Diuretics Flashcards
The OATs are responsible for active secretion of what substances? (also give examples)
weak acids like loops and thiazides
What other substance is secreted by OATs besides weak acids and loops and therefore competes with them?
uric acid
Where do CAI act in the kidney tubule?
proximal tubule
Where do osmotics attract water in the kidney tubule?
mainly proximal nephron or proximal convoluted tubule but can be anywhere in kidney tubule
Where do loop diuretics mainly act in the kidney?
in the thick ascending limb of Henle
Where do thiazides mainly act in the kidney?
the early distal tubule
Where do the K+ sparing diuretics typically act in the kidney?
early collecting duct
Where does aldosterone act in the kidney?
the early collecting duct.
The more Na+ reaches the lumen of collecting duct what other minerals typically also leave the body with it?
K+ ions and H+ goes with potassium
Which type of diuretics are contraindicated in CHF and pulmonary edema because they draw water from the cells and increase the filling pressure of the heart?
osmotic diuretics.
What group of drugs are considered the only true diuretics?
osmotic diuretics
Major example of an osmotic diuretic used?
mannitol
How does mannitol act as a diuretic?
it will go throughout the body attracting water independent of sodium resulting in increased urine volume
Uses for mannitol?
inc. fluid drainage therefore dec. IOP in closed angle glaucoma
dec ICP draws water from brain
In oliguric states (e.g rhabdomyolysis) it enhances myoglobin elimination
What is the major stem to remember the CAIs?
“zolamides”
What are some major CAIs we mentioned in this chapter?
acetazolamide and dorzolamide
Major S/E mannitol?
hypovolemia
What is indirectly blocked in the mechanism by which CAIs act on the proximal tubule?
the Na+/H+ antiport
What also has a strong influence on the Na+/H+ exchanger in the proximal tubule?
Ang II
What are the uses for CAIs?
glaucoma
acute mountain sickness
metabolic alkalosis
What are some side effects of CAIs?
bicarbonaturia and acidosis (non anion gap metabolic acidosis)
hypokalemia
hyperchloremia
paresthesias
renal stones
sulfonamide hypersensitivity
Why do you get hyperchloremia with use of CAIs?
because you have competing anions in the urine
both bicarb and Cl- are in urine and Cl- easier to reabsorb so nephron will try to reabsorb it.
What stem can help you remember the drugs considered loops?
“semide”
What drugs did we discuss are important loops to remember?
furosemide
torsemide
ethacrynic acid
Sulfonamide containing drugs have cross allergenicity with what other drugs?
CAIs
All loop diuretics (except ethacrynic acid)
thiazides
sulfa antibiotics
celecoxib
MOA of loop diuretics.
Na+/K+/2Cl- transporter inhibition
What ion in the triple transporter blocked by loops is responsible for the potential which helps Mg2+ and Ca2+ to be reabsorbed?
K+
Loops lose ?
Ca2+
Which of the diuretics is the most powerful?
loops
“semi” stem semi truck (is big)
Uses for loop diuretics?
hypertension (although thiazides are used here more commonly)
refractory edema
hypercalcemia (bisphosphonates more often used)
What are some side effects of the use of loops?
- sulfonamide hypersensitivity (not ethacrynic acid)
- hypokalemia and alkalosis
- hypocalcemia
- hypomagnesemia
- hyperuricemia (actively secreted by OAT)
- ototoxicity (may say feels fullness in ears or ringing in ears called tinnitus) (this effect more seen in ethacrynic acid >furosemide)
target the same pump in the ears
Hypokalemia tends to go with alkalosis or acidosis?
alkalosis
What are some drug interactions with loops?
- aminoglycosides (enhanced ototoxicity)
- lithium (chronic loop administration, dec. clearance)
- digoxin (inc. toxicity due to electrolyte disturbances) ***** hypokalemia enhances digoxin toxicity.
An important distinction between loops and thiazides?
Loops lose calcium and thiazides save Ca2+
MOA of thiazides.
inhibit the Na+/Cl- co-transporter
Thiazides hyper polarize what cells in the body?
smooth muscle cells (vasodilation) and pancreatic beta cells (decreased insulin release)
What are the important thiazides to remember?
hydrochlorothiazide
chlorthalidone
indapamide
What are the major uses of thiazides?
hypertension, CHF
Nephrolithiasis (calcium stones)
nephrogenic diabetes insipidus
Explain the process by which thiazides are beneficial in the treatment of nephrogenic diabetes insipidus.
In nephrogenic diabetes insipidus the V2 receptors on collecting ducts are uncoupled/damaged; therefore, the reabsorption of water via aquaporin channels is impaired.
We use HCTZ because now you are forcing loss of sodium in the urine which greatly reduces plasma volume. Now RAAS is activated > Ang II activates the reabsorption of sodium and water gets reabsorbed.
Only has this effect when person has nephrogenic diabetes insipidus
What are the S/E’s of thiazides?
sulfonamide hypersensitivity
hypokalemia and alkalosis
hypercalcemia
hyperuricemia (actively secreted by the OAT)
hyperglycemia
hyperlipidemia (except indapamide)
Some interactions with thiazides? (What other drug should you be careful to use with it because of increased toxicity?)
digoxin (inc. toxicity due to electrolyte disturbances)
Combining K+ sparing diuretics with ACEIs or ARBs may cause hyperkalemia or hypokalemia?
hyperkalemia
What is the benefit of using eplerenone over spironolactone?
eplerenone is a selective aldosterone blocker but is devoid of antiandrogenic effect
MOA of aldosterone antagonists.
aldosterone - receptor antagonist
stops aldosterone effects of sodium reabsorption therefore no drive to create potassium secretion
What are the major uses of spironolactone?
hyperaldosteronic states
adjunct to K+ wasting diuretics
antiandrogenic uses (female hirsutism)
CHF
Mechanism of action of amiloride and triamterene
blocks Na+ channels in collecting tubules
Be able to reproduce chart on different diuretics, their MOAs and urinary electrolytes and pH changes.
Be able to draw out major channels that drugs to PCT, thick ascending loop of Henle, Distal Tubule and collecting duct affect.
The major uses for amiloride and triamterene?
adjunct to K+ wasting diuretics
lithium induced nephrogenic diabetes insipidus (amiloride)
