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Diuretics Pharmacology Flashcards

1
Q

What part of the nephron do CA inhibitors act on?

A

PT

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2
Q

CA inhibitors MOA

A

Inhibition of CA causes bicarbonate excretion to go up. Being alkaline, makes urine basic.

Enhanced Cl- reabsorption that results in acidosis

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3
Q

What are the major clinical uses for CA inhibitors?

A

To alkalinize urine in cysteinuria
To reduce intraocular pressure
Manage seizures
Give prohpx for mountain sickness

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4
Q

What is the one CA inhibitor named?

A

Acetazolamide

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5
Q

What are the side effects of acetazolamide?

A

Metabolic acidosis

K+ loss in urine acutely that goes away

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6
Q

MOA of osmotic diuretics

A

PCT: isoosmotic so not reabsorbed, and it retains water (minor effect)

LOH: wipes out hypertonicity of medulla by increasing medullary blood flow; results in less water reabsorbed in DLH

(Change renal hemodynamics resulting in less water reabsorption in TDLH)

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7
Q

Effects of osmotic diuretics on LOH

A

Extract water from tissues
Decrease blood viscosity
Inc medullary renal flow, reduce tonicity

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8
Q

What is an example of an osmotic diuretic?

A

Mannitol

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9
Q

What are the side effects of mannitol?

A 
Volume overload (bc large dose and osmolarity up)
Contraindicated in cardiac failure
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10
Q

Do osmotic diuretics cause more free water excretion?

A

yes

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11
Q

What are osmotic diuretics still used for?

A

Dialysis disequilibrium
Reduce intracranial pressure
Reduce intraocular pressure

These effects are very immediate

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12
Q

MOA of Loop diuretics

A 
Inhibit Na/K/2Cl symporter in TALH
Causes MD to inc filtration by blocking it from sensing Na (uses NaKCl transporter to)
Up biosynthesis of prostaglandins
Inc total RBF
Maintain GFR
Renin secretion increases
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13
Q

Do loop diuretics affect the urine concentrating ability?

A

Yes, decrease ability to concentrate

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14
Q

How do loop diuretics affect the filtration fraction?

A

Increase by about 5%

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15
Q

What about prostaglandins and loop diuretics

A

More prostaglandins made which increase blood flow to kidneys

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16
Q

How to loop diuretics change the afferent artery?

A

Decrease resistance to inc GFR

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17
Q

How do loop diuretics contribute to renin release?

A

Inhibiting the macula densa
Activating SNS
Stimulating intrarenal bareoreceptors

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18
Q

Loop diuretics increase excretion of which ions?

A 
NaCL
K
H
Ca
Mg
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19
Q

Which kind of diuretic is the most potent NaCL mobilizer and diuresis inducer?

A

Loop diuretics

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20
Q

What are the therapeutic uses for loop diuretics?

A

Edema, inc. cardiac, hepatic, renal, pulmonary
Hypercalcemia
Protect against renal failure (esp post-op)
Wash out toxins

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21
Q

Where does furosemide enter the nephron?

A

Secreted in by proximal tubule

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22
Q

Why does furosemide have a high therapeutic window?

A

In renal disease patients, PCT secretions are reduced so you can give a lot more of drug

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23
Q

Why do you need to make sure that people on loop diuretics stay well hydrated?

A

So they don’t form kidney stones of Ca from increased urinary excretion

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24
Q

What kind of vascular changes does furosemide cause?

