Diuretics Flashcards
What is a diuretic
A substance/drug that promotes diuresis
They work by increasing renal excretion of water and Na
They decrease the ECV
What are the ways in which diuretics work and what diuretics come under each category
Direct action on cells to block Na transporters in luminal membrane - loop, thiazide and K sparing diuretics
Antagonise aldosterone - aldosterone antagonists
Modification of filtrate content - osmotic diuretics
Inhibit action of carbonic anhydrase in brush border and PCT cells - interferes with Na and bicarbonate reabsorption in PCT
How do loop diuretics work
Loop diuretics block apical NKCC2 transporter
Results in decreased medullary tonicity causing decreased water reabsorption and a net reslut of Na and water loss
Act in the loop of Henle
Why is there a decreased reabsorption of Ca and Mg when loop diuretics are used
Normally K moves into lumen via K channels to create a +ve luminal potential to help drive reabsorption of positively charged ions, Mg and Ca
Loop diuretics prevent K being carried across apical membrane so there is no movement of K into lumen via K channels -> no +ve luminal potential so there is decreased reabsorption of Ca and Mg
When are loop diuretics used in treatment
Treat symptoms of HF - decreases afterload/preload
Acute pulmonary oedema
Treat fluid retention and oedema in: nephrotic syndrome, renal failure, liver cirrhosis
Hypercalcaemia - loop diuretics impair Ca reabsorption to increase Ca excretion
How do thiazide diuretics work
Thiazide diuretics act early in the DCT and block Na-Cl transporters
Cause increased Na and water loss by blocking Na absorption
Do not decrease Ca or Mg reabsorption as NKCC2 not affected
They decrease Ca loss in urine
When are thiazide diuretics used
In treatment of hypertension but have a risk of hypokalaemia
How do potassium sparing diuretics work
K sparing diuretics act on late DCT and CD
They are either inhibitors of ENaC or are aldosterone antagonists
Both work by decreasing ENaC activity -> also reduce K loss
Can produce hyperkalaemia due to reduced K loss - risk increased if used with ACEI, K supplements or patients with renal impairment
When are aldosterone antagonists used
In long term treatment of HF - shown to decrease mortality
Treatment for ascites and oedema in cirrhosis
Additional therapy in hypertension not controlled by ACEI+CCD+thiazide
Treatment of hypertension due to Conn’s syndrome
When are ENaC blockers used
Used in combination with K losing diuretics to minimise K loss
How might diuretics lead to hypokalaemia
Diuretics lead to decreased circulating volume -> activate RAAS
This increases aldosterone causing increased Na reabsorption and increased K secretion causing hypokalaemia
Loop and thiazide diuretics increase Na and water delivery to DCT and CD so there is increased Na reabsorption by principal cells in DCT and CD resulting in a favourable electrochemical gradient for K secretion
Increased Na and water delivery means there is a faster flow rate of filtrate in tubule lumen so there is a lower K concentration in the lumen so favourable concentration for K secretion
When are diuretics used
Congestive HF
Nephrotic syndrome
Liver cirrhosis - with ascites and oedema. Use spironolactone
Kidney failure - loop diuretics
Acute pulmonary oedema
HF
Hypertension
Hypercalcaemia - loop diuretics
Cerebral oedema - osmotic diuretics
Glaucoma - carbonic anhydrase inhibitors
How does congestive HF cause ECF expansion
Congestive HF causes decreased CO resulting in decreased renal perfusion and increased systemic venous pressure
This causes oedema
Congestive HF leads to RAAS activation -> Na and water retention and expansion of ECF
How does nephrotic syndrome cause ECF expansion
Nephrotic syndrome increases GBM permeability to protein -> protein filtered and lost in urine
Results in low plasma albumin -> decreases oncotic pressure -> peripheral oedmea -> decreased circulatory volume -> RAAS activated -> Na and water retention and ECF expansion and oedema
How does liver cirrhosis cause ECF expansion
Liver cirrhosis causes decreased albumin synthesis -> low plasma albumin -> low oncotic pressure -> oedema
Portal hypertension causes increased venous pressure in splanchnic circulation -> high venous and low oncotic pressure which causes movement of fluid in peripheral capillaures -> into peritoneal cavity -> ascites
Both of theses decrease circulatory volume -> acitve RAAS
