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Flashcards in Diuretics and other Kidney Drugs Deck (54)
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What is the general mechanism of diuretics?

Mechanism secondary to increased excretion rate of solutes (usually sodium) to increase the excretion rate of water


How do drugs get past glomerular filtration?

Glomerular filtration of drugs not bound to plasma albumin or a1-acid glycoprotein


Which carries help with proximal tubule secretion?

Proximal tubular secretion by carriers organic anion transporter proteins, oatp mdr1 gene product (p-glycoprotein 170)


Where is most of the sodium reabsorbed in the nephron?

Proximal tubule


What are the 5 classes of diuretics?

1) Osmotic diuretics 2) Carbonic anhydrase inhibitors 3) Thiazide diuretics 4) Loop diuretics 5) Potassium sparing diuretics


What are the general features of osmotic diuretics?

- Filtered but not reabsorbed - Decrease water reabsorption - Frequently enhance sodium and potassium excretion via solute drag


What are the therapeutic uses of mannitol (3)?

1) Glaucoma: acutely reduce intraocular pressure 2) Cerebral edema: acutely reduce intracranial pressure 3) Mixed results in pigment-related AKI (acute kidney injury)


In general when is mannitol used?

Used when need to increase serum osmolality to shrink cells


What are the proximal effects of carbonic anhydrase inhibitors?

- Block bicarbonate reabsorption in the proximal tubule - Secondarily inhibit sodium reabsorption - Increase urinary excretion of Na, bicarbonate - Cause metabolic acidosis that leads to loss of diuretic effect


What are the distal effects of carbonic anhydrase inhibitors?

- In collecting tubule, Na + is reabsorbed in exchange for secretion of K+ from principal cell and H + from intercalated cell into urine - CA inhibition decreases H + availability and therefore increases urinary K + secretion - Can lead to hypokalemia


What are the therapeutic uses of CA inhibitors?

- Metabolic alkalosis - Familial hypokalemic periodic paralysis - Open-angle glaucoma - Decrease ciliary body secretion of bicarbonate into aqueous humor - Mountain sickness - Generates metabolic acidosis, stimulates respiration


What are the side effects of CAIs?

- Hypokalemia - Calcium stones due to alkalinization of urine - Hypersensitivity reactions due to sulfonamide residue


What is the mechanism of action of thiazide diuretics?

- Inhibition of NaCl symporter (thiazide-sensitive cotransporter, TSC, NCC) in distal convoluted tubule - Increase Na and Cl excretion
- Block urinary diluting capacity only 


What are the effects of thiazides on K and Ca excretion?

- Increase distal Na delivery and therefore K excretion
- Enhance Ca reabsorption
   - Volume depletion enhances proximal tubule Ca absorption
   - Can be used in prevention of kidney stones


What are the therapeutic uses for thiazides?

- Hypertension
- Edema
- Calcium nephrolithiasis
- Nephrogenic diabetes insipidus


What are the benefits of thiazide diuretics?

- inexpensive
- first line agent for mild to moderate HTN
- increase boen density in elderly women




What are the side effects of thaizide diuretics?

•Hypersensitivity reactions


What is the mechanism of action of loops diurectics (ie furosemide)?

•Inhibit Na-K-2Cl symporter (bumetanide sensitive cotransporter, BSC1, NKCC2)
   –in thick ascending limb
•Increase in Na, Cl excretion
•Block urinary diluting  AND concentrating capacity
•Increase distal Na delivery and therefore K excretion
•Increase Ca, Mg excretion


What should be monitored in patients taking diuretics (ie also excreting Na)?

Must also monitor Na intake


What are the therapeutic uses of loop diuretics?

•Acute pulmonary edema
   –Relief of symptoms due to rapid increase in venous capacitance following iv administration
•Edema from cardiac, hepatic, renal causes
•Hypertension refractory to other diuretics
•Used in conjunction with saline to treat hypercalcemia


What side effects are associated with loop diuretics (4)?

- Electrolyte abnormalities
   - Volume depletion
   - Hypokalemia
   - Excess Ca++ and Mg++ excretion
- Hyperuricemia (be careful with gout patients)
- Ototoxicity
- Hypersensitivity reactions





How is furosemide administered?

IV and PO formulations
   - 50% bioavailability with high variability



What percentage of furosemide is bound to albumin in plasma?



How is furosemide excreted?

50% is excreted via urine (kidneys)


Urine concentration in furosemide usage is correlated with what electrolyte effect?

Urine concentration is correlated wiht natriuretic effect


What is the half life of furosemide?

1-2 hours; one of the shortest in its class


What conditions would lower the effects of loop diuretics?

•Chronic Kidney Disease
   –Decreased renal blood flow and anionic metabolites reduce diuretic renal excretion rate
•Nephrotic syndrome
   –Hypoalbuminemia increases Vd and decreases renal excretion rate 


What is the mechanism of action of K sparing diuretics?

•Inhibit sodium reabsorption by principal cells of late distal tubules and collecting ducts
•Decrease potassium excretion
•Act either
   –directly on epithelial Na channel (ENaC)
   –indirectly by antagonism of aldosterone at the mineralocorticoid receptor (MR)


What are the indications for amiloride (K sparing diuretic)?

•In combination with thiazides or loop diuretics
   –to decrease risk of hypokalemia (except for cases of aldosterone excess)

•Liddle’s disease
   –to reduce excess Na uptake by mutated constituitively active form of ENaC

•In combination with lithium
   –to block Li uptake into principal cell and inhibit Li-induced diabetes insipidus


What type of diuretic is spironolactone?

Aldoesterone receptor antagonist (also a K sparing diuretic)