Topic 8 Flashcards by melissa griffith

Carbonic anhydrase inhibitors and adenosine antagonists work on what part of the kidney

proximal convoluted tublule

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Loop diuretics work on what part of the kidney

Thick ascending limb of Henle’s Loop

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Thiazides work on what part of the kidney

cortical region of the Ascending Loop of Henle

Distal convoluted tubule

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K+ sparing and adenosine antagonists work on what part of the kidney

Cortical collecting tubule

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Vasopressin antagonists work on what part of the kidney

Medullary collecting tubule

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Common uses for diuretics include

Congestive heart failure
Hepatic Ascites
Nephrotic Syndrome
HTN

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Diuretic categories include

1) Carbonic Anhydrase Inhibitors
2) “Loop” Diuretics
3) Thiazides
4) Potassium-Sparing Diuretics

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1: Carbonic Anhydrase (CA) Inhibitors Work by

inhibiting carbonic anhydrase in the proximal tubule epithelium
-With CA blocked, the reaction shifts to the right and bicarbonate accumulates in the urine

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Carbonic Anhydrase (CA) Inhibitors: Sodium is less able to be exchanged for H⁺ in the tubules so H⁺ is

retained while Na⁺ is lost (with the bicarbonate).
*Sooo…urine becomes more alkaline, water follows the bicarbonate into the tubules (causing diuresis) and the patient experiences a metabolic acidosis

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Carbonic Anhydrase (CA) Inhibitors: increase urinary excretion of

Na+ (small)
K+ (a lot)
Bicarb (a lot)
volume of urine increases (medium)

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Carbonic Anhydrase (CA) Inhibitors: drug name

Acetazolamide (Diamox)

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Carbonic Anhydrase (CA) Inhibitors: Rarely used in \_\_\_\_\_ but You may see patients on acetazolamide who
have

cardiovascular surgery

glaucoma or high-elevation sicknes

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Carbonic Anhydrase (CA) Inhibitors: Theoretically useful for

“trapping” chemicals in alkalinized urine

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Acetazolamide

(Diamox)

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2: Loop Diuretics act on the

ascending Loop of Henle

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Loop Diuretics are also called

“High Ceiling” diuretics because the dose-response curve is close to linear
Non-Potassium-Sparing

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Loop Diuretics work by

blocking the co-transport of Na⁺/K⁺/2Cl ̄ from the tubular lumen back into circulation.
increase renal blood flow by inducing the expression of COX-2

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Loop Diuretics are the most

efficacious of all diuretics and work incredibly fast

within minutes when given IV

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Loop Diuretics increase urinary excretion of

Na+ (a lot)
K+ (medium)
Ca++ (a lot)
Increases volume of urine (a lot)

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COX-2 is referred to as the

“ungood” cyclooxygenase NSAIDS-preferentially block in inflamed tissues

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Cyclooxygenases help produce

prostaglandins which are powerful vasodilators of renal arteries

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\_\_\_\_\_\_\_\_ may interfere with loop diuretic function in
compromised patients (hepatic cirrhosis, nephrotic syndrome)

NSAID’s

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Loop diuretics are generally the diuretic of choice even in patients with

compromised renal function.

Also useful for hypercalcemia and hyperkalemia.

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Loop Diuretics: *Because they are fast-acting and

incredibly efficacious, Loop Diuretics are the #1 choice for

edema in emergency situations (such as pulmonary edema from decompensated congestive heart failure)

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Loop Diuretics: Perfusion Uses

1) Get rid of extra fluid on bypass (*Chemical hemoconcentrators) 2) Get rid of excess K⁺ 3) Help maintain *urine production/renal function* in low output states on bypass

Loop Diuretics ***Recent evidence suggests giving loop diuretics simply to keep urine flowing and thus ‘help’ the kidneys is

NOT appropriate and may be deleterious in the long run! | *This is still, however, a common practice

Loop diuretics side effect

Ototoxicity particularly when used with aminoglycoside antibiotics

Loop diuretic: drug names

Furosemide (Lasix) Ethacrynic acid (Edecrin) Bumetanide (Bumex) Torsemide (Demadex)

Furosemide

(Lasix)

Ethacrynic acid

(Edecrin)

Furosemide Very commonly used during and

peri-bypass

Furosemide has a _________ therefore the potential for “We always put some lasix in the pump” mentality

Wide margin of safety/therapeutic window

Furosemide duration of action when given IV (on | pump)

~2 hours

Furosemide Typical adult pump dose is

2.5-5.0 mg (20-40 mg bolus if the patient’s receiving chronic diuretic therapy)

Ethacrynic Acid (Edecrin) : ____ commonly used than furosemide

less

What is Like furosemide but greater potential for oxotoxicity

Ethacrynic Acid (Edecrin)

Bumetanide

(Bumex)

Torsemide

(Demadex)

what is like furosemide and ethacrynic acid -Much less frequently used

Bumetanide (Bumex) | Torsemide (Demadex)

what is Generally utilized as “physician’s preference” or when desired response is not achieved by furosemide

Bumetanide (Bumex) | Torsemide (Demadex)

#3: Thiazide Diuretics: Act on the

cortical region of the Ascending Loop of Henle and the distal convoluted tubule

Thiazide Diuretics are also called

“Ceiling Diuretics” because of their “flattening” dose/response curve

Thiazide Diuretics work by

Na⁺/Cl- transport/reabsorption on the luminal side of the thick part of the Ascending Loop of Henle and the Distal Convoluted Tubule.

Thiazide Diuretics causes NaCl to concentrate in the

tubular fluid (and H₂O obediently follows = increased urine production)

Thiazide Diuretics have to actually get into the

tubular lumens via renal excretion...so thiazides lose | efficacy in patients with decreased renal function.

