Chapter 15: Diuretics & Other Drugs That Act on the Kidney Flashcards
Carbonic anhydrase inhibitors
The effects of this diuretic agent are predictable from in which segment of the nephron?
Proximal convoluted tubule
Loop diuretics
The effects of this diuretic agent are predictable from in which segment of the nephron?
Thick ascending limb of LoH
Thiazides
The effects of this diuretic agent are predictable from in which segment of the nephron?
Distal convoluted tubule
K+ sparing diuretics
The effects of this diuretic agent are predictable from in which segment of the nephron?
Cortical collecting tubule
The kidney filters plasma water and solutes at the glomerulus at a very high rate (_____ L/day) and must recover a significant percent- age of most of these substances before excretion in the urine.
180 L/day
A shift in body electrolyte and pH balance involving elevated serum chloride, diminished bicarbonate concentration, and a decrease in pH in the blood. Typical result of bicarbonate diuresis
Hyperchloremic metabolic acidosis
A shift in body electrolyte balance and pH involving a decrease in serum potassium and an increase in blood pH. Typical result of loop and thiazide diuretic actions
Hypokalemic metabolic alkalosis
Loss of urine-concentrating ability in the kidney caused by lack of responsiveness to antidiuretic hormone (ADH is normal or high)
Nephrogenic diabetes insipidus
Loss of urine-concentrating ability in the kidney caused by lack of antidiuretic hormone (ADH is low or absent)
Pituitary diabetes insipidus
This segment carries out isosmotic reabsorption of amino acids, glucose, and numerous ions.
It is the major site for sodium chloride and sodium bicarbonate reabsorption.
It is responsible for 60–70% of the total reabsorption of sodium.
Proximal convoluted tubule
What is the mechanism of action of carbonic anhydrase inhibitors?
The mechanism of action is inhibition of carbonic anhydrase in the brush border and cytoplasm
What are the causes of high anion gap metabolic acidosis (HAGMA)?
MUDPILES:
- Methanol
- Uremia
- DKA
- Paraldehyde
- Isoniazid, Iron
- Lactic Acid
- Ethanol, Ethylene glycol
- Salicylates
What are the causes of normal anion gap metabolic acidosis (NAGMA)?
HARDUP:
- Hyperalimentation
- Acetazolamide
- RTA
- Diarrhea
- Ureteral diversion
- Pancreatic fistula
This segment pumps sodium, potassium, and chloride out of the lumen into the interstitium of the kidney.
It is also a major site of calcium and magnesium reabsorption.
Thick ascending limb of LoH
Reabsorption of sodium, potassium, and chloride are all accomplished by a _____, which is the target of the loop diuretics.
This cotransporter provides part of the concentration gradient for the countercurrent concentrating mechanism in the kidney and is responsible for the reabsorption of 20–30% of the sodium filtered at the glomerulus.
Na+/K+/2Cl– carrier (NKCC2)
This loop diuretic is a moderately effective uricosuric drug if blood volume is maintained.
Ethacrynic acid
This is an important toxic effect of the loop agents.
Ototoxicity
The site of significant dilution of urine
Loop of Henle
Toxicities of Loop diuretics:
Hemoconcentration Hypokalemic metabolic alkalosis Hypovolemia and cardiovascular complications Ototoxicity Sulfa allergy
The DCT actively pumps sodium and chloride out of the lumen of the nephron via the _____.
Na+/Cl– carrier (NCC)
What is the mechanism of action of thiazide diuretics?
Inhibit Na+/Cl- transporter in distal convoluted tubule.
Cause moderate diuresis and reduced excretion of calcium.
Side effects of thiazide diuretics:
HyperGlycemia
HyperLipidemia
HyperUricemia
HyperCalcemia
Uses of thiazide diuretics:
- Hypertension
- Mild heart failure
- Chronic renal calcium stone formation can sometimes be controlled with thiazides because they reduce urine calcium concentration.
- Nephrogenic diabetes insipidus.
Cortical collecting ducts
- Last tubular site of sodium reabsorption
- Under the influence of aldosterone
- Primary site of acidification of the urine
- Last site of potassium excretion
- Sites of action of the potassium-sparing diuretics
A potasium-sparing diuretic that causes gynecomastia
Spironolactone
Side effects of spironolactone and eplerenone:
- Hyperkalemia
- Impotence
- Benign prostatic hyperplasia
- Hyperchloremic metabolic acidosis
- Gynecomastia (spironolactone only)
This is a potassium sparing diuretic (Na blocker), inhibiting ENaC epithelial sodium channels in cortical collecting duct, reduces Na reabsorption and K
excretion
- Amiloride
2. Triamterine
Because they are freely filtered at the glomerulus but poorly reabsorbed from the tubule, they remain in the lumen and “hold” water by virtue of their osmotic effect.
Osmotic diuretics
What is the major location for the action of osmotic diuretics?
Proximal convoluted tubule
Indications of osmotic diuretics (e.g. mannitol)
- Rhabdomyolysis
- Hemolysis
- Increased intracranial pressure
- Acute glaucoma
Site of action of ADH agonists and antagonists
Medullary Collecting Duct
Diuretics causing acidosis
- Carbonic anhydrase inhibitors
2. K+-sparing diuretics
Diuretics causing alkalosis
- Loop diuretics
2. Thiazides
A drug that increases the formation of dilute urine and is used to treat SIADH is
ADH Antagonists
demeclocycline and conivaptan or tolvaptan
