Kidney drugs Flashcards

54
Q

What are some ADH inhibitors that prevent/reduce its secretion from the posterior pituitary?

What do they do?

A
  1. Glucocorticoids, such as Prednisolone
  2. Lithium
  3. Ethanol & Alcohol
  4. Phenytoin (humans)

Inhibit ADH secretion

These result in dilute urine as no aquaporin water channels inserted in collecting tubules for reabsorption of water into interstitial fluid ⇄plasma.

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55
Q

What are some ADH inhibitors that prevent/reduce its action on the collecting ducts?

What do they do?

A
  1. Glucocorticoids - at second-messenger level, non-competitive inhibitors
  2. Vincristine (cancer chemotherapy agent) -** **Blocks microtubule action that inserts aquaporin water channels
  3. Calcium - Hypercalcaemic animals will have Nephrogenic Diabetes Insipidus, ie., their collecting tubules don’t respond to ADH they’re able to produce
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56
Q

Name an ADH stimulators that act on secretion in the posterior pituitary.

A

Nicotine (human relevance) - Stimulates ADH secretion

Results in concentrated urine as aquaporins inserted into collecting tubules, allowing water to be transported out of tubular filtrate into interstitial fluid ⇄plasma.

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57
Q

Name an ADH simulator (not stimulator) that acts on the collecting ducts.

A

**Desmopressin - **Used in diagnosis & management of Central Diabetes Insipidus, in which not enough of or no ADH is secreted by the posterior pituitary gland.

(lack of ADH production; use with water-deprivation test to diagnose DI)

Acts on collecting ducts’ V2 receptors - mimics ADH

(doesn’t really stimulate ADH but it mimics it)

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58
Q

What are four classes of diuretics that increase sodium excretion in:

  1. Proximal Convoluted Tubule
  2. Thick Ascending Limb of the Loop of Henle
  3. Distal Convoluted Tubule
  4. DCT & Collecting Ducts
A
  1. PCT: Carbonic anhydrase inhibitor & osmotic diuretics
  2. Thick ascending limb LOH: Loop diuretics
  3. DCT: Thiazide diuretics
  4. DCT & CD: Potassium-sparing diuretics
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59
Q

How does carbonic anhydrase inhibitor act to increase secretion of sodium (and water) from the kidney?

A

Carbonic anhydrase catalyses the reaction that produces carbonic acid, which dissociates into hydrogen ion (acid) and bicarbonate, a buffer in blood plasma

By inhibiting the enzyme, carbonic acid isn’t made from water & CO2:

↓ rate of reaction: CO2 + H2O ⇆ H2CO3 (⇆ H+ + HCO3-)

A lack of carbonic acid means there will be no dissociation into protons & bicarbonate:

∴ ↓ availability of H+ + HCO3- inside cell & ↓ availability of CO2 in filtrate

Results in inhibition of H+ secretion = ↓ reabsorption of Na+ HCO3-

Sustained inhibition of H+ secretion can lead to metabolic acidosis, due to too much hydrogen proton in plasma and too little carbonate to buffer it.

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60
Q

How do Loop Diuretics work on the thick ascending limb of the Loop of Henle to increase sodium excretion and water excretion from the kidney?

A

Loop diuretics inhibit the Na+-K+-2 Cl- symporter in plasma membrane of thick ascending LoH

Urine volume ↑

Renal blood flow ↑ (drugs are also vasodilators)

Normally, the symporter transports these solutes into the interstitial fluid/plasma OUT of the filtrate. Loop diuretics instead cause these ions to stay inside the filtrate through to the distal convoluted tubule, so water doesn’t flow out into the interstial fluid and the urine can’t be concentrated in the collecting ducts.

Drug potency = can cause 25% of filtered sodium to be excreted

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61
Q

What is an example of a Loop Diuretic?

A

furosemide / frusemide

also:

piretamide

bumetanide

ethacrynic acid

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62
Q

How do thiazide diuretics work on the DCT to increase sodium and water secretion from the kidney?

A

Thiazide diuretics inhibit Na+-Cl- symporters in the luminal membrane of DCT

Urine volume ↑

Impaired concentrating ability in DCT because sodium & chloride are not reabsorbed, so water stays in the filtrate.

Potency = can cause 10% of the filtered sodium to be excreted.

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63
Q

How do potassium-sparing diuretics work on the DCT & collecting ducts to increase sodium & water excretion from the kidney?

A

They blocks CD cell’s aldosterone receptors ∴

↓ in number of sodium channels on cell’s apical side
↓ in number of Na+-K+-ATPase pumps on basolateral side - normally these keep sodium levels low in cell by pumping sodium into the extracellular fluid/plasma.
↓ water reabsorption
↓ Na+ retention
↑ K+ retention

Potency: 5% of Na+ excreted
NB: Side effect of amiloride & triamterene is hyperkalaemia

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64
Q

Name some potassium-sparing diuretics that work on the DCT & collecting ducts to increase sodium and water excretion.

A

aldosterone inhibitors & sodium-channel blockers:

spironolactone

amiloride

triamterene

NB: Side effect of amiloride & triamterene is hyperkalaemia

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65
Q

Osmotic diuretics, such as mannitol, work on the early PCT to increase sodium & water secretion. How does it work?

A

Osmotic diuretics like mannitol are polar, inert compounds that don’t get reabsorbed by renal tubules.

Instead, they end up in filtrate, increasing osmolarity of filtrate to pull in water from tissues.

Some ↑ sodium excretion

Potency: dose-dependent

* Used to treat poisonings in dogs & cats; forced diuresis hastens elimination of poisons.
* Also used to maintain tubular function in acute renal failure with furosemide, the Loop Diuretic

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66
Q

Why are ACE-inhibitors considered diuretics for use in the case of oedema?

A

These inhibit ACE, secreted by the lungs, to prevent formation of Angiotensin II

Angiotensin II stimulates production of aldosterone, which would cause Na+ retention & water retension - not what you want in case of oedema

Potency: 5% of Na+ excreted

* vets use to treat in chronic heart failure

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67
Q

How do xanthines, which are inotropes, increase sodium and water excretion, as needed in the case of oedema?

A

Xanthines inhibit phosphodiesterase in cardiac myocytes and renal epithelial cells
↑ cAMP
↑ cardiac contractility (positive inotrope), to ↑ cardiac output in chronic heart failure

↓ NaCl reabsorption by renal tubules
* weak diuretic, used in CHF

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