Like “Loops”, thiazides increases renal blood flow through

COX-2 inducement of prostaglandin synthesis

what is structurally related to Acetazolamide, but | cause much more diuresis

thiazide diuretics

what was the original diuretic used for edema

Chlorothiazide (Thiazide diuretic)

what is the only thiazide available for parenteral use

Chlorothiazide

Chlorothiazide adult pump dose

500 mg

Thiazide diuretics are not

potassium sparing

thiazide diuretics increase urinary excretion of... and decrease urinary excretion of...

Increase: Na+, K+, Volume of urine (all same amount) Decrease: Ca++ (small amount)

Thiazide Diuretics: Perfusion Uses

-Like the “Loops” thiazides get rid of extra (edema) fluid and potassium. - decrease SVR due to relaxation of arteriolar smooth muscle -HTN

Thiazides promote the reabsorption of

calcuim

Compared to “Loops”, long-term use results in significantly less decrease in

bone density (hip fractures are decreased by 1/3rd)

Since thiazides can (uniquely) cause the production of | hyperosmolar urine it’s used in

diabetes insipidus

what are the “second-line” treatments (after “Loops” for the edema of heart failure).

thiazide diuretics

Thiazide Diuretics: drug names

Chlorothiazide (Diuril) | Hydrochlorothiazide (HCTZ) (Microzide)

Chlorothiazide

(Diuril)

Hydrochlorothiazide

(HCTZ) (Microzide)

what is Like chlorothiazide except it’s MORE potent but has the SAME efficacy and is NOT given parenterally

Hydrochlorothiazide

Use in fixed combinations for Rx of HTN: | Hyzaar=

HCTZ + Losartan

Thiazide-like Diuretics: drug names

Chlorthalidone (Hygroton) Indapamide (Lozol) Metolazone (Zaroxolyn)

Chlorthalidone

(Hygroton)

Chlorthalidone (Hygroton) is commonly used to treat

HTN

Indapamide

(Lozol)

Indapamide (Lozol) is Partially excreted by the

GI tract, so useful in advanced renal failure

Metolazone

(Zaroxolyn)

#4: Potassium-Sparing Diuretics Function in the

collecting tubules (ducts) to prevent Na⁺ reabsorption and K⁺ excretion

Potassium-Sparing Diuretics Antagonize

aldosterone

GFR stands for

``` “G” = mineralocorticoids (aldosterone) “F” = glucocorticoids (cortisol) “R” = androgens (testosterone precursors) ```

Potassium-Sparing Diuretics Used to treat

HTN, often in combination with chlorothiazide or hydrochlorothiazide

Potassium -Sparing Diuretics are Significantly less _____ than its non-potassium-sparing alternatives

efficacious

Potassium-Sparing Diuretics increase urine production of... and decrease urine production of...

increase: Na+ (small), volume of urine (medium) decrease: K+ (medium)

Potassium-Sparing Diuretics Problematic in patients with

hyperkalemia

Potassium-Sparing Diuretics (Direct Aldosterone Antagonists) drug names

Spironolactone (Aldactone) | Eplerenone (Inspra)

Spironolactone

(Aldactone)

Eplerenone

(Inspra)

Potassium-Sparing Diuretics (Direct Aldosterone Antagonists): Used as adjunctive therapy in

heart failure –Statistically decreases mortality and helps prevent pathological “remodeling” of the heart

Spironolactone is the diuretic of choice for

liver failure patients with edema

Potassium-Sparing Diuretics (Direct Aldosterone Antagonists): Ineffective when used on patients with

Addison’s Disease

Potassium-Sparing Diuretics (Indirect-Acting Aldosterone Antagonists): work by

Blocking the Na⁺ transport channels affected by | aldosterone rather than aldosterone itself.

Potassium-Sparing Diuretics (Indirect-Acting Aldosterone Antagonists): VERY similar to direct aldosterone antagonists except they

can be used in Addison’s Disease patients

Potassium-Sparing Diuretics (Indirect-Acting Aldosterone Antagonists): drug names

Triamterene (Dyrenium) | Amiloride

Triamterene

(Dyrenium)

#5 Osmotic diuretics works by

Small non-metabolized molecules filtered through the glomerulus that osmotically carry water with them

Osmotic Diuretics are given parenterally as they cause

severe diarrhea when given orally

Mannitol very commonly given on bypass or added to the

prime solution

Osmotic diuretics work in the

proximal tubule and the descending Loop of Henle | which permit the free passage of H₂O

Osmotic diuretics are Commonly used to “draw” fluid into the

intravascular space and decrease interstitial edema but... its controversial

Osmotic diuretics are used to maintain urine flow following

acute renal injury

Osmotic diuretics are used to decrease

cerebral edema

Osmotic diuretics are Problematic in patients with

oliguric/anuric renal failure

Osmotic diuretics: When in doubt a “test dose” is given prior to administration. -If urine output is

<50ml/hour for three hours after a 12.5 gram IV dose, AVOID.

Osmotic diuretic drug name

Mannitol (Osmitrol)

Mannitol

(Osmitrol)

Mannitol (Osmitrol) is a

small molecule categorized as a “sugar alcohol”

Mannitol is usually supplied as a

20% solution

RULE #1 when giving mannitol:

Check the bag/bottle for precipitated crystals!!!!

Mannitol is excreted (not metabolized) within

one hour, so repeat doses can be given

Mannitol MUST be given slow IV or what will occur

profound transient hypotension will occur due to skeletal muscle vasodilation

Mannitol Typical adult CPB priming and/or intraoperative dose is

12.5-25 grams