L4 - Diuretics Flashcards
1
Q
Diuretic
A
Increased urine production
2
Q
Natriuretic
A
Loss of sodium in urine
3
Q
Aquaretic
A
Loss of water without electrolytes
4
Q
Carbonic anhydrase inhibitor mechanism of action
A
Inhibit carbonic anhydrase in the PCT Inhibits: - HCO3- reabsorption - Na+ reabsorption via sodium/ HCO3- cotransporter in the PCT therefore more delivered to the EnaC channels distally - therefore more K+ is secreted
5
Q
When are carbonic anhydrase inhibitors used
A
In glaucoma and mountain sickness
6
Q
Side effects on carbonic anhydrase
A
Metabolic acidosis
Hypokalaemia
7
Q
Name of osmotic agent
A
Mannitol
8
Q
Osmotic agent mechanism of action
A
- Osmolarity is more negative in the lumen due to mannitol therefore water is diffused out of the tubule down the osmotic gradient
- Increased diuresis without electrolyte loss therefore urine is more dilute
- acts everywhere in the nephron especially the PCT
- Reduces intracellular pressure
9
Q
When are osmotic agents used
A
Raised intracranial pressure in ITU - intensive treatment unit
10
Q
Osmotic agent side effects
A
- hypernatremia
- dehydration
11
Q
SGLT 2 inhibitors mechanism of action
A
- inhibits glucose and Na+ reabsorption in the PCT
- more Na+ delivered to the ENaC channels distally in the DCT and collecting duct
- therefore more K+ secreted
- more Na+ delivered to the macula densa in the DCT therefore RAAS not activated
- increased uric acid secretion
12
Q
When are SGLT 2 inhibitors used
A
Diabetes
Hypertension
Hyperuricaemia
13
Q
SGLT2 inhibitor effects
A
Decrease plasma glucose Decrease body weight Decrease blood pressure Decrease plasma uric acid Decrease glomerular hyperfiltration
14
Q
Loop diuretic mechanism of action
A
- Inhibits the NKCC2 channel in the ascending limb of the loop of Henle
- decreases Na+ and K+ reabsorption
- decreased ROMK function
- decrease Mg2+ and Ca2+ reabsorption
- more Na+ delivered to ENaC therefore more K+ secreted
15
Q
What percentage of sodium is reabsorbed in ascending limb of the loop of Henle
A
25%
16
Q
When is furosemide given
A
Heart failure
Hypertension
Hyperkaleamia
Hypercalcaemia
17
Q
Effects of furosemide
A
- loss of water and sodium
- loss of Ca2+
- hypokalaemic metabolic alkalosis
18
Q
Thiazides diuretic mechanism of action
A
- Inhibits Na+ Cl- co transporter in the DCT
- Facilitates the NCX to reverse therefore Na+ is transported from the blood the the tubule and Ca2+ is reabsorbed into blood
- increased Ca2+ reabsorption (also stimulated by PTH)
- more Na+ is delivered to ENaC channels in the collecting duct therefore more K+ is secreted
19
Q
What percentage of sodium is reabsorbed in the DCT?
A
5%
20
Q
Effects of thiazides diuretics
A
Loss of water and sodium
Hypokalaemic metabolic alkalosis
Increased calcium reabsorption
21
Q
Thiazide side effects
A
Hypokalaemic metabolic alkalosis Hyperuricaemia - gout Arrhythmia Hyponatraemia Hyperglycaemia- Increased glucose uptake - with beta blocker Increased cholesterol and triglyceride - bad for diabetics Erectile dysfunction Hypercalcaemia
22
Q
Amiloride
A
PCT:
- inhibits NHE
- abolishes 80% of ang II secreting H+
DCT:
- inhibits ENaC channels
- decreased reabsorption of Na+
- K+ sparring
23
Q
Spironolactone
A
Aldosterone receptor antagonist
- aldosterone normally attaches to intracellular mineralocorticosteroid receptors which would increase ENaC expression and Na/K+ ATPase expression
24
Q
ADH antagonists - Aquaretics mechanism of actions
A
- reduces expression of aquaporins
- therefore diuretic but not natriuretic - produces dilute urine
25
When are aquaretics used?
