Pharm 8- Diuretics Flashcards
What are some common uses for diuretics?
CHF Hepatic Ascites Nephrotic Syndrome HTN
How does hepatic ascites occur?
Advanced liver disease; increased portal vein pressure, liver sweats fluid produces proteins like albumin. COP goes down and fluid not held inside intravascular space as well
Nephrotic Syndrome
Too much protein release in the urine, results in lots of edema; aldosterone retains sodium as a reflex
What are the 4 categories of diuretics?
- Carbonic anhydrase inhibitors 2. Loop diuretics 3. Thiazide diuretics 4. Potassium-Sparing Diuretics
How do carbonic anhydrase inhibitors work?
Inhibit carbonic anhydrase in the proximal tubule epithelium; catalyzes reaction: Co2+H2O -> H2Co2(carbonic acid) -> Bicarb + H+ Shift equation to the right and bicarb accumulates in the urine; sodium less able to be exchanged for H+ in the tubules so H+ is retained while Na+ is lost (w/ bicarb)
What is an example of a carbonic anhydrase inhibitor?
Acetazolamide (Diamox)
Why is Acetazolamide (Diamox) rarely used in cardiovascular surgery?
Doesn’t produce a whole lot of urine; causes metabolic acidosis and we are already worried about our patients being acidotic on bypass
What conditions does acetazolamide (Diamox) commonly treat?
Acute Mountain Sickness Glaucoma (decreases intra-ocular pressure)
Why are carbonic anhydrase inhibitors useful for trapping chemicals?
Urine is alkalized (release bicarb) The higher pH favors A- and B; therefore acids get trapped.
Where do loop diuretics act on?
Ascending loop of henle
Other names for Loop diuretics?
Non-potassium sparing High ceiling diuretics Yellow Zipper drugs (humans) Waiting Room Puddle drugs (animals) “Chemical hemoconcentrator”
Why are loop diuretics called high ceiling diuretics?
The dose-response curve is close to linear (that is, there is no ceiling)
How do loop diuretics work?
Block co-transport of Na+/K+/2Cl- from the tubular lumen back into circulation; so much NaCl is not reabsorbed that downstream nephron sites cannot compensate for that loss Increase RBF by inducing expression COX-2
What is the most efficacious of all the diuretics?
Loop Diuretics
How fast do loop diuretics work?
Within minutes when given IV
COX-2
“Ungood” cyclooxygenase NSAIDS preferentially blocked in inflamed tissues
What do cyclooxygenases do?
Help produce protaglandins which are powerful vasodilators of renal arteries
Why would NSAIDs interfere with loop diuretics?
Interferes in compromised patients (hepatic cirrhosis, nephrotic syndrome) because NSAIDS block COX (reduces vasodilation) and loop diuretics work to induce COX (increase vasodilation, increase RBF)
What is the #1 choice diuretic for edema in emergency situations?
Loop Diuretics; fast-acting, efficacious Pulmonary edema from decompensated CHF
What else might Loop Diuretics treat?
Hypercalcemia Hyperkalemia
What are some causes of hypercalcemia?
Endocrine Malignancy Granulomatous Diseases Miscellaneous
What are some Perfusion Uses of Loop Diuretics?
- Rid of extra fluid (chemical hemoconcentrators) 2. Get rid of excess K+ 3. Maintain urine production/ renal function
What does recent evidence suggest in regards to loop diuretics and urine?
Giving loop diuretics simply to keep urine flowing and thus “help” the kidneys is not appropriate and maybe deleterious in the long run
What are the side effects of loop diuretics? Since they are predictable
- Ototoxicity (particularly w. aminoglycoside antibiotics) 2. Hypotension 3. Hypomangesemia 4. Hyperuricemia 5. Hypokalemia
What are the two commonly used loop diuretics?
Furosemide (Lasix) Ethacrynic acid (Edecrin)
What are some of the advantages to using Furosemide (Lasix)?
Inexpensive has been used forever wide margin of safety/therapeutic window therefore the potential for using often 2 hour duration of action when given IV on pump
What is the duration of action of Furosemide (Lasix)?
2 hour duration of action when given IV on pump
What is the typical adult pump dose of Furosemide?
2.5-5.0 mg (20-40 mg bolus if the patient is receiving chronic diuretic therapy)
Why isn’t ethacrynic acid (edecrin) used as often as furosemide (lasix)?
Greater potential for ototoxicity
What are two of the less common diuretics that are used?
Bumetanide (Bumex) Torsemide (Demadex)
When are the two less common diuretics used?
“Physician’s preference” When desired response is not achieved by furosemide (lasix)
Where do thiazide diuretics act?
Act on the cortical region of the ascending loop of henle
What is another name for thiazide diuretics?
Non-potassium sparing Ceiling Diuretics (because of their “flattening” dose/response curve
How do thiazide diuretics work?
Block Na+/Cl- transport/reabsorption on the luminal side of the thick part of the ascending loop of henle and the distal convoluted tubule NaCl concentrates in the tubular fluid and water follows increasing urine production
Why would thiazides lose efficacy in patients with decreased renal function?
Thiazides must actually get into the tubular lumens via renal excretion since they work on the luminal side of the thick part of the ascending loop of henle; with decreased renal function there would be decreased renal excretion
How do thiazides increase renal blood flow?
COX-2 Inducement of prostaglandin synthesis
What are thiazides structurally related to?
Acetazolamide; but causes much more diuresis
What is the only thiazide available for parenteral use (that we can use on bypass)?
Chlorothiazide
What was the original diuretic used for edema?
Chlorothiazide
What is the typical adult pump dose of chorothiazide?
500mg
What are the perfusion uses of thiazide diuretics?
