Diuretics -Duan Flashcards
1
Q
What do kidneys regulate?
A
- body fluid volume and osmolarity
- electrolyte balance
- acid-base balance
- blood pressure
2
Q
What do the kidneys secrete?
A
- erythropoitin
- 1,25-dihydroxy vitamin D3 (vitamin D activation)
- renin-angiotensin-aldosterone
- prostaglandin
3
Q
What do the kidneys excrete?
A
- Metabolic products
- Foreign substances (pesticides, chemicals etc.)
- Excess substance (water, etc)
4
Q
T or F
The kidneys function in gluconeogenesis
A
T
5
Q
What are the 2 major components of the kidney?
A
1) Glomerulus
2) Tubule system (sites of reabsorption, secretion, and excretion)
6
Q
What is this:
a compact cluster of convoluted capillaries, site of filtration, functioning to remove certain substances from the blood before it flows into the convoluted tubule.
A
Glomerulus
7
Q
What does the tubule system of the kidney do?
A
sites of reabsorption, secretion, and excretion
8
Q
What is the renal corpuscle made up of?
A
Glomerulus and Bowman’s capsule
9
Q
How do you get everything to filter within the glomerulus?
A
Glomerulus is very high pressure–> creating a pressure gradient that allows for (passive) filtration (starling forces of filtration)
10
Q
The net filtration pressure= (favoring force- opposing force)
What is the favoring force?
What is the opposing force?
A
Favoring: Capillary blood pressure (BP)
Opposing: Blood colloid osmotic pressure (COP) and Capsule pressure (CP)
11
Q
What is the glomerular filtration rate?
A
the volume of fluid filtered from the glomerular capillaries into the Bowman’s capsule per unit time (125 mL/min=180L/day)
12
Q
What is the equation for GFR?
A
(Urine concentration X urine flow)/(plasma concentration)
13
Q
Clinically, creatinine clearance or estimates of creatinine clearance based on the serum creatinin level are used to measure (blank)
A
GFR
14
Q
What are the factors that alter filtration pressure and change GFR?
A
- Increased RBF (vasodilators)-> increased GFR
- Decreased plasma protein-> Increased GFR, Causes edema
- Hemoorhage-> decreased capillary BP-> decreased GFR
- Molecular weight
- Charges of the molecule
15
Q
How do you regulate GFR?
A
-renal autoregulation
-neural regulation
-hormonal regulation
(adjust renal BP and resulting blood flow)
16
Q
What is this:
glomeruli in inner part of cortex and long loops of Henle which extend deeply into medulla
A
Juxtamedullary nephron
17
Q
Blood flow through vasa recta in medulla is (fast/slow)
A
slow
18
Q
Medullary interstitial fluid is (hypoosmotic/hyperosmotic)
A
hyperosmotic
19
Q
The juxtamedullary nephron maintains (Blank) in addition to filtering blood and maintaining acid-base balance and concentrate urine
A
osmolality
20
Q
What is this:
glomeruli in outer cortex and short loops of Henle that extend only short distance into medulla.
A
Cortical nephron
21
Q
Blood through the the cortex is (fast/slow)
A
fast
22
Q
The majority (70-80%) of nephrons are (blank).
A
cortical
23
Q
Cortical interstitial fluid is isosomotic at (blank)
A
300 mOsm
24
Q
Reabsorption is a (blank) process beginning with the active or passive extraction of substances from the tubular fluids into the renal interstitium (the CT that surrounds the nephrons). Then these sustances are transported from the interstitium into the (blank). These transport processes are driven by (blank, blank and blank)
A
2-step
bloodstream
Starling forces, passive diffusion, and active transport
25
In the proximal convoluted:
- Tubule (PCT), reabsorption occurs when (blank) needs to be maintained.
- (blank) ions are reabsorbed back into the bloodstream.
- (blank, blank, and blank) are all actively transported into the blood
(blank) percent organic solutes are reabsorbed
(blank and blank) are actively secreted from the blood into the tubule
pH (acid/base balance)
Biocarb
Glucose, AAs and K+ are all actively transported into the blood
70-80%
H+ and toxins
26
How does the Na+ H exchanger work?
puts sodium into the PCT and excretes hydrogen into the urine
27
What does carbonic anhydrase do?
makes Co2 and H20 into H2Co3
28
What is the descending limb of the loop of henle highly permeable to?
