Diuertics Flashcards
What is a more appropriate name for diuretics
Natriuretics
-actually implies that you are losing Na, water follows
What works at the proximal convoluted tubule
Acetaxoalmide
CAI
What works at the descending loop of Henle
Nothing, no drugs target this specific area
What drugs target the ascending loop of henle
Loop diuretics
Furosemide
What drugs target the distal convoluted tubule
Thiazides
What drugs target the collecting ducts
K+ sparing diuretics
Spironolactone, amiloride
How does acetazolamide (CAI) work at the proximal convoluted tubule
Inhibits reabsorption of HCO3- in the proximal convoluted tubule
How do loop diuretics work int he ascending loop of henle
Inhibit the Na/K/Cl cotransporter , resulting in the retention of Na, Cl, and water
How do thiazides work in the distal convoluted tubule
Inhibits reabsoprtion of Na and Cl in distal tubule, resulting in retention of water
What is the most commonly used diuretics
Thiazides
What is the most efficious diuretics
Loop
How do K+ sparing diuretics like spinronolactone and amiloride work in the collecting duct
Spironolactone is an aldosterone antagonsit, mediates reabsorption of Na and secretion of K
Amiloride block Na channels
Prevent loss of K
Where does most bicarbonate get reabsorbed
Proximal convoluted tubule
Where does most water get reabsorbed (and Na)
Proximal convoluted tubule
As you move through the nephron, how is Na reabsorbed
Less and less. Most reabsoprtion in the proximal convoluted tubule
How do you want to stop water reabsoprtion in the proximal convoluted tubule
Block H to indirectly block luminal Na pump
- H comes from bicarbonate in urine
- CA breaks down HCO3- into CO2 and water
- now can move into cell
- more CA in cell puts it back together to get HCO3-
- HCO3- can one get reabsorbed into the blood
Use Carbonic anhydrase inhibitor to block the H
Luminal pump in the proximal convoluted tubule
Na/H pump
Basolateral membrane pump in proximal convoluted tubule
Na/K pump
-puts the Na back in the blood
How does carbonic anhydrase inhibitor work in the proximal convoluted tubule?
- if CA is inhibited, can no longer break down HCO3-
- H20 and CO2 cant move into the cell and cant form H inside the cell
- Na stays in the urine (along with water), this is how it works as a diuretic
also not reabsorbing any bicarbonate
-results in metabolic acidosis, peeing out bicarbonate
What is a side effect of CAI used systemically
Metabolic acidosis. Not reabsorbing any bicarbonate, peeing it out
What what do we use CAI in order to not get the side effect of metabolic acidosis
Used topically for glaucoma
What part of the loop of henle do we target with drugs
Thick ascending limb
What do loop diuretics do to calcium
Lose calcium
What kind of luminal pump does the loop of henle have
Na/K/Cl pump
-all get into the cell
In the loop of henle, what does the influx of K do through the Na/K/Cl pump?
Increases intracellular K, which is already high. There is another channel for the cell to just leak it back out into the urine.
- this changes membrane potential and causes the cells to separate from each other a little bit
- when this happens, Mg and Ca2+ can get reabsorbed
How does Ca and Mg get reabsorbed in the nephron
In the ascending loop of henle, K is pumped into the cell via Na/K/CL pump. Since intracellular K is already high, the cell leaks the K back out into the urine. This causes a membrane potential change which then separates the cells a little bit. When this happens, Mg and Ca can get reabsorbed through that space between the cells
What happens if K does not come in and then leak out in the ascending limb of henle?
Do not reabsorb Mg and Ca
How do loop diuretics work
Block the Na/K/Cl transporter
- can reabsorb Na (or water)
- decrease K into the cell, no membrane potential change, no reabsorbtion of Mg to Ca, pee it out.
- loops stop all 5 of these ions from reabsorbing
Which kind of drug will prevent Ca or Mg reabsoprtion
Loop diuretics like furosemide
What kind of drugs save calcium
Thiazides
What do thiazides do to Ca
Save it
What is the luminal transporter in the distal convoluted tubule?
Na/Cl transporter
Also has a Ca2+ channel in it too
Ca2+ channel and the Na/Cl transporter in the distal convoluted tubule
- pathway for Ca to be reabsorbed
- PTH regulates this
- takes calcium out of urine and puts it into blood
What do thiazides block?
The Na/Cl transporter in the distal convoluted tubule
How do thiazides work in the distal convoluted tubule
Block the Na/Cl transporter
-Na stays in the urine=diuretics
How does blocking the Na/Cl transporter in the distal convoluted tubule effect Ca
Leaders to increased Ca2+ reabsorption
-if you block the Na/Cl pump, it will increase the activity of the Na/Ca pump that is present on the basolateral membrane to make up for the lack of Na being brought in, causing more Ca2+ reabsoprtion
Postmenapausal women and diuretics
Give thiazides to decrease risk of osteoporosis
What direction should you give to increase blood Ca?
Thiazides
What diuretics will decrease urinary Ca?
Thiazides
What regulates Ca2+ being absorbed
PTH
Where are the principal and intercalated cells found in the nephron
In the collecting tubule
What are the transporter on the lunminal side of the collecting tubule?
Principle cells
- Na channel
- K channel
Intercalated cell
-H transporter
why are most diuretics K wasting?
