Diuretic agents Flashcards
(43 cards)
What are the three carbonic anhydrase inhibitors? What is their mechanism of action?
Acetazolamide (diamox)
Dorzolamide (Azopt)
Brinzolamide (Trusopt)
Block H2CO3 production which drives H+ exchange, so with decreased H+ secretion, this leads to decreased Na+ reabsorption and increased loss of Na+ and water in the urine
What do CA inhibitors cause? What is this helpful in the treatment of?
a decrease in H+ secretion, treatment of acute mountain sickness (which results from a decrease in CO2 as ventilation increases, raising pH), prevents H+ secretion to try and lower pH.
What are some adverse effects of CA inhibitors?
Hyperchloremic metabolic acidosis (increased HCO3- in lumen increases Cl- reabsorption in collecting tubule)
Hypokalemia (increased Na+ in urine increased the Na/K+ exchanger in the distal tubule=more K+ excretion)
Hyperuricemia
A patient is taking acetazolamide and suffers a gouty attack. Why?
Due to hyperuricemia because these drugs are acids and their excretion competes with uric acid
What are some contraindications for CA (-amide) use?
Sulfa hypersensitivity (major) Hepatic cirrhosis (there will be an accumulation of NH4+)
What are the two effects of loop diuretics?
#1 Blocks the NKCC2 transporter to reduce medullary concentration gradient to impair reabsorption of urine in collecting duct #2 induces PG synthesis in the kidney which causes diminished salt transport, furthering diuretic action and causing renal and systemic vasodilation
What are the indications for loop diuretics?
CHF, pulmonary edema, and hypercalcemia (due to decreased K+ gradient which decreases reabsorption of Mg and Ca2+)
What are some major adverse effects of loop diuretics?
Hypochloremia, hypokalemic metabolic alkalosis (H+ follows K+ out), IRREVERSIBLE OTOTOXICITY, hyperuricemia
What are the loop diuretics? Which are sulfa derivatives and which are not?
Sulfa: Furosemide (lasix), bumetanide (bumex), torsemide (demadex)
Non-sulfa: ethacrynic acid
You have a patient with a sulfa allergy so you put them on ethacrynic acid. What should you be particularly concerned about? What other drug class should you not prescribe?
Ototoxicity, AMINOGLYCOSIDES
Contraindications for loop diuretics
Sulfa sensitivity (except e.a.) Drug interactions (COX inhibitors, AGs, Lithium (increased Na+ loss increases Li+ retention), Digoxin (loss of K+ protective effect))
What are THE thiazide diuretics?
Hydrochlorothiazide and Chlorothiazide
What are compounds related to thiazides?
Chlorothalidone, metolazone, quinethazone, indapamide
What is the MOA of thiazide action? What is this effect dependent on?
Inhibits the NCC transporter in the eartly distal tubule so the dilution of urine is blocked
Dependent on PG synthesis
What are the main clinical indications for thiazide diuretics?
HYPERTENSION, nephrolithiasis, nephrogenic DI
What is one beneficial and one harmful effect of the increase in ATP-dependent K+ channel opening?
Beneficial: Causes vasodilation due to hyperpolarization of VSMC membranes
Harmful: reduced insulin secretion from Beta cells
What is one beneficial effect of the increased luminal Na+ concentration on Ca2+ excretion?
In the treatment of renal calculus, this will increase Ca2+ reabsorption due to an increase in luminal Na+ concentration, thereby decreasing Ca2+ excretion
What is the only drug that is useful in renal insufficiency due to its liver excretion? What is it also useful for?
Indapamide; causes pronounced vasodilation due to calcium channel blocking effects and it does not increase plasma lipids as much as other thiazids
What condition does loop and thiazide diuretics cause?
Hypokalemic metabolic alkalosis
What condition does a CA inhibitor cause?
Hyperchloremic metabolic acidosis
Which diuretics work at low GFR?
Loop diuretics and metolazone (thiazide type)
What are the two classes of potassium sparing diuretics?
Aldosterone antagonists and direct inhibitors of Na+ flux
What is the MOA for K+ sparing diuretics?
Blocks Na+ reabsorption but does not induce secretion of K+
What is an indication for using K+ sparing diuretics?
Hypokalemia and minimizing alkalosis of other diuretics (due to H+ loss), used in combination with other drugs