H20
| does this via osmosis
29
The ascending limb of the loop of henle has (blank) permeability to H20 and is often called the (blank) segment
low
| diluting
30
The ascending loop of henle is responsible for (blank) percent of H20 reabsorption BUT can increase to 50%
15%
31
The (blank) of the loop of henle allows for the passive and active transport of salts such as Na+ to move out of the tubules and be reabsorbed
thick ascending limb
32
How do you get Cl- out of the urine into the ascneding limb of the loop of henle and back into the blood stream?
NKCC2-> K/Cl- symport
33
What happens to most of the potassium in the tubules?
it goes into the lumen to get excreted as urine through potassium channels
34
How are Mg2+ and Calcium reabsorbed in the thick ascending limb?
via the paracellular shunt pathway
35
What is the main function of the loop of henle?
to create a concentration gradient in the medulla of the kidney by mean of a countercurrent multiplier system. So we can conserve water and ions :)
36
The loop of henle creates an area of (blank) deep in the medulla, near the collecting duct
high urea
37
How does the countercurrent multiplier system work?
- filtrate entering the descending limb becomes progressively more concentrated as it loses H20
- blood in the vasa recta removes water leaving the loop of henle
- The ascending limb pumps out Na+, K+, Cl- and filtrate becomes hypo-osmotic
38
The Distal convoluted tubule (DCT) is (blank) to H20. What gets reabsorbed in the DCT?
relatively impermeable
| NaCl (creating more dilute urine)
39
What are the 2 cell types present in the collecting tubule?
Principle cells and intercalated cells
40
Where does aldosterone affect the kidney? What does aldosterone do?
in the principle cells of the collecting tubule
| affects the level of sodium and the final level of potassium in the urine
41
(blank) determines the expression of aquaporin channels that provide a physical pathway for water to pass through the principle cells in the collecting tubule
Vasopressin (ADH Antidiuretic hormone)
42
(blank) cells of the collecting tubule come in (blank) and (blank) varieties and participate in acid-base homeostasis
Intercalated
43
What do intercalated cells due?
put H+ into urine and Bicarb into blood-> i.e make urine acidic
44
In the collecting tubule, what drives the reabsorbtion of chloride into the blood and the efflux of potassium into the urine?
the Inward diffusion of sodium creating a gradient in the lumen
45
(blank) increases the activity of both apical Na+ channels and the Na+/K+ ATPase. What will this lead to?
Aldosterone
| Sodium reabsorption and potassium secretion
46
(Blank) controls the water permeability of principal cells in this segment
Antidiuretic hormone (ADH, or vasopressin)
47
ADH regulates the insertion of (blank) into principal cells in the apical membrane
aquaporin-2 (AQP2)
48
What will your urine be like if you have low ADH?
dilute
49
How does vasopression (ADH) work?
ADH-> AC-> cAMP-> increased PKA activity-> phosphorylated proteins= water channels on apical membrane
50
Intercalated cells participate in acid-base homeostasis, how?
a-intercalated cells secrete acid and reabsorb bicarb
| b-intercalated cells secrete bicarb and reabsorb acid
51
How do a-intercalated cells secrete acid?
| reabsorb bicarb?
-via an apical H+ ATPase and H-/K+ exchanger
-
52
How do b-intercalated cells secrete bicarb?
| How do they reabsorb acid?
- Via pendrin a specialist apical Cl-/HCO3- exchanger
| - Via a basal H+-ATPase
53
What is the equation for amount excreted?
Amount of solute excreted= (amount filtered) + (amount secreted) - (amount reabsorbed)
54
When there is excess water in the body and body fluid osmolarity is reduced, the kidney can exrete urine with an osmolarity as low as (blank).
Conversely, when there is a deficient of water and extracellular fluids osmolarity is high, the kidney can excrete urine with a concentration of about (blank) mOsm/liter.
50
| 1200 to 1400
55
What are the basic requirements for forming a concentrated or diluted urine?
