Diuretics Flashcards
(125 cards)
1
Q
first area of nephron where filtrate is formed?
Is it permeable to water?
A
glomerulus
yes, extremely water permeable
2
Q
what percent of what is reabsorbed in the proximal convoluted tubule?
A
65% filtered Na+,K+, Ca++ and Mg ++
85% of NaHCO3
nearly 100% of glucose and amino acids
and isosmotic reabsorption of water
3
Q
what drugs work at the proximal convoluted tubule
A
carbonic anhydrase inhibitors
and adenosine antagonists (under investigation)
4
Q
what is reabsorbed in the descending limb of Henle’s loop?
A
passive reabsorption of water via aquaporins
5
Q
what is reabsorbed in the thick ascending loop of Henle (TAL)
A
15-25% of filtered Na, K and Cl is actively reabsorbed
secondary reabsrotion of Ca++ and Mg++
6
Q
what areas of nephron have little to no water permeability
A
thick ascending loop of Henle
Distal convoluted tubule
7
Q
where do loop diuretics work
A
thick ascending loop of Henle (TAL)
8
Q
what is reabsorbed in the distal convoluted tubule?
A
4-8% of filtered Na, and Cl- is actively reabsorbed
9
Q
what controls reabsorption in distal convoluted tubule?
A
parathyroid hormone
10
Q
where do thiazide diuretics work
A
distal convoluted tubule
11
Q
what is reabsorbed in collecting tubule
A
2-5% of Na reabsorption coupled with K+ and H+ secretion
12
Q
where do K sparing diuretics work?
A
collecting tubule
13
Q
where do vasopressin antagonists work
A
collecting duct
14
Q
how is water reabsorbed in collecting duct
A
aquaporins
15
Q
where does mannitol work in nephron
A
PCT and thin descending loop
16
Q
where is final volume of urine determined? what electrolyte is effected the most here?
A
corticol collecting tubule system
potassium
17
Q
what type of drugs all end in -vaptan
A
vasopressin antagonists
18
Q
NSAID’s block action of what?
A
loop diureticss
19
Q
what is the subtype of prostaglandin that effects Na reabsorption? where does it take place?
what other effect does it have on nephron
A
PGE2 blunts Na reabsorption in thick ascending loop
also blunts ADH-mediated water transport in collecting tubules
20
Q
name 4 natriuretic peptides and where they are synthesized
A
- ANP - synthesized in heart
- BNP - synthesized in heart
- CNP synthesized in CNS
- urodilatin - synthesized in kidney
21
Q
what natriuretic peptides increase GFR and exhibit diuretic activity
A
ANP and BNP
22
Q
what agent acts on BNP and is indicated for acute decompensated heart failure
A
nesiritide
23
Q
what are the effects of urodilatin
A
- blunts Na reabsorption, effecting Na uptake channels and NA/K ATPase in collecting tubule
- decrease glomerular afferent vasomotor tone
(increases GFR) - increase glomerular efferent vasomotor tone
(increases GFR)
24
Q
the collecting duct has an overall charge that is + or -?
A
negative
25
what 3 types of electrolyte movement takes place in collecting tubule system
1 sodium reabsorbed via Na/K ATPase pump.
2 K and H are excreted into the lumen
3 sodium also enters collecting tubule from lumen epithelial Na channel.
26
what effect does aldosterone have on collecting tubule system?
decrease in aldosterone brings in more Na in exchange for K
27
what electrolytes are collected in the interstitium (blood) at the collecting tubule? what electrolytes are lost
interstitium holds onto sodium and calcium, and
| loses potassium
28
what effect does ADH have at collecting duct?
creates aquaporins so water is reabsorbed into interstitium
29
what kind of transporters are present in the PCT?
symporter allows Na and carbonic acid reabsorption into interstitium
antiporter allows Na to travel from lumen to PCT and H+ ions to travel from PCT to lumen
30
what type of transporters are present in TAL?
Na/K ATPase pump to interstitium
Cl- channels to interstitium
Na and Cl symporter from lumen to TAL
31
what transporter is effected by loop diuretics?