A

Venodilation somehow

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25
What are the side effects of furosemide?
``` Hypokalemia - give supplement pH disorders esp alkalosis BUN up Hyperglycemia Hyperuricemia Ototoxicity and sialadentitis ```
26
What are some major drug interactions of furosemide?
Li+ urinary excretion Indomethacin - prostaglandin inhibitor Probenecid - inhibits furosemide secretions Warfarin - compete for protein binding
27
What are the three loop diuretics
Furosemide Bumetanide Torsemide
28
Which is most potent loop diuretic?
Bumetanide
29
How do loop diuretics cause hypokalemia?
Increased distal sodium delivery causes lots of reabsorption in distal CT and CD, making a steep gradient for K+ to be secreted into (-) lumen
30
Thiazide diuretics MOA
Inhibit NaCl reabsorption in Na/K aldosterone-independent segment of distal tubule
31
Which diuretics are used chronically?
Thiazides
32
What ions do thiazide diuretics affect?
Increase Mg excretion | Decrease Ca excretion (unlike loops)
33
What are the uses for thiazides?
``` Edema from CHF, cirrhosis, nephrotic Hypercalciurea/calcium stones Reduce blood pressure Augment antihypertensives Osteoporosis - dec urine calcium Nephrogenic DI ```
34
Why are thiazides used in HT?
Unknown how, but they are vasodilators
35
What is the difference between class I and II diuretics?
Class I - use when GFR > 50 mL Class II - use when GFR between 50-30
36
What are the Class I thiazides?
Hydrochlorothiazide Clorthalidone Quinethazone
37
What are the Class II thiazides?
Metolazone | Indapamide
38
What are the aldosterone antagonists?
Spironolactone | Eplenerone
39
Are aldosterone antagonists K sparing or wasting?
Sparing
40
Spironolactone PK
pro-drug extensively metabolized
41
Side effects of spironolactone
Hyperkalemia | Gynecomastia, hirsutism, uterine bleeding
42
Clinical uses for aldosterone antagonists
Think CHF! Also cirrhosis
43
Why is eplenerone better than spironolactone?
Much more mild side effects
44
What do aldosterone antagonists do to ion levels?
Increase Na excretion | Decrease K excretion
45
What are the K-sparing diuretics (class)?
Triamterene | Amiloride
46
What are the side effects of K sparing?
Hyperkalemia | Megaloblastic anemia in pts with cirrhosis
47
What is MOA of K sparing
Inhibit Na reabsorption in late distal tubule
48
Where does ANP act?
Induces guanylyl cyclase to make cGMP, which inhibits Na reabsorption
49
What is the ANP drug?
Nesiritide
50
Nesiritide MOA for Na excretion
Inhibits CNG nonspecific cation channel in CD | Inhibits RAAS
51
Why is nesiritide useful in CHF?
Decreases systemic vascular resistance through NO production Decreases LV filling pressure Increase cardiac output
52
What is the best combo for hypertension?
Diuretics with ACE inhibitors
53
What diuretic would you give to someone with mild to moderate hypertension?
Thiazide
54
When would you absolutely need to use a loop diuretic instead of another in terms of GFR?
GFR below 30
55
What diuretic would you give to someone with severe hypertension who doesn't respond to thiazides?
Loop diuretics
56
What would you give to someone who has acute pulmonary edema or a hypertensive crisis?
Furosdemide
57
What drug class should patients avoid while using loop diuretics?
NSAIDs
58
What diuretic would you give to a patient with hyperuricemia?
K sparing or aldosterone antagonist
59
What diuretic would you give to a patient with cirrhosis?
Spironolactone
60
Are thiazides or K-sparing diuretics more useful for antihypertensives?
Equally useful PUNK'D
61
Where are V1 receptors found?
Vascular smooth muscle
62
What does AVP do when it binds to V1?
PLC cascade that causes vasoconstriction
63
Where are V1 receptors found?
Principal cells in collecting ducts
64
What type of cascade is coupled to the V2 receptor?
GS GPCR cascade that causes PKA phosphorylation of AQP2, resulting in translocation to apical membrane
65
What are the V1-receptor agonists?
vasopressin (discontinued) | terlipressin
66
Why do you use V1 receptor agonists
GI and vascular smooth muscle contraction
67
What are the clinical uses for V1 agonists
Post-op ileus | Reduce bleeding during acute hemorrhagic gastritis
68
What are the causes of diabetes insipidus
Inadequate AVP secretion (central) | Insufficient kidney response to AVP (nephrogenic)
69
How can you distinguish between nephrogenic DI and central DI?
Give a V2R agonist (desmopressin) and see if urine osmolarity increases. If it does, they have central. If not, nephrogenic.
70
What is the most common causes of central DI?
Head injury, CNS ischemia, tumors, V2R gene mutations
71
How are thiazide diuretics helpful in DI?
Cause mild depletion of EC water and Na, activating renal compensation to increase reabsorption in PCT. Reduces volume delivered to distal tubule.
72
What are the three drug classes that can cause SIADH?
Psychotropics Sulfonylureas Vinca alkyloids
73
How are V2 receptors targeted in SIADH patients
Demeclocycline which antagonists V2R
74
What are the selective V2R antagonists?
Tolvaptan | Conivaptan
75
What is the black box warning for V2R antagonists?
Can only be used in a hospital setting

OS Renal (25 decks)

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