- controlled secretion of ADH
- High osmolarity of renal medulla (so you can have a gradient to allow for water reabsorption in the presence of high ADH)
56
What happens to your urine if you add vasopression (ADH)?
it becomes more concentrated
57
All diuretics act on the (blank) surface EXCEPT for the (Blank)
luminal
| Aldosterone antagonists
58
Where are osmotic diuretics filtered?
| All other diuretics are not filtered there why?
glomerulus
Because they are bound to plasma proteins
59
Diuretics not filtered at the glomerulus are transported into the nephron by (blank) or (blank) transporters located in the proximal tubule
organic acid (A-) or organic base (C+)
60
What is the MOA of carbonic anhydrase inhibitors and how does it get into the lumen to work?
- inhibits Carbonic Anhydrase in lumin and basolateral membrane (type IV) and cytoplasm (type II)
- via organic acid transporter in PCT
61
What does carbonic anhydase do?
increased HCO3- excretion
| increased Na+, K + (distally), H20 excretion
62
What will carbonic anhydrase do to your urine?
make it alkaline due to decreased urea and increased HCO3
63
How is carbonic anhydrase self-limiting in diuretic action?
it stops its diuretic action when metabolic acidosis occurs as HCO3- decreases
64
What are the non-diuretic uses of carbonic anhydrase inhibitors?
A Family GAME
- Alkalinizing urine for excretion of weak acids
- Familial hypokalemic periodic paralysis
- Glaucoma (decrease aqueous humor formation)
- Altitude (mountain) sickness (decreased CSF and pH)
- Metabolic Alkalosis
- Epilepsy (seldom used)
65
What are the adverse effects of carbonic anhydrase?
A PACE
```
Acidosis (metabolic),
Potassium depletion (hypokalemia)
Allergic reactions (sulfonamide-based)
Calcium nephrolithiasis
Encephalopathy
(other: drowsiness, dizziness, parasthesia, bone marrow toxicity, skin rashes)
```
66
What are the contraindications for carbonic anhydrase inhibitors?
patients with cirrhosis of the liver->Can lead to hepatic encephalopathy
This is due to the alkalization of urine causing retention of urea
67
What are the four important osmotic diuretics?
- Mannitol
- Glycerin
- Isosorbide
- Urea
68
Osmotic diuretics (mannitol, glycerin, isosorbide, urea) are (blank) filtered by the glomerulus. They undergo (blank) reabsorption.
freely
| limited
69
What is the mechanism of action of osmotic diuretics?
adding particles to increase water excretion therefore quantity of water retained is proportional to the quantity of solute administered
70
Where do osmotic diuretics primarily act?
in the PCT and to a lesser extent in the ascending loop of henle
71
What are the clinical uses of Osmotic diuretics?
(AAA ID)
- Acute tubular necrosis
- Anuria in hemolysis or rhabdomyolysis (prophylaxis)
- Angle-closed glaucoma (reduce intraocular pressure)
- Increased Intracranial pressure (used as the DOC)
- Dialysis disequilibrium
72
What are the adverse effects of osmotic diuretics?
- dehydration
- hypernatremia (serium Na concentration > 145 mEG/L)
- If admin too rapidly IV, can cause cell dysfunction
73
Diuretic access to the tubule lumen is decreased by...?
decreased renal blood flow (decreased GFR)
| increase levels of compounds or drugs also transported by organic acid and base transporters
74
What are examples of compounds/drugs that are ALSO transported by organic acids and bases thus inhibiting diuretic access to the tubule lumen?
alph-ketoglutarate catecholamines
uric acid
choline histamine antibiotics cimetidine probenecid
75
Diuretics that act proximally are (blank) even though 70-80% of the filtered load is handled there. Why?
weak
their actions are counteracted by more distal reabsorption mechanisms
76
Diuretics that act (blank) are weak because only 5-10% of the filtered load is involved.
distally
77
Loop diuretics are strong because....?
- an important transport mechanism is inhibited (Na+,K+,2Cl- co-transporter)
- the affected site handles a large fraction of the filtered load (15-50%)
- More distal mechanisms are not able to compensate
78
Production of a concentrated urine requires a (blank)
hypertonic medulla
79
Production of a dilute urine requires a (blank) by reabsorbing Na+ w/o H20.
hypotonic filtrate
80
T or F
| diuretics acting distal to the loop of henle (i.e thiazides) affect the concentration of urine
False, they affect dilution but not concentration
81
Loop diuretics block the reabsorption of (blank) in the (blank). so it impairs both (blank and blank)
- Na+ w/out water
- ascending limb of henle
- Concentration and dilution
82
Diuretics are used to reduce (blank) by doing what? How?
