Diuretics Flashcards
how does mannitol work
this is an osmotic diuretic that works across the whole nephron. it is freely filtered in the glomerulus and increases the osmolarity of the filtrate in the nephron therefore causing more water excretion from the plasma. lowering blood volume and pressure
the other diuretics are not freely filtered in the glomerulus, how do they get into that space
through the organic anion transporters - OAT. this is part of their elimination in the urine as they are removed via these OATs
how does frusemide work
frusemide will inhibit the NKCC2 ion cotransporter. thus resulting in disruption to the nephron cell RMP, thus affecting the reabsorption of ions such as Na+ resulting in increased excretion of this ion
what normally occurs at the TAL in terms of reabsoprtion of ions
the NKCC2 co transporter transports K+, Na+ and Cl- into the cell at the apical membrane. when this is happening the Cl- is transported out of the cell by the CLC-K2 channels and into the blood at the apical membrane. And the K+ are exported by the ROMK channels into the nephron at the basolateral membrane.
this creates a negative RMP inside the cell which drives the reabsorption of cations into the cell and back into the blood
how does the use of TAL diuretics such a frusemide affect things down stream
there is now increased Na+ in the filtrate compared to what there should be. hence the Na+/k+ transporters in the DCT will uptake more Na+ at the expense of K+ resulting in increased k+ excretions as well.
indications of loop diuretics
HTN, oedema, hyperkalaemia
side effects of the loop diuretics
this is frusemide
side effects include hyponatraemia, hypokalaemia, Mg2+ and Ca2+ depletion, uric acid retention, hearing loss
where do the thiazides work and what are some examples
bendroflumethiazide, these work on the DCT
what is the mechanim of action for bendroflumethiazide
it will bind to an inhibit the action of the NCC1 transporter at the apical membrane of the distal convoluted tubule. this means that no Na+ can be reabsorbed at the DCT. thus increasing Na+ and water loss in the urine.
why are the thiazides more modest diuretics
they affect Na+ reabsorption further down the nephron so there is less Na+ excretion. this also means less K+ losses as there is no extra K+ removed for Na+ reabsorption.
indications of the thiazide loop diuretics
pulmonary oedema, hypertension
site of action and an example of a K+ sparing diuretic- mineralocorticoid receptor inhibitor
these act in the DCT on aldosterone regulated Na+/K+ ATPase pumps, spironolactone
how does aldosterone normally work in the kidneys
aldosterone will act on the DCT and it will increase Na+/K+ ATPase pump synthesis and activity. thereby causing more Na+ reabsorption in the DCT, thus increasing blood volume and CO.
how does spironolactone work
this drug is an aldosterone antagonist, competitively binding to it and preventing translocation of the mineralocorticoid receptor once aldosterone is bound.
it is thus a K+ sparing diuretic as there is no transcription effects on the Na+/K+ ATPase pump. thus there is less removal of K+ from the cell and hence more Na+ and water removal
ADRs of spironolactone
Hyperkalaemia, Gynaecomastia
GI disturbances
