Diuretics and Renal Replacement Therapy Flashcards
What is a diuretic?
A substance/drug that promotes diuresis
Increased renal excretion
What percentage is the normal fractional excretion of Na+?
Less than or equal to 1%
Aldosterone increases the expression of which channels/transporters?
Na/K/ATPase
ENaC
K+ channels
How do loop diuretics work and give an example?
Act on the loop of Henle
Block NKCC2 cotransporter
Eg. Furosemide
How do thiazides work and give an example?
Act on early DCT
Block NaCl cotransporter
Eg. Metolazone
How do K+ sparing diuretics work and give an example?
Act on late DCT and CD
Block ENaC channels
Eg. Amiloride
How do aldosterone antagonists work and give an example?
Eg. Spironolactone
Competitive inhibition of aldosterone on principle cells in late DT and CD
How does mannitol work?
Use small molecules to increase osmolarity of filtrate
Increased water excretion (decreased water reabsorption)
How are carbonic anhydrase inhibitors used as a diuretic?
Prevents uptake of bicarbonate as it cannot from water and CO2 to enter the cells
However can lead to metabolic acidosis due to all the bicarbonate in the urine
How do loop diuretics affect magnesium and calcium?
Magnesium and calcium reabsorption rely on the gradient of the thick ascending limb LOH
Therefore loop diuretics inhibit their reabsorption
Increased loss of calcium and magnesium
Can cause hypocalcaemia and hypomagnesiumia
Why are loop diuretics chosen to help heart failure failure and acute pulmonary oedema?
They are very potent diuretics
What can we use loop diuretics to treat?
Heart failure Pulmonary oedema Nephrotic syndrome Renal failure Liver cirrhosis Hypercalcaemia
Why are thiazides good diuretics for the elderly?
Blocking Na+ reabsorption increases the Ca2+ reabsorption
Good for the elderly who are prone to osteoporosis
Why are thiazides ineffective in renal failure?
Less potent as only 5% sodium reabsorption inhibited
What are thiazides widely used for and why?
Hypertension
Decreased effective circulating volume and cause vasodilation
What is the potential problem when using thiazides?
Hypokalaemia
Why are K+ sparing diuretics often a bad choice?
Mild diuretics therefore cannot cope with large volume increases
Can produce severe hyperkalaemia esp if used in conjunction with ACEi, K+ supplements or in pts with renal failure
What is the preferred drug to treat ascites and oedema in cirrhosis?
Spironolactone
Which diuretics are often used in conjunction for heart failure?
Spironolactone
Loop diuretics
Why do we have to be careful when using diuretics?
Decreased circulatory volume and reduce perfusion pressure to the kidneys
This can activate RAAS
Causes water retention (counter productive)
Describe nephrotic syndrome
Increase in glomerular BM permeability to proteins
Proteinuria
Low plasma albumin - decreased oncotic pressure - oedema
What is ascites?
Free fluid in the peritoneal cavity
Describe hepatic encephalopathy
Reversible syndrome of impaired brain function
Occurs in cirrhosis with advanced liver failure
Causes confusion and comas
Signs - constructional apraxia (cannot draw a 5 pointed star) and flapping tremors
Includes elevated ammonia levels in blood
Hypokalaemia can cause this
Name some adverse effects of diuretics
Potassium abnormalities Decreased blood volume - postural hypotension, dehydration Increased uric acid levels - gout Glucose intolerance Raised LDLs Erectile dysfunction (thiazides) Gynaecomastia (spironolactone)
