Diuretics Flashcards
two aspects of perfusion think renal function
bad renal function, how its addressed on bypass
PROXIMAL CONVULTED TUBULe diuretics
CARBONIC ANHYDRASE INHIBTORS ADENOSINE ANTAGONIST
thick ascending limb loop of henle drugs diuretics
loop diuretics
distal convoluted tubule diuretics
thiazides
cortical collecting tubule diuretics
K sparing diuretics adenosine antagonists
medullary collecting ducts diuretics
vasopressin antagonists
common uses for diuretiucs
CHF,HEPATIC ASCITES,NEPHROTIC SYNDROME,HTN,
Hepatic ascites
increased portal vein pressure liver starts to sweat fluid. end stage liver failure colloid pressure decreases because of decreased protein. goes into abdomen. think african kids starving
nephrotic syndrome
high aldosterone levels. lose glucose amino acids and proteins. colloid pressure goes down. causes fluid overload
htn
stiff arteries need fluid relief
diuretic categories
carbonic anhydrase inhibitors. loop diuretics, thiazides, potassium sparing diuretics
1: Carbonic Anhydrase (CA) Inhibitors
least important to us not very strong. • *Work by inhibiting carbonic anhydrase in the proximal tubule epithelium
• Carbonic anhydrase catalyzes
• With CA blocked, the reaction shifts to the right and bicarbonate accumulates in the urine.
odium 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 (explain), water follows the bicarbonate into the tubules (causing diuresis) and the patient experiences a metabolic acidosis (explain again).
-Acetazolamide
(Diamox) Carbonic Anhydrase (CA) Inhibitor. Rarely used in cardiovascular surgery (why?) causes metabolic acidosis
-You may see patients on acetazolamide who have glaucoma
…or high-elevation sickness
2: Loop Diuretics
• Act on the ascending Loop of Henle
-Also called “High Ceiling” diuretics because the dose-response curve is close to linear (that is, there’s no “ceiling”)
how loop diuretics work
Loop diuretics work by blocking the co-transport of Na+/K+/2Cl ̄ from the tubular lumen back into circulation.
• So much NaCl is not resorbed that downstream nephron sites cannnot compensate for that loss.
loop diuretics are most
efficacious (what’s this?) of all diuretics and work incredibly fast (within minutes when given IV).
• Called the “yellow zipper” drugs of human medicine (or the “waiting room puddle” drugs in veterinary medicine) work fast. good for bypass
loop diuretics additional mechanism
Loops” also work to increase renal blood flow by inducing the expression of COX-2
• COX-2 is referred to as the “ungood” cyclooxygenase NSAIDS (what’s this?) preferentially block in inflamed tissues
cyclooxygenase produces
prostaglandins which are powerful
vasodilators of renal arteries.
nsaids may
may interfere with loop diuretic function in compromised patients (hepatic cirrhosis, nephrotic syndrome)
loop diuretics doc for
patients w/ renal function. pulmonary edema because they act fast
doc for hypercalcemia and hyperkalamia
loop diuretics
loop diuretics aka
non potassium sparing diuretics
loop diuretics perfusion uses
1) Get rid of extra fluid on bypass (duh!)
*Chemical “hemoconcentrators”
2) Get rid of excess K⁺
What is normal K⁺ again?
3) Help maintain urine production/renal
function (**!!!) in low output states on
bypass (what might these be?) may be deliterious. may be giving lasix when you dont need it like when youre down on flow
sides of loops
hypotension,hyperuricemia, hypokalemia,hypomagnesemia,ototoxicity (aminoglycoside antibiotics)
furosemide
lasix. • Very commonly used during and peri-bypass.
• Very inexpensive
• Has been used forever
• Wide margin of safety/therapeutic window
therefore the potential for “We always put
some lasix in the pump” mentality
• ~2 hour duration of action when given IV (on
pump)
ethacrynic acid
edecrin. Loop diuretic. Less commonly used than furosemide
• Like furosemide but greater potential for
oxotoxicity
Bumetanide and Torsemide
(Bumex) and (Demadex). -Like furosemide and ethacrynic acid -Much less frequently used -Generally utilized as “physician’s preference” or when desired response is not achieved by furosemide.
Thiazide Diuretics
Act on the cortical region of the Ascending Loop of Henle *Also called “Ceiling Diuretics” because of their “flattening” dose/response curve
thiazide diuretics. how they work
-Thiazide diuretics work blocking Na⁺/Cl¯
transport/reabsorption on the luminal side of
the thick part of the Ascending Loop of Henle
and the Distal Convoluted Tubule.
