Lecture 5 - Diuretics Flashcards

1
Q

What is the function of diuretics?

A

Increase production of urine to eliminate water from the body

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2
Q

What is the purpose of diuretics removing excess water from the body?

A

Reducing plasma volume + cardiac output
Reduce BP
Reduce oedema/Ascites

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3
Q

What are drugs called that increase excretion of sodium and water resulting in increased urine volume?

A

Diuretics

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4
Q

What is Diuresis?

A

Excretion of water in urine

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5
Q

What is natriuresis?

A

Excretion of sodium in the urine

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6
Q

What are the 5 classes of diuretics?

A

Carbonic anhydrase inhibitors
Osmotic diuretics
LOOP DIURETICS
POTASSIUM SPARING DIURETICS
THIAZIDE AND THIAZIDE-LIKE DIURETICS

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7
Q

What is the main ion which most diuretics interfere witht the normal reabsorption of?

What diuretic doesn’t do this?

A

Na+

Osmotic diuretics

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8
Q

What part of the nephron do carbonic anhydrase inhibitor diuretics work on?

A

PCT

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9
Q

What part of the nephron do osmotic diuretics work on?

A

Whole nephron (most effect at PCT)

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10
Q

What part of the nephron do Loop Diuretics work on?

A

Loop of Henle

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11
Q

What part of the nephron do Thiazide and thiazide like diuretics work on?

A

DCT

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12
Q

What part of the Nephron do potassium sparing diuretics work on?

A

DCT and Collecting Duct

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13
Q

How do carbonic anhydrase inhibitors act as diuretics?

A

Inhibit carbonic anhydrase
Less carbonic acid broken down into H20 and CO2
Less CO2 diffuses into PCT cell
Less H2CO3 made from CO2 + H20 so less HCO3- and H+ made

Since theres less H+ in the PCT cell the Na+/H+ exchanger works less so less Na+ reabsorbed into the PCT cell (more lost in urine)

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14
Q

What are Flozins?

How are they similar to a diuretic but aren’t a diuretic?

A

Inhibit SGLT-2 reducing the absorption of Na+ since less glucose being reabsorbed
(Less Na+ reabsorbed = less water reabsorbed)

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15
Q

What is an example of an osmotic diuretic?

A

Mannitol

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16
Q

How do osmotic diuretics work?

A

Increase water excretion by acting as an osmole drawing and keeping water in nephron

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17
Q

Why are osmotic diuretics not used in patients with heart failure and pulmonary oedema?

A

It expands the extracellular fluid volume initially as it travels to the kidneys

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18
Q

When are osmotic diuretics used?

A

Acute renal failure due to shock or trauma (increase extracellular fluid volume)

Acute drug poisoning (elimates drugs reabsorbed from renal tubules)

Decreases intracranial and Intra ocular pressure before surgery

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19
Q

How can using osmotic diuretics lead to hyponatraemia and hypernatraemia at different stages?

A

Initially causes hyponatraemia due to extracellular fluid expansion

Then excess use leads to dehydration and hypernatraemia

20
Q

What channels do Loop diuretics block in the loop of Henle?

A

NKCC channels

21
Q

How does loop diuretics block NKCC channels in the LOH lead to a diuretic affect?

A

Less Na+, K+ and 2Cl- reabsorbed into the cell so more stays in the LOH lumen

Water stays with the ions

22
Q

What other affect can loop diuretics have on the body?

A

Hypocalcaemia
Hypomagneseamia

23
Q

How can loop diuretics cause hypomagnesaemia and Hypocalcaemia?

A

The NKCC channel gets blocked means less Na+, Cl- and K+ reabsorbed, this means less K+ leak back across into the lumen via ROMK so the lumen doesn’t become positively charged

This means theres less repelling force so less Mg2+ and Ca2+ reabsorbed via paracellular transport

24
Q

What is the most potent type of diuretic and why?

A

Loop Diuretics

They block NKCC channels which maintains the osmotic gradient

25
Q

What are some loop diuretics?

