renal essay - pharmacology Flashcards
What class of diuretic is frusemide?
Loop diuretic
What transporters does frusemide inhibit, and where?
NKCC2 co-transporters on the apical surface of the thick ascending loop of Henle
What is the effect of frusemide blocking NKCC2 co-transporters?
Reduced sodium reabsorption in the loop of Henle increases the delivery of sodium to the distal tubule above its reabsorptive capacity. This results in a net loss of sodium and therefore water.
How is frusemide delivered to its site of action in the Loop of Henle?
It is 98% protein bound, so cannot be filtered at the glomerulus. Instead, it enters the vasa recta and is taken up by OATs (organic anion transporters) on the basolateral surface of tubular cells and delivered to the tubular lumen where it can act of NKCC2 co-transporters.
What is the effect of frusemide at the macula densa?
Inhibition of NKCC2 co-tranpsorters impair Tubuloglomerular Feedback. This prevents the release of renin, as there is increased sodium levels in the distal tubule
What is the effect of frusemide outside of the kidneys?
Vasodilatory effect in systemic vasculature, increasing venous capacitance
Why must the dose of frusemide be increased in patients with renal impairment and proteinuria?
Albumin that has entered the urinary space due to an interrupted filtration barrier will rebind to frusemide in the tubule, reducing the amount of active drug. In addition, hypoalbuminaemia will reduced frusemide delivery to the kidneys, increasing the volume of distribution.
Why is frusemide contraindicated in patients with gout?
it can potentiate urate reabsorption
Why is the dose requirement for frusemide higher in a metabolic acidosos?
Organic anions from acids will compete with frusemide for the OATs, meaning there will be decreased delivery of frusemide to the tubules
What other diuretic is often combined with frusemide to increase the effect?
A thiazide - decreases distal tubule reabsorption of sodium
What drug class can be used with frusemide to decrease its dose will increasing urine output and maintaining GFR?
SGLT-2 inhibitors, e.g. empagliflozin
Why are ACE inhibitors/ARBs often used in conjunction with frusemide?
They protect the glomerulus by reducing glomerular pressure, which together with frusemide reduces damage to the kidneys
What are some examples of thiazide diuretics?
bendroflumethiazide, chlorothiazide
What is the mechanism of action of thiazide diuretics?
Inhibit sodium/chloride reabsorption in the distal convoluted tubule by competitively binding to the apical sodium/chloride cotransporters.
What kidney pathology is incidentally improved by thiazide diuretics?
Calcium calculi - thiazides promote calcium reabsorption in the distal tubule, preventing excess excretion of calcium into the ducts of the kidney
