diuretics Flashcards

1
Q

what is a diuretic

A

promotes diuresis ( increased production of urine)

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2
Q

what drug is mannitol and what is it used for

A

osmotic diuretic

cerebral oedema

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3
Q

what are the 5 classes of diuretics

A

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

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4
Q

what is a synergistic effect

A

interaction between two or more things when the combined effect is greater than if you added the things their own

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5
Q

osmotic pressure

A

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

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6
Q

where do osmotic diuretics act

and what is an example

A

glomerulus

mannitol

glomerular capillaries have high permeability to water and electrolytes
20% of plasma is filtered into bowman space and PCT

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7
Q

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

A

forced diuresis for example in poisoning
acute glaucoma - too much water in eye so hypertension in the eye
cerebral oedema - slow infusion

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8
Q

Can you use sodium chloride or glucose for the same purpose as mannitol as also osmotic processes

A

no because they are reabsorbed whilst mannitol is not reabsorbed

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9
Q

Why should you have a slow infusion to treat cerebral oedema

A

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

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10
Q

where do carbonic anhydrase inhibitors work

how does it work

A

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

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11
Q

example of carbonic anhydrase inhibitor

how does it work

A

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

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12
Q

what is acetazolamide used for

A

Glaucoma - inhibits CA in eyes to reduce the formation of aqueous tumour e
Adjunct therapy in metabolic alkalosis
Prophylaxis of altitude sickness

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13
Q

side effects of acetazolamide

A

Dizziness and light headache
Blurred vision
Loss of appetite and stomach upset

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14
Q

what diuretics work on the Loop of hence and TAL

A

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

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15
Q

example of loop diuretic and how does it work

when is it used

A

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

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16
Q

side effects of furosemide

A

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

17
Q

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

A

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

18
Q

what diuretic acts on the DCT

A

thiazide diuretics
DCT - also impermeable to water
5% of sodium reabsorbed
co-transport with chloride

19
Q

how do thiazides work

A

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

20
Q

example of thiazide diuretic and action

A

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

21
Q

when are thiazides used

A

long term diuretics
congestive HF
hypertension

22
Q

What are the unwanted effects of hydrochlorothiazide

A

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

23
Q

what type of diuretics act on the collecting duct

A

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
24
Q

zona occlude are know as what

A

tight junctions

25
Q

potassium sparing diuretics block the ENaC blocker - what example of drugs and how do they work

A

triamterene and amiloride

directly block the epithelial soiudm channel in distal tubule , collecting tubules and collecting ducts
used in conjunction with loop and thiazide diuretics to maintain potassium balance

26
Q

what are the unwanted effects of triamterene

A

hyperkalaemia
gastrointestinal disturbance
idiosyncratic reactions like rashes

27
Q

what is an example of aldosterone antagonist and how do they work and what are they used for and what are the unwanted effects

A

early phase - increasing opening of the ENaC
late phase - promotes DNA transcription
increase synthesis of ENaC, increase synthesis of sodium, potassium and ATPAse

used in conduction with loop and thiazide to maintain potassium balance
HF
hyperaldosteronism - primary conns and secondary due tp hepatic cirrhosis

unwanted effects
hyperkalamai - fatal if ACEi prescribed
gastrointestinal disturbance
menstrual disorders or testicualr atrophy

28
Q

55yr women hypertension has been treated with furosemide and hydrocholorothiazide for peripheral oedema. At regular check up still has ankle oedema. 2.8 potassium

what would be the best option
increase thiazide or add spironolactone

A

Add spironolactone - still has ankle oedema - want to add something else
Look at value of potassium is 2.8 - very low - low potassium dangerous can still induce arrhythmias so need to add a diuretic that conserves potassium

29
Q
patent with congestive HF becomes refractory to a loop diuretic if normal dose where progressively increase. 4.0 potassium 
what do you do next 
increase furosemide 10 fold 
aadd thiazide 
add spironolactone
A

Add spironolactone

Furosemide - wont work increase is already 5 fold
Thiazide - in terms of diuretic good as different mechanism however already lose potassium with it and potassium is already at lower limit
Spironolactone conserves potassium

30
Q

effects of ANGII

A

sympathetic activity
tubular sodium, chloride reabsorption and potassium excretion dn water retention
adrenal cortex with aldosterone
arterial vasoconstriction
increase blood pressur e
pituitary gland posteireo lobe so ADH collecting duct increasing water absorption

31
Q

antihypertensive

A

used to treat hypertension - all anti-proteinuria effect s therefore very valuable for use in CKD

32
Q

ACEi example and action , use and unwanted effects

A

enalapril
inhibit production of angiotensin II
high blood pressure, especially useful in reducing oedema resulting from HF
chronic renal failure and antiproteinuric effect

unwanted - headache , cough, dizziness and hyperkalamia

33
Q

SGLT2 inhibitors treat diabetes prevent what

A

glucose reuptake

glucose lost in urine - preserve diabetic kidney