45 terms

Pharmacology: Diuretics

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