Na, Cl symporter in TAL
32
what transporter is effected by thiazide diuretics
Na, Cl Symporter in the distal convoluted tubule
33
where do sodium channel blockers work?
Na channels in collecting duct that bring Na into nephron from lumen
34
where is calcium and magnesium taken up from lumen into nephron
tight junctions in the TAL
35
what is the MOA of carbonic anhydrase inhibitors?
| what does this do physiologically?
inhibit bicarbonate reabsorption in the PCT
| the bicarbonate loss leads to diuresis and hyperchloremic metabolic acidosis (since bicarb is basic)
36
what are the 4 indications of carbonic anhydrase inhibitors?
1. glaucoma (most common)
2. urinary alkanlization
3. metabolic alkalosis
4. acute mountain sickness
37
acidic urinary conditions can cause what?
| excessive urinary alkalinization can cause what?
kidney stone formation from uric acid and cysteine insolubility (too much CAI)
kidney stone formation from calcium (too little CAI)
38
what is the MOA of CAI's on glaucoma
decrease intraocular pressure by reducing production of aq humor
39
how long do CAI's work
single use only.
| Works for 2-3 days
40
main toxicity related to CAI's is what
```
acidosis in blood leading to:
renal stones
K wasting
drowsiness
paresthesias
hypersensitivity reactions
```
41
what are the 2 contraindications for CAI's
```
hepatic disease
sulfa allergy ( no sulfa drugs with it)
```
42
what is the trade and generic name of a systemic CAI
acetazolamide (Diamox)
43
what is the goal of adenosine receptor antagonists?
avoid K wasting
44
what transporter is effected by loop diuretics
Na/K/2Cl transporter
45
loop diuretics require secretion by what?
OATS in PCT
46
what is the affect of loop diuretics on NaCL
reduces absorption of NaCl in the thick ascending loop
47
what is the effect of loop diuretics on K?
diminishes lumen positive potential from K+ recycling ( this increases Mg and Ca excretion
48
what is the effect of loop diuretics on COX-2
induces expression of COX-2, increasing prostaglanding production, and increasing renal blood flow
49
what are 4 most common indications for loop diuretics?
1. edematous conditions
2. hyperkalemia and hypercalcemia
3. acute renal failure
4. anion overdose (toxic ingestion of bromide, fluoride, iodide, and other dyes)
50
what are 7 toxicities related to loop diuretics?
1. hypokalemic metabolic alkalosis
2. ototoxicity
3. hyperuricemia
4. hypomagnesemia
5. allergic rxns
6. hyponatremia
7. dehydration
51
what are the contraindications of loop diuretics?
1. sulfa allergy
2. excessive use is dangerous in:
cirrhosis
kidney failure
heart failure
52
what loop diuretic can be used with a sulfa allergy?
ethacrynic acid (Edecrin)
53
what are 4 loop diuretics generic names
1. furosemide
2. bumetanide
3. ethacrynic acid
4. torsamide
54
what are 4 loop diuretics trade names
1. Bumex = bumetanide
2. Edecrin = ethacrynic acid
3. Lasix = furosemide
4. Demadex = torsemide
55
what are the conversions for furosemide, torsemide, and bumetanide IV and PO?
Furosemide Torsemide Bumetanide
IV = 20g => IV=PO=20 mg => IV=PO= 1 mg
PO= 40 mg
56
what is the highest dose of HCTZ?
25 mg
57
what is the MOA of thiazide diuretics
1. secreted by OATS in PCT
2. inhibit NaCl reabsorption from luminal side of epithelial cells in the distal convoluted tubule
3. enhance calcium reabsorption
58
what are the indications of thiazide diuretics?
1. hypertension
2. heart failure
3. nephrolithiasis due to idiopathic hypercalciuria
4. nephrogenic diabetes insipidus
59
what are the toxicities related to thiazides (5)?
```
hypokalemic metabolic alkalosis
hyperuricemia
impaired carbohydrate tolerance
hyperlipidemia
hyponatremia
```
60
what are the contraindications of thiazide diuretics?
