart failure, ascites, nephrotic syndrome, hypertension
  • hypoK+, hypoNa+, metabolic alkalosis, hyperuricemia, hearing loss
17
Q

The paradoxical effect of thiazide diuretics in diabetes insipidus. Why loop diuretics wont work in this case?

A
  1. they are given
  2. decrease sodium reabsorption in distal tubule
  3. increase urinary excretion
  4. decrease volume of blood and extracellular volume in general
  5. increase proximal sodium and water reabsorption
  6. decrease distal delivery of sodium and water
  7. decrease urine output

Because there would be disruption in the osmotic gradient in the medulla
too much sodium would be left in the tubules, water wouldn’t be reabsorbed = more water in the urine

18
Q

Distal convoluted tubule

A
  • NCC –> the primary sodium and chlorine transporter in the luminal membrane
  • reabsorption –> nacl, ca
  • PTH –> maintains calcium levels in the blood by regulating the amount of calcium channels
19
Q

Thiazide diuretics

  • name
  • mechanism
A

-Hydrochlorothiazide

  • secretion –> sodium, Cl, K, Mg, H, water
  • vasodilation –> secondary effect
  • inhibit NCC receptor –> sodium levels in urine increase and sodium levels intracellularly decrease –> increase activity of Na+-Ca2+ levels –> increased levels of calcium will be reabsorbed in exchange for sodium –> beneficial in hypercalciuria
  • should be used carefully in patients with type 2 diabetes –> decrease insulin secretion because causes hyperpolarization of pancreatic beta cells
20
Q

Thiazide diuretics

  • indication
  • side effects
A
  • hypertension, pulmonary edema, hypercalciuria, heart failure (mild)
  • hypoK+, hypoCa2+, hyperglycemia
21
Q

Furosemide and Hydrochlorothiazide

  • which one is more potent?
  • which one is more efficient?
A
  • Hydrochlorothiazide - lower amount is needed to cause a response
  • Furosemide - cause much higher sodium elimination in the urine
22
Q

Collecting tubule

A
  • inward diffusion of sodium leaves lumen negative which drives reabsorption of chlorine and efflux of K
  • ADH increases the number of aquaporin channels –> reabsorption of water is increased

-Principle cells: responsible for sodium reabsorption by the activity of aldosterone.

  • Intercalated cells: alpha and beta
  • alpha –> responsible for the secretion of hydrogen, maintains acid levels
  • beta –> regulate bicarbonate secretion and reabsorption
23
Q

What happens when aldosterone activates principal cells in the collecting tubule?

A
  • rapid effects –> increase number of sodium channels opening, increase activity of ATP pump, increase sodium reabsorption
  • delayed effects: active the synthesis of different proteins, leading to a increase in the number of sodium channels
24
Q

Why do we pee a lot when we drink alcohol?

A

Alcohol inhibits the secretion of ADH in the pituitary gland –> low amount of water is reabsorbed back in the collecting tubule

25
Q

Why do we pee less when smoke?

A

Smoking increases the secretion of ADH in the pituitary –> high amount of water is reabsorbed

26
Q

Potassium-sparing diuretics

-name

A
  • Aldosterone antagonist - Spironolaction
  • like aldosterone antagonist - Amiloride
  • limited diuretic action
  • anti-hypertensive effect
  • sodium channels are inhibited –> not very potent because a low level of sodium is reabsorbed in this part of the tubule
27
Q

Aldosterone antagonist - Spironolaction

  • mechanism
  • indication
  • unwanted effects
A
  • compete with aldosterone for its intracellular receptor
  • hyperaldosteronism, heart failure, ascites, hypertension
  • hyperK+, metabolic acidosis, gynaecomastic, menstrual disorders
28
Q

Like aldosterone antagonist - Amiloride

  • mechanism
  • indication
  • unwanted effects
A
  • inhibit luminal sodium reabsorption via channels
  • with K+ losing diuretics
  • hyperK+, GI disorders
29
Q

Osmotic diuretics

  • name
  • mechanism
A

-Mannitol

  • increase more water excreted than sodium
  • given intravenously
  • filtered in the glomerulus and not reabsorbed by the nephron –> increase osmotic pressure in the urine
  • opposite effect as ADH
  • it has effect where water is permeable and easily crosses the membrane
30
Q

Osmotic diuretics

  • indications
  • unwanted effects
A
  • to reduce intracranial and intraocular pressure

- expansion of the extracellular volume, hypoantremia, headache

31
Q

Drugs that have effect on the Proximal convoluted tubule

A

ACETOZALOMIDE

32
Q

Drugs that have effect on the Thick ascending limb

A

FUROSEMIDE

33
Q

Drugs that have effect on the Distal convoluted tubule

A

HYDROCHLOROTHIAZIDE

34
Q

Drugs that have effect on the collecting tubules

A

SPIRONOLACTON

AMILORIDE

Pharmacology (29 decks)

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