Diuretics Flashcards
What is the main function of diuretics?
A substance or drug that tends to increase the discharge of urine.
How can edema develop from NaCl imbalance?
When NaCl intake is greater than output, e.g. in congestive heart failure or renal failure, edema develops.
What is the Na+/K+ ATPase?
It exchanges 3 Na+ for 2 K+, thereby keeping a low Na+ concentration and a high K+ concentration within the cell.
What is the longest and most absorptive part of the nephron?
Proximal Tubule
What is the major determinant of ECF volume?
NaCl
What is mainly absorbed and secreted in the PT?
NaCl and NaHCO3 are absorbed
Organic Acids and Bases are secreted
What is the macula densa and what is its role?
It is a sensor in the TAL of the Loop of Henle. It detects NaCl and decreases in concentration will cause 2 responses:
(1) it decreases resistance to blood flow in the afferent arterioles via vasodilation, which increases glomerular capillary hydrostatic pressure and helps return glomerulus filtration rate (GFR) toward normal, and
(2) it increases renin release from the juxtaglomerular cells of the afferent and efferent arterioles, which are the major storage sites for renin.
What is the primary therapeutic goal of diuretics?
The primary therapeutic goal of diuretic use is to reduce edema
Where do diuretics generally enact their effects?
Except for spironolactone and some ADH antagonists, diuretics generally exert their effects from the luminal side of the nephron.
How do most diuretics reach the urine?
Most other diuretics are tightly protein bound and undergo little filtration. They reach the urine via secretion across the proximal tubule.
What are the carbonic anhydrase inhibitors?
- Acetazolamide
- Dichlorophenamide
- Methazolamide
- Dorzolamide
What is the site of action of the carbonic anhydrase inhibitors?
Proximal Tubule
Acetazolamide MOA
Reversible inhibition of carbonic anhydrase which leads to the inhibition of the reabsorption of HCO3- in the proximal tubule
Acetazolamide PK
Well absorbed orally
Acetazolamide Secretion Mechanism
Renal secretion is via the organic acid transporter
Acetazolamide SE
– Metabolic acidosis
– Hypokalemia
– Calcium phosphate stones
Acetazolamide Contraindications
Cirrhosis (increased urine pH
reduces NH3 secretion and thereby increases serum NH3)
Acetazolamide Indications
– Diuretic agent: weak, but ok as backup
– Glaucoma: reduction of intraocular pressure
– Urinary alkalinization: drug overdose/some stones
– Acute mountain sickness
How does acetazolamide lead to the increased serum levels of NH3?
Acetazolamide increases the excretion of HCO3- which will alkalinized the urine. The alkalinization of urine causes the NH3 in the collecting duct (CD) to not be protonated to NH4+ which would trap it in the CD. It can therefore just diffuse back as NH3.
Dichlorophenamide Class and Action
CA Inhibitor
30X more potent than acetazolamide
Methazolamide Class and Action
CA Inhibitor
5X more potent than acetazolamide
Dorzolamide Class and Action
CA Inhibitor
Topical variant used for ocular disease like glaucoma to avoid systemic effects
Mannitol MOA
Osmotic diuretic
Where does mannitol enact its effects?
Major osmotic effects in proximal tubule and descending limb of the loop of Henle; collecting ducts too, if ADH is present - water permeable parts of the nephron
How does mannitol reach the kidney?
Filtration via the glomerulus
Mannitol PK
NOT orally absorbed-must be injected IV to reach the kidneys
Mannitol SE
– Major toxicity due to increased plasma osmolality. This moves water out of cells into ECF potentially worsening heart failure. In addition, Na+ follows water movement out of cells leading to hyponatremia.
– Acute pulmonary edema
– Dehydration
What exacerbates the SE of mannitol?
Anything that would impair filtration
Mannitol Contraindications
– Congestive heart failure
– Renal failure
– Pulmonary edema
Mannitol Indications
– Maintain or increase urine volume
– Reduce intracranial pressure
– Reduce intraocular pressure (glaucoma)
What is the main transporter on the apical side of the TAL in the Loop of Henle?
- Na+/K+/Cl- cotransporter into the cell
What is the role of K+ with the Na+/K+/Cl- cotransporter in the TAL of the LoH?
K+ diffuses back into the lumen creating (+) charge in lumen which aids in the absorption of other cations like Ca and Mg
What are the Loop Diuretics?
Furosemide
Bumetanide
Torsemide
Ethacrynic Acid
Loop Diuretics MOA
Act primarily by blocking the Na+/K+/2Cl- co- transporter in the apical membrane of the thick ascending limb of Henle’s loop.
- Increase urinary water, Na+, K+, Ca2+, and Mg2+ excretion.
What is the most effective diuretic class?
The Loop Diuretics. They can cause excretion of up to 20% of the filtered Na+.
What is a secondary effect of the loop diuretics?
Also cause dilation of the venous system and renal vasodilation – effects that may be mediated by prostaglandins.
Furosemide MOA
– Inhibits the Na+/K+/Cl- cotransporter
What can cause metabolic acidosis with hypokalemia?
Acetazolamide
What are the effects of furosemide?
– Reduces reabsorption of Na+, K+, Cl- as expected, but also Ca2+ & Mg2+ due to loss of (+) luminal charge
– Renal vasodilation improves renal blood flow