9/11- Pharmacology and the Kidney I: Diuretics Flashcards Preview

MS2 Renal > 9/11- Pharmacology and the Kidney I: Diuretics > Flashcards

Flashcards in 9/11- Pharmacology and the Kidney I: Diuretics Deck (36)
1

What hormone primarily regulates the serum sodium level?

A. ADH (anti-diuretic hormone)

B. ALdosterone

C. Renin

D. WCH (water controlling hormone)

What hormone primarily regulates the serum sodium level? 

A. ADH (anti-diuretic hormone)

B. ALdosterone 

C. Renin 

D. WCH (water controlling hormone)

2

Clinical manifestations of excess salt (volume overload) in the body include:

A. Increased thirst

B. Peripheral edema

C. ?

D. ?

Clinical manifestations of excess salt (volume overload) in the body include: 

A. Increased thirst

B. Peripheral edema

C. ? 

D. ?

- Increased thirst is more for hypernatremia

3

Define:

- Natriueresis:

- Aquaresis:

- Diuresis:

- Diuretic:

- Natriueresis: increased renal excretion of sodium

- Aquaresis: excretion of water without electrolyte loss

- Diuresis: increased urine excretion

- Diuretic: substance that increases the excretion of urine (caffeine, alcohol, cranberry juice)

4

Body volume disturbances reflect what? Dysnatremias reflect what?

Body volume disturbances reflect sodium content changes

- Volume depletion: loss of Na and water

- Volume overload: retention of Na and water

Dysnatremias reflect water balance

- Hyponatremia- too much ADH

- Hypernatremia- in access to water, DI

5

What are the proximal tubule transport mechanisms?

NaHCO3 reabsorption is most relevant to diuretic action in the PCT

- Na-H exchanger in luminal membrane (Na in; H out)

- H couples with HCO3- in lumen before CA converts it to H2O and CO2

- CO2 is taken up over apical membrane to reverse reaction, creating HCO3 and H inside cell

---- H can then be pumped out by Na-H exchanger

---- HCO3 pumped over basal membrane 

6

What is the mechanism of Acetazolamide? Effects?

Carbonic anhydrase inhibitor in the proximal tubule

Effects:

- Na bicarbonate diuresis

- Hyperchloremic metabolic acidosis

7

Clinical uses of Acetazolamide?

- Glaucoma: Decreases the rate of aqueous humor formation with decrease in intraocular pressure

- Urinary alkalinization: uric acid and cysteine are more soluble in alkaline urine

- Metabolic alkalosis: diuretic induced

- Acute mountain sickness: acidosis leads to increased ventilation.

8

Toxicity of Acetazolamide?

(Recall: CA inhibitor)

- Hyperchloremic metabolic acidosis

- Hypokalemia (renal K wasting)

9

How do diuretics induce renal K wasting?

Increased distal Na delivery drives K secretion

- High aldosterone

10

What is the mechanism of Mannitol? Effects?

Osmotic diuretic

- Prevents water reabsorption in the proximal tubule and tDLH (freely water permeable)

- Opposes ADH action in the collecting tubule

Effect = increased urine volume

- Reduced Na reabosrption (Increase in urine flow rate decreases the contact time between fluid and tubular epithelium)

11

What are the clinical uses of osmotic diuretics?

- Cerebral edema: decreased ICP - alter Starling forces so that water leaves cells and reduce intracellular volume

- Acute congestive glaucoma: reduction of intraocular pressure

- Increase urine volume to prevent an oliguric phage of an AKI in setting of Hemolysis or Rhabdomyolysis.

(Not typically liked/used by nephrologists)

12

Toxicity of osmotic diuretics?

- Extracellular volume expansion along with hyponatremia: extracts water from cells

(This effect can complicate CHF and may produce florid pulmonary edema)

- Dehydration and hypernatremia: can ultimately lead to excessive free water losses

13

What diuretics work in the proximal tubule?

- Acetazolamide

- Osmotic diuretics (mannitol)

14

What are the transport mechanisms in the loop of Henle?

Apical:

- Na-K-2Cl cotransporter

- K channel

Basal:

- Na-K exchanger

- K-Cl cotransporter

15

What are the main diuretics that work in the LoH?

What channel/process do they block?

Loop diuretics: Furosemide

- Inhibits Na-K-2Cl co-transporter in TALH (thick)

16

What are the effects of loop diuretics?

- Very potent diuretic

- Induce NaCl diuresis

- Decrease positve lumen, the driving force for Mg2+ and Ca2+ absorption, cause an increase in Mg2+ and Ca2+ excretion

- Cause K+ wasting

- Induce renal prostaglandin synthesis that increases renal blood flow and vasodilation

17

Clinical Uses of loop diuretics?

- Acute pulmonary edema

- Edematous conditions: heart failure, cirrhosis, nephrotic syndrome

- Hypercalcemia and Hyperkalemia

- SIADH

Hypertension:

- Refractory cases

- Associated with renal insufficiency or heart failure

- Hypertensive emergencies

18

How do loop diuretics help with SIADH?

