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Diuretics Flashcards

1
Q

What are the 4 main functions of the kidneys?

A
  • Regulatory
  • Excretory
  • Endocrine
  • Metabolism
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2
Q

What kind of things do the kidneys regulate?

A
  • Fluid balance
  • Acid-base balance
  • Electrolyte balance
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3
Q

What endocrine substances do the kidneys produce?

A
  • Renin
  • Erythropoietin
  • Prostaglandins
  • 1-alpha calcidiol
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4
Q

What kind of things do the kidneys metabolise?

A
  • Vitamin D
  • Polypeptides e.g. insulin
  • Drugs e.g. morphine, paracetamol
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5
Q

What is the effect of a diuretic?

A

Increased production of urine (doesn’t necessarily get rid of salt)’

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6
Q

What is the definition of a natriuretic?

A

A drug that induces loss of sodium in urine

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7
Q

What is the definition of an aquaretic?

A

A drug that causes loss of water without loss of electrolytes

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8
Q

What is the primary site of action of osmotic diuretics?

A

Work throughout the tubule but primary action at the PCT

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9
Q

What is the primary site of action of Thiazides?

A

Primarily act at the DCT

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10
Q

What is the primary site of action of ADH blockers?

A

Primarily act at the collecting duct

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11
Q

What is the primary site of action for SGLT2 inhibitors?

A

Primarily act at the PCT

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12
Q

Where do loop diuretics act?

A

At the loop of Henle

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13
Q

What is the primary site of action for K+ sparing diuretics?

A

Act mainly at the DCT

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14
Q

Explain the mechanism of action of carbonic anhydrase inhibitors

A
  1. Inhibit carbonic anhydrase therefore, stop breakdown of H2CO3 in the lumen
  2. More NaHCO3 is lost in urine
  3. As there is more Na is delivered to the collecting duct this activates ENaC channels which absorb Na+ in exchange for K+ therefore causing increased loss of K+ and hypokalaemia
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15
Q

In What circumstances are carbonic anhydrase inhibitors most commonly used? Why are they not commonly used as a diuretic?

A

Used in glaucoma and mountain sickness

Not frequently used as tolerance develops after 2-3 days

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16
Q

What is the mechanism of action of osmotic agents ?

A

Osmotic agents remain in the lumen of the kidney tubule, as they’re osmotically active they draw water into the tubule by osmosis

Net effect of loss of water

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17
Q

Name the most commonly used osmotic agent?

A

Mannitol

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18
Q

What are the risks of using osmotic agents as diuretics?

A

Risk of Hypernatriemia as no salt is lost, just water

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19
Q

Explain the mechanism of action of SGLT2 inhibitors as diuretics

A

Inhibit the SGLT2 ( sodium, glucose co transporter) at the proximal convoluted tubule. Therefore promotes Na+ excretion (natriuretic) and glucose excretion

Leads to decreased plasma glucose, decreased body weight, decreased blood pressure, decreased plasma uric acid, decreased glomerular hyperfiltration

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20
Q

What is a side effect of SGLT2 inhibitors?

A

Patients can become hypoureamic

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21
Q

Where in the loop of henle do diuretics normally act?

A

Act at the thick ascending limb

22
Q

Explain the mechanism of action of loop diuretics

A

Loop diuretics block the NKCC2 transporter which normally reabsorbs 25% of sodium

23
Q

What are the main effects of a loop diuretic?

A
  • Loss of sodium and water
  • Hypokalaemic metabolic alkalosis
  • Increased calcium loss ( can be used to treat hyper calcaemia)
24
Q

Why do you see hypokalaemic metabolic alkalosis when using loop diuretics?