The collecting duct doesn’t see much Na because it is the last place for Na to be reabsorbed
- but if on a diuretic, more Na here
- leads to increased K loss
Na and K in the principle cells of the collecting tubules
Na comes in and K goes out, it is a coupled process
When the principal cells of the collecting tubule secretes K, what do the intercalated cells do
Secrete H+ back into the urine along with it
K loss in the collecting duct equals what
H loss
If something is K wasting, what else is it?
H wasting
Hypokalemia=alkalosis
If something is K sparing, what else is it
H sparing
Hyperkalemia=acidosis
How does amiloride work in the collecting tubule
Blocks the Na pump
- K+ sparing because now K+ not leaving
- also H sparing too
- acidosis and hyperkalemia
Which drug that works in the collecting tubule will cause acidosis and hyperkaleima?
Amiloride
- blocks the Na pump
- K+ sparing because now K not coming in either
- this also means that H is being spared
How does aldosterone work in the collecting tubule
- retains Na/H20 by binding its receptors there
- increases Na reabsorption which increases water reabsorption
- wastes H and K
What is a problem in the collecting tubule that can lead to hypokalemia and alkalosis?
Hyperaldosteronism
How do spironolactone and eplerenone work in the collecting tubule
- block the aldosterone receptors
- does not increase Na, so not wasting K or H
What is the exception to the rule for K and H being lost together when things work on K in the collecting duct?
Carbonic Anhydrase Inhibitors
- cause K loss
- but cause acidosis
- cant reabsorb bicarbonate
What is the name of the Carbonic Anhydrase Inhibitor used
Acetazolamide
What are CAI most commonly used for
Eyedrops for glaucoma
MOA of CAI in the eye
Inhibits CA in the ciliary body of the eye where it decreases the rate of aqueous humor formation (and decreases IPO)
MOA of CAI
Can’t break down HCO3
- stays in the urine
- water and CO2 can’t move into the cell
- cant form H inside the cell
- Na and water stay in the urine as well.
Need H to make the Na/H pump work, otherwise, cant get Na into the cell
Therapeutic uses of CAI (acetazolamide)
- glaucoma: closed angle glaucoma
- acute mountain sickness: above 10,000. Prevents weakness, breathlessness, dizziness, nausea, and cerebral and pulmonary edem by inducing acidosis before you go into the mountains
Adverse effects of CAI (acetazolamide)
Metabolic acidosis (2-3 days of use) if used systemically
What is a common name for CAIs
Anything that ends in -zolamide
MOA of loop diuretics (furosemide, “-semide”)
Blocks the Na/K/Cl transporter
- cant reabsorb Na or water
- decreased K into cell, decreases Mg, and Ca reabsorbtion as well
Therapeutic uses of loop diuretics (furosemide)
- acute pulmonary edema
- CHF (thiazides better choice, but loop used acutely if waking up with swollen feet)
- edema
Pharmacokinetics of loop diuretics
Short half life
Duration of action is 1-4 hours
Adverse effects of loop diuretics (furosemide)
Ototoxicity: tinnitus, hearing impairment, sense of fullness in ears
-occurs due to inhibition of Na/K/Cl cotransporter in the inner ear
Hypokalemia alkalosis
-wastes K and H
MOA of thiazides
Block the Na/Cl transporter in the distal convoluted tubule
- Na stays in the urine
- increased Ca reabsoprtion
What are the thiazides most commonly used
HCTZ and chlorthalidone
Therapeutic uses of thiazides
- HTN
- CHF
- Hypercalciuria: good for patients with calcium stones in the urinary tract. Pull Ca2+ out of urine and put back into blood.
- nephrogeniic diabetes insipidus
How does a diuretic like thiazides work for diabetes insipidus
Pt has trouble repsponding to ADH receptor and loses a lot of water without Na
- give diuretic
- will lose Na now, along with the water
- plasma vol decreases, which causes increased RAAS
- ANGII on the PCT will cause reabsoprtion of more Na and now water too
Adverse effects of thiazides
Hypokalemia alkalosis
Hypercalcemia
Hyperglycemia and hyperlipidemia
Why do thiazides cause hyperglycemia and hyperlipidemia
Inhibiting insulin release from beta cells
Which K sparing drugs are used for heart failure
Spironolactone and eplerenone
How do spironolactone and eplerenone treat heart failure
Block aldosterone
What are the weakest diuretics
K sparing
- spironolactone
- eplerenone
- amiloride
When do we use K sparing drugs
In combo with other diurites
Which K sparing drug is not used for heart failure
Amiloride
MOA of spironolactone and eplerenone
Aldosterone receptor antagonists
Therapeutic uses of spironolactone and eplerenone
- diuretics
- hyperaldosteronism
- heart failure
- female hirsutism (only spironolactoen)
Which K sparing drug works well for female hirsutism
Spironolactone because it also blocks the androgen receptor
Adverse effects of spironolactone and eplerenone
Spironolactone may cause hynecomastia in males and irregular menstrual cycle in females
Hyperkalemia
MOA of amiloride
Block the Na channels in collecting tubules
Actions of amiloride
Used in combo with other diuretics to maintain normal K levels
Adverse effects of amiloride
Hyperkalemia
