Drugs and the Kidney Flashcards
In what parts of the kidney is NaCl and water reabsorbed?
The proximal tubule, the loop of henle, the distal tubule and the collecting ducts
What proportion of NaCl and water is reabsorbed in the proximal tubule?
60-70%
What proportion of NaCl and water is reabsorbed in the loop of Henle?
20-30%
What proportion of NaCl and water is reabsorbed in the distal tubule and collecting ducts?
5-10%
In what part of the kidney is potassium reabsorbed?
The loop of henle
In what part of the kidney is potassium secreted?
In the distal tubule and collecting ducts
What are diuretics?
Drugs which increase sodium and water excretion by decreasing sodium and chloride reabsorption
What are the 4 classes of diuretics?
loop diuretics, thiazide diuretics, potassium sparing diuretics, osmotic diuretics
What is frusemide?
A loop diuretic
What is the mechanism of action of loop diuretics?
Inhibits sodium/potassium/2cholride carrier in the loop of henle to prevent sodium reabsorption and therefore water reabsorption and also by increasing the amount of sodium in the distal tubule which decreases water reabsorption
What are the pharmacokinetics of loop diuretics?
Well absorbed, onset in less than an hour, binds strongly to plasma proteins so will undergo tubular secretion, duration of action is 3-6 hours
What are the adverse effects of loop diuretics?
hypokalaemia, metabolic alkalosis, hypovolaemia and hypotension
Why do loop diuretics cause hypokalaemia?
Because they cause an increase in sodium in the distal tubules which results in increased sodium reabsorption which means there is increased potassium secretion (due to sodium/potassium ATPase)
What are the clinical uses of loop diuretics?
pulmonary oedema, heart failure, liver cirrhosis, renal failure, hypertension
What is the mechanism of action of thiazide diuretics?
Inhibits sodium/chloride cotransporter in the distal tubule which prevents sodium reabsorption which prevents water reabsorption
What are the pharmacokinetics of thiazide diuretics?
Orally active, maximum effect after 4-6 hours and have 8-12 hours of duration
What are the adverse effects of thiazide diuretics?
hypokalaemia and gout
Why do thiazide diuretics cause gout?
Because they inhibit the tubular secretion of uric acid
What are the clinical uses of thiazide diuretics?
hypertension and severe resistant oedema
When are potassium sparing diuretics used?
In combination with potassium losing diuretics to prevent potassium loss - this is particularly important in patients with heart failure
What are the two types of potassium sparing diuretics?
Aldosterone receptor antagonists (spironolactone) and non aldosterone receptor antagonits (triameterene and amiloride)
What is the mechanism of action of aldosterone receptor antagonist potassium sparing diuretics?
Potassium sparing diureitcs are aldosterone receptor antagonists which leads to inhibition of activation of sodium channels and prevents synthesis of sodium/potassium ATPase in the collecting ducts - overall this will lead to decreased sodium reabsorption but only at a relatively low level but will also prevent potassium secretion
What is the mechanism of action of non aldosterone receptor antagonist potassium sparing diuretics?
Inhibits sodium channels which leads to reduced sodium reabsorption and reduced potassium secretion
What are the pharmacokinetics of spironolactone?
orally active, slow onset, short half life but metabolite has long half life
What are the adverse effects of spironolactone?
Hyperkalaemia, gastrointestinal upset
What are the clinical uses for spironolactone?
in combination with loop or thiazide diuretics, heart failure, hyperaldosteronism
What are osmotic diuretics?
Pharmacologically inert - they are filtered but not reabsorbed so the water will follow them and be prevented from being reabsorbed as well - does not affect sodium reabsorption
What are the clinical uses of osmotic diuretics?
Raised intracranial pressure and raised intraoccular pressure and prevention of acute renal failure
Why is the kidney susceptible to toxicity?
Because it receives a high blood supply, it concentrates things, metabolism may create reactive chemical species and is controlled by extra renal events (BP, nerves etc)
What are the mechanisms of kidney toxicity?
ROS causing cell damage, interference with calcium metabolism, protein or enzyme binding (may inhibit enzyme function or cause an autoimmune response)