- In LoH, Na reabsorption without water concentrates the medulla (hypeosmolar medulla provides urine concentrating ability)

- Loop diuretics block Na reabsorption in LoH, getting rid of hyperosmolar medulla and blocks responses to ADH

19

Toxicity of loop diuretics?

- Hypokalemic metabolic alkalosis

- Hypomagnesemia

- Hyperuricemia (hypovolemia-associated enhancement of uric acid reabsorption in the proximal tubule)

- Ototoxicity (hearing loss; dose-related)

20

What are the transport mechanisms in the distal convoluted tubule?

Apical:

- Na-Cl cotransporter

- Ca transporter

Basal:

- Na-K- ATPase

- Na-Ca exchanger

- Cl channel 

21

What is hydrochlorothiazide (HCTZ) (broad class)?

Thiazide diuretic

22

What channel do thiazide diuretics block?

Inhibits Na-Cl cotransporter in the DCT

23

What are the effects of thiazide diuretics?

(Blocks Na-Cl contransport)

- Induce NaCl diuresis

- Icrease Ca reabsorption:

--- In the PCT, thiazide-induced volume depletion -> enhanced Na and passive Ca reabsorption

---- In the DCT, lowering IC Na by thiazide -> more Na/Ca exchange in teh basolateral membrane

- Renal K wasting

24

What are some clinical uses of thiazide diuretics?

- HTN

- Heart failure

- Renal stones due to idiopathic hypercalcuria

- Nephrogenic diabetes insipidus

25

How do thiazide diuretics help in diabetes insipidus?

- The absence of ADH (central DI) or resistance to ADH actions in the kidney (nephrogenic DI)

---- Causes rapid loss of water and an increase in osmolality

- Thiazide-induced Na losses -> more Na reabsorption in the proximal tubule and decreases urine formation

26

Toxicity of thiazide diuretics?

Hypokalemic metabolic alkalosis

Hyperuricemia

Hyponatremia

- Hypovolemia-induced elevation of ADH

- Reduction in the diluting capacity of the kidney

- Increased thirst

Hyperglycemia

- Impaired insulin release

- Diminished tissue utilization of glucose

Hyperlipidemia

27

What are the ion transporters at play in the collecting duct?

Apical:

- Na channel (into cell)

- K channel (into lumen)

- H2O (into cell)

Basal:

- ALD action (Mineralocorticoid receptor, MR)

- ADH receptor

- Na-K-ATPase

INTERCALATED CELLS

Apical:

- H-ATPase (pumping H into lumen)

Basal:

- HCO3-Cl exchanger (HCO3 out, Cl into cell) 

28

____ diuretics inhibit the effects of aldosterone at the late distal and cortical collecting tubules

K-sparing diuretics inhibit the effects of aldosterone at the late distal and cortical collecting tubules

29

What are the mechanisms of action/blocked transporters of K-sparing diuretics?

1. Direct antagonism of mineralocorticoid receptors (aldosterone)

- Spironolactone

- Eplerenone

2. Inhibition of Na entry thru ion channels in the luminal membrane

- Amiloride

- Triamterene

30

What are the effects of K-sparing diuretics?

- Increase urine NaCl excretion

- Hyperkalemia

- Metabolic acidosis

31

What are clinical uses of K-sparing diuretics?

- Primary and secondary hyperaldosteronism

- Heart failure

- Cirrhosis

32

What is toxicity of K-sparing diuretics?

- Hyperkalemia

- Hyperchloremic metabolic acidosis: like type IV renal tubular acidosis (similar to type IV RTA)

- Gynecomastia: spironolactone-adrogen receptor (dihydrotestosterone) (painful breasts)

33

How can you measure diuretic effectiveness?

- Depletion of extracellular volume to treat hypertension or edematous states is easily measured as a decrease in body weight

- Check Daily Weights

- “I’s & O’s” are usually inaccurate and net changes over time are rarely available

 - Plasma electrolytes are limited in value

34

Describe diuretic resistance- what could cause it?

- Normal Response: Compensation

- Inadequate Dose

- Inadequate control of salt intake

- Drug interactions (e.g., NSAIDs)

- Reduced bioavailability: (CHF, CKD, Hypoalbuminemia)

35

How do you deal with diuretic resistance?

- Assess Compliance with Salt restriction and medicine intake. If necessary, measure the amount of salt and diuretic in the urine 

- Discontinue NSAIDs

- Adjust the dose of the diuretic in patients with renal impairment

- Switch to intravenous administration to overcome problems associated with impaired absorption

- Switch to a continuous intravenous infusion of a loop diuretic to avoid postdiuretic salt retention

- Combine loop diuretics with other diuretics, preferably a thiazide diuretic

36

What diuretics work at the:

- Proximal tubule

- LoH

- DCT

- Collecting tubule

Proximal tubule

- Carbonic anhydrase inhibitors

- (Osmotic agents)

LoH

- Furosemide

- Bumetanide

- Ethyacrinic acid

DCT

- Thiazides

Collecting tubule

- Aldosterone receptor antagonists (spironolactone)

- Epithelial sodium channel inhibitors (amiloride)