In part 1, I talked renal physiology to warm you all up!๐๐
In part 2, we are talking pharmacology and how we combine๐
See ๐งต below
Iโm presenting the whole talk at the fabulous #SOA23 ..book now!
eventsforce.net
#FOAMed #POCUS #FOAMcc #medtwitter
In part 2, we are talking pharmacology and how we combine๐
See ๐งต below
Iโm presenting the whole talk at the fabulous #SOA23 ..book now!
eventsforce.net
#FOAMed #POCUS #FOAMcc #medtwitter
There are 5 classes of diuretics we can consider.
You donโt have to just use furosemide! Everyoneโs favourite loopโฆ
Letโs use our physiology and pharmacology knowledge to combine some of them, to achieve good natriuresis as well as diuresis๐๐๐คทโโ๏ธ
You donโt have to just use furosemide! Everyoneโs favourite loopโฆ
Letโs use our physiology and pharmacology knowledge to combine some of them, to achieve good natriuresis as well as diuresis๐๐๐คทโโ๏ธ
Starting:
1/3 Carbonic anhydrase inhibitors.
Acetazolamide being one.
en.m.wikipedia.org
Good for the alkalotic, fluid overloaded patient, (as many ICU a patients often are). A mild diuresis is achieved with this one, so itโs a good additive choice.
1/3 Carbonic anhydrase inhibitors.
Acetazolamide being one.
en.m.wikipedia.org
Good for the alkalotic, fluid overloaded patient, (as many ICU a patients often are). A mild diuresis is achieved with this one, so itโs a good additive choice.
2/3 it acts at the PCT.
- Na+ is actively and passively reabsorbed in exchange for H+ and K+
- HCO3- then combines with H+ in the tubule, to form carbonic acid
- Carbonic anhydrase (CA) then catalyses formation of CO2 and H2O.
- CO2 diffuses into the cell
- Na+ is actively and passively reabsorbed in exchange for H+ and K+
- HCO3- then combines with H+ in the tubule, to form carbonic acid
- Carbonic anhydrase (CA) then catalyses formation of CO2 and H2O.
- CO2 diffuses into the cell
3/3
- CO2 meets water to form carbonic acid, catalysed by CA.
- HCO3- and H+ form again
- H+ passes out in the urine and HCO3- is retained in the blood
- CA inhibitors block that process, alkalinising the urine and lowering plasma pH๐
Urine pH>8 negates their effect โ ๏ธ
- CO2 meets water to form carbonic acid, catalysed by CA.
- HCO3- and H+ form again
- H+ passes out in the urine and HCO3- is retained in the blood
- CA inhibitors block that process, alkalinising the urine and lowering plasma pH๐
Urine pH>8 negates their effect โ ๏ธ
1/3 Now thereโs the popular ones - loops! The site of action is in the name!
Furosemide / bumetanide, to name a few. They tend to be a good, safe first consideration. They promote diuresis over natriuresis though. Watch for hyponatraemia and hypokalaemia!
en.m.wikipedia.org
Furosemide / bumetanide, to name a few. They tend to be a good, safe first consideration. They promote diuresis over natriuresis though. Watch for hyponatraemia and hypokalaemia!
en.m.wikipedia.org
2/3
- Na+/2Cl-/K+ are pumped into the cell
- Na+ and K+ are also actively exchanged
- CL-/Mg2+/Ca2+ are co-transported in, aided by the fact the tubular lumen now has a resting net positive charge after the first 2 steps.
- Na+/2Cl-/K+ are pumped into the cell
- Na+ and K+ are also actively exchanged
- CL-/Mg2+/Ca2+ are co-transported in, aided by the fact the tubular lumen now has a resting net positive charge after the first 2 steps.
3/3
- Loops inhibit the Na/2Cl-/K+ pump
- There is a moderate to strong diuresis, with the side effect of electrolyte imbalance when used long-term.
- Tinnitus can result as the same pump exists in the inner ๐
They are good anti hypertensives due to natriuresis
- Loops inhibit the Na/2Cl-/K+ pump
- There is a moderate to strong diuresis, with the side effect of electrolyte imbalance when used long-term.
- Tinnitus can result as the same pump exists in the inner ๐
They are good anti hypertensives due to natriuresis
1/3 Now thereโs the thiazide diuretics.
*Have you noticed all these drugs mess with our bodyโs love of retaining sodium?!*๐๐คทโโ๏ธ
Bendrofluazide being the popular one, as well as Indapamide. These primarily work at thiazide receptors in the at the DCT.
en.m.wikipedia.org
*Have you noticed all these drugs mess with our bodyโs love of retaining sodium?!*๐๐คทโโ๏ธ
Bendrofluazide being the popular one, as well as Indapamide. These primarily work at thiazide receptors in the at the DCT.
en.m.wikipedia.org
- Na+ and CL- are co-transported across from the lumen into the blood.
