Lecture 1 - Diuretics Flashcards
1
Q
What are the thiazide diuretics?
A
hydrochlorothiazide
chlorthalidone
metolazone
2
Q
What are the loop diuretics?
A
furosemide
ethacynic acid
3
Q
What is a potassium sparing diuretic?
A
spironolactone
4
Q
Thiazide, loop, and potassium sparing diuretics are _______ diuretics
A
classic
5
Q
Other than classic diuretics what is the other group of diuretics?
A
solute and/or water excretion altering (not clinically used as diuretics)
6
Q
_____ = osmotic diuretic
A
mannitol
7
Q
______ = carbonic anhydrase inhibitor
A
acetazolamide
8
Q
_______ = vasopressin receptor antagonist
A
tolvaptan
9
Q
_______ = sodium/glucose co-transport 2 inhibitor
A
dapagliflozin
10
Q
Definition of a diuretic?
A
agents which increase urine flow
11
Q
Clinically, what do diuretics do?
A
- renal solute excretion (sodium and water)
- block sodium reabsorption and water will follow later
12
Q
Aim of therapy for diuretics?
A
- only need to decrease sodium reabsorption a few %
- change of 5% has a great effect
13
Q
How much % of Na is reabsorbed?
A
99.6%
14
Q
How many mmol/day of Na is excreted?
A
100
15
Q
If Na reabsorption decreases to 95% then ____ mmol/day of Na is excreted
A
1250
16
Q
Where does dapagliflozin work?
A
blocks glucose and sodium reabsorption (so it’s excreted, and then water will follow and be excreted as well)
17
Q
Where does mannitol work?
A
increases H2O excretion
18
Q
Where does acetazolamide work?
A
Increases excretion of HCO3
19
Q
Where does hydrochlorothiazide and metolazone work?
A
increase NaCl excretion
20
Q
Where does furosemide work?
A
Increases Na, Cl, and K excretion and Mg, Ca will follow
21
Q
Where does spironolactone work?
A
blocks Na reabsorption
22
Q
Where does tolvaptan work?
A
ADH (vasopressin receptor antagonist)
23
Q
make fucking sense of slide 5 and 6
A
kay
24
Q
Where do thiazide diuretics work?
A
In distal tubule (primary site of action) to:
- Increase NaCl excretion (decrease reabsorption)
- Decrease Ca excretion (increase reabsorption) - loop diuretics do the opposite
*they have some proximal tubular effect but it is not normally important (it is only important when combined with loop diuretic)
25
____ diuretics - may decrease blood pressure without a perceivable volume loss, low dose is usually effective (with decreased toxicity)
thiazide
26
For elderly patients, ____ diuretics are a problem
loop
*Because they increase the calcium excretion (decrease the Ca reabsorption) and can contribute to osteoporosis or other bone diseases
27
What is the formula for BP?
BP = CO x TPR
28
Describe how thiazide diuretics decrease blood pressure
- increase NaCl excretion
- decrease blood volume
- decreases cardiac output (which decreases BP - think of the BP formula)
- apparent tolerance = no diuresis?
- blood volume and CO returns to normal
- blood pressure stays down and may decrease further
29
Problems with thiazide diuretics?
* *in addition to electrolyte problems
- increased incidence of other risk factors for CV disease
- hyperglycemia (decreased insulin release, decreased tissue utilization)
- increased LDL levels (must monitor)
- increased incidence of ED
- plasma volume contraction due to increased urine loss
- increased proximal tubule reabsorption, response to fluid loss
- increased lithium; urea reabsorption
30
What are thiazide diuretics used for?
- edema
| - hypertension
31
Advantages of thiazide diuretics?
- orally active, low toxicity, no postural hypotension
| - potentiate other antihypertensive drugs
32
____ diuretics include furosemide, bumetanide, ethacrynic acid (non sulphonamide)
Loop
33
___ _____ diuretics are very potent and efficacious
high ceiling
34
Why are high ceiling diuretics dangerous?
up to 20% of filtered load excreted
35
Loop diuretics:
| ____ and ____ application
oral
| IV
36
Loop diuretics:
| Increase _____ production which results in vasodilation
prostaglandin
37
Where are loop diuretics useful?
in acute pulmonary edema - because it vasodilators veins
38
___ may decrease function of loop and thiazide diuretics
NSAIDs
39
MOA of loop diuretics?
- increases Na, Cl, and K excretion and Mg, Ca follow (excreted)
- inhibits renal diluting ability and abolishes the renal concentrating ability, urine becomes isotonic or slightly dilute
40
Problems with loop diuretics?
* in addition to electrolyte imbalances
- deafness - never combine with aminoglycoside antibiotics
- chronic dilution hyponatremia (due to excrete of an isotonic urine)
41
Uses of loop diuretics?
- good in renal insufficiency (GFR < 50 mL/min)
| - edema (pulmonary); hypertension (not as sole medication); hypercalcemia (opposite to thiazides); heart failure
42
What do you need to caution if a patient is not responding to a loop diuretic? And how do you manage it?
- caution regarding circulating chloride concentration
- add a thiazide diuretic
* metolazone often used for this
43
What is the main electrolyte problem with thiazide and loop diuretics?
Potassium depletion
- not a problem in healthy patients
- more a problem if low potassium already a problem (heart failure, cirrhosis, etc.)
44
What are the two major causes of potassium depletion?