A
  1. Blockage of NKCC2 means more Na is delivered to the collecting ducts, promoting expression of ENaC
  2. ENaC absorbs sodium in exchange for a K+, so more potassium lost in urine leading to hypokalaemia
25
Name some loop diuretics
* Bumetanide * Furosemide
26
Explain the mechanism of action of thiazides diuretics
1. Thiazide diuretics **inhibit the Na/Cl co transporter** in the collecting duct 2. Causes loss of Na and water, hypokalaemic metabolic acidosis and increased calcium reabsorption (opposite of loop diuretics)
27
How do thiazide like diuretics cause increased calcium absorption ?
Blockage of Na/Cl cotransporter causes **lower intracellular levels of Na** which facilitates calcium reabsorption by the **calcium/ Na exchanger**
28
Name some thiazide diuretics
* Bendroflumethiazide * Indapamide
29
What is the normal effect of aldosterone on the kidney tubule?
Aldosterone increases expression of **ENaC** and **NKATPase** in the principal cells of the collecting duct
30
What is the mechanism of action of potassium sparing diuretics?
Block ENaC at the luminal surface of the renal tubule
31
Name a potassium sparing diuretic
Amiloride
32
Name an aldosterone antagonist
Spironolactone
33
Name an ADH Antagonist
Tolvaptan
34
Explain how ADH antagonists work
1. ADH Antagonists act on the V2 receptor where ADH would normally bind 2. Competitive inhibition means that ADH cannot bind to V2 to cause insertion of AQP2 channels 3. Net effect- aquaretic (no loss of Na+)
35
When would you use ADH antagonists e.g. tolvaptan?
* To treat **hyponatraemia** * To prevent **cyst enlargement** in adult polycystic kidney disease
36
What is an unwanted side effect that lithium can have on the kidneys? Explain how this occurs
1. Lithium used to treat bipolar but can also **inhibit ADH** 2. Patients can become **polyuric** due to the diuretic effect that occurs as lithium has a negative effect on GPCR Gs that leads to **reduced DNA Synthesis of AQP channels**
37
How does alcohol have a diuretic action?
Alcohol **inhibits** the release of **ADH**
38
How does caffeine have a diuretic effect?
Caffeine causes an **increase in GFR** and **decreases** the tubular **reabsorption** of sodium
39
What are some of the general adverse drug reactions that can occur when giving diuretics?
* Hypovolaemia and hypotension (RAAS will kick in causing acute kidney injury) * Electrolyte disturbances * Metabolic abnormalities ( depends on individual drug) * Anaphylaxis/ photosensitivity rash (rare)
40
What are some specific adverse drug reactions to **thiazides**?
* Gout * Hyperglycaemia (concern in diabetics) * Erectile dysfunction * Increased LDLs and Triglycerides * Hypercalcaemia
41
What are some of the common adverse drug reactions with **furosemide**?
* Otoxicity (affects the ears) * Alkalosis * Increased LDL and TG * Gout
42
What are some of the common adverse drug reactions with **Bumetanide** (loop diuretics)?
Myalgia
43
What are some of the common adverse drug reactions with **spironolactone**?
* Hyperkalaemia * Impotence * Painful gynaecomastia
44
Which diuretics would be used to treat hypertension?
* **Thiazide diuretics** ( have a vasodilator effect as well as diuretic effect) * **Spironolactone** (Loop diuretics- used less as body can accommodate)
45
Which diuretics would be used to treat heart failure?
* Loop diuretics * Spironolactone * Used alongside ACEi/ ANG II antagonists and Beta blockers
46
Which diuretics would you use to treat decompensated liver disease?
* Spironolactone * Loop diuretics
47
What would you give to treat nephrotic syndrome?
* Loop diuretics (big doses often needed) * +/- thiazides * +/- potassium sparing diuretics/ potassium supplements
48
Why can furosemide loose it’s effect in nephrotic syndrome?
1. Furosemide needs to be **bound to albumin** to get into the blood, 2. in nephrotic syndrome = **low albumin** so less for furosemide to bind 3. Also, patients with nephrotic syndrome get **gut oedema**, further **reducing absorption** of furosemide
49
Why do you need a large amount of furosemide in patients with CKD?
* Patients with CKD have **reduced number of kidney tubules** * Normally furosemide gets from the blood to the PCT Lumen by **OAT** transporters OAT1/3/4 * but in CKD these are **overloaded with other toxins** * Therefore less available to transport furosemide across
50
What is Bartter’s and Gitelman syndrome?
Both are **autosomal recessive** syndromes are a result of **impaired sodium chloride reabsorption** causing mild **volume depletion** * Bartter’s defect is at **thick ascending limb** of loop of Henle * Gitelman’s defect is at **DCT**
51
What is Liddles syndrome?
* ENaC channels are stuck in an **always on** state causes **hypertension** * Autosomal **dominant** disorder

Clinical Pharmacology (25 decks)

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