- Na+ and K+ are exchanged actively
- CL- is also filtered from the lumen across into the blood, maintaining electro neutrality.
- Na+ and K+ are exchanged actively
- CL- is also filtered from the lumen across into the blood, maintaining electro neutrality.
The Na/Cl pump is inhibited by the drug, promoting a diuresis.
These, like loops, can inhibit urate metabolism and thus worsen gout.
They are a good natriuretic and anti hypertensive as a result.
These, like loops, can inhibit urate metabolism and thus worsen gout.
They are a good natriuretic and anti hypertensive as a result.
K+ sparing diuretics work at the collecting duct.
Weakly natriuretic, they are good combo drugs, but ineffective sole anti hypertensives.
Some are direct aldosterone antagonists - spironolactone
Others work directly on the Na/K pump itself - amiloride
en.m.wikipedia.org
Weakly natriuretic, they are good combo drugs, but ineffective sole anti hypertensives.
Some are direct aldosterone antagonists - spironolactone
Others work directly on the Na/K pump itself - amiloride
en.m.wikipedia.org
As you see here in the principal cell, there is exchange of Na+ and K+ under active transport. Chloride follows, again to maintain electro neutrality.
Remember, aldosterone potentiates sodium reabsorption and potassium excretion.
Remember, aldosterone potentiates sodium reabsorption and potassium excretion.
Remember osmosis?
Yup - movement of water through a semi permeable membrane from an area of high solute concentration, to a lower one, down a concentration gradient. Here it is again!
This becomes relevant when talking about the final classโฆ
Yup - movement of water through a semi permeable membrane from an area of high solute concentration, to a lower one, down a concentration gradient. Here it is again!
This becomes relevant when talking about the final classโฆ
Osmotic diuretics
Mannitol is the most commonly used, the love of the neuro unit!
Interestingly, these macromolecules actually cause a volume expansion initially.
The principal effect is at the PCT and descending loop, as these are permeable to water.
en.m.wikipedia.org
Mannitol is the most commonly used, the love of the neuro unit!
Interestingly, these macromolecules actually cause a volume expansion initially.
The principal effect is at the PCT and descending loop, as these are permeable to water.
en.m.wikipedia.org
Mannitol is non reabsorbable and prevents the normal absorption of water by interposing a countervailing osmotic force. As a result, urine volume increases.
The diuresis can result in severe hypotension, dehydration and electrolyte imbalance (hypernatraemia in particular)
The diuresis can result in severe hypotension, dehydration and electrolyte imbalance (hypernatraemia in particular)
The illustration above uses the collecting duct as the example.
Deliberate, as through their osmotic effects, they also oppose the action of ADH here.
They can reduce intracranial pressure and promote prompt removal of renal toxins (free radical scavenger๐คทโโ๏ธ๐ค)
Deliberate, as through their osmotic effects, they also oppose the action of ADH here.
They can reduce intracranial pressure and promote prompt removal of renal toxins (free radical scavenger๐คทโโ๏ธ๐ค)
I just wanted to make mention of aminophylline in here.
A nonselective adenosine receptor antagonist and phosphodiesterase inhibitor.
Dilates airways, can treat acute heart failure perhaps via a degree of inotropicity AND act as a diuretic.
en.m.wikipedia.org
A nonselective adenosine receptor antagonist and phosphodiesterase inhibitor.
Dilates airways, can treat acute heart failure perhaps via a degree of inotropicity AND act as a diuretic.
en.m.wikipedia.org
Adenosine receptor antagonism results in afferent renal arteriolar vasodilation - thus increased GFR๐
A wonder drug then๐คทโโ๏ธ Obvious side effects are tachphylaxis, tachycardia, dehydration and electrolyte imbalance.
frontiersin.org
A wonder drug then๐คทโโ๏ธ Obvious side effects are tachphylaxis, tachycardia, dehydration and electrolyte imbalance.
frontiersin.org
So:
Get to the point Jonny! What do we do in reality? How can they be combined?
This is where the JICS Mix comes in.
The combo in the table has been used very effectively for short term offloading. Remember to keep a close check on electrolytes and terminate when balance ๐
Get to the point Jonny! What do we do in reality? How can they be combined?
This is where the JICS Mix comes in.
The combo in the table has been used very effectively for short term offloading. Remember to keep a close check on electrolytes and terminate when balance ๐
Thatโs it for now. Happy natriuresis folks!
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