6. Diuretics Flashcards
Uses of diuretics?
HTN & edema (CV, renal or endocrine)
Normal GFR? Amount that ends up in urine? Amount that is reabsorbed?
125ml/min
1ml/min
124ml/min
What is the most important pump throughout the kidney for Na reabsorption?
Basal Na-K ATPase –> causes electronegatively & low intracellular [Na] –> gradient for Na absorption from lumen
It is always present. The luminal pump changes depending where you are
What does Carbonic Anhydrase (CA) do?
Convert CO2 + H2O into carbonic acid/H2CO3 (in lumen) & the reverse of this same reaction (within renal cell)
What is the overall “goal” of CA actions with regard to Na absorption?
Lumenal pump brings Na into the cell & pumps H into the lumen
The overall goal of CA is to use bicarb absorption cycle to provide Hs for the Na pump
How is bicarb & H movement tied to Na absorption in the proximal tubule?
H is pumped out of the renal cell (into the lumen) while Na is pumped inside the cell
H is then attached to bicarb (HCO3-) to form carbonic acid (H2CO3)
Carbonic Anhydrase converts carbonic acid into CO2 & H2O in the lumen
CO2 & H2O diffuse into cell
CA converts CO2 & H2O back into carbonic acid
Carbonic acid donates it H (to the Na pump) & then is pumped out of the basal bicarb pump
How much of Na absorption happens in the proximal tubule? TAL of Loop of Henle? Distal Convoluted Tubule? Collecting Duct?
50%
25%
10%
5%
What is Acetazolamine?
CA inhibitor that acts in the proximal tubule to decrease Na absorption
What diuretic acts on the proximal tubule?
Acetazolamine
What is the adverse side effet that limits current usage of Acetazolamine? What is an “unconventional” use of the drug?
Acidosis (no longer pumping out H in exchange for Na)
Treat altitude sickness (acidosis increases Hb release of O2)
What pump is involved with Na absorption in the TAL?
A lumenal pump which pumps Na & K (and 2 Cl which isn’t really important) into the cell
How is Na absorption in the TAL related to Mg & Ca absorption? How do loop diuretics cause Mg & Ca loss?
K is pumped into the cell with Na
High intracellular K causes K to move back into the lumen via K leak channels
This movement of K back into the lumen creates a + charge which drives Mg & Ca to be absorbed via paracellular routes
If block Na absorption –> block K movmement through leak channel –> no driving force for Mg or Ca –> Ca & Mg stay in lumen & are excreted
What diuretic acts on the TAL of the loop of henle?
Furosemide
What is Furosemide?
Diuretic which blocks action of Na/K/Cl pump in TAL of loop of henle
What is the most powerful diuretic?
Furosemide
What is the loop diuretic?
Furosemide
What are the uses of Furosemide?
Pulmonary edema
CHF
Renal disease (increase RBF & increase urine output in acute renal failure)
Hypercalcemia
Adverse effects of furosemide?
Hypocalcemia Hypomagnesium Hypokalemia Hypovolemia Hearing loss
What type of diuretic increases Ca & Mg secretion? Which increases Ca absorption?
Furosemide (Loop diuretic)
Thiazides (DCT)
What diuretic acts on the DCT?
Thiazides
What are thiazides?
Diuretic which blocks Na-Cl pump in the DCT
How is Ca flow related to Na reabsorption in the DCT? How do thiazides cause increase Ca in the body?
If block Na pump on lumen with thiazides –> no Na coming into cell, but Na is still leaving the cell due to basal pump –> very low Na inside cell –> causes Na to move back into the cell via a basal Ca-Na pump
In this way, Na is “uselessly” cycled from inside the cell to outside via the Na-K & Na-Ca pumps. Every time Na goes through this cycle a Ca is reabsorbed
Which type of diuretic is moderately powerful?
Thiazides
Uses of thiazides?
HTN
Hypercalciuria & renal stones
Osteoporosis
DI (decrease polyuria)
NOT effective for renal disease
How is Na reabsorbed in the CD?
Na brought into the cell without an accompanying anion –> increase + charge within cell –> causes K to be secreted
What are the NON-Potassium sparring diuretics? How do they cause K loss?
Acetazolamine
Furosemide
Thiazide
All increase the amount of Na in urine. CD tries (& fails) to off set this by absorbing more Na which is linked to K secretion
What are the Potassium sparring diuretics? How do they prevent K loss?
Spironolactone
Triamterene & Amiloride
Na aborption is coupled to K secretion. Both are inhibited
What is natriuresis?
Na excretion
What are the natriuretic effects of non-K sparring diurectics transient?
Compensation mechanisms (Ang, aldosterone, ADH) compensate after 2 weeks
If somebody has Hyokalemia, what is/are the diuretic(s) that will correct the problem fastest?
Amiloride & Triamterene
What are Amiloride & Triamterene? How do they work?
Diuretics that block Na transporter in CD
What is Spironolactone? How does it work?
Diuretic that blacks the action of aldosterone in CD –> decreased activity of aldo transcription factor –> less creation of Na-K pump & Na transporter
Which diuretics work in the CD?
Spironolactone
Amiloride & Triamterene
What is the lumenal Na tansporter in the CD called?
ENaC (epithelial Na channel) in the principal cell
Which diuretics are weak?
CD diuretics
What are the uses of the CD diuretics?
Used in conjunction with other diuretics to prevent K loss (too weak to work by themselves for HTN)
Spironolcatone is used for Conn’s syndrome (primary hyperaldosteronism) & hepatic cirrhosis (secondary hyperaldosteronism)
Which diuretic has a slow onset of action? Why?
Spironolactone
Is effecting protein expression, not the transporters directly
What are the adverse effects of CD diuretics?
Hyperkalemia (especially if in combo with beta blockers or ACE inhibitors)
What is the osmotic diuretic?
Mannitol
What is mannitol? How does it work?
Osmotic diuretic
Increase plasma osmolarity –> increase fluid extraction from bodies interstitial space
Increase osmolarity in the kidney lumen (mannitol filtered & not absorbed) –> less of a driving force for water absorption –> water loss
Uses of manitol?
Reduce ICP in cerebral edema
Reduce intraocular pressure in glaucoma
Maintain renal function in acute renal failure
Adverse events with manitol?
Expansion of ECF volume –> pulmonary congestion or heart failure
Which drug can cause gynecomastia in males & menstrual abnormalities in females? How?
Spironolactone
Cross reactivity with other steroid receptors
