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What are the 2 major determinants of urinary volume and composition

1) Glomerular filtration
2) Tubular transport

Most diuretics work by

Inhibit renal reabsorption of ions and water

Name 4 conditions that diuretics are commonly used for

Renal disease, hypertension, CHF, edema

Carbonic anhydrase inhibitors work at what site


Osmotic diuretics work at what site

PCT and descending loop (where water can move through in or out of the nephron)

Thiazides work where?


Loop Diuretics work on the

Ascending loop

Potassium sparing diuretics work on the

Collecting ducts and DCT

All of the diuretics affect sodium transport besides

Osmotic Diuretics

Osmotic diuretics MOA

Increases the osmotic concentration > brings water into the blood or tubule and decreases water reabsorption (keeps the water in the tube) (takes water from intracellular and causes it to be extracellular) as well as limit renal reabsorption passively

What affect do osmotic diuretics have on renin

Inhibits renin because causes more fluid inside blood vessels and therefore increases blood pressure > body won't want to release renin

Osmotic diuretics have what effects on urine and key ions

Increases excretion of all and increases volume of urine

What is bad about osmotic diuretics

Can increase extra-cellular fluid and lead to pulmonary edema in people with CHF

What are 3 other adverse effects of osmotic diuretics?

Hypersensitivity, glycerol metabolism > hyperlycemia and glycosuria, headache, N & V

Osmotic diuretics are used for

CSF pressure reduction, intraocular pressure reduction, and prophylaxis of renal failure

The increased blood flow due to osmotic diuretics will cause?

Limited reabsorption so the reabsorption of things like sodium and urea are going to be less, thus reducing the medullary concentration of these molecules which will in turn inhibit the reabsorption of water from the descending tubule

Methylxanthenes mild diuretic MOA

Increase HR thereby increasing CO which increases GFR thus inhibiting sodium reabsorption because more liquid is going through tubule at a faster rate

Do osmotic diuretics work only in the kidney?

No they work systemic also

Carbonic anhydrase normal function

Step 1: In the PCT as Na gets pumped in H gets pumped out > the combines with bicarbonate in the tubule to form carbonic acid > luminal carbonic anhyrase turns carbonic acid into CO2 and water > the CO2 diffuses into the luminal cell and combines with water > cellular carbonic anhydrase takes CO2 and water to make carbonic acid once again > an H dissociates and is pumped out (step 1) and then the bicaronate goes into the blood to bind proteins (H+)

So what do carbonic anhydrase inhibitors do

Block the breakdown of carbonic acid to CO2 and water

Why do we care and what does this have to do with diuretics?

If we don't make carbonic anhydrase in the cell and it doesn't dissociate to make H and HCO3 then there is no H to be pumped out of the cell whenever sodium is reabsorbed and therefore sodium reabsorption doesn't occur

What is bad about blocking the carbonic anhydrase?

There is no bicarbonate to bind H+ in the blood > overtime can get acidosis

What is the only other adverse effect of carbonic anhydrase inhibitors?

Allergic reactions in patients hypersensitive to sulfonamides

What affects do CAIs have on urine volume and the major electrolytes?

Increase in everything but great increase in K+ excretion

These diuretics do what to the acidity of urine

Decrease it

Where do CAIs work at


Major indication for CAIs

Open-angle Glaucoma

Why glaucoma?

There is carbonic anhydrase in the eye, inhibiting it will decrease the rate of aqueous humor formation

Where do thiazides work


Thiazide MOA

Block Na/Cl symporter in DCT > increased sodium in urine > keeps water in tubule

Thiazide effects on urine volume and major electrolytes

Increase in all but reduce in Ca2+ excretion

Thiazides are used for what 4 things

Idiopathic hypercalcinuria
Diabetes insipidus

Adverse effects of thiazides (3)

Electrolyte imbalance
Increase in LDL and triglycerides
Drugs removed by renal excretion may be less effective

Thiazides should absolutely not be used with what agent

Quinidine (antiarrhythmic); leads to VTach and VFib due to hypokalemia

Loop diuretics are the

Strongest diuretics

Loop MOA

Block NA, K, 2Cl transporter

Where do loops work

Ascending tubule

Loop effects on urine volume and major electrolytes

Increases K+ excretion and greatly increases everything else

Use of Loop diuretics

Edema due to CHF, nephrotic syndrome, heart failure with pulmonary edema, hypercalcemia, cirrhosis

Loops are normally not used for

Hypertension (short half life)

Adverse effects of loop

Hypokalemia, hyponatremia, hypocalcemia, hypercholesterolemia, hyperglycemia, dehydration, postural hypotension, hypocalcemia, hypersensitivity, ototoxicity

Spironolactone MOA

Aldosterone antagonist ; blocks aldosterones effect in collecting ducts, Na channels don't get made

Triameterene and amiloride MOA

Inhibit electrogenic Na+ transport in DCT

Treatment of primary aldosteronism use


Potassium sparing diuretics on urine volume and major electrolytes

Slight increase in everything, K+ excretion reduced

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