Diuretics Flashcards
Which class of diuretics acts on the PCT?
carbonic anhydrase inhibitors
Explain the mechanism of action of diuretics that reduce potassium loss during sodium diuresis and provide two examples.
Potassium-sparing diuretics work in the collecting duct. They block sodium uniport channels that exclusively reabsorb sodium. Usually, this sodium reabsorption is coupled with excretion of a potassium ion to maintain charge balance. So, blocking sodium reabsorption here will reduce potassium secretion, but still cause diuresis. Two examples are amiloride and triamterene.
How do loop diuretics cause diuresis?
inhibition of the Na/K/2Cl transporter in the loop of Henle
What are the three thiazide-like diuretics?
(1) Indapamide (Lozol)
(2) Chlorthalidone (Hygroton)
(3) Metolazone (Diulo, Zaroxolyn)
Which class of diuretics is the most effective?
loop diuretics
Which loop diuretic can be used in patients with a sulfa allergy?
ethacrynic acid (Edecrin)
Describe how osmotic diuretics work and provide an example.
Osmotic diuretics provide an osmotic force that keeps water in the urine despite sodium reabsorption.
What are the toxicities associated with aldosterone antagonists?
(1) hyperkalemia
(2) hyperchloremic metabolic acidosis
(3) BPH
(4) gynecomastia
(5) impotence
What are the indications for osmotic diuretics?
reduction of intracranial/intraocular pressure, increase urine volume
What are the toxicities associated with loop diuretics?
(1) hypocalcemia/hypomagnesemia
(2) dehydration
(3) saline-responsive metabolic alkalosis
(4) ototoxicity
(5) hyperuricemia
Which diuretic is administered as a prodrug?
ethacrynic acid (Edecrin)
What are the indications/contraindications of CA inhibitors?
indications:
(1) acute mountain sickness
(2) glaucoma
(3) metabolic alkalosis
(4) urinary alkalinization (drug trapping)
contraindications:
(1) metabolic acidosis
(2) sulfa allergies
Because they increase renal blood flow, this class of diuretics can be used in cases of acute renal failure.
loop diuretics
These diuretics block sodium chloride reabsorption in the DCT.
thiazides and thiazide-like
Describe the characteristic structure of thiazide diuretics.
two connected rings, sulfa moiety, chlorine substituent
What are the toxicities associated with thiazide diuretics?
(1) decreased carbohydrate tolerance
(2) hypokalemic metabolic alkalosis
(3) hyperuricemia (same as loops)
(4) hyperlipidemia
(5) hyponatremia
What are the indications of ADH antagonists, and one example?
SIADH, or any situation in which ADH levels are acutely elevated
example provided is Demeclocycline (Declomycin)
Both amiloride and triamterene share two common contraindications (which are?), but triamterene has an additional one, which is ________.
They share K supplements and ACE inhibitors because they both increase serum potassium, but triamterene is also contraindicated in patients with kidney stones due to poor solubility.
Which toxic effects can occur with excessive administration of ADH antagonists?
(1) nephrogenic diabetes insipidus
(2) renal failure
Which aldosterone antagonist can be used for hypertension or CHF in combination with other diuretics?
spironolactone (Aldactone)
There is some evidence of chronically elevated aldosterone levels and damage to cardiac tissue involved in CHF.
Which two structural modifications will increase natriuretic/diuretic activity of CA inhibitors, but decrease their CA inhibiting effect?
(1) amine substitution
2) substitution of sulfamoyl with another electrophilic group (carboxylic acid, etc.
Which structural motif is required for CA inhibitor activity?
unsubstituted sulfamoyl group
What toxicities are associated with carbonic anhydrase inhibitors?
(1) renal potassium wasting
(2) renal stones
(3) drowsiness/paresthesia
(4) hyperchloremic metabolic acidosis
Explain how thiazide diuretics cause increased calcium reabsorption.
As less sodium is brought into tubular cells and eventually into peritubular capillaries, sodium-calcium antiporters are activated and bring some of that sodium back into the cell while pumping calcium out. This lowers intracellular calcium levels, so more is brought in from the urine.
What are some clinical uses of loop diuretics?
(1) edematous conditions, specifically pulmonary edema
(2) decrease calcium/mag reabsorption
(3) increase renal blood flow