Diuretics and drugs acting on the kidney Flashcards
Thiazide diuretics:
- how do they work
- what different conditions are they used in?
Mechanism of action:
-reduce NaCl reabsorption in distal tubule and cause water to be pulled into tubule
Uses:
- mild heart failure
- hypertension
- severe resistant oedema
- nephrolithiasis (it increases ca2+ reabsorption)
- nephrogenic diabetes insipidus (mechanism not understood)
What are the adverse effects of thiazide diuretics?
- Hypokalaemia
- Metabolic acidosis
- Hypovolaemia and hypotension
- hyperuricaemia may precipitate gout
- depletion of Mg2+
- male sexual dysfunction
- impaired glucose tolerance
Loop diuretics:
- how do they work?
- When are they used?
Mechanism:
Inhibits the Na+-K+-2Cl− symporter in the thick ascending limb of the loop of Henle to inhibit sodium, chloride and potassium reabsorption
Used to reduce salt and water overload:
- acute pulmonary oedema
- chronic kidney failure
- hepatic cirrhosis with ascites
- chronic heart failure
- nephrotic syndrome
Used to increase urine volume in:
- acute kidney failure
- resistant hypertension
used to reduce acute hypercalcaemia
What are the adverse effects of loop diuretics?
- Hypokalaemia and therefore increases the toxicity of digoxin and class 3 antiarrythmic drugs
- metabolic alkalosis as it increases H+ secretion into the tubule
- hypovolaemia and hypotension
- depletion calcium and magnesium
- increased plasma uric acid
Potassium sparing diuretics - what are the three different diuretics available?
- Amiloride and Trameterene
- Spironalactone
Amiloride and Trameterene:
-how do they work?
work to block sodium channels in late distal and collecting ducts
Spironalactone:
- how does it work?
- when is it used?
Mechanism:
- blocks aldosterone receptors = increase excretion of sodium and decrease excretion of potassium
- -given alone causes hyperkalaemia
Uses:
- limited diuretic action
- used in conjunction with agents that cause hypokalaemia
- heart failure
- conn’s
- resistant HTN
- secondary hyperaldosteronism
How does IV mannitol exhibit a diuretic effect? when is this used?
Mechanism:
- increases osmolality of filtrate
- opposes absorption of water in parts of nephron freely permeable to water (proximal tubule)
- secondarily decrease sodium conc. in tubule and less sodium is reabsorbed
Used:
- prevention of acute hypovolaemic urine failure
- for acutely raised ICP or intraocular pressure as drug doesn’t enter eye or brain
Carbonic anhydrase inhibitors:
- how do these work?
- what are these used for?
Mechanism:
-block the effect of carbonic anhydrase to prevent HCO3- reabsorption into interstitium
=sodium isn’t reabsorbed and water and potassium follow
=alkaline diuresis and a metabolic acidosis
Uses:
- in glaucoma/after eye surgery to decrease aqueous humour production
- prophylactic for altitude sickness
- some forms of infantile epilepsy
Name some vasopressin antagonists? how do these affect the kidney?
Examples:
- lithium
- demeclocyclin
- vaptans (tolvapatan used in SIADH)
Action on the kidney:
-this stops ADH inserting aquaporins in the collecting tubule and therefor decreases water reabsorption
Name some SGLT2 inhibitors? How do these effect the kidney?
Examples:
-canaglifozin, dapaglifozin, empaglifozin
Mechanis:
- inhibits SGLT2 transporter in the 1st segment of the proximal tubules
- 90% glucose can’t be reabsorbed
Uses:
-T2DM
How do NSAIDs affect the kidney? when is this of importance?
Inhibit COX and therefore inhibit prostaglandin formation = afferent arteriole doesn’t become vasodilated
This is of importance in conditions where renal blood flow is dependant on this vasodilator effect = decrease GFR
(liver cirrhosis/heart failure/nephrotic syndrome)
what is the triple whammy effect?
ACEI + diuretic + NSAID = triple whammy
- ACEI cause vasodilation of efferent arteriole (as angiotensin III causes vasoconstriction of efferent arteriole)
- NSAID causes vasoconstriction of afferent
- diuretic causes lower circulating volume
What can cause an osmotic diuresis?
- hyperglycaemia
- use of iodine based radiocontrast dyes as they’re filtered and not reabsorbed (only worry about this in pts with borderline cardiovascular status as they may get hypertension)
