Diuretic Pharmacotherapy Flashcards
What is diuresis?
Process of producing more urine, More urine output decreases systemic volume and reduces edema
What is the most important ion in diuresis?
Na
When excess sodium is excreted, water follows and the result is increased ____
urine volume
What is natriuresis?
Excess sodium excretion in urine, Water follows salt, pull salt out and water will follow
What ions play minor roles in Diuresis?
K and Cl
Kidney initially filters ___ and other molecules such as glucose and urea at the ___
Na, K, Cl
At the glomerulus
Systemic concentration of these molecules (Na, K, Cl, Glucose and Urea) and urine concentration of these molecules is governed by _____ in distinct portions of the nephron
Rate/amount of reabsorption
What is the percentage of water reabsorbed in the PCT and what Diuretics work here?
65%
Acetazolamide and Osmotic Agents
What is the percentage of water reabsorbed in the Thick ascending limb and what diuretics work here?
15-25%
Loop agents
What is the percentage of water reabsorbed in the DCT and what diuretics work here?
4-8%
Thiazides
What is the percentage of water reabsorbed in the collecting tubule and what diuretics work here?
2-5%
Aldosterone antagonists
What diuretics work on the collecting duct?
ADH Antagonists and Osmotics Agents
What is reabsorption of 65% of filtered Na/K/Ca and Mg, 85% of NaHCO3 and nearly 100% of glucose and amino acids?
PCT
Bicarbonate + H =
Carbonic Acid
What is the function of Carbonic Anhydrase? CA
Breaks down carbonic acid in lumen AND forms bicarbonate and H from Carbon dioxide and water in PCT cells
Most relevant solutes to diuretics action are __ and ___ (In PCT)
NaHCO3 and NaCl
What Receptor do we have diuretics that will target it and what receptor dont we have diuretics that will target it?
Yes - CA Receptor
Dont - NHE3 Receptor
- -
- Pharmacologically block bicarbonate reabsorption by blocking carbonic anhydrase
- Increase urinary pH, decrease total body pH
- Highest permeability to water, so osmotic diuretics have the greatest effect here (mannitol)
-
-
- Hypochoremic alkalosis-> Hyperchloremic Acidosis
- Urinary Ca/Phosphorus less soluble in urine with increased pH (Develop stones)
- Not really used for “diuretic” effect bc does not appreciably affect Na (increase NaCl reabsorption in the rest of the nephron)
What are the site of action of Carbonic anhydrase inhibitors? and How do they work?
PCT
Block Bicarbonate Uptake
What is the prototype of Carbonic anhydrase Inhibitors? and What are other types?
Acetazolamide - Prototype
Dichlorphenamide and Methazolamide - Others
Clinical indications of Carbonic anhydrase inhibitors? - - - -
- Glaucoma (MC indication for CA Inhibitors, reduces aqueous humor formation)
- Urinary alkalinization (Increasing pH of urine decreases uric acid, cystine and other weak acid reabsorption)
- Metabolic alkalosis
- Acute Mountain Sickness (Decreases CSF formation and pH)
Toxicity of Carbonic Anhydrase Inhibitors: - - - - -
- Hyperchloremic Metabolic Acidosis
- Renal Stones
- Renal Potassium wasting
- Drowsiness
- Nervous Systemic tox in patients with renal failure
What is filtered by glomerulus but NOT REABSORBED and promotes water diuresis (More solute in lumen)?
Osmotic Diuretics
Prototype of Osmotic Diuretics?
Mannitol
Where do Osmotic Diuretics have major effects?
PCT and Descending limb of Loop of Henle
-
-
- Increase Urine volume
- Decrease intracranial Pressure
- Decrease intraocular Pressure
-
-
- Extracellular volume expansion
- Dehydration (Hyperkalemic & hypernatremia)
- Hyponatremia
T/F: osmotic diuretics are filtered by the glomerulus but not reabsorbed.
TRUE
Osmotic diuretics promote _______
water diuresis
T/F: osmotic diuretics has a direct effect on ion transporters.
FALSE (NO direct effect)
What is the protypical osmotic diuretic?
mannitol
How must mannitol be given?
parenterally (poor oral absorption)
Where do the major effects of osmotic diuretics occur?
In the PCT & the descending limb of loop of Henle
What are the clinical indications of osmotic diuretics?
- increase urine volume (used when avid Na retention decreases efficacy of loop or thiazide)
- decrease intracranial pressure
- decrease intraocular pressure
What toxicities occur with osmotic diuretics?
- extracellular volume expansion
- dehydration (hyperkalemia & hypernatremia)
- hyponatremia (due to impaired renal fxn, mannitol is retained IV & extracts water from cells causing dilution)
Which transporter is found in the thick ascending limb of the LoH that is blocked by loop diuretics?
Na/K/2Cl co-transporter
What are the clinical points for the thick ascending limb of the LoH?
- selectively block NaCl reabsorption, increasing the “salt” content of the urine, and therefore the water content.
- manipulating this section of the nephron can be very helpful in producing significant increases in urine volume and fluid loss.
What are the global effects of the thick ascending limb of the LoH?
- increase salt & water loss at the expense of global K loss, as well as Ca & Mg loss
- great target for dz states associated with fluid accumulation and edema
- can be a drug target to help treat hyperkalemia & hypercalcemia
T/F: loop diuretics indirectly inhibit Ca & Mg reabsorption
TRUE
Which diuretics is the most effective in terms of urine volume?
loop diretics
What are the prototypical loop diuretics?
furosemide and ethacrynic acid
T/F: loop diuretics can be rapidly absorbed and eliminated by the kidney via glomerular filtration.
TRUE
T/F: loop diuretics induce COX-2 expression
TRUE
T/F: Loop diuretics decrease renal blood flow and GFR
FALSE (increase)
Which transporter facilitates reabsorption of Na & Cl in the DCT?
Na/Cl transporter
Which transporters promote Ca release to blood within the DCT?
Ca/Na countertransporter and Ca/H ATPase
T/F: the DCT is relatively permeable to water.
FALSE (impermeable)
