Diuretics Notes

Diuretics

Function: Increase the excretion of Na+ and water

Clinical uses

a) Treatment for oedema in heart failure

-Reduces oedema

-Vasodilation may be a useful side effect in heart failure- it decreases venous return so reduces ventricular dilation and also decreases peripheral resistance

b) Treatment for hypertension

-Reduce circulating volume

-Vasodilation

c) Treats cerebral oedema-osmotic diuretics

-Dehydration of inflamed tissue

Types

-Loop diuretics

-Thiazides

-Pottasium sparing diuretics

-Osmotic diuretics (rarely used)

Potency –correlates with site of action, generally earlier they act more potent the drug

-Proximal-tubule diuretics, e.g osmotic diuretics are most potent proximal tubule has large capacity for water reabsorption. But some water is reabsorbed by distal nephron, reducing the overall effect

-Loop diuretics: Furosemide exert a large effect at loop of henle

-Distal tubule diuretics: Thiazides, exert only a mild effect, because relatively little sodium is normally reabsorbed at site of action

1) osmotic diuretics

Mannitol

-Infused intravenously, increasing plasma osmolarity- this draws water from oedematous and all other tissues

-Freely filtered at glomerulus so generates a large osmotic potential in the lumen at the proximal tubule, opposing osmotic gradient for paracellular absorption of water

Side effects

-Urinary content of sodium and other ions is higher due to solvent drag, high flow rate reduces opportunity for solute reabsorption

Dehydration- also seen in people with diabetes, where there is increased excretion of glucose which is a natural osmotic diuretic, increases the osmotic pressure, so more water is excreted into the renal tubule

-Seldom in practise, confined to patients with cerebral oedema, i.e meningioma (tumour of the meninges)- leads to inflammation, results in cerebral oedema, this leads to raised intra-cranial pressure, so more brain tissue is damaged leading to more inflammation- viscious cycle- brain herniates foramen magnum- breathing stops

Also used in those resistance to other diuretics

2) Loop Diuretics

Furosemide

-Absorbed from the GI tract, given by mouth, in urgent situation- acute pulmonary oedema given intravenously

-They are strongly bound to plasma protein so don’t pass directly into glomerular filtrate, but are secreted in proximal convoluted tubule by organic acid transport and reaches the TAL

-Rapid onset of action, short half life, multiple actions

i) Inhibits the Na/K/CC cotransporter in the luminal side thick ascending limb of Henle by binding with its Cl- binding site

-This leads to sodium dieresis

-Reduction in medullary osmotic concentration, this reduces the potency of other concentrating mechanisms such as ADH

ii) Vasodilator effect on vasa recta may contribute to washout of medullary concentration gradient, so more water is excreted than reabsorbed

iii) Renal vasodilator increases GFR- increased GFR should not normally lead to increased urine flow beacuase of glomerulotubular balance , but in patients with heart failure-reduced GFR is the primary reason for sodium retention, correction of low GFR leads to sodium loss

iv) Systemic vasodilator – increases cardiac output with people with cardiac failure-soincreasing renal perfusion and increasing GFR- this effect declines and reverses as dieresis reduces effective circulating volume

Side effects

-Exessive Na+ and water loss are common in elderly patentis- lead to hypovolameia, hypotension

-Hypokalaemia: Pottasium loss is substantial- due to distal convoluted tubule’s attempt to reclaim sodium results in increased potassium, hydrogen are excreted- due to blockage of Na/K/CC greater concentration of Na+ reaches the distal convoluted tubule, this increases the activity of the Na/K...

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