Renal Diuretics Flashcards
What is a diuretic?
A substance that increases urin production
What are the characteristics of a therapeutically useful diuretic?
- Increases sodium excretion
- Increases water excretion
How much glomerular filtrate is produced by the kidneys?
What are the four sites of the nephron where diuretics work?
- Proximal Tubule
- Thick Ascending Loop of Henle
- Distal Tubule
- Collecting Duct
What is the role of carbonic anhydrase in the proximal convoluted tubule?
Catalyses generation of H
The descending loop of henle is permeable to what molecule?
H2O
How does the tonicity of the filtrate change as it descends the loop of henle?
Increasingly hypertonic
What transporter mediates sodium absorption in the thick ascending loop of henle?
Na+/K+/2Cl co-transporter
(powered by NaK ATPase)
How does potassium cycling int the thick ascending loop of henle facilitate magnesium and calcium absorption?
Produces an electrical current that is the driving force for a current along the paracellular spaces
In what part of the nephron does potassium recycling occur?
Thick ascending loopof henle
How is sodium reabsorbed in the proximal distal tubule?
Na+/Cl- cotransporter
How is sodium reabsorbed in the late distal tubue?
Facilitated diffusion through selective amiloride-sensitive channels
How does aldosterone affect the late distal tubule?
Stimulates K+ secretion by…
- Stimulating basolateral-membrane Na/K ATPase
- Increase number of Na+ and K+ channels in luminal membrane
What determines water permeability in the collecting duct?
ADH
Antidiuretic hormone
Arginine vasopressin
What are the 5 classes of diuretics
- Osmotic diuretics
- Carbonic anhydrase inhibitors
- Loop diuretics
- Thiazides
- Distal diuretics (K+sparing)
What is an osmotic diuretic?
Drug that exerts diuretic effect due to physical retention of water within tubular lumen rather than a direct effect on Na+ channels
What are the three properties of an osmotic diuretic?
- Freely filtered by glomeruli
- Remain in tubular lumen in high concentration
- Pharmacologically inert
Give an example of an osmotic diuretic
Mannitol
What is acetazolamide?
Carbonic anhydrase inhibitor
What is carbonic anhydrase?
Enzyme that catalyzes the reaction:
CO2 + H2O <–> H2CO3 <–> H+ + HCO3-
How do carbonic anhydrase inhibitors exert their diuretic effects?
- Decrease the conversion of CO2 and H2O to H+ and HCO3-
- Decrease amounts of HCO3- = decreased Na+ and HCO3- co-transport reabsorption
- Diminished reabsorption of Na+ in proximal tubule leads to increased Na+ load in distal tubule
- Increased reabsorption of Na+ in exchange for K+secretion in distal tubule
What are the consequences of using a carbonic anhydrase inhibitor?
- K+ urinary loss
- Alkaline urine (HCO3- not absorbed)
- Metabolic acidosis (HCO3- not absorbed)
Where do loop diuretics work?
Ascending loop of henle
What is the mechanism of action of a loop diuretic?
Inhibit Na+/K+/2Cl- co-transporter sysstem
What type of diuretic is furosemide?
Loop diuretic
What are 4 characteristics of loop diuretics?
- Can be administered p.o. or i.v.
- Highly protein bound in blood
- Actively secreted in proximal tubule by organic acid pathway
- Act on luminal side of tuuble to inhibit Na+ absorption
How do loop diuretics effect calcium and magnesium?
Inhibit reabsorption of calcium and magnesium
What molecule confers carbonic anhydrase activity to certain thiazide diuretics?
Sulfamyl group
-SO2NH2
What is the mechanism of action of thiazide diuretics?
How do thiazide diuretics affect calcium?
Increase calcium reabsorption
Where do potassium-sparing diuretics exert their effects?
Distal tubule
Why are potassium-sparing diuretics used?
For potassium-conserving properties with thiazides or loop diuretics
What are the 2 types of potassium-sparing diuretics?
- Aldosterone antagonists
- Sodium-channel blocking agents
What is spironolactone?
What is amiloride?
Sodium-channel blocking agent
Patient on diuretics presents with lethargy, confusion, seizures. Why?
Patient is hyponatremic.
Possibly due to….
- Increased ADH secretion
- Augmente thirst from ADH, angiotensin II leading to increased water intake
- Decreased free water clearance
Patient on diuretics presents with weakness and arrhythmia. Why?
Hypokalemia
(with all diuretics unless potassium-sparing monotherapy)
Patient on diuretics presents with cardiac arrest. Why?
Hyperkalemia
(Potassium sparing diuretic)
Which diuretic is contraindicated in diabetics?
High dose Thiazides
(possibly due to hypokalemia which inhitits insulin secretion from pancreatic Beta-cells)
Which diuretics can lead to metabolic alkalosis?
Which diuretics can lead to metabolic acidosis?
Carbonic anhydrase inhibitors & potassium-sparing diuretics
Which diuretic is associated with antiadrenergic and prosteogenic effects?
Spironolactone
What are the three main indications for diuretic therapy?
- Generalized edema states
- Acute pulmonary edema
- Hypertension
What are three conditions associated with generalized edema?
- Congestive heart failure
By what mechanism do diuretics help with pulmonary edema?
Vasodilatory effect reduces preload
