Diuretics Flashcards
What are the different classes of diuretics?
Loop diuretics Thiazide diuretics K+ sparing diuretics Aldosterone antagonists Osmotic diuresis Carbonic anhydrase inhibitors
In general, how do diuretics work?
Promote diuresis by increasing the renal fractional excretion of Na+ (& therefore water) to reduce the ECF volume by blocking reabsorption of Na+ (& therefore water).
What is the location and mechanism of action of loop diuretics? Give an example.
Secreted in PCT (via organic anion pathway), act within lumen of loop of Henle
Blocks Na+/K+/2Cl co-transporter (NaKCC2)
Very potent diuretics (as ~25% of Na+ is reabsorbed in the loop of Henle)
Also blocks calcium & potassium reabsorption
e.g. furosemide, bumetanide
Treatment:
- heart failure: diuretic effect + vaso/venodilatation (reduces preload & afterload)
- acute pulmonary oedema (caused by left heart failure)
- fluid retention & oedema of: nephrotic syndrome, renal failure, cirrhosis of liver (add to spironolactone)
- hypercalcaemia (replace fluids with IV)
What is the location and mechanism of action of thiazide diuretics? Give an example.
Secreted in PCT, act within lumen of early DCT
Blocks Na+/Cl- co-transporter
Less potent diuretic compared to loop diuretics (therefore ineffective in renal failure)
Also increases calcium reabsorption and reduces potassium reabsorption
e.g. bendroflumethiazide, metrolazone
Used to treat hypertension (via vasodilatation)
What is the location and mechanism of action of K+ sparing diuretics? Give an example.
Secreted in PCT, act within lumen of late DCT & collecting duct
Blocks ENaC
Reduce loss of K+
e.g. amiloride, triamterene
What is the location and mechanism of action of aldosterone antagonists (diuresis)? Give an example.
Competitive inhibition of aldosterone reduces sodium reabsorption by ENaC in principal cells (& spare K+) (and reduces Na+/K+/ATPase activity)
e.g. spironolactone, eplerenone
Reduce loss of K+
Spironolactone used to treat:
- primary hyperaldosteronism
- ascites & oedema in cirrhosis
- added to loop diuretics in heart failure (reduces mortality in congestive heart disease via a non-renal effect)
What is the location and mechanism of action of osmotic diuretics? Give an example.
Molecules freely filtered at the glomerulus but not reabsorbed -> increases the osmolarity of filtrate -> Na+ & water follow -> more Na+ & water lost in urine
e.g. mannitol
Treats cerebral oedema
What is the location and mechanism of action of carbonic anhydrase inhibitors? Give an example.
Acts in PCT and interferes with Na+ and HCO3- reabsorption via carbonic anhydrase
Can cause metabolic acidosis
e.g. acetazolamide
Treats glaucoma (reduced production of aqueous humor)
How can diuretics cause hypokalaemia?
Loop diuretics/thiazide diuretics block sodium & water reabsorption in the loop of Henle/early DCT
By increasing Na+ & water delivery to the late DCT & collecting duct, more Na+ is reabsorbed by principal cells (electrical gradient favours K+ excretion) AND the increased flow washes away luminal K+ (chemical gradient favours K+ secretion)
Also, reduction in ECF volume (less water reabsorbed) activates RAAS -> aldosterone increases Na+ reabsorption -> more K+ secreted (maintains electroneutrality)
How can diuretics cause hyperkalaemia?
K+ sparing diuretics and aldosterone antagonists reduce ENaC activity directly and indirectly respectively.
This reduces sodium reabsorption, so less K+ is needed to be secreted in order to maintain electroneutrality, and less K+ is lost in urine
How can the effects on potassium by diuretics be predicted/managed?
Monitor [Na+] & [K+]
Add K+ supplements if required when using loop/thiazide diuretics
Add loop/thiazide diuretics to K+ sparing/aldosterone antagonist diuretics if required
What are some adverse side-effects of diuretics?
Hypo/hyperkalaemia Hypovolaemia (monitor weight & BP, ?signs of dehydration) Hyponatraemia Increased uric acid -> gout Glucose intolerance Increased LDLs Erectile dysfunction (thiazides)
Give an example of a substance with diuretic effects, and explain why.
Alcohol (inhibits ADH release)
Coffee (increases GFR and reduces Na+ reabsorption)
Lithium/demeclocyline (inhibits ADH action on collecting ducts)
What are some diseases which causes diuresis?
Diabetes mellitus (glucose in filtrate causes osmotic diuresis)
Diabetes insipidus (cranial: reduced ADH release from pos. pituitary gland)
Diabetes insipidus (nephrogenic: poor response of collecting ducts to ADH)
Psychogenic polydipsia (increased fluid intake due to real or perceived sensation of thirst)