1) Secondary hyperaldosteronism (due to plasma volume depletion)
- increased renin
- increases angiotensin 2
- increased aldosterone
- Na reabsorption at expense of K (and H) loss
2) Increased Na delivery from distal tubule
- due to inhibition of Na reabsorption in loop and distal tubule
- collecting tubules therefore increase Na reabsorption - to conserve sodium
45
Describe the potassium depletion treatment
1) dietary intake - apricots and bananas
2) potassium chloride tablets - chloride salt - dilute solution
3) slow - potassium tablets - ulceration
4) emergencies require IV KCl - repeat cautiously until potassium rises
5) potassium sparing diuretics
- weak diuretics
- give with other diuretics to decrease K loss
- may cause hyperkalemia
*Never coming potassium sparing diuretics with K supplements*
46
List 3 potassium sparing diuretics
- spironolactone
- triamterene
- amiloride
47
How does spironolactone work?
- blocks aldosterone receptor
| - prevents cardiac remodelling (fibrosis, cardiac collagen proliferation) - may delay progression of failure
48
How does triamterene and amiloride work?
-decreases sodium permeability
49
B-blockers, ACEi's and ARB's may also increase plasma _____ concentrations
potassium
50
B-blockers decrease potassium _____ cells
entering
51
ACEi's and ARB's decrease ______ concentrations
aldosterone
52
So potassium depletion is one electrolyte disturbance, what is another?
Extracellular Volume Depletion
- furosemide - kidney unable to concentrate or dilute
- excrete an isotonic urine
- inability to concentrate urine (save water)
- simply drink more water to excrete solutes
- inability to dilute urine (excrete excess water)
- ingest hypotonic solution - excrete isotonic urine
- net loss of electrolytes including plasma sodium
- chronic dilution hyponatremia
53
Describe calcium as an electrolyte disturbance
- Thiazides decrease calcium excretion, good for hypocalciuria
- Furosemide increases calcium excretion, good for hypercalcemia
54
Describe how volume depletion and increased proximal tubule reabsorption can be a problem.
1) uric acid excretion
- initially increased but decreased with chronic administration (gout?)
2) Lithium - increased proximal tubular reabsorption
- toxicity is a concern (same clinical concern for digoxin)
55
List the 4 uses of diuretics
- tissue edema
- hypertension
- hepatic cirrhosis
- cardiac failure
56
Describe how diuretics treat tissue edema
- fluid shift into the extracellular space has exceeded 3 to 4 L due to salt and water retention
- Loop diuretic (furosemide) preferred
- if no response to loop diuretic, check for low serum chloride concentration
- fluid excreted in urine is taken from the "vascular space", allow time for this to be replaced by the interstitial (oedematous) fluid - go slow! otherwise CV collapse
57
Describe how diuretics treat hypertension
- 1st line single therapy (thiazide diuretic)
- but possible increase in LDL and plasma glucose (not metabolically neutral)
- good as second medication to treat sodium and water retention
* which is a common side effect of other anti-hypertensives
58
Describe how diuretics treat hepatic cirrhosis
- sodium/water accumulates in the abdomen and/or tissue
- abdominal fluid movement into vascular space may be a concern
- slower than fluid movement from interstitial to vascular space
- aggressive treatment will remove fluid faster from the vascular space than can be replaced fly the abdominal fluid
59
Describe how diuretics treat cardiac failure
- fluid retention increases vascular volume
- helps to increase preload and stimulate the heart
- as failure continues so does fluid retention
- preload increases to levels causing edema
- diuretics decrease vascular volume
- successful treatment of heart failure requires adequate control of vascular volume
60
What are osmotic diuretics?
osmotically active compounds in the plasma
61
List 4 properties for a perfect osmotic diuretic
- filtered
- not reabsorbed
- pharmacologically inert
- resistant to alteration
*osmotically active compounds "hold" onto water - high urine volume - little sodium
62
List 3 uses of mannitol (IV) and glycerol (oral)
- vascular surgery
- renal transplant
- ophthalmological procedures
63
Where do osmotic diuretics work?
they block water reabsorption so they increase water excretion
64
What is an example of a carbonic anhydrase inhibitor?
Acetazolamide (Diamox)
65
Describe carbonic anhydrase inhibitors (ex. acetazolamide)
- very weak diuretics
- inhibit carbonic anhydrase
- decreases reabsorption of bicarbonate in proximal tubular cells
- increase bicarbonate excretion (with some sodium)
66
Uses of carbonic anhydrase inhibitors (ex. acetazolamide)
- in severe alkalosis (increases renal excretion of bicarbonate)
- alkalinization of filtrate ionizes acidic drugs
- ionization increases renal excretion ex. salicylate
67
List 3 main uses of carbonic anhydrase inhibitors (ex. acetazolamide)
- acute mountain sickness
- increasing excretion of weak acids
- glaucoma - decreases aqueous humor formation
68
MOA of carbonic anhydrase inhibitors (ex. acetazolamide)
increase renal excretion of bicarbonate
69
Conivaptan is a ????
ADH Antagonist
70
ADH (vasopressin) increases water _____ (no effect on electrolytes)
reabsorption
71
How does conivaptan work?
Blocks the ADH receptor in the collecting tubules
| *Increases water excretion without electrolytes
72
____ is increased in heart failure and syndrome of inappropriate ADH (SIADH) secretion. The chronic increased water reabsorption may produce ______.
vasopressin (ADH)
hyponatremia (diluted sodium)
73
What can ADH antagonists produce?
nephrogenic diabetes insipidus (increased urine flow due to lack of a renal effect of ADH)
74
Main uses of conivaptan (ADH antagonist)
SIADH (relatively new)
75
MOA of ADH antagonists
block ADH receptors, increase water excretion
76
Dapagliflozin is a ??
Sodium glucose Co-transport 2 (SGLT2) inhibitor
77
What is sodium glucose co-transport 2?
the major site of glucose reabsorption in the proximal tubule
90% is via the SGLT2
blockade of this transport increases urinary excretion of glucose
*associated with a small decrease in plasma glucose
78
SGLT2 inhibitors associated with?
a decrease in blood pressure and weight