1. sulfa allergy
2. excessive use is dangerous in:
cirrhosis
kidney failure
heart failure
(same as loop contraindications)
61
what is the minimum ClCr level for use of thiazide diuretics?
what 2 thiazide diuretics may be used if this isn't met?
30
indapamide and metolazone
62
list the thiazide diuretics generic names (6)
1. chlorothiazide
2. chlorthalidone
3. hydrochlorothiazide
4. indapamide
5. methylclothiazide
6. metolazone
63
what drugs listed as thiazides are considered "thiazide like"
1. chlorthalidone
2. indapamide
3. metolazone
64
what is the MOA of K-sparing diuretics?
1. aldosterone antagonists
| 2. Epithelial Sodium Channel (ENaC) inhibitors
65
what drugs are considered aldosterone antagonists?
spironolactone and eplerenone
66
what drugs are considered Epithelial Sodium Channel (ENaC) inhibitors ?
amiloride and triamterene
67
how do the aldosterone antagonizing K sparing diuretics work (MOA)
bind to mineralcorticoid receptor to reduce Na+ reabsorption in collecting duct
68
how do the ENaC inhibiting K-sparing diuretics work (MOA)
interfere with Na entry in apical membrane of collecting tubule
69
what are the indications of K-sparing diuretics?
I. Hyperaldosteronism:
II. Myocardial Infarction
III.Hypertension
70
what are 5 toxicities related to K-sparing diuretics?
1. hyoperkalemia
2. hyperchlormemic metabolic acidosis
3. gynecomastia
4. acute renal failure
5. kidney stones
71
what are 4 conditions of hyperaldosteronism
1. heart failure
2. cirrhosis
3. nephrotic syndrome
4. diminished effective intravascular volume
72
what is the K-sparing drug of choice for cirrhosis
spironolactone
73
what is the K-sparing drug of choice for myocardial infarction
eplerenone
74
what are the K-sparing drugs of choice for hypertension
amiloride
| triamterene
75
what are the K-sparing drugs that can cause gynecomastia
spironolactone and eplerenone
76
what are the K-sparing drugs that can cause kidney stones
triamterene
| amiloride
77
what are the contraindications for K-sparing drugs
1. chronic renal insufficiency
| 2. concomitant use with K supplementation or drugs that increase K levels
78
why are osmotic diuretics only given IV
IV causes diuresis
| PO causes osmotic diarrha
79
where do osmotic diuretics work in the nephron
primarily proximal convoluted tubule
| also descending loop of henle
80
what is the MOA of osmotic diuretics
filtered by the glomerulus but not reabsorbed, causing water retention in the lumen (promoting diuresis).
81
what are indications of osmotic diuretics
1. to increase water excretion in preference to Na+ (increasing urine volume)
2. reduce intracranial pressure
3. reduce intraocular pressure
82
what are 5 toxicities related to osmotic diuretics?
1. extracellular volume expansion
2. dehydration
3. hyperkalemia
4. hypernatremia
5. hyponatremia
83
when is hyponatremia seen with osmotic diuretics?
in renal dysfunction
84
what can be done to prevent extracellular volume expansion with osmotic diuretics
wait for fluids to move into cell
85
list the K sparing diuretics?
1. amiloride
2. eplerenone
3. spironolactone
4. triamterene
86
what is the MOA of ADH antagonists?
inhibit ADH at the V2 receptor in the collecting tubule
87
what are the indications of ADH antagonists
1. syndrome of inappropriate ADH secretion (SIADH)
| 2. heart failure (most common use)
88
what must be monitored in pt's using ADH antagonists?
