Renal system

The most important physiological functions of the kidney include (i) regulating extracellular fluid volume, (ii) maintaining the concentration of electrolytes (e.g. Na⁺, Cl^-, K⁺, Ca²⁺, Mg²⁺), (iii) regulating acid-base balance, (iv) excreting waste products (e.g. urea, drugs, uric acid), (v) conserving essential nutrients and (vi) synthesising erythropoietin, vitamin D and renin. The key functional units of the kidney are nephrons consisting of a glomerulus, proximal convoluted tubule, Loop of Henle, distal convoluted tubule and collecting duct, which together reabsorb around 99% of the plasma filtered at the glomerular capillaries. Important hormones that act on renal tubules are aldosterone (which stimulates Na⁺ reabsorption in the distal tubule), vasopressin (which stimulates water reabsorption in the collecting duct) and parathyroid hormone (which stimulates Ca²⁺ reabsorption). The renin-angiotensin system is a key local defence of glomerular filtration, especially when it is threatened by reduced renal perfusion, and has wider systemic effects that preserve extracellular fluid volume and blood pressure. Renal function is expressed as the glomerular filtration rate which is normally greater than 100 mL/min but declines progressively with age. Chronic renal impairment may be the consequence of systemic or renal disease but acute reversible deteriorations may occur because of pre-renal (e.g. dehydration), renal (e.g. drug toxicity), or post-renal (e.g. ureteric obstruction) causes.

CPT-02-09-01 - Renal physiology	CPT-02-09-01 What are diuretics?
CPT 02_09 - Drugs affecting renal function - therapeutic	CPT 02_03_03 - Drugs affecting respiratory function - adverse

Diuretics

Diuretics are particularly useful in treating the water and salt retention caused by heart failure.

Common side effects like muscle cramps arise from the loss of too much sodium, potassium or magnesium. Prescribers should be aware of the risk of diuretic-induced hypokalaemia.

There are three main types of diuretic, each of which works by affecting a different part of the kidneys:

Loop diuretics- prescribed for fluid retention (oedema), particularly in the lungs. These drugs are very fast acting, but of short duration and induce dramatic water loss.

e.g. furosemide, bumetanide and occasionally torasemide.

Furosemide can be prescribed with potassium chloride to maintain potassium levels.

Thiazide diuretics- fast acting but of longer duration than the loop diuretics, with less dramatic water loss. These are commonly used at low dose in the management of hypertension.

e.g. bendroflumethiazide, hydrochlorothiazide and indapamide

Potassium-sparing diuretics- these are a weaker type of diuretic which increase water loss, but prevent loss of too much potassium. Potassium-sparing diuretics are usually prescribed to treat water retention due to heart failure

e.g. spironolactone and eplerenone (aldosterone antagonists), triamterene and amiloride (act on epithelial sodium channels, ENaCs)

Potassium-sparing diuretics are not usually necessary in the routine treatment of hypertension, unless hypokalaemia develops.

Other diuretics

Osmotic diuretics such as mannitol, given by intravenous (IV) infusion, can be used to treat cerebral oedema and raised intraocular pressure (e.g. in glaucoma patients).

Carbonic anhydrase inhibitors such as acetazolamide (administered orally or IV) and dorzolamide and brinzolamide (topically applied) are diuretics used to treat glaucoma.

Drugs from these different families can be prescribed in fixed-dose combinations, which can be used when compliance using separate medications is an issue. Examples include furosemide with triamterene or spironolactone, co-triamterzide (triamterene plus hydrochlorothiazide), co-amilofruse (amiloride plus furosemide) and co-amilozide (amiloride plus hydrochlorothiazide). Dorzolamide and brinzolamide can be prescribed in fixed-dose combination with the beta blocker timolol, for the management of raised intraocular pressure and glaucoma, in patients for whom single agent beta blocker therapy is inadequate.

Pharmacology - Diuretics

A 16 minute video re-capping the structure/functions of the kidney, followed by an overview of the action of different types of diuretics. Produced by Armando Hasudungan (http://armandoh.org/).

Diuretics are particularly useful in treating the water and salt retention caused by heart failure.

Common side effects like muscle cramps arise from the loss of too much sodium, potassium or magnesium. Prescribers should be aware of the risk of diuretic-induced hypokalaemia.

There are three main types of diuretic, each of which works by affecting a different part of the kidneys:

Loop diuretics- prescribed for fluid retention (oedema), particularly in the lungs. These drugs are very fast acting, but of short duration and induce dramatic water loss.

e.g. furosemide, bumetanide and occasionally torasemide.

Furosemide can be prescribed with potassium chloride to maintain potassium levels.