Gets ride of edema (fluid) and potassium decreases SVR due to relaxation of arteriolar smooth muscle Second Line treatments (after loops) for edema of CHF Causes hyperosmolar urine used in diabetes
What sets thiazides apart from the other diuretics?
Promotes the reabsoprtion of calcium; long-term results compared to loops result in significantly less decrease in bone density (hip fractures) decreased by 1/3
What diuretic is used in diabetes insipidus and why?
Thiazide diuretics; cause the production of hyperosmolar urine
Diabetes insipidus
kidneys are unable to conserve water, producing a large amount of dilute urine
What are some examples of thiazide diuretics?
Chlorothiazide (Diuril) Hydrochlorothizide (HCTZ, Microzide)
How is HCTZ (Microzide) different from chlorothizide (Diuril)?
HCTZ is more potent but has the same efficacy and is not given parenterally
How is HCTZ used to tx HTN?
Used in fixed combinations for the treatment of HTN; Hyzaar = HCTZ + Losartan (ACE blocker)
What are some thiazide-like diuretics?
Chlorthalidone (Hygroton) Indapamide (Lozol) Metolazone (Zaroxolyn)
Which thiazide-like diuretic is commonly used to treat HTN?
Chlorthalidone (Hygroton)
Which thiazide-like diuretic is partially excreted by the GI tract, so useful in advanced renal failure?
Indapamide (Lozol)
Where do potassium-sparing diuretics function?
In the collecting tubules (ducts) to prevent Na+ reabsorption and K+ excretion
What do potassium-sparing diuretics do?
Antagonize aldosterone
How are potassium-sparing diuretics typically used to treat HTN?
In combination with diuril or hydrochlorothiazide
How does the efficacy of potassium-sparing diuretics compare to the efficacy of non-potassium-sparing diuretics?
Potassium-sparing diuretics are signficantly less efficacious than its non-potassium sparing alternatives
In what patients might potassium-sparing diuretics present a problem?
Problematic in patients with hyperkalemia; such as patients with polycystic kidney disease
What are the two types of potassium sparing diuretics?
Direct Aldosterone Antagonists Indirect Aldosterone Antagonists
What are some direct aldosterone antagonists?
Spironolactone (Aldactone) Eplerenone (Inspra)
What do direct aldosterone antagonists resemble chemically?
Sex steroids
What drugs are used as an adjunctive therapy in heart failure? Why?
Direct Aldosterone Antagonist (Potassium sparing diuretic); statistically decreases mortality and helps prevent pathological remodeling of the heart
What is the diuretic of choice for liver failure patients with edema?
Spironolactone (Aldactone) (Direct aldosterone antagonist/Potassium-sparing diuretic)
Cushing’s Disease
Too much adrenal function
Addison’s Disease
Not producing aldosterone; hypoadrenocortisone
What patient population would direct aldosterone antagonists not be effective in?
Addison’s Disease because they are not producing enough aldosterone; therefore, a non-direct aldosterone antagonist would be much more benficial
How do indirect acting aldosterone antagonists work?
Block the Na+ transport channels affected by aldosterone rather than aldosterone itself
What are some indirect-acting aldosterone antagonists?
Triamterene (Dyrenium) Amiloride (Midamor)
What are osmotic diuretics?
Small non-metabolized molecules filtered through the glomerulus that osmotically carry water with them
How are osmotic diuretics administered?
Parenterally; because they cause severe diarrhea if given orally
What are some examples of osmotic diuretics?
Mannitol (osmitrol) Urea/Glucose (rarely if ever given)
Where do osmotic diuretics work?
Proximal tubule and the descending loop of henle which permit the free passage of water
How are osmotic diuretics relevant to perfusionists?
Commonly used to draw fluid into the intravascular space and decrease interstitial edema; maintain urine flow following acute renal injury; use to decrease cerebral edema
Why might osmotic diuretics be controversial as far as being used to draw fluid into intravascular space?
mannitol dilutes the blood
In what patient population might mannitol be problematic?
In patients with oliguric/anuric renal failure (Lookup why….?)
Describe the test dose that should be given with osmotic diuretics (Mannitol)
If urine output is <50ml/hour for three hours after a 12.5 gram IV dose; AVOID.
What is mannitol (osmitrol) categorized as?
A small molecule categorized as a “sugar alcohol;” familiar cousins xylitol and sorbitol
What percent solution is mannitol usually supplied in?
20% solutions 20g/ 100ml
What is Rule #1 when giving mannitol?
Check the bag/bottle for precipitated crystals!!
What is important about the administration of mannitol when relating to perfusion?
Excreted (not metabolized) within one hour, so repeat doses can be given. Must be given slow IV or profound transient hypotension will occur due to skeletal muscle vasodilation
What would happen if mannitol is not given slow IV?
Profound transient hypotension will occur due to skeletal muscle vasodilation
What is the typical adult CPB prime mannitol/ and or intraoperative dose?
12.5-25 grams (but not standard, some give more some give less)
What type of diuretic does this represent?
Carbonic Anhydrase (CA) Inhibitor
What type of diuretic does this represent?
Loop Diuretics
What type of diuretic does this represent?
Thiazide diuretics
What type of diuretic does this represent?
Potassium-sparing diuretics
Which type of diuretic works here?
Carbonic Anhydrase Inhibitor (Proximal convoluted tubule)
Osmotic Diuretics (Proximal convolution tubule AND descending loop of Henle)
Which type of diuretic works here?
Loop Diuretics (thick part of ascending loop of Henle)
Which type of diuretic works here?
Thiazides (distal convoluted tubule and luminal side of the ascending loop henle)
Which type of diuretic works here?
Potassium sparing diuretics (Collecting tubule and duct)