A

Furosemide

26
Q

When are loop diuretics used?

A

Severe oedema from congestive heart failure

Treating Hypercalcaemia
Acute pulmonary oedema
Acute Hyperkalaemia or acute Hypercalcaemia

27
Q

How can loop diuretics lead to metabolic alkalosis?

A

Loss of water leads to increased concentration of bicarbonate ions in blood making it more alkaline

28
Q

What are some side effects of loop diuretics?

A

Hypovolaemia
Hyponatraemia
Hypokalaemia
Hypomagnesaemia
Hypocalcaemia
Metabolic alkalosis
Postural hypotension

29
Q

What channel do Thiazide and Thiazide like diuretics block?

A

Na+/Cl- cotransporter in the DCT

30
Q

How does Thiazide/Thiazide like diuretics cause a diuretic effect?

A

Blockage of the Na+/Cl- cotransporter means less Na+ reabsorbed into DCT cell so less Na+ reabsorbed into vasa recta

Less Na+ in vasa recta means less water follows it into the vasa recta

31
Q

How can thiazide lead to Hypercalcaemia?

A

Blocks the Na+/Cl- cotransporter of the DCT cell
This dec conc of Na+ in cell (steeper grad from interstitium into cell)
This is more favourable for the Na+/Ca2+ antiporter on the basolateral membrane of the cell so more Ca2+ reabsorbed into interstitium and then vasa recta

32
Q

What is an example of a Thiazide/thiazide like diuretic?

These are 1st line antihypertenisves

A

Bendroflumethiazide
Indapamide

33
Q

What can Thiazides be used to treat?

A

Essential hypertension
Mild heart failure
Osteoporosis (since increases calcium reabsorption)

Nephrogenic diabetes Insipidus polyuria

34
Q

How do Potassium sparing diuretics work?

A

Block ENAC channels in the Collecting duct cells

Means less Na+ reabsorbed into cell and vasa recta so more water lost

35
Q

How do aldosterone antagonists have a diuretic affect while also being Potassium sparing?

A

Aldosterone leads to more Na+/K+ ATPases to be expressed in the collecting duct so more Na+ reabsorbed so more water follows it

Also decreases Expression of ROMK channels preventing K+ leaking back into the lumen of the collecting duct

36
Q

What is a potassium sparing diuretic?

A

Amiloride

37
Q

What is an example of an aldosterone antagonist?

A

Spironolactone

38
Q

What can aldosterone antagonists and potassium sparing diuretics be used to treat?

A

Secondary Hyperaldosteronism
Chronic Heart Failure
Cirrhosis
Nephrotic syndrome
Treats hypertension

39
Q

Why can aldosterone antagonists and potassium sparing diuretics not be used in patients with Chronic renal failure?

A

Can lead to hyperkalaemia

Leads to less aldosterone being made

This leads to less ROMK being created

Means less K+ lost

Since patients with renal failure have a decreased GFR plasma conc of K+ increase

40
Q

Where amino acids completely reabsorbed from the filtrate via active transport?

A

PCT

41
Q

When theres an increase in conc of potassium the conc of what hormone increases and why?

A

Inc aldosterone

Leads to more ROMK being expressed so more K+ can be lost

42
Q

How can loop diuretics result in hypokalaemia?

A

NKCC blocked
Less Na+ reabsorbed
More Na+ delivered to DCT and CD
More Na+ reabsorbed through ENAC channels
K+ lost through ROMK
Leads to hypokalaemia

43
Q

What part of the nephron is the glucose reabsorbed?

A

PCT

44
Q

Where is most of the Urate and creatinine secreted?

A

PCT

45
Q

What is the main hormone that affects K+ excretion?

A

Aldosterone (due to ROMK)

46
Q

What is the main transporter driving electrolyte reabsorption in the LOH?

A

NKCC transporter

47
Q

How does aldosterone affect membrane permeability to sodium?

A

Increases it