Pharmacolgy of drugs acting on the kidney Flashcards
How do diuretics fundamentally increase urine output?
By interfering with salt reabsorption in the nephron
What is the fundamental indication for diuresis?
Diseases associated with increase in the ICF volume (oedema)
What is the main driving force behind formation of interstitial fluid?
Capillary pressure
Why does protein (e.g. albumin) filtered at the glomerulus always appear in the urine?
Cannot be reabsorbed
Why does decreased blood volume cause decreased cardiac output?
Starling laws- lower preload
How does the nephrotic syndrome cause oedema?
Loss of protein causes decreased oncotic pressure ????????
For what two reasons does hepatic cirrhosis cause odoema?
Increased portal pressure; combined with decreased albumin
(also made worse by activation of RAAS)
Why are carbonic anhydrase inhibitors now obsolete?
Tachyphylaxis
Why are potassium-sparing diuretics used?
To try and modulate the amount of potassium being excreted (for example with use of loop and thiazide diuretics- correct the hypokalaemia)
Where must the diuretics be in order to have their effects?
Within the filtrate (because they act at the apical membrane)
Why do diuretics rarely gain access to the filtrate by filtration at the glomerulus? How do they gain access?
Most are protein-bound (not filtered)
Organic anion transporters (acidic drugs e.g. thiazides and loops)
Organic cation transporters (basic drugs)
What is the basic mechanism of action of loop diuretics?
Inhibits the triple co-transporter in the thick ascending loop of Henle
What drives the movement of calcium and magnesium across the tight junctions?
Transepithelial potential caused by potassium
What are two adverse effects of loop diuretics other than hypokalaemia? Why is this?
Hypocalcaemia and hypomagnesia. Ablation of the trans-epithelial potential driving Mg and Ca reabsorption
Where do furoesemide and bumetanide bind to the triple transporter?
The chloride site
What other action of loop agents is beneficial in pulmonary oedema?
Indirect venodilation
Why does diuretic efficacy decrease in nephrotic syndrome?
Becomes bound to protein in the filtrate
The toxicity of which drugs can be enhanced by loop diuretics? What is the cause?
Cardiac glycosides (e.g. digoxin) and Class III antidysrythmics
Hypokalaemia
How is acid-base balance shifted in loop diuretics?
Towards alkalosis (metabolic)- increased secretion of hydrogen
What is the mechanism of action of the thiazide diuretics?
Blocks the NaCl co-transporter in the distal tubule
What are the adverse effects of thiazide diuretics?
Hypokalaemia
Hypercalcaemia
Hyperuricaemia (gout)
Metabolic alkalosis
Hypovolaemia/hypotension
Male sexual dysfunction
Impaired glucose tolerance
What other action of thiazide diuretics makes them useful in the treatment of hypertension?
Indirect vasodilatory effect
Considering the effect of thiazide diuretics in calcium reabsorption, what other indication is there for their use?
Increased re-absorption of calcium- nephrolithiasis
What are the effects of aldosterone?
Increases synthesis of the Na/K ATPase and increases the synthesis of a protein which activates ENaC (epithelial sodium channel)
How do spironolactone and eplerenone work?
Competitive aldosterone antagonists
Given alone, what do potassium-sparing diuretics cause?
Hyperkalaemia