ECF volume
| decreasing total Na+ content through either reabsorbtion back into the plasma or secretion into the urine
83
What do diuretics do to ECF?
Total Na+ retention?
Urine volume?
Urina Na+ content?
decrease ECF
decrease Na+ retention
increase urine volume
increase urine Na+ content
84
What does the ending -Zolamide indicate?
Carbonic Anhydrase (CA) inhibitors
| Zola eat Carbs
85
What does the ending -thiazide indicate?
thiazide diuretics :)
86
What does the ending -one indicate?
aldosterone antagonists
| Aldoster-ONE
(except for chlorthaidone, thats a thiazide one)
87
What does the ending
| -semide indicate?
Loop or "high ceiling" diuretics
| cuz loops are "semi"-circles
88
What does the ending -azone indicate?
Thiazide related
| cuz has 2 of the same letters as thiazide so it is related to it
89
What are the carbonic anhydrase inhibitors (CA)?
- acetazolamide
- dorzolamide
- dichlorphenamide
90
What are the thiazide diuretics (Na+/Cl- symport inhibitors)?
hydrochlorothiazide
| chlorothiazide
91
What are the aldosterone antagonists?
Spironolactone
| Epleronone
92
What are the Na+ channel inhibitors?
Amiloride
| Triamterene
93
What are the ADH antagonists?
Lithium
| Demeclocycline
94
What are the thiazide related drugs?
Chlorthalidone
Indapamide
Metolazone
Quinethazone
95
What are the loop or "high ceiling" diuretics (Na+ K 2Cl- symport inhibitors)?
Furosemide
Torsemide
Bunetanide
Ethacrynic acid
96
What are the osmotic diuretics?
- mannitol
- glycerin
- isosobide
- urea
97
What are the two types of K+ sparing diuretics?
Aldosterone antagonists
| Na+ channel inhibitors
98
What are the contraindications for Osmotic diuretics?
CHF
| Severe renal disease
99
There are 2 categories of loop diuretics, sulfonamide and non sulfonamide.
What are the sulfonamide derivatives?
What are the non-sulfonamide derivatives?
Furosemide
Torsemide
Bumetanide
Ethacrynic acid
100
What is the mechanism of action of loop diuretics and how do they get where they need to go? What does this result in?
- Reach the lumen via the organic acid transporter
- NKCC2 innhibitos in the ascending limb of henle loop
- Decrease hyperosmolarity in medulla
101
What are the most effective diuretics and why?
Loop diuretics because the inhibit important transporter NKCC2 (this site handles a large fraction of the filtered load (15-50%)
More distal mechanisms are not able to compensate
102
What are some other actions of Loop diuretics besides decreasing BV?
- Increased loss of K+ and H+
- decreased + potential
- Increase excretion of Ca2+ and Mg2+ in urine
- increased prostaglandins by inducing COX2 expression
- increased excretion of acid and NH4+
103
When you have high doses of furosemide (loop diuretic) and bumetamide (loop diuretic), what can happen?
-can inhibit CA and increase HCO3- excretion
104
Loop diuretics can increase (blank) independent of diuretic activity
blood flow
105
What loop diuretic increases renal blood flow?
furosemide
106
What loop diuretics decrease pulmonary congestion in CHF?
Furosemide and ethacrynic acid
107
Since loop diuretics bind to plasma proteins and access the tubule lumen via organic acid transporters, what happens if other compounds compete for these spots such as NSAIDs or Probenecid or in pnts with renal disease?
may have to increase the dose of the loop diuretic
108
What are the clinical uses of loop or "high-ceiling" diuretics?
1. edema-related
| 2. electrolyte or drug-related
109
What are the edema related situations you should give loop diuretics for?
- Emergency situations of acute pulmonary edema
- CHF, acute renal failure, nephrotic syndrome, hepatic cirrhosis particularly when refractory to less efficacious diuretics
110
What are the electrolyte or drug-related situations you should give loop diuretics for?
- acute hypercalcemia
- hyperkalemia
- useful for anion overdose (Br-, Fl-, I-) in addition to saline
111
What can torsemide do that is special?
can decrease BP without diuresis (useful for mild to moderate HTN)
112
What are the adverse effects of loop diuretics?