blood pressure
| sodium levels
89
name the ADH antagonists
Conivaptan
| Tolvaptan
90
what ADH antagonist is given orally
tolvaptan
91
what ADH antagonist is given IV
conivaptan
92
which ADH antagonist has the most adverse effects? Why
conivaptan
| is nonselective for V1 and V2 receptor antagonism
93
what ADH antagonist is V2 receptor selective
tolvaptan
94
when should ADH antagonists be used for SIADH
when water restriction fails
95
how do ADH antagonists work on pt's with heart failure
1. decrease peripheral vascular resistance
| 2. increased cardiac output
96
what are 2 toxicities related to ADH antagonists
1. nephrogenic diabetes insipidus
| 2. renal failure
97
why give thiazide diuretic 30 minutes before a loop diuretic?
so no compensation takes place in distal convoluted tubule.
| if thiazide gets in first, it can reach site of action more efficiently
98
why are diuretics given in combination
1. different MOA gives good synergistic effects
| 2. prevent compensation by kidney
99
how should thiazides and loop diuretics be given together?
thiazide 30 minutes before loop
100
what are 4. causes of edematous states
1. heart failure
2. kidney disease and renal failure
3. hepatic cirrhosis (ascites)
4. idiopathic edema
101
what MOA in heart failure causes edema?
| what is usually used to treat this?
1. decreased cardiac output leading to decreased renal blood flow leading to Na and water retention.
loop diuretics
102
excessive diuresis in heart failure can lead to what
decrease venous return, further impairing cardiac output
103
heart failure induced edema does what initially?
increase intravascular volume and venous return to heart
| long term, this compensatory mechanism is harmful
104
diuretics have what effect on acute renal failure?
helpful in short term, no effect on long term outcomes
105
list 3 cautions when using diuretics with chronic renal failure
1. risk of hyperkalemia
2. thiazides don't work for monotherapy if CrCl is less than 30 ml/min
3. avoid acetazolamide
106
why should acetazolamide be avoided in pt's with chronic renal failure
exacerbates acidosis
107
what type of edema causes can cause your shins to feel like memory foam?
what should be used to treat this
peripheral edema
| loop diuretics
108
what condition is frequently associated with hyperkalemia at early stages?
what can be used to treat this
Diabetic Nephropathy inducing kidney disease or renal failure
loop diuretics or thiazide diuretics
109
what condition is resistant to loop diuretics
hepatic cirrhosis (ascites)
110
what causes Na retention in hepatic cirrhosis
1. decrease renal perfusion
2. decrease plasma volume
3. decrease oncotic pressure
4. elevated aldosterone levels
111
why is decreased oncotic pressure seen with hepatic cirrhosis
albumin is made in liver
| without it fluid seeps out of blood
112
what has been proven to be effective against hepatic cirrhosis
aldosterone antagonists
113
aggressive diuresis can cause what harmful effects in pt's with hepatic cirrhosis (5)?
1. deplete intravascular volume
2. hypokalemia
3. metabolic acidosis
4. hepatorenal syndrome
5. hepatic encephalopathy
114
idiopathic edema is most common in who?
women between 20-30
115
what are 3 treatment options for idiopathic edema
1. salt restriction
2. compression stockings
3. spironolactone (if others don't work)
116
diuretics treat what 4 non-edematous states?
1. hypertension
2. nephrolithiasis
3. hypercalcemia
4. diabetes insipidus
117
what is used in treating hypertension
thiazides (successful in monotherapy, enhanced in combination tx)
118
loop diuretics are reserved to treat hypertension in patients with what?
1. mild renal insufficiency (CrCl <30-40 ml/min)
| 2. heart failure
119
2/3 of kidney stones contain what?
calcium
120
what symptom is associated with nephrolithiasis
kidney stones
121
what are 4 common underlying causes of nephrolithiasis
1. defect in Ca reabsorption in PCT
2. hyperparathydroidism
3. too much vit D
4. sarcoidosis
122
what are therapy options for nephrolithiasis
1. thiazide diuretics (cause Ca reabsorption in DCT)
2. increase fluid intake
3. reduce salt intake
123
what is the tx for hypercalcemia
loop diuretics and IV saline infusion
124
diabetes insipidus is caused by what?
deficient production or inadequate response to ADH
125
what is a tx for diabetes insipidus?
| what symptoms does it treat
thiazide diuretics
| reduce polyuria and polydipsia