Thiazide diuretics- fast acting but of longer duration than the loop diuretics, with less dramatic water loss. These are commonly used at low dose in the management of hypertension.

e.g. bendroflumethiazide, hydrochlorothiazide and indapamide

e.g. spironolactone and eplerenone (aldosterone antagonists), triamterene and amiloride (act on epithelial sodium channels, ENaCs)

Potassium-sparing diuretics are not usually necessary in the routine treatment of hypertension, unless hypokalaemia develops.

Other diuretics

Osmotic diuretics such as mannitol, given by intravenous (IV) infusion, can be used to treat cerebral oedema and raised intraocular pressure (e.g. in glaucoma patients).

Carbonic anhydrase inhibitors such as acetazolamide (administered orally or IV) and dorzolamide and brinzolamide (topically applied) are diuretics used to treat glaucoma.

Diuretic action in the kidney

A 9 minute video reviewing the structure of the nephron and the location and action of diuretics.

Diuretics are particularly useful in treating the water and salt retention caused by heart failure.

Common side effects like muscle cramps arise from the loss of too much sodium, potassium or magnesium. Prescribers should be aware of the risk of diuretic-induced hypokalaemia.

There are three main types of diuretic, each of which works by affecting a different part of the kidneys:

Loop diuretics- prescribed for fluid retention (oedema), particularly in the lungs. These drugs are very fast acting, but of short duration and induce dramatic water loss.

e.g. furosemide, bumetanide and occasionally torasemide.

Furosemide can be prescribed with potassium chloride to maintain potassium levels.

Thiazide diuretics- fast acting but of longer duration than the loop diuretics, with less dramatic water loss. These are commonly used at low dose in the management of hypertension.

e.g. bendroflumethiazide, hydrochlorothiazide and indapamide

e.g. spironolactone and eplerenone (aldosterone antagonists), triamterene and amiloride (act on epithelial sodium channels, ENaCs)

Potassium-sparing diuretics are not usually necessary in the routine treatment of hypertension, unless hypokalaemia develops.

Other diuretics

Osmotic diuretics such as mannitol, given by intravenous (IV) infusion, can be used to treat cerebral oedema and raised intraocular pressure (e.g. in glaucoma patients).

Carbonic anhydrase inhibitors such as acetazolamide (administered orally or IV) and dorzolamide and brinzolamide (topically applied) are diuretics used to treat glaucoma.

Drugs acting on the kidney (3) 2017-18

This is a slide set (13 slides) covering osmotic diuretics and carbonic anhydrase inhibitors. It also discusses aldosterone and vasopression activity in the kidney, as well as the mechanism of action of SGLT2 inhibitors. The final slides discuss gout and the mechanisms employed by current anti-gout medications. It is an updated version for the 2017-18 academic year. Provided by Prof. JA Peters, University of Dundee School of Medicine.

Diuretics are particularly useful in treating the water and salt retention caused by heart failure.

Common side effects like muscle cramps arise from the loss of too much sodium, potassium or magnesium. Prescribers should be aware of the risk of diuretic-induced hypokalaemia.

There are three main types of diuretic, each of which works by affecting a different part of the kidneys:

Loop diuretics- prescribed for fluid retention (oedema), particularly in the lungs. These drugs are very fast acting, but of short duration and induce dramatic water loss.

e.g. furosemide, bumetanide and occasionally torasemide.

Furosemide can be prescribed with potassium chloride to maintain potassium levels.

Thiazide diuretics- fast acting but of longer duration than the loop diuretics, with less dramatic water loss. These are commonly used at low dose in the management of hypertension.

e.g. bendroflumethiazide, hydrochlorothiazide and indapamide

e.g. spironolactone and eplerenone (aldosterone antagonists), triamterene and amiloride (act on epithelial sodium channels, ENaCs)

Potassium-sparing diuretics are not usually necessary in the routine treatment of hypertension, unless hypokalaemia develops.

Other diuretics

Osmotic diuretics such as mannitol, given by intravenous (IV) infusion, can be used to treat cerebral oedema and raised intraocular pressure (e.g. in glaucoma patients).

Carbonic anhydrase inhibitors such as acetazolamide (administered orally or IV) and dorzolamide and brinzolamide (topically applied) are diuretics used to treat glaucoma.

Drugs acting on the kidney (1 and 2) 2017-18

This a is a slide set (22 slides) covering some of the drugs acting in the kidney. The presentation begins with a general overview, then outlines the causes of odema, and diseases with fluid retention which respond to diuretics (slides 5 & 6). Following a slide illustrating the main sites of diuretic action in the nephron, loop and thiazide diuretics are discussed along with the mechanism of potassium loss from the kidney. The final slides describe the action and uses of potassium sparing diuretics. This is an updated version of the lecture series for the 2017-18 academic year. Provided by Prof. JA Peters, University of Dundee School of Medicine.