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Diuretics Flashcards

1
Q

MOA of Mannitol

A

filtered into tubular space and significantly increases osmolarity resulting in impairment of fluid reabsorption (and some Na+)

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2
Q

Nephron segments that mannitol acts on

A

Segments permeable to water: PCT, descending limp of Henle, and CT (w/ADH)

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3
Q

Route of administration of mannitol

A

IV (not orally absorbed)

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4
Q

Adverse effects of mannitol

A

increases plasma osmolarity (esp. with decreased GFR), if mannitol is in ECF it moves water out of cells and can worsen heart failure, hyponatremia

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5
Q

Contraindications of mannitol

A

CHF, chronic renal failure, acute pulm. edema

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6
Q

Indications of mannitol

A

Acute renal faillure, intracranial pressure, intraocular pressure (assuming BBB is intact), promote renal excretion of toxic substances

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7
Q

Name the 4 drugs in the carbonic anahydrase inhibitor class

A

acetazolamide, dichlorphenamide, methazolamide, dorzolamide

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8
Q

MOA of acetazolamide

A

CA inhibitor - blocks the reabsorption of HCO3 in the PCT

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9
Q

MOA of dichlorphenamide

A

CA inhibitor - blocks the reabsorption of HCO3 in the PCT

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10
Q

MOA of methazolamide

A

CA inhibitor - blocks the reabsorption of HCO3 in the PCT

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11
Q

MOA of dorzolamide

A

CA inhibitor - blocks the reabsorption of HCO3 in the PCT

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12
Q

Adverse effects of CA inhibitors

A

METABOLIC ACIDOSIS (due to loss of HCO3), and HYPOKALEMIA (due to increased Na+ in the lumen that gets exchanged with K+ in the CT), Ca2+ phosphate stones (due to alkalination of tubular fluid), drowsiness, paresthesias, hypersensitivity rxn

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13
Q

Contraindication of CA inhibitors

A

HEPATIC CIRROHOIS (due to increased urine pH leading to decreased NH3 secretions leading to increase NH3 in the serum –> hyperammonemia –> encephalopaties)

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14
Q

Indications of CA inhibitors

A

glaucoma, increased CNS pressure, therapeutic alkalination of the urine (ion trapping in drug ODs), altitude sickness (Bohr effect)

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15
Q

Rank the potency of the various CA inhibitors

A

Acetazolamide (x), Methazolamide (5x), dichlorphenamide (30x)

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16
Q

Which CA is used for topical prep for ocular use

A

Dorzolamide

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17
Q

What is the MOA of furosemide

A

(loop diuretic) blocks the Na+/K+/2Cl- co-transporter

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18
Q

What is the MOA of bumetanide

A

(loop diuretic) blocks the Na+/K+/2Cl- co-transporter

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19
Q

What is the MOA of torsemide

A

(loop diuretic) blocks the Na+/K+/2Cl- co-transporter

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20
Q

What is the MOA of ethacrynic acid

A

(loop diuretic) blocks the Na+/K+/2Cl- co-transporter

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21
Q

Besides causing diuresis what other therapeutic effect do the loop diuretics have

A

dilation of the venous system (renal vasodilation) mediated by PGs (improves RBF)

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22
Q

What portion of the nephron do the loop diuretics affect

A

Thick ascending loop of Henle

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23
Q

How are the loop diuretics secreted into the nephron

A

organic Acid transporter

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24
Q

Adverse effects of the loop diuretics

A

hyponatremia, HYPOKALEMIA, Ca2+ and Mg2+ depletion, METABOLIC ACIDOSIS, OTOTOXICITY, mild hyperglycemia