-ototoxicity and transient deafness
-diabetogenic (furosemide and bumetanide)
-compete for binding to serum proteins with drugs, such as warfarin and clofibrate
-reduced clearance of Li+
-Due to competition for binding to organic acid transporter can have:
increased nephrotoxicity w/ cephalosporins
increased ototoxicity with aminoglycosides antibiotics
increased salicylate toxicity
-Hyperuricemia (due to increased reabsorption of uric acid in proximal tubule caused by decreased vascular volume)
-hypomagnesemia
-severe vascular volume decrease
-hyponatremia if pnt drinks too much water
-can increase LDL and TAG levels
113
What are the contraindications for loop or "high-ceiling" diuretics?
- severe Na+ and volume depletion
| - hypersensitivity to sulfonamides (for sulfonamide-based loop diuretics)
114
How do thiazide diuretics work? In what conditions are thiazide diuretics effective?
- produce diuresis with increased Cl-.
| - In both acidic and alkaline conditions
115
High concentrations of some thiazides inhibit (blank) which lead to increased loss of (blank)
CA
| HCO3-
116
T or F
All thiazides have similar pharmacological actions but differ in duration of action, extent of CA inhibition, maximally effective dose, binding to serum proteins.
T
117
Thiazide diuretics enter the nephron via the (blank). Also they compete with (blank) and can cause an increase in these levels.
organic acid transporter
| Uric acid
118
What is the mechanism of action of thiazides?
inhibit Na and Cl in urine (NCC) in the distale tubule-> which results in increase in Na+ and Cl- in urine
119
The actions of thiazies depend partly on an increase in (blank) in the kidney
prostaglandinsq
120
Are thiazide strong or weak diuretics and why?
weak because they work on the distal tubule where only 5% of filtered Na+ is reabsorbed where they act
121
What are the effects of thiazide diuretics on calcium?
Increases Na+/Ca2+ exchange -> Increased reabsorption of Ca2+
122
Thiazide diuretics cause less distortion of the (blank) since they cause a modest diuresis and affect the excretion of several ionic species.
ECF
123
What are the clinical uses of thiazide diuretics?
- Treat edema associated with CHF, hepatic cirrhosis, PMS
- HTN (actions involve direct effects on vascular SM)
- Ca2+ nephrolithiasis
- Bromide intoxication
- Diabetes insipidus
124
What are the adverse effects of thiazide diuretics?
- Increassed cholesterol (5-15% - transient) & LDL
- Hypokalemia with prolonged therapy
- Associated with arrhythmias
- Hyperglycemia
- Hypokalemic metabolic alkalosis
- Hyperuricemia
- Hyponatremia
125
What are the contraindications of thiazide diuretics?
- Patients hypersensitive to sulfonamides
| - Effectiveness reduced by NSAIDs
126
Whats the difference b/w thiazides and thiazide-like diuretics?
Chemically similar to thiazides but do not inhibit CA
127
What is this:
- A thiazide-like diuretic
- anti-hypertensive actions independent of diuretic activity
- used with loop diuretics in cases of renal failure
Indapamide
128
What is this:
- A thiazide-like diuretic
- Efficacious & can be given in combination with a loop diuretic
- Can be effective with renal insufficiency
Metolazone
129
Why can you get hypokalemia with thiazide like diuretics?
| Why is this important?
-K+ and H+ exchanged for Na+ in the distal nephron
-because hypokalemia can cause:
EKG abnormalities
Cardiac arrhythmias
Muscular weakness
Drowsiness
Confusion
Loss of sensation
Increased binding of cardiac glycosides
130
What is an example of an aldosterone antagonist?
spironolactone (structural analog of aldosterone)
131
What does spironolactone turn into after first pass in the liver? What does this do?
into canrenone which is an active metabolite
-Competitively blocks binding of aldosterone to its receptor
(aldosterone must be present for these drugs to be effective)
132
What are the clinical uses of aldosterone antagonists?
- Primary and secondary hyper-aldosteronism
- Hypokalemia
- Given with other diuretics used to treat hypertension & CHF
- CHF
- Cirrhosis of the liver & nephrotic syndrome
- To avoid excessive loss of K+
133
T or F
| Spironolactone found to have significant benefit independent of its diuretic effects
T
134
What are the adverse effects of Aldosterone Antagonists (potassium sparing diuretics)?
- Hyperkalemia
- Can increase serum Li+
- Metabolism of cardiac glycosides
- Reversible gynecomastia in males
- Tumorigenic in rats
- Hyperchloremic metabolic acidosis (due to decrease H+ secretion)
135
What are some potassium sparing diuretics that are non-aldosterone antagonists?
How do they enter the nephron?
- Triamterene, Amiloride
| - Organic base transporter
136
What is the mechanisms of action of triamterene,amiloride (non-aldosterone antagonists that are potassium sparing diuretics)?
Inhibits the sodium channel in principle cells (ENaC)
137
What is the overall effect of non-aldosterone antagonists?
In the blood:
- Increase Potassium
- Decreased sodium
- Increased NH4+
138
What are the clinical uses of non aldosterone potassium sparing diuretics?
- Used in combination with other diuretics to decrease K+ loss when treating edemas associated with CHF, cirrhosis of the liver, etc.
- Amiloride has antihypertensive effects that are additive with those of the thiazides
139
What are the adverse effects of non aldosterone potassium sparing diuretics?
Hyperkalemia
| Decreased effects of cardiac glycosides
140
What are the adverse effects of Triamterene?
- Increase uric acid and increase chance of gout
- inhibit dihydrofolate reductase and cause megaloblastic anemia if pnt has cirrhosis of liver
- has a low solubility and can precipitate in urine and cause stones
141
What are four edematous conditions?
CHF
Hepatic cirrhosis and ascites
Pulmonary edema
Cerebral edema
142
How do you treat CHF?
thiazides, loop diuretics and aldosterone antagonists
143
How do you treat Hepatic cirrhosis and ascites?
-treat with thiazide, loop and K+ sparing diuretics
144
How do you treat pulmonary edema?
Treat aggressively with loop diuretics
145
How do you treat cerebral edema?
Treat with osmotic diuretics for direct effects
146
How do you treat nephrotic syndrome?
How do you treat acute renal failure?
How do you treat chronic renal failure?
w/ thiazide diuretics and decreased salt intake
use osmotic diuretics or loop diuretics
treat aggressively with loop diuretics
147
How do you treat HTN?
- Treat with decreased salt intake
| - Add thiazides, can also add K+ sparing or loop diuretics
148
How do you treat nephrolithiasis?
- treat with thiazides to increase calcium reabsorption
| - decrease salt intake
149
How do you treat hypercalcemia?
- treat with loop diuretics to increase calcium excretion
| - add normal saline to prevent contraction of extracellular space, can add K+ sparing diuretics as needed
150
How do you treat nephrogenic diabetes insipidus?
Treat with thiazide or loop diuretics to reduce plasma volume and contract the extracellular space
151
What is diabetes inspidius and how do you treat it (any type)?
polyuria due to decrease ADH
-treat with thiazides or loop diuretics (paradoxically) which cause salt depletion and contraction of ECF-> which leads to proximal tubule reabsorption of Na+ and decrease volume of fluid reaching the distal tubule.
SO it works by creating a reflexive state to absorb water
152
What are the 2 types of diabetes insipidus (DI)?
- Central DI
| - Nephrogenic DI
153
What type of DI is this:
| decreased ADH levels due to injury, tumors or infection
Central DI
154
How do you treat central DI?
```
arginine vasopressin (AVP=ADH)
Vasopressin analogs (desmopression and lypressin)
-chlorprpamide, a sulfonylurea, which increases actions of ADH
```
155
What is nephrogenic DI?
decreased ADH responsiveness due to hypercalcemia, hypokalemia, post-obstructive renal failure, lithium
156
What is the treatment for nephrogenic DI?
-ADD thiazides
-Amiloride (blocks Li)
-NSAIDs i.e indomethacin
(decrease prostaglandin synthesis-> increase response to ADH)
157
What is SIADH?
syndrome of inappropriate secretion of ADH= too much ADH
158
How do you treat SIADH?
loop diuretics (decrease ability to concentrate urine)
DEMECLOCYCLINE (cant use with liver dysfunction)
Vaptans
Lithium (not commonly used, it can damage kidneys)
159
How does demeclocycline work?
a tetracycline that decreases actions of ADH
