Diuretics and Kidney Failure Drugs Flashcards
What are functions of the kidney?
• Regulatory
o Fluid balance
o Acid-base balance
o Electrolyte balance
• Excretory
o Waste products
o Drug elimination
• Glomerular filtration & tubular secretion
• Endocrine
o Renin angiotensin aldosterone system
o Erythropoetin
o Prostaglandins
• Metabolism o Vitamin D o Polypeptides • Insulin • Parathyroid hormone
What are the types of diuretics? Examples? Where do they act?
Carbonic anhydrase inhibitors - acetazolamide - PCT
Osmotic diuretics - mannitol - PCT/LOH
Loop diuretics - furosemide - LOH - Thick Ascending Limb
Thiazides - Bendroflumethiazide, indapamide - DCT
Potassium sparin diuretics - Spironolactone, amiloride - late DCT and CD
Digoxin
What is an example of a carbonic anhydrase inhibitors? What are their mechanism of action?
Acetazolamide
Inhibits carbonic anhydrase, reduces NaCl and HCO3 reabsorption in the proximal convoluted tubule
Example of osmotic diuretic. MOA?
Mannitol
Excreted into the lumen of the tubule and has osmotic draw into the lumen
Used in raised intracrhail pressure to remove fluid from body
Example of thiazides, MOA? ADRs?
Bendroflumethiazide
Hydrochlorothiazide
Indapamide
DCT
Inhibits NaCl transporter in DCT preventing NaCl reuptake leading to retention of water in urine – only causes small diuresis but helps with blood pressure control - decrease preload and so decrease BP in the short term
Gout (hyperuricaemia), erectile dysfunction, dyslipidaemia, hypokalaemia, hyponatraemia, hypercalcaemia
Example of loop diuretic? MOA? ADRs?
Furosemide, bumetanide
Thick ascending limb LOH
Inhibits NaKCC channel in thick ascending limb of the Loop of Henle and prevents reabsorption of sodium, potassium and hence water. Strong diuretic.
ADR:
Ototoxicity, myalgia, hyponatraemia, hypokalaemia, hypocalcaemia
