18. Diuretics and Drugs in Kidney Failure Flashcards
What are the four roles of renal physiology?
Regulatory, excretory, endocrine, metabolism.
What are the regulatory factors of renal physiology?
Fluid balance, acid-base balance, electrolyte balance.
What are the excretory factors of renal physiology?
Waste products, drug eliminations - glomerular filtration and tubular secretion.
What are the endocrine factors of renal physiology?
Renin-angiotensin-aldosterone, erythropoetin, prostaglandins.
Where is angiotensinogen secreted?
The liver.
Where is renin secreted?
Renin.
What is the role of renin?
Converts angiotensinogen to angiotensin I.
What are the metabolic factors of renal physiology?
Vitamin D, polypeptides - insulin and PTH.
Where do carbonic anhydrase inhibitors act?
At the PCT.
What is the mechanism of action of carbonic anhydrase inhibitors?
Acts at PCT to prevent carbonic anhydrase in tubule, reabsorption of Na+ ions is affected.
What are carbonic anhydrase inhibitors used for?
Topical treatment for glaucoma.
What are the risks of using carbonic anhydrase inhibitors as diuretics?
Metabolic acidosis and hypokalaemia.
Name an osmotic diuretics.
Mannitol.
What is the mechanism of action of osmotic diuretics?
Increase osmotic gradient systemically.
What are the risks of osmotic diuretics?
Excessive water loss -> hypernatraemia.
What are osmotic diuretics currently used for?
Severe cerebral or pulmonary oedema.
What is the mechanism of action of ADH antagonists?
Reduce concentrating ability of urine in collecting ducts.
Name an ADH antagonist.
Lithium or demeclocycline.
Name a loop diuretic.
Furosemide.
What is the mechanism of action of loop diuretics?
Act on NKCC2 transporters on thick ascending limb of loop of Henle so directly prevent Na_ and Cl- reabsorption. Concurrent excretion of Ca2+ and Mg2+ too.
What are the risks of loop diuretics?
Hypokalaemia.
What are indications of use of loop diuretics?
Heart failure and liver failure.
What are the DDIs for loop diuretics?
Aminoglycosides - risk of ototoxicity and nephrotoxicity. Digoxin or steroids - risk of hypokalaemia.
What is the mechanism of action of thiazides?
Act on Na+-Cl- symporter and promote Ca2+ reabsorption.
What are the ADRs of thiazides?
Hypokalaemia, hypercalcaemia, hyperuricaemia, risk of erectile dysunction.
What are the indications of use of thiazides?
Heart failure and hypertension, also kidney stones (calcium reabsorption from urine)
What are the DDIs for thiazides?
Digoxin or steroids - risk of hypokalaemia. B-blockers - risk of hyperglycaemia, hyperlipidaemia, hyperuricaemia.
Name a potassium sparing diuretic.
Amiloride.
What is the mechanism of action of potassium-sparing diuretics?
Act on ENaC channel in late DCT and collecting duct.
What is the important DDI with potassium-sparing diuretics?
ACE inhibitors - risk of hyperkalaemia.
Name a aldosterone antagonist.
Spironolactone, eplerenone.
What is the mechanism of action of aldosterone antagonist?
Inhibit action of aldosterone on mineralocorticoid receptors so affect Na+K+ATPase and ENaC protein synthesis.
What is the half life of spironolactone?
18-24 hours so can be used long term.
What are the ADRs of aldosterone antagonists?
Hyperkalaemia, androgenic cross-reactivity -> gynaecomastia.
What are the indications of aldosterone antagonists?
Heart failure, hypertension, liver failure, hyperaldosteronism.
What are the general ADRs of any diuretic use?
Anaphylaxis/rash, hypovolaemia, hypotension, electrolyte disturbance, and metabolic abnormalities.
What is the mechanism of action of digoxin?
Inhibits tubular NaKATPase.
What is the mechanism of action of amiloride?
Inhibits Na channels in DCT/CD, K+ sparing.
What can cause apparent diuretic resistance?
Incomplete treatment of primary disorder, continuation of high Na+ intake, non-compliance, poor absorption, volume depletion decreases filtration and increases aldosterone, NSAIDs can reduce renal blood flow.
What are some key considerations of prescribing in chronic renal failure?
Avoid nephrotoxins if possible, reduce dosages, monitor renal function and drug levels, watch out for hyperkalaemia, uraemia patients may bleed.
How is hyperkalaemia managed?
Identify cause, ECG, treat with drugs.
Which drugs can treat hyperkalaemia?
Calcium gluconate, insulin/dextrose, calcium resonium, sodium bicarbonate, salbutamol.
What are the features of hyperkalaemia on ECGs?
Tall tented T waves, QRS elongation, fewer P waves.