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25
Contraindications of the loop diuretics
patients susceptible to hypokalemia, patients of digoxin
26
Indication for the loop diuretics
ACUTE pulm edema, edema with CHF, acute hypercalcemia, hyperkalemia, hypertension
27
What loop diuretic drug can you use for a patient that has a hypersensitivity rxn to other loop diuretics
Ethacrynic acid (last resort as it has nepho and ototoxicity)
28
What is the most efficacious diuretic that can cause up to 20% excretion of filtered Na+
Loop diuretics
29
What is the MOA of the thiazides and thiazide-like drugs
inhibit the Na+/Cl- co-transporter in the distal convoluted tubule (cortical TAL and early distal tubule)
30
What are the thiazide-like drugs
Metolazone, indapamide, and chlorthalidone
31
Rank the order of half lives of the loop diuretics
Bumetanide (1hr)
32
Which loop diuretic is the most potent
Bumetanide is 40x the potency of Furosemide
33
What is the most commonly prescribed class of diuretics
Thiazides: because they are milder than loop diuretics and have a longer duration of action
34
What conditions will decrease the bioavailability of the thiazides
renal disease, hepatic disease, and CHF
35
Adverse effects of the thiazides
hyponatremia, HYPOKALEMIA, dehydration, METABOLIC ALKALOSIS, hyperuricemia, HYPERGLYCEMIA (linked to hypokalemia), HYPERLIPIDEMIA, weakness, fatigue, paresthesia, hypersen. rxn
36
Contraindications of the thiazides
patient susceptible to hypokalemia
37
Indications of the thiazides
hypertension, CHF, nephrotic syndrome and other Na+ retaining states, used to reduce tubular Ca2+ conc to prevent kidney stones
38
What other electrolyte is decreased in the tubular fluid with the thiazides
Ca2+ (since the Na+/Cl- co-transporter on the apical side is blocked the cell becomes deficient in Na+ and therefore the activity of the Na+/Ca2+- co-transporter on the basolateral is increased, resulting in more Ca2+ transported out of the lumen and out of the cell on the basolateral side)
39
Rank the potency of the thiazides and the thiazide-like diuretics
Chlorothiazide (0.1x), Hydrochlorothiazide (x), cholthalidone (x), metolazone (10x), and indapamide (20x)
40
Which distal nephron diuretic can be efficacious in patients with sever renal insufficiency (can also be given in combo with loop diuretics)
Metolazone
41
What condition will cause the thiazides to be relatively ineffective
Renal insufficiency (decreased GFR --> less fluid reaches the DT --> impact of thiazides)
42
Rank the half lives of the thiazides/ thiazide-like diuretics
Chlorothiazide (1.5hr) , Metolazone (4-5hrs), Indapamide (10-22hrs), Chlorthalidone (44hrs)
43
What is the MOA of spironolactone
competitive antagonist of aldosterone (binds to the cytosolic MR in principal cells and blocks aldosterone action of up regulating Na+/K+ pump and the H+ efflux pump in the intercalcated cells)
44
What is the net effect of spironolactone on electrolytes in the DCT and CT
Decreases Na+ (and water) reabsorption, and increased K+ and H+ reabsorption (Potassium sparing diuretic)
45
PK of spironolactone
takes up to 2 day to be effective. Half life of 20hrs. Taken orally
46
Contraindications of spironolactone
HYPERKALEMIA
47
Adverse effects of spironolactone
Hyperkalemia, metabolic acidosis, gynecomastia, amenorrhea
48
Indications for spironolactone
LIVER CIRRHOSIS, patients with increased plasma levels of aldosterone, HTN w/ thiazides or loop diuretics
49
MOA of epleronone
competitive antagonist of aldosterone (Potassium sparing diuretic)
50
Major differences between spironolaction and epleronone
Epleronone does not cross react with androgen receipts and does not cause gynecomastia but is more expensive
51
What drugs should NOT be co-administered with spironolactone
Any drugs that might also cause hyperkalemia: ACE INHIBITORS, K+ supplements, renin inhibitors, NSAIDs, etc)
52
In what disease states should spironolactone be avoided
Any disease states that could cause hyperkalemia: diabetes mellitus, multiple myeloma, renal insufficiency
53
What is the MOA of amiloride
blocks the Na+ channels in the apical membrane of the late distal tubule and CT (potassium sparing diuretic)
54
What is the net effect of amiloride on the electrochemical gradient in the tubule
By blocking the Na+ channel the cells in the DT and CT become more negative and therefore attract more K+ and more H+ into the cell leading to increased reabsorption (potassium sparing diuretic) - relatively weak diuretic
55
What is the MOA of triameterene
blocks the Na+ channels in the apical membrane of the late distal tubule and CT (potassium sparing diuretic) - relatively weak diuretic
56
What are the half lives of amiloride and triameterene
21 hours and 4 hours respectively
57
How are amiloride and trimeterene secreted into the nephron
secreted in the PCT via the organic base transporter
58
What are the adverse effects of amiloride and triameterene
HYPERKALEMIA, metabolic acidosis, nausa, vomiting, hyponatremia
59
Indications for amiloride and trimeterene
edema, usually given with another diuretic (often with thiazide or loop diuretic - combo and normalize K+ excretion)
60
Contraindications of amiloride and trimeterene
HYPERKALEMIA, same as other K+ sparing diuretics avoid giving with disease conditions or drugs that can cause hyperkalemia)
61
MOA of Demeclocycline in diuretic context
inhibits ADH in the CT (tetracycline ABX)
62
Toxicity of Demeclocycline
Nephrotoxic
63
MOA of Lithium in diuretic context
inhibits ADH in the CT (Psych drug for mania)
64
Toxicity of Lithium
Nephrotoxic
65
MOA of tolvaptan
V2 vasopressin (ADH) receptor antagonist
66
MOA of conivaptan
V1a and V2 vassopressin (ADH) receptor antagonist
67
MOA of mozavaptan
V2 vasopressin (ADH) receptor antagonist
68
Indication for conivaptan
IV for euvolemic hyponatremia
69
Adverse effects of V2 vasopressin receptor antagonists
hypernatremia, thirst, dry mouth, hypotension, dizziness
70
Indications for the V2 vasopressin receptor antagonists
SIADH euvolemic or hypervolemic hyponatremia, CHF
71
Physiological effect of V2 vasopressin receptor antagonists
induces increased dose-dependent production of dilute urine
72
What diuretic is indicated for hepatic cirrhois
spironolactone
73
Which thiazide/thiazide like drug is metabolized extensively by the liver
indapamide

Block 4 Pharm (9 decks)

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