Flashcards in 31 - Renal Drugs Pt. 2 Deck (38):
What is a diuretic?
increases solute excretion to increase the volume of urine
What is an aquaretic?
Increase water but not solute excretion
What is a natriuretic?
Increases excretion of sodium
What is a saluretic?
Increases the excretion of sodium and chloride
What is a kaliuretic?
Increases the excretion of potassium
What are 2 medical conditions that diuretics are used to treat?
What are the primary and secondary sites of action of carbonic anhydrase inhibitors?
-Primary - PCT lumen
-Secondary - distal collecting duct
What is the major effect of carbonic anhydrase inhibitors in the nephron?
Causes excretion of sodium bicarbonate, i.e. Sodium bicarb remains in the urine
What are carbonic anhydrase inhibitors expected to cause - metabolic acidosis / alkalosis?
They cause acidosis, so can be used to treat metabolic alkalosis
Carbonic anhydrase inhibitors affect the secretion of the following ions: Na, K+, H+, HCO3 and H2PO4. Secretion of which ones are increased or decreased by these drugs?
-Increased - Na, K+, HCO3 and H2PO4 increased.
-Decreased - H+
What is the example of the carbonic anhydrase inhibitor we need to remember? Why is it regarded as a potassium wasting drug?
-A lot of Na+ reaches the distal nephron, K+ exchanged to absorb that Na+. Exchanged K+ is excreted
Open angle glaucoma, presurgical relief of glaucoma pressure, altitude sickness and counteracting diuretic induced metabolic alkalosis. These are all treated with what type of diuretic?
Carbonic anhydrase inhibitor (Acetazolamide)
Allergic reactions, metabolic acidosis, increased circulating ammonia, kidney stones, bone marrow depression, parasthesia and tingling can all be caused by _
Carbonic anhydrase inhibitor (Acetazolamide)
What patients should not use acetazolamide?
Patient's with liver cirrhosis - Renal ammonia returns to system, can worsen hepatic encephalopathy
What is the mechanism of osmotic diuretics? What is the effect on the medullary salt gradient? What is the primary site of action in the nephron?
-Draws water from tissues into blood, increase renal blood flow and thus urine
-It washes out the gradient
-Loop of Henle
What is the effect of osmotic diuretics on ADH activity?
Prevents the action of ADH (water reabsorption) because salt gradient is disrupted i.e. can't resorb water even if dehydrated
Osmotic diuretics affect the excretion of Na+, K+, Ca++, Mg++, CL-, HCO3- and H2P04. What is increased and what is decreased from this list?
It increases the excretion of EVERYTHING.
What are the 2 examples of osmotic diuretics we need to know? Which can cause hyperglycemia?
-Glycerin (may cause hyperglycemia after metabolism)-Mannitol
Acute renal failure, tubular necrosis, dialysis disequilibrium, acute glaucoma for high intraoccular pressure. These are all uses of _
Hyponatremia and dehydration are potential side effects of _
What are 3 populations that should be cautious about using osmotic diuretics?
- Pulmonary congestion as it can become pulmonary edema
- Patients with Anuria
- Patients with intracranial bleeding (Mannitol)
What is the primary site of action of the loop diuretics i.e. where in the loop? How do they enter the lumen?
-Thick ascending limb of loop of Henle
-Organic ion transporters in proximal tubules
What is the specific transporter inhibited by the loop diuretics? What is its effect on the medullary ion gradient? What is its effect on urine volume and concentration?
-Na, K, Cl Symporter
-Diminishes the ion gradient
-Increases urine volume, Increased concentration
Loop diuretics affect excretion of Na+, K+, H+, Ca++, Mg++, Cl-, HCO3- and H2PO4-. Excretion of which are increased and which is decreased?
ALL ion excretion is increased. None are spared
What are the 4 examples of loop diuretics provided? Which is uniquely metabolized in the kidney vs. liver (glucuronidation)?
-Furosemide (Glucuronidation in kidney)
Among the loop diuretics, which is also a weak carbonic anhydrase inhibitor and can increase venous capacitance? Being able to increase venous capacitance makes this drug useful for what 2 conditions?
-Heart failure and pulmonary edema
How do loop diuretics circumvent limits of salt excretion i.e. why they are referred to as high ceiling diuretics?
Prevent salt transport into the macula, therefore no tubuloglomerular feed back to limit excretion rates
Acute pulmonary edema, Congestive heart failure, Nephrotic Syndrome, Edema and ascites from cirrhosis, chronic renal failure and hypertension (second line treatment). These are all potential uses of what group of drugs?
What class of diuretic is likely to cause hyponatremia, hypokalemia, volume depletion, hyperurecemia and metabolic alkalosis? What specific agent is associated with ototoxicity? Which is contraindicated with sulfonamide sensitivity?
-Ethacrynic acid (ototoxicity)
-Furosemide (Sulfonamide sensitivity)
Regarding mechanism, how thiazide diuretics work?
They block the sodium chloride symporter.
How do the thiazide diuretics get to the urine? What part of the nephron do they act on?
-Enter urine via organic ion transporters in proximal tubule
-Act in distal convoluted tubule
What is the difference between the symporters targeted by loop diuretics and thiazide diuretics?
-Loop diurectics target Na, Cl, K symporter
-Thiazide diuretics target Na, Cl symporter
What is the source of energy for the NaCl symporter?
-basolateral Na+/K+ antiporter
Thiazide diuretics affect the excretion of Na+, K+, H+, Ca++, Mg++, Cl-, HCO3- and H2PO4-. What is the only one that is decreased? Why?
-Only calcium secretion is decreased. All others increased
-Blocks the activity of sodium calcium symporter
Why are thiazide diuretics not limited by tubuloglomerular feedback? What can happen to plasma calcium with prolonged use of thiazide diuretics?
-They act distal to the macula
-Plasma calcium can go up with prolonged use
What are the two examples of thiazide diuretics that we need to know? What is the example of thiazide like provided (1)?
-Thiazide: Hydrochlorothiazide and Chlorothiazide
-Thiazide like: Metolazone
What is the effect of the thiazide diurectics of the medullary salt gradient and how does this affect water reabsorption during dehydration?
No effect on salt gradient, therefore ADH can still work in distal tubules during dehydration.