-Consequently, NaCl concentrates in the
tubular fluid (and H₂O obediently follows =
increased urine production)
thiazide caveot
This also means that thiazides have to
actually get into the tubular lumens via renal
excretion…
…so thiazides lose efficacy in patients with
decreased renal function. need high urine production to get in. lasix can work on blood side
Thiazide Diuretics similar to loops because
Like “Loops”, thiazides increases renal blood
flow through COX-2 inducement of
prostaglandin synthesis.
• Structurally related to Acetazolamide, but
cause much more diuresis.
original diuretic used for edema
chlorothiazide. *Chlorothiazide is the only thiazide available
for parenteral use (of relevance to you!)
*Typical adult pump dose is 500mg
thiazide effects on electrolytes
increased urinary excretion of Na,K, vol. decrease excretion of calcium (sparing)
Thiazide Diuretics
Perfusion Uses
Like the “Loops” thiazides get rid of extra
(edema) fluid and potassium.
- systemic vascular resistance due to
relaxation of arteriolar smooth muscle
*So how do these two effects
synergize?getting rid of fluid and creating more capacitance for fluid by dilating
These are “second-line” treatments (after
“Loops” for the edema of heart failure.
-HTN
thiazide advantage over loop
Thiazides promote the reabsorption of calcium. *Compared to “Loops”, long-term use results in significantly less decrease in bone density (hip fractures are decreased by 1/3rd)
ince thiazides can (uniquely) cause the
production of hyperosmolar urine (what’s
this?) it’s used in diabetes insipidus (?)
allows people to concentrate urine because of lack of adh
potassium sparing diuretics
• Function in the collecting tubules (ducts) to
prevent Na⁺ reabsorption and K⁺ excretion. Antagonize aldosterone
mineralocorticoids(aldosterone) is produced
in glomerulosa
zona fasciculata
glucocorticoids
cortisol
Zona reticularis
androgens
testosterone precursors
Potassium-Sparing Diuretics
• Used to treat HTN, often in combination
with
thiazides. not efficacious by themselves
potassium sparing are problematic in
patients with hyperkalemia
(like who?) like patients on bypass or renal failure
Potassium-Sparing Diuretics
Direct Aldosterone Antagonists
Resemble sex steroids chemically. Used as adjunctive therapy in heart failure
– Statistically decreases mortality and helps
prevent pathological “remodeling” of the heart
diuretic of choice for
liver failure patients with edema
*Spironolactone
Potassium-Sparing Diuretics
Direct Aldosterone Antagonists
***Ineffective when
used on patients with Addison’s Disease because they have hypo adrenal function. not producing aldosterone. so giving this drug will have no effect
Potassium-Sparing Diuretics
Indirect-Acting Aldosterone Antagonists
*Block the Na⁺ transport channels affected by
aldosterone rather than aldosterone itself.
-VERY similar to direct aldosterone
antagonists except they can be used in
Addison’s Disease patients (why?)
5: Osmotic Diuretics
Small non-metabolized molecules filtered through the glomerulus that osmotically carry water with them. Given parenterally as they cause severe diarrhea if given orally (why?) good for renal patients • Mannitol very commonly given on bypass or added to the prime solution • Urea and glucose rarely (if ever) used (so feel free to ignore)
Osmotic Diuretics works
Work in the proximal tubule and the
descending Loop of Henle which permit the
free passage of H₂O
Osmotic Diuretics
Perfusion Relevance
Commonly used to “draw” fluid into the
intravascular space and decrease interstitial
edema but…why might this be controversial? because it increases hct.
Osmotic diuretics used to maintain flow
for renal failure. prevents accumulation of crap in kidneys. also good for cerebral edema. good for patients who smash their head
Osmotic Diuretics -Problematic in patients
oliguric(little urine)/anuric (no urine) renal failure (why?) will go into urine and pull fluid and cause htn.
dont give mannitol when urine output is less than
<50ml/hour for three
hours after a 12.5 gram IV dose, AVOID.
Mannitol is 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
“And I will be quite
ANNOYED. crank up flow it will wear off
Mannitol (Osmitrol) is a small molecule
categorized as a “sugar alcohol” With its familiar cousins xylitol and sorbitol.
Mannitol is usually supplied
as a 20% solution. *What does this mean??! 20g per 100 ml • RULE #1 when giving mannitol: “Check the bag/bottle for precipitated crystals!!!!
Check the mannitol bag/bottle
for precipitated
crystals!!!! because
beacause it will concentrate in the crystalsand you wont be giving as much plus its crystals dummy
