Flashcards in Diuretics Deck (40)
What are the general uses of diuretics?
(1) Edema (accumulation of fluid in body in cardiovascular, renal, endocrine disease)
(3) Other diseases (described later)
What is the functional unit of the kidney?
T/F Mechanism of Na re-absorption is the same the each segment.
FALSE; it diffes in various segments
How much GFR do you have per minute? How much urine actually leaves the body?
125 ml/min; only <1ml/min
What is the mechanism of Na re-absorption? (4)
(1) Unidirectional transport of Na is dependent on the polarity of the renal tubular cells
(2) Na transport proteins are present only in luminal or apical membrane
(3) Na-K-ATPase present only in basal and lateral membrane
(4) Two membranes are separated by tight junctions
What drug works in the proximal tubule? What is its mechanism of action? Is this a direct or indirect effect?
Acetazolamide; carbonic anhydrase inhibitor inhibit NaHCO3 reabsorption; indirect effect (blocks the activity of bicarbonate transport which indirectly blocks the sodium transport)
How much Na is reabsorbed in the proximal tubule?
~50% of filtered Na (and water)
What drug works in the Thick Ascending Limb of the Loop of Henle? What is its mechanism of action? Is this a direct or indirect effect?
Furosemide; inhibits NaCl reabsorption from Na/K/2Cl cotransporter (inhibitor); direct
What are the most powerful diuretics?
Loop diuretics (Furosemide)
(1) Pulmonary edema, chronic heart failure
(2) Increases renal blood flow which is useful in patients with renal disease
(3) Increase urine flow in acute renal failure
(4) Increase Ca excretion, useful in hypercalcemia
Furosemide- Adverse effects
(1) Increase K excretions, causes hypokalemia
(2) Increase Mg excretion, prolonged use causes hypomagnesemia
(3) Large doses may cause hypovolemia (circulatory collapse)
(4) Large doses may cause hearing loss, especially when given with aminoglycoside antibiotics
How much NaCl is reabsorbed in the Loop of Henle?
What drug works in the DIstal Tubule? What is its mechanism of action?
Thiazides (Hydrocholorthiazide); blocks the Na/Cl co-transporter
How much NaCl is reabsorbed in the Distal Tubule?
T/F Furosemide and Hydrocholorothiazide do not interact.
What is the difference between Furosemide and Hydrocholorothiazide?
Hydrochlorothiazide increases Ca retention instead of excretion which is important for calcium regulation
What are the 2 ways in which Thiazides induce Ca retention?
(1) Increased passive paracellular reabsoprtion
(2) Increase reabsorption in the DCT
- Hypertension, either alone or in combination with other drugs
- an increase in serum Ca with long-term use is useful for osteoporosis
- reduce Ca excretion and are useful in idiopathic hypercalciurea to prevent calcium stone formation
- useful in decreasing polyuria in nephrogenic diabetes insipidis (unknown mechanism)
What is the difference between early fall (1-2 weeks) and late fall of Hydrochlorothiazide?
- Early fall in BP is due to decrease in extracellular fluid
- Late fall in BP is due to decrease in proximal reabsorption
Hydrocholorothiazide- Adverse Effects
- Increase K excretion and cause hypokalemia
T/F Hydrochlorothiazide is not effective in renal disease.
What drugs are used within the collecting duct? What is their mechanism of action?
Spironolactone (aldosterone receptor antagonist); triamterene & amiloride (block epithelial Na channels)
How much NaCl is reabsorbed in the collecting duct? Why is it important to have a diuretic for such a small amount of NaCl reabsorption?
~3-5%; they are potassium sparing diuretics (when you are using other diuretics this is where the loss of potassium occurs)
What is the transient natriuresis of diuretics? (3)
(1) Diuretics produce transient natriuresis
(2) After 1-2 days there is an activation of compensatory salt retaining mechanisms (release of angiotensin, aldosterone and ADH, and hyperactivity of distal segments)
(3) There is a new balance between intake and excretion of Na as long as the diuretic is continues
How does hypokalemia occur in the collecting duct?
Renal compensation is going to reabsorb Na in the CCD which is coupled to K secretion which causes hypokalemia
Spironolactone is an aldosterone antagonist. What does aldosterone receptor do?
The aldosterone receptor is a transcription factor that induces the genes encoding the epithelial sodium channel and the sodium/potassium ATPase
Why are potassium-sparing drugs used in combination with thiazides or loop diuretics?
because they prevent K loss from the body
(1) Primary hyperaldosteronism (Conn's syndrome) and Secondary hyperaldosteronism due to hepatic cirrhosis complicated by ascites
(2) slow onset of action, requiring several days for full effect
Adverse effects of potassium sparing diuretics?
Hyperkalemia that is increased in patients with renal disease
- the risk is increased when used with antihypertensive drugs (B blockers, ACE inhibitors)