Diuretics Flashcards
What effect do Carbonic anhydrase inhibitors have on the urine?
Alkalinize the urine…more bicarbonate is excreted
What effect do carbonic anhydrase inhiitors have on chloride reabsorption?
Increase it…this can cause acidosis
Specific example of carbonic anhydrase inh?
aetazolamide
What does carbonic anhydrase normally do?
Converts H2CO3 to water and carbon dioxide to be reabsorbed
What are osmotic diuretics?
They are small molecules that are filtered but not reabsorbed.
What is their effect on the proximal convoluted tubule?
Inhibit Na and H20 reabsorption b/c they keep the osmolarity of the urine seo high that it needs to retain water.
What are the net effects of osmotic diuretics?
Increase urine volume
Specific osmotic diuretics?
Mannitol
Do osmotic diuretics reduce intracranial and intraocular pressure?
Yes. Immediately
What is the mechanism of action for loop diuretics?
They inhibit the Na-K-2Cl transporter,
Also inhibit the ability of the macula densa to sense NaCl, stimulate biosynthesis of prostaglandin, increase total renal blood flow
Loop Diuretics do what?
They are the most potent class of diuretics in mobilizing NaCl, Increase urinary excretion of K and H. Increase excretion of Ca and Mg.
Therapeutic uses of Loop Diuretics?
edema of cardiac, hepatoic, or renal origin
Also used in hypercalcemia to mobilize calcium
Protect against renal failure
Washout toxins
Antihypertensive
How do loop diuretics effect pulmonary edema?
1) Decrease pulmonary wedge pressure
2) Increase compliance of pulmonary vessels
3) Increase peripheral venous capacitance
4) Reduce left ventricular filling pressure
5) cause brisk diuresis
What is the most important thing the loop diuretics do?
Inhibit the macula densa
How does furosemide work?
Inhibits NaCl reabsorption in Thick ascending Limb of Henle. MUST BE SECRETED. It has to come into the Proximal convoluted Tubule, travel to the thick ascending loop of henle, and then prevent NaCl reabsorption from the inside.
How must you prescribe furosemide in people with renal diesase?
Must give larger doses b/c if they have kidney disease, their excretion mechanism is broken so you must give them more drug.
What are the pharmacological effects of furosemide?
Urinary excretion of K and H
urinary excretion of calcium and magnesium
increase in renal prostaglandins
increase in Venous capacitance
Side effects of furosemide?
warch for hypokalemia and pH disorders (mostly alkalosis)
Elevated BUN, hyperglycemia, hyperuricemia
Ototoxicity, sialadentitis (salivary gland inflammation)
What drug interactions must be watched for?
interactions with Lithium
indomethacin
probenecid
warfarin
What is significant about Bumetanide
forty times more potent than furosemide
What are the three segments of the Distal convoluted Tubule and collecting Duct?
1) Na-K aldosterone independent segment (NaCl absorbed without water)
2) Aldosterone sensitive segment (Na exchanged for Potassium and Hydrogen)
3) Sodium load segment
WHere do thiazide diuretics act?
DCT
What is a big difference between thiazide and loop diuretics?
Thiazide diuretics decrease the urinary excretion of calcium.
Uses of Thiazide diuretics?
reduction in edema due to CHF, cirrhosis, nephrotic syndrome
Hypercalciurea
Renal calcium stones
Reduction of bp in essential hypertension
osteoporosis
Diabetes insipidous
When are class I thiazides used?
When GFR is above 50
When are class II thiazides used?
When GFR is below 50
Adverse effects of thiazides?
Depletion phenomena
Retention phenomena
Metabolic changes
Hypersensitivity
Two types of cells in DCT and CD?
Type A and Type B
Type A cells are….
hormonally responsonsive (regulated by aldosterone) Na absorption and K secretion
Type B cells are…
Load dependent. The more Na is delivered, the more is absorbed in exchange for K
How do aldosterone antagonists work?
Bind to aldosterone receptors in the cytoplasm and prevent them from getting into the nucleus. Prevents NaCl cahnnels from being placed in cell membrance. Cuts down on sodium transport
Toxicity of Carbonic Anhydrase Inhibitors?
Metabolic acidosis (more Cl- reabsorption), K+ loss
Do osmotic diuretics interfere with urea absorption and impair cortico…. gradient?
Yes
What would you use to treat dialysis disequilibrium syndrome and/or increased intraocular pressure?
Mannitol )osmotics)
What is the mechanism behind the loops losing calcium?
Inhibition of the NK2C transporter in the thick ascending limb destroys the gradient between the lumen and the cell. Usually, NK2C works and then K moves back out through the potassium channel thus creating a positively charged lumen. This positive charge of the lumen with the negative charge of the cell draws in calcium and mg under physiologc conditions.
Name the potassium sparing diuretics
The K STAys……Spironolactone, Triamterene, Amilioride
How does spironolactone work?
Prevents ENac channels from being produced by binding to the aldo receptor in the cytoplasm and preventing its translocation to the nucleus. No Na taken in, no K released.
The 3 class 1 thiazides are:
Hydrochlorothiazone, chlorothalidone, quinethazone
The class II thiazides are
Metolazone, indepamide
What loop can you give with warfarin?
Bumetanide
