RENAL: Diuretics Flashcards
What is the function of diuretics?
- Cause increase in urine output (diuresis)
- Many also increase excretion of Na (natriuresis) and K (producing hypokalaemia)
- Used in hypertension, acute pulmonary oedema, HF
What are the 2 major groups of diuretics?
- Increase in only H2O excretion
- Vasopressin antagonists
- Increase in electrolyte and H2O excretion
- Loop diuretics
- Thiazides diuretics
- K-sparing diuretics
Describe the mechanism of action of diuretics
- Diuretics act at specific sites of nephron and collecting ducts
- Site 1 - Thick loop of Henle - NKCC symporter, 25% Na reabsorbed. Transport of NaCl by a co-transporter for Na, K, 2Cl (NKCC). Thick ascending loop impermeable H2O. Interstitial fluid in this medulla region becomes hypertonic. Aids re-absorption of H2O from collecting duct (increased by ADH)
- Site 2 - DCT -NCC symporter, 5% Na reabsorbed. Reabsorption of Na/Cl
- Site 3 - Principal cells of collecting duct - ENaC, Aldosterone sensitive, <5% Na reabsorbed - Na is reabsorbed (through ENaC channels) in exchange for K efflux (through K channels) - Stimulated by aldosterone
- Site 4 - V2 receptor, ADH stimulates V2 receptors to increase H2O reabsorption
Describe the use of V2 receptor antagonists
E.g. Vaptans, such as Tolvaptan
V2 receptors found on renal collecting duct (V1 receptors found on VSMCs)
Stimulation V2 receptors by ADH leads to expression of aquaporins and increase in H2O reabsorption
Can be used to:
- Reduce blood volume in congestive heart failure
- Reduced excretion of fluid and congestion → Pulmonary + peripheral oedema
- V2 receptor antagonists can reduce H2O reabsorption
- Lowers congestion problems
- Increase H2O loss in liver associated ascites (oedema in belly) e.g. cirrhosis
- Increase H2O loss in conditions associated with increased ADH levels e.g. tumours producing ADH or medications increasing secretion of ADH
Describe the action of agents that affect both electrolyte and H2O excretion
Drugs increase urine volume by increasing excretion of Na (natriuresis) as where Na goes→ H2O follows (via osmosis)
Na major determinant ECF volume
⬆️Na excretion, ⬆️H2O excretion, leads to ⬇️ECFV → ⬇️Blood volume, ⬇️Interstitial fluid
⬇️Oedema (HF related) and related symptoms (breathlessness, ankle swelling)
Describe the action of loop diuretics
E.g. Furosemide
- Inhibit NKCC co-transported at thick ascending loop of Henle (Site 1) - ⬇️Reabsorption of Na, K, 2Cl- marked loss of these electrolytes
- Prevents concentration of cortico-medullary interstitial fluid and therefore reduces effect of ADH on collecting duct (less osmotic drive) - ⬆️H2O loss
Used for:
- Chronic heart failure - ⬇️ECFV, ⬇️Congestion
- Produces vasodilation due to ⬆️PCI2 released in blood vessels, useful in:
- Acute renal failure - ⬆️RBF
- Acute pulmonary oedema - ⬇️Capillary pressure
Compensation mechanisms/Side effects:
- ⬆️Na uptake via ENac (site 3) - Increase K excretion (hypokalaemia)
- ⬆️RAAS (drop in blood volume) - Ang II- increase NHE (PCT) - H+ loss (metabolic alkalosis)
Describe the action of thiazide diuretics
E.g. Bendrofluazie
- Inhibit NCC co-transporter at DCT (site 2)
Compensation mechanisms/Side effects:
- ⬆️Na uptake via ENaC (Site 3) - Increases K excretion (hypokalaemia)
- ⬆️RAAS (drop in blood volume) - Ang II- increase NHE (PCT) - H+ (metabolic alkalosis)
Uses:
- Treatment of hypertension
- Diuresis causes ⬇️blood volume → ⬇️CO
- Major effect is causing vasodilation - ⬇️TPR
- Mild heart failure - ⬇️ECFV - ⬇️Oedema
Describe the action of K-sparing diuretics
Weak diuretic action
Reduce Na reabsorption w/o losing K - Act at collecting duct (Site 3)
Spironolactone:
- Competitive antagonist of aldosterone
- CVS diseases linked to overproduction of aldosterone → volume overload e.g. Heart failure
Amiloride:
- Blocks ENaC
- Reduces Na reabsorption and K loss
