Diuretics Flashcards
What is direusis?
Increased formation of urine by the kidney
What is a diuretic?
A substance that promotes direusis thereby causing.a reduciton in ECF volume
What diuretics have a site of action of the proximal tubule?
Carbonic anhrydrase inhibitors, osmotic direutics (also acts at other sites)
What direutics act at the loop of henle?
Loop direutics (furosemide)
What direutics act in the distal convuluted tubule?
Thiazide direutics, metalosone, impamide,
What directuics act at the collecting duct?
Potassium sparind direutics such as Enac blockers amiloride, and aldosterone antaogonists such as spialoactone
What are the different classes of direutics?
Loop direutics, thiazide direutics, K+ sparing direutics, inhitbtors of carbonic anhyrdarse, and osmotic direutics
What transporters do loop diretuics block?
Na-K-2Cl transporter in the loop of henle
What do thiazide direutics block?
Block the Na- Cl co transporter in the early distal tubule
What receptors do potassium sparing direutics block?
Block the epithelia Na+ channles
How does spiroloactone work?
Is a competitive inhbitor of the aldosterone whihc acts to increase sodium reabsortption by using ENaC
How do osmotic direutics work?
They increase the osmolarity of the filrate, and therefore reudcing the water and Na+ reabsopriton thourghout the filtrate
How do carbonic anhydrase inhibotrs work?
Onhibiting the action of the enzyme carbonic anhydrase and therfore interferring wiht Na and HCO3- reabasoprtion in the promximal convutued tubule
What are some of the features of the loop direutics action?
Screted in the lumen in the PCT (vai the organic anion pathway) and travel downstream to the loop of jenle, and they are very potent direuctics and they account for 25-30% of sodium reabsorption, and segments beyond have a limited capacity for the transport of sodium and water
Name some loop doreutics
Furosoemide and bumetimide
When are loop doreutics used?
In heart failure for their direutic effect and their ability to vaso and veno dilate therefore reducing the afterload and the preload and in acute pulmonary odema furosemide is given for direuitic action, as well as fluid retion and odema in nephrontic syndrome, renal failure and corrhosis of the liver and auseful in the trestment of hypercalcemia as it impairs calcium absorption inthe loop of henle
What are some of the features of the action of thiazide direutics?
Secreted in the lumen of the PCt, travel downstream and then balcok the Na-Cl transporter to increase Na and Ca loss in the urine, they are less potent direutics and therefore commonly used in hypertension, and have a higher incidence of hypokalmeia
Name a thiazide direutic
Bednorflumethiazide
What are the features fo of the action of potassium sparing diruetics
Are mold direutics that affect only 2% of sodium reabsorbtion, reduce the Na+ channel activity, and reduced the losss of K+ adn can therefore produced life threatening hyperkalemia, especially if used with ACE inhibitors
When would we use aldosterone antagtnosists such as spirolonactone?
Best treatment for hypertension due to hyperaldosterisom in Chnns sundrenal, and preffered drug for ascites and aodmea during cirrhosis, adn os used in addition to loop diretuics in heart failure can confer a survival advantage
Where wouold uyou use Enac such as amilorqide?
Mild direutics, that are usually used in combination with K+ sparing direutics to avoid an excessive loss of potassium
How do loop and thisaizide dipretuitcs cause hypokalmemia?
There is increase Na+ and h20. Develivery ot the late distal tubule, which causes increased absorption by principal cells, and a favourable gradient for K+ excretion, and also faste flow of filtrate meaning that K+ secreted si washed away quicker and the lower concentration of K+ in the urine means that there is a favourable gradient for K+ secretion, and this is therefore causes kpre potassium in urine and therefore possible hypokalemia
Ehat also contronitues to hypokalmia in loop direutics patients?
Excess direusis reduces the ECf volume, and causes activation of the RAAS system, causing an increase in aldosterone secretion, and increase in Na absorption and K secretion and therefore an increased amount of K in the urine
Why can hyperkalmeia occur woth K+ sparing direutics?
So the blcokage of ENac or the reduced action fo aldosterone reducing the activity of Na K Atpase and ENac channels reduces the absorption of sodium, therefore causing increased secretion of potassium and causes Hyperkalemia
Why do tou get exapnsion of the ECF in hear failure?
There is an increase in systemic venous pressure, and this cuases periphral odema and therefor efluid moves from intravascular to the itnersitial compartment and a redcued ejection fraction causes a reduction in renal output, and this leads to decreased renal perfusion pressure and also activation of RAAS causing increased fluic in the ECF compartment
What is neprhotic symdrome?
An glomeuluar diseasse causing an increase in the basement membrane permeability ot proteins, and therefore proteins are lost inuirne causing a reduced plasma albumin, adn reuslting in a low plasma Oncotic pressure causing a peripheral oedema and the reduced circulating volume also activates the RAAS
How does cirrhosis of the liver cause a odema?
There is reduced albumin sythesis in the liver, and therefore the hypoalbumenia results in a low plasma oncotic pressure, and portal hypertension causing increased pressure in the splanchic circulation and therefore there is movement offliid from the visercal peritoneal capillaries to the peritoneal cavity and therefore forms an ascites