Hyponatraemia
| Prevents cysts enlargement in adult poly cystic kidney disease
26
Name of ADH antagonist
Tolvaptan
Lithium
Demeclocycline
27
Lithium
Treats bipolar disorder
| Side effect - inhibits ADH therefore diuretic and can dehydrate rapidly
28
Acetazolamide
Carbonic anhydrase inhibitor
Acts on PCT
Side effect: hypokalaemic metabolic acidosis
29
Furosemide side effects
```
Hypokalaemia metabolic alkalosis
Hypomagnesia
Ototoxicity
Increased lipids, triglycerides and glucose reabsorption - bad for diabetics
Gout
```
30
Examples of thiazides
Bendroflumethiazides
| Indapamide
31
Aldosterone receptor antagonist examples
Spironolactone
Canrenone
Eplerenone
32
Alcohol
Inhibits ADH release but DOESN’T block the receptor
Decreases water resorption
Urinate more
33
Caffeine
Increased GFR
| Decreased tubular sodium reabsorption
34
Generic adverse drug reactions
Hypovalaemia and hypotension:
- activates RAAS
- can lead to AKI
Electrolyte disturbance
Metabolic abnormalities
Anaphylaxis/ photosensitivity rash
35
Spironolactone side effects
Hyperkalaemia - arrhythmia
Impotence
Painful gynaecomastia
36
Bumetanide
Loop diuretic
| Can cause myalgia
37
Aminoglycoside interactions
E.g gentamicin
| Ototoxic therefore do not give with loop diuretic like furosemide
38
Digoxin interaction
Used in atrial fibrillation
Narrow therapeutic window
Can cause hypokalaemia therefore do not give with thiazides and loop diuretics
Can cause increased digoxin binding and toxicity
39
Beta blockers and thiazides effects
Hyperglycaemia
Hyperlipidemia
Hyperuricaemia
40
Steroid interactions
Decrease K+ reabsorption
| Therefore do not give with thiazides or loop diuretics
41
Lithium interactions
Thiazide - increases lithium toxicity
| Loop diuretic - reduces lithium level
42
Carbamazepine
Anti- epileptic
Used with thiazides and loop diuretics can cause hyponatreamia
43
Hypertension
Thiazide - vasodilation and diuretic
Spironolactone
Loop diuretic - body quickly accommodates
Ace inhibitors
ARB
CCB
B blockers
44
Heart failure
- causes secondary hyperaldosteronism due to low BP
- loop diuretic - can cause hypokalaemia
- spironolactone as adjunct to decrease hypokalaemia
- ACEi
- ARB
- B blocker
- SGLT2
- Tolvaptan
45
Decompensated liver disease
Normally causes low K+
Spironolactone - K+ sparing
Loop diuretics
- Tolvaptan
46
Nephrotic syndrome
Large dose of loop diuretic
+/- thiazides
+/- K+ sparing diuretic and K+ supplements
47
Chronic kidney disease
Decrease GFR
- Water and sodium retention
- acidosis as less H+
- hyperkaleamia
- loop diuretic
- AVOID potassium sparring diuretics
48
Diuretic resistance
chronic renal failure :
- OATs transport things non specifically therefore completes with furosemide
- reduced nephron number
Nephrotic syndrome
- gut oedema therefore less absorption of furosemide
- hypoalbuminaemia therefore less carriers for furosemide
Heart failure
- furosemide transported less due to low circulation
49
Lifestyle advice
- decrease salt intake
- exercise
- less fluid intake
50
Refractory oedema
In heart failure patients higher concentration of drugs are required and there is less effect
- check salt intake
- give furosemide IV if gut oedema
- minimal effective dose adapted
On day 1 works well but day 3 to 4 more Na+ reabsorbed due to upregulation
51
Bartter’s syndrome
Extreme furosemide effect
| Hypotension
52
Gitelman’s syndrome
Congenital
100% thiazide effect
Hypotension
53
Liddle’s syndrome
Increased ENaC activity
Hypertension
More sodium and water reabsorption
