Where do Carbonic Anhydrase Inhibitors operate?
Proximal Convoluted Tubule
Name the site of the nephron that is the side of organic acid and base secretion.
Proximal convoluted tubule
What action of the nephron is necessary for most diuretics to work?
Secretion into the nephron at the proximal convoluted tubule, which is the site of the organic acid/base secretory system
Why do many diuretic drugs cause hyperuricemia (gout)?
They compete w/ uric acid for secretion at the organic acid/base secretory system
What are the primary uses of Acetazolamide?
Open angle glaucoma
Mountain sickness (prophylactic use)
Many loop diuretics contain sulfur. For a patient with a sulfur allergy, which loop diuretic can be used?
Ethacrynic acid
What category of drugs is the DOC for pulmonary edema?
Loop diuretics
Loops are the most efficacious diuretic because they "play" with what percent of filtered sodium load?
25%
Your patient has hypercalcemia (excess calcium in the blood). What class of diuretic can you give?
Loop
"Loops Lose Calcium
What is a unique adverse effect of loop diuretics?
Ototoxicity
the drug concentrates in the cochlea and can cause hearing loss
For the following drug classes, should K+ be monitored, always replaced, or other?
- Loops
- Thiazides
- Potassium sparing
- Loops: ALWAYS replace K+
- Thiazides: diet is usually enough, but you can supplement or prescribe low Na+ diet
- K sparing: NEVER supplement
Why does potassium depletion occur with loops and thiazides?
When BP drops, the body kicks in the RAAS. Aldosterone salvages Na by kicking out K.
What do thiazides contain that may cause hypersensitivity (Stevens-Johnson Syndrome) in some patients?
Sulfur
In what part of the nephron do thiazides operate?
distal tubule
Your patient has a renal disorder. Instead of a thiazide (which requires secretion into the nephron by the secretory system), what could you prescribe?
A thiazide-analog or a loop (because it is more efficacious to begin with, even though it still requires secretion)
How much of the filtered sodium load is targeted by Thiazides?
10% ("marginal" diuretics)
Thiazides drop TPR via two mechanisms. Explain.
1. decrease volume, decrease BP, decrease TPR
2. decrease vasoconstrictive ability of arteries (due to Na/Ca loss)
Producing hyperosmolar urine is unique to what class of diuretics?
thiazides
For CHF, in which a lot of volume should be dropped quickly, what class of diuretic is preferred?
Loops
Complete the sentence with "emia" or "uria"
Thiazides can be used to treat hypercalc_____.
hypercalcuria
(decrease Ca excretion, so fewer stones are formed)
Loops, on the other hand, lose calcium, so they treat hypercalcemia -- you wouldn't want to give them to a hypercalcuric, who already has too much Ca excretion and is forming stones.
What class of diuretics is used to treat nephrogenic diabetes insipidus?
Thiazides
Can thiazides cause hypercalcemia or hypocalcemia?
Hypercalcemia, because they retain Ca.
Thiazides inhibit insulin release, causing what adverse effect?
hyperglycemia --> Diabetes mellitus
Chlorthalidone is considered to be:
a) thiazide
b) thiazide analog
c) thiazide-like
C) thiazide like
What benefit does Chlorthalidone (thiazide-like) have over thiazides?
May improve CHF survival more than thiazides.
What benefit do thiazide analogs have over thiazides?
Can be used in renal disease
What is the "extra action" of Indapamide, a thiazide analog?
Direct arterial vasodilation
Where do potassium sparing diuretics operate?
Collecting tubule ("distal distal" convoluted tubule)
How do potassium sparing diuretics operate? (by blocking what?)
Block RAAS
What is the operation of K+-sparing diuretics dependent on?
Presence of aldosterone
K+-sparing diuretics are often combined with what classes of diuretics?
Thiazides or loops (to inhibit the body's reflex RAAS response). A potassium sparing drug potentiates the thiazide (or loop).
Unlike loops and thiazides, what adverse effect might Potassium sparing diuretics cause?
hyperkalemia
Spironolactone and Eplerenone are potassium-sparing diuretics. How do they work?
Aldosterone competitive antagonists
MOA: without aldosterone, distal distal tubule cells aren't stimulated to express Na/K channel and Na isn't reabsorbed. K is retained.
Spironolactone is rapidly converted to what active metabolite?
Canrenone
What is a unique adverse effect of Spironolactone? (Eplerenone does this too, but not as much)
Estrogenic actions: gynecomastia in males and menstrual irregularities in females
Some potassium sparing diuretics are aldosterone competitive antagonists. How do the others operate?
Amiloride and Triamterene are Na+ transporter blockers. They block the transporter that aldosterone induces.
What are the osmotic diuretics, and what compound do they "play" with?
Mannitol and urea
Trick question! They only move water (increase water excretion)
Osmotic diuretics are a mainstay for treating what condition?
raised intracranial pressure (ICP)