Lecture 6: Basic Pharm of Diuretics Flashcards Preview

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Flashcards in Lecture 6: Basic Pharm of Diuretics Deck (29)
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1

MOA for carbonic anhydrase inhibitors; where?

- In PCT
- Prevents luminal dehydration of H2CO3 to CO2
- Prevents intracellular rehydration of CO2 to H2CO3
- Decreases HCO3- reabsorption

2

Why does diuretic effect of carbonic anhydrase inhibitors diminish over time?

As the H2CO3 is excreted, the body is not able to produce enough to keep up with excretion and eventually these inhibitors will have nothing to act on.

3

Where are carbonic anhydrase inhibitors most commonly used?

- CSF
- Aqueous humor of the eye (glaucoma)

4

MOA for osmotic agents - mannitol; where do they affect?

PCT, Thin Descending limb, Collecting duct

Is a non-reabsorbable solute that causes a countervailing osmotic force, as water comes into the lumen to try and balance out the concentration of mannitol. This leads to increases urine volume and excessive water loss.

5

Adverse effects of Mannitol?

- ECF volume expansion (complicates CHF)
- Dehydration
- Hyperkalemia
- Hypernatremia

*The Hyperkalemia and natremia arise from the loss of water from the cells which increases the ion concentrations in cells causing ions to diffuse out in attempt to reach equilirbrium

6

Clinical application for osmotic agents (mannitol)?

Reduce intracranial and intraocular pressure

7

MOA for loop diuretics and where in kidney do they affect?

Thick ascending limb

- Inhibit the NKCC2 co-transporter, so Na+, K+, and 2 Cl- are staying in lumen. K+ is not diffusing out of the cell to create membrane potential necessary to reabsorb Mg2+ and Ca2+ via paracellular pathway.

8

Adverse effects of loop diuretics?

- Hypomagensia
- Hypokalemic metabolic alkalosis
- Ototoxicity

9

What causes the hypokalemic metabolic alkalosis w/ loop diuretics?

Increased Na+ delivery to the collecting duct (since it's not being reabsorbed), promotes the increased excretion of K+. The increased Cl- promotes the excretion of H+

10

What can increase chances of ototoxicity?

Loop diuretic used in conjunction w/ aminoglycosides

11

What are the clinical applications of loop diuretics?

- Edema (acute pulmonary edema)
- Acute hypercalcemia
- Hyperkalemia
- Anion OD
- ARF

12

MOA for Thiazides and where in kidney do they work?

- Distal Convolute tubule

- Inhibit the Na+/Cl- transporter (electrically neutral) which lower intracellular Na+ and enhances Na+/Ca2+ exchange in basolateral membrane, increasing reabsorption of Ca2+

13

Adverse effects of Thiazides?

- Hypokalemic metabolic alkalosis

- Impaired CHO tolerance (bad for diabetics)

14

Clinical application for Thiazides?

- HTN
- Heart failure

15

What are the 2 Aldosterone antagonists; difference; where do they work?

- Collecting Tubules
- Eplerenone (selective)
- Spironolactone (non-selective)

16

MOA for eplerenone (aldosterone antagonist)?

Is selective for the aldosterone (mineralcorticoid) receptor, blocks the receptor, and prevents the aldosterone mediated Na+ reabsorption (ENaC channel) and K+ excretion by inhibiting the Na+-K+ATPase.

17

MOA for spironolactone (aldosterone antagonist)?

Non-selective, acts on other targets such as androgen and progesterone receptors, but will also act on the aldosterone receptor.

18

Adverse effects of Eplerenone?

Hyperkalemia - reduced urinary excretion of K+

19

Adverse effects of Spironolactone?

- Gynecomastia (Off-target effect)

- Hyperkalemia (reduced urinary excretion of K+)

20

Clinical application of aldosterone antagonists (eplerenone and spironolactone)

- Excessive activity on the mineralcorticoid receptors (Conn's syndrome)

- Hyperaldosteronism (heart failure and nephrotic syndrome)

21

Where does ADH act in the kidney?

In the collecting tubules, acts on V2 receptors (Gs protein-coupled receptors) which increases cAMP mediated increase of AQP2 channels, which increases the permeability of the collecting tubule to water.

22

Which ADH antagonists directly bind to the V2 receptor?

The Vaptans (Conivaptan and Tolvaptan)

23

How does Lithium act as an antagonist to ADH?

Reduces the ADH-induced increases in cAMP after ADH binds its receptor

24

Adverse effects of ADH inhibitors?

- Nephrogenic diabetes insipidus
- Renal failure
- Dry mouth
-Thirst

25

Clinical applications of ADH inhibitors?

- CHF
- SIADH

26

What does adenosine do at the pre-glomerular afferent arteriole?

- Reduces blood flow to the glomerulus (i.e GFR)
- Key signaling molecule in the process of tubuloglomerular feedback

27

What are the modest non-specific adenosine receptor antagonists?

Caffeine and theophylline

28

MOA for adenosine receptor antagonists

- In PCT: interfere with NHE3 (Na+ / H+ exchanger)

- Collecting tubule: interfere collecting tubule K+ secretion

29

Why are adenosine receptor antagonists being highly researched?

They are not K+ wasting , induce diuresis, and stops tubuloglomerular feedback