Diuretics Flashcards
What is an example of an osmotic diuretic?
Mannitol, possibly glucose
What is acetazolamide?
A carbonic anhydrase inhibitor
What are some examples of thiazide diuretics?
Hydrochlorothiazide, metolazone
What are some examples of loop diuretics?
Furosemide, bumetanide, ethacrynic acid (non-sulfonamide)
What are some examples of potassium sparing diuretics?
Spironolactone, eplerenone
What is conivaptan?
An anti-diuretic hormone antagonist
What is dapaglifozin?
A sodium glucose transport inhibitor
3rd line drug
What is a diuretic?
An agent that increases urine flow to block sodium reabsorption/increase sodium excretion
What is the typical GFR?
100-120 ml/min
What occurs in the proximal tubule?
Glucose and HCO3 (bicarbonate) are reabsorbed
What occurs in the ascending loop of henle?
Na, K and 2 Cl are pumped out and Ca and Mg follow
Water is not reabsorbed
What occurs in the distal tubule?
NaCl is reabsorbed
Ca is excreted
What occurs in the collecting ducts?
Water is reabsorbed in the presence of ADH (vasopressin) to concentrate urine
Na is reabsorbed while K is excreted when aldosterone is present
What are osmotic diuretics?
Osmotically active (hold onto water) compounds in the plasma. Stops water reabsorption, giving a high urine volume with little sodium
Filtered, not reabsorbed, pharmacologically inert and resistant to alteration
Mannitol, glucose
What can osmotic diuretics be used for?
Mannitol (IV), glycerol (oral) used for vascular surgery, renal transplant and opthalmological procedures
How can glucose become an osmotic diuretic?
In diabetes mellitus, there is so much glucose in the blood that it is not all reabsorbed in the proximal tubule. The glucose goes to parts of the kidney that have never seen it and holds onto water.
What are carbonic anhydrase inhibitors?
Very weak diuretics that inhibit carbonic anhydrase. Thus decreases HCO3 reabsorption and increases HCO3 excretion (with some Na) in proximal tubule
Acetazolamide
What are the uses of carbonic anhydrase inhibitors?
Severe alkalosis
Alkalinization of filtrate ionizes acidic drugs (increases renal excretion of aspirin)
Glaucoma
What is acute mountain sickness?
When someone goes to high altitudes and they hyperventilate due to the decreased oxygen. This causes decreased CO2 (increased bicarbonate)
What do thiazide diuretics do?
Increase NaCl excretion and decrease Ca excretion in the distal tubule (opposite of loop diuretics)
Some proximal tubular effect, only important when combined with loop
Hydrochlorothiazide
Up to 5% off filtered load
How does dose of thiazide diuretics affect its effect?
Lower dose is just as effective as higher dose, just takes longer to work. Will have fewer side effects.
What can thiazide diuretics do to blood pressure?
May decrease blood pressure with decreased blood volume and cardiac output. An apparent tolerance occurs (no diuresis) as blood volume and Co return to normal. But blood pressure stays low or lowers due to the decreased peripheral resistance (vasodilation)
What are the advantages of using a thiazide diuretic?
It is orally active with low toxicity. Gives no postural hypotension.
Can potentiate other antihypertensive drugs
What problems could thiazide diuretics cause?
Hyperglycemia due to decreased insulin release and tissue utilization
Increased LDL levels
Erectile dysfunction
Hypovolemia
What happens due to hypovolemia?
Increased proximal tubule reabsorption which could increase lithium and urea (bad for gout) absorption
What are thiazide diuretics used for?
Edema and hypertension
What do loop diuretics do?
Increase prostaglandin production (vasodilation)
Increases Na, Cl, K and Mg excretion
Should loop diuretics be used for a long period of time? Why?
Not too long. They are very potent and efficacious high ceiling diuretics (up to 20% off filtered load) which could cause too much fluid loss.
What diuretic can be used in acute pulmonary edema?
Loop diuretics due to venous vasodilation
What drug can decrease the function of loop and thiazide diuretics?
NSAIDS
What might loop diuretics do to the urine? How?
The kidney may lose the ability to dilute or concentrate the urine, making it isotonic.
If you drink a lot water, it will excrete electrolytes to make it isotonic
What problems can loop diuretics cause?
Deafness when combined with aminoglycoside antibiotics
Chronic dilutional hyponatremia due to isotonic urine
What are loop diuretics used for?
For renal insufficiency (GFR
What do you do if a patient is not responding to a loop diuretic?
If refractory, add a thiazide diuretic because their blocking in the proximal tubule increases the delivery to the loop, giving the loop diuretic something to block
What are the 2 major causes of potassium depletion?
Secondary hyperaldosteronism and increased distal delivery
How can secondary hyperaldosteronism cause potassium depletion?
Plasma volume depletion causes an increase in renin which thus causes the activation of angiotensin II and increases aldosterone. This causes pumps to work to reabsorb Na at the expense of K
How can increased distal delivery cause a postassium depletion?
The increased distal delivery is due to inhibition of Na reabsorption in the loop and distal tubule
Collecting tubules will then increase Na reabsorption to conserve sodium
How can potassium depletion be treated?
Dietary intake (apricots, bananas)-not helpful KCl tablets Slow K tablets IV 40 meq KCl in emergencies K sparing diuretics
What are potassium sparing diuretics?
Weak diuretics given with other diuretics to decrease K loss but may cause hyperkalemia
Never combine with K supplements
Work is collecting tubule
What do spironolactone and eplerenone do?
Blocks aldosterone receptor which causes reabsorption of Na at expense of K.
What does triamterene do?
Decrease sodium permeability so K is not excreted.
What else can increase plasma K levels?
beta-adrenoceptor antagonists, ACE inhibitors and ARBs
What do ADH antagonists do?
Blocks the ADH receptor in the collecting tubules so vasopressin is unable to increase water reabsorption.
Thus increases water excretion without the electrolytes
What happens to vasopressin in heart failure and syndrome of inappropriate ADH secretion (SIADH)?
Vasopressin is increased, so there is chronic increased water reabsorption which can produce hyponatremia
What are ADH antagonists used for?
Syndrome of inappropriate ADH secretion (SIADH) when water restriction alone is not effective
What is nephrogenic diabetes insipidus?
Increased urine flow due to the lack of a renal effect of ADH
Bitter urine
What do sodium glucose co-transport 2 (SGLT2) inhibitors do?
Blocks the sodium glucose cotransporter in the proximal tubule to increase glucose excretion.
Causes small decrease in blood glucose
What causes sodium and extracellular volume depletion?
Inability of kidney to concentrate or dilute urine (isotonic urine) due to furosemide
Inability to concentrate urine (save water) -Drink more wayer to excrete solutes
Inability to dilute urine (excrete excess water)-Ingest hypotonic solution
What should be done in the case of hypocalciuria?
Use thiazide diuretics to decrease Ca excretion
Use in the case of stones in the ureter
What should be done in the case of hypercalcemia?
Use furosemide to increase Ca excretion
What happens during volume depletion and increased proximal tubule reabsorption?
Uric acid excretion is initially increased but then decreased
The proximal reabsorption of lithium is increased (toxic)
What does it mean if edema is present?
Fluid shift into the extra cellular space has exceeded 3-4L
Salt and water retention
Congestive heart failure, hepatic cirrhosis, renal failure
What is the first line therapy for hypertension?
Thiazide diuretic or good as a second medication
What occurs during cardiac failure?
Decreased blood pressure (kidney retains Na and H2O) causing increased intravascular volume and increased left ventricular filling pressure (but decreased contractility) and increased pulmonary and venous pressure (loop diuretic useful)
