diuretics Flashcards
what is a diuretic
promotes diuresis ( increased production of urine)
what drug is mannitol and what is it used for
osmotic diuretic
cerebral oedema
what are the 5 classes of diuretics
Osmotic
Carbonic anhydrase inhibitors
Loop
Thiazides
Potassium sparing
Most diuretics inhibit reabsorption of sodium at different levels of the renal tubular system
More sodium is excreted and more water is excreted because water follows sodium osmotically
Sometimes combinations of diuretics are used to create this synergistic effect
what is a synergistic effect
interaction between two or more things when the combined effect is greater than if you added the things their own
osmotic pressure
Osmotic pressure is defined as the pressure that must be applied to the solution side to stop fluid movement when a semipermeable membrane separates a solution from pure water
isosmotic - having the same osmotic pressure - this is what filtrate is
where do osmotic diuretics act
and what is an example
glomerulus
mannitol
glomerular capillaries have high permeability to water and electrolytes
20% of plasma is filtered into bowman space and PCT
osmotic diuretics increase the plasma osmolarity( conc of solution expressed as total number of solute particles per litre), they filter at glomerulus and are poorly reabsorbed so increase the osmotic pressure therefore decreasing water reabsorption from the nephron
it does not enter the brain or eye but draws fluid from tissues
when can this type of diuretic be used
forced diuresis for example in poisoning
acute glaucoma - too much water in eye so hypertension in the eye
cerebral oedema - slow infusion
Can you use sodium chloride or glucose for the same purpose as mannitol as also osmotic processes
no because they are reabsorbed whilst mannitol is not reabsorbed
Why should you have a slow infusion to treat cerebral oedema
drag water from around the cells , if inject too fast or to high conc will dehydrate the cells so water comes out of cells to
where do carbonic anhydrase inhibitors work
how does it work
PCT - reabsorption of sodium and water and bicarbonate
70% Na
carbonic anhydrase normally reversibly catalysis between water and CO2 to form carbonic acid
If inhibit carbonic anhydrase then hydrogen ion not generated inside the cell anymore therefore exchanges does not work - sodium rmians in lumen of the tubular therefore water will remain in the urine and this is how diuretics work
example of carbonic anhydrase inhibitor
how does it work
Acetazolamide
Supresue hydrogen ion production and thus reduce sodium/hydrogen exchange - less sodium reabsorption
Increase excretion of bicarbonate ( accompanied by sodium, potassium and water? Causing mild alkaline urine and metabolic acidosis
Effect is self limiting
what is acetazolamide used for
Glaucoma - inhibits CA in eyes to reduce the formation of aqueous tumour e
Adjunct therapy in metabolic alkalosis
Prophylaxis of altitude sickness
side effects of acetazolamide
Dizziness and light headache
Blurred vision
Loss of appetite and stomach upset
what diuretics work on the Loop of hence and TAL
loop diuretics
decedning - permeabel to water , intersititum is hyper osmotic - water is absorbed
TAL - impermeable to water and reabsorption of soiudm and potassium and chloride via co-trnasport
electrostatic gradient due to ion movement from lumen to blood - so potassium, calcium and sodium move into blood
chloride ion recylced
example of loop diuretic and how does it work
when is it used
furosemide and inhibits cotransproter of sodium potassium and chloride
Cause 15-25% of filtered sodium to be excreted - torrential urine production
Result in increased osmotic pressure in filtrate delivered to distal tubule ( decreases water reabsorption)
Use - chronic or acute - pulmonary oedema
Heart failure
Hypertension
Hepatic cirrhosis complicated by ascites
Nephrotic syndrome
Renal failure
side effects of furosemide
Unwanted effects - directly related to drug renal action
Hypovolemia /hypotension - excessive sodium lsos and diuressi
Hypokalemia - potassium loss
Metabolic or contraction alkalosis - increase plasma bicarbonate.
Unwanted effects - unrelated to drugs renal action ( rare)
Dose related hearing loss
Allergic reactions, rashes, bone marrow depression
64yr man congestive HF is admitted to A&E with signs of acute pulmonary oedema. Immediately treated with oxygen by face mask, morphine for respiratory distress, nitrates as vasodilators to reduce the pre-load as well as a bolus of diuretics intravenously to stimulate diuresis
which diuretic of choice would be used
Diuretic of choice would be furosemide - acts so quickly and eliminates large volume of urine, mistake to give mannitol - can cross in alveoli and can make it worse
what diuretic acts on the DCT
thiazide diuretics
DCT - also impermeable to water
5% of sodium reabsorbed
co-transport with chloride
how do thiazides work
Normally
Sodium gets in by contrasporter with choir and into blood exchange via potassium through channel
Calcium in through apical channel and into blood by calcium sodium exchanger
Thiazide blocks sodium transport so cannot get into the cell so remain in the lumen and drags water with it - increases osmosis in tubule
side effect could be hypercalcaemia - more calcium transported into blood due to ions
example of thiazide diuretic and action
hydrocaholorothiazide
block the sodium chloride co-transporter resulting in higher osmolarity of urine and decreased water reabsorption
effect is self-limiting
lower blood volume - renin secretion - angiotensin formation and aldosterone secretion - limitation of the effect of thiazides
- not as potent and slower than furosemide - thiazides are long term diuretics used for hypertension dn congestive HF
when are thiazides used
long term diuretics
congestive HF
hypertension
What are the unwanted effects of hydrochlorothiazide
hypokalaemia, metabolic alklasois ( in loop)
hypercalcaemia
hypomagnesaemia
hyponatraemia
hyperuricaemia precipitating gout - thiazide competes with uric acid fro tubular secretion
hyperglycaemia - impaired pancreatic release of insulin and diminished tissue utilisation of glucose
higher plasma cholesterol level
what type of diuretics act on the collecting duct
potassium sparing diuretics
exchange with potassium and hydrogen ahappens in CD - activity is dependent on tubular concentration of sodium
activity is regulated by aldosterone ( a hormone secreted by the adrenal cortex)
potassium goes down basolateral exchanges with sodium
normally
Aquaporins and special channel for sodium ions
Sodium into blood exchanging with potassium and potassium eliminated in the urine
Sodium gets into cell through epithelium sudden channels
Electrostatic charge on the apical side
Increasing number of aquaporins to increase at membrane - increase activity and epithelial sodium channels at apical membrane but not increase activity number of sodium potassium atpases - because of these lots of potassium eliminated in the urine,
2 subclass of diuretics here so what happens because of this is that you don't get sodium transported inside the cell so cant transport sodium to the blood the other subclass of this is anti-aldosteronism and inhibit the effect of aldosterone so can't use sodium in water. Potassium kept in the blood
zona occlude are know as what
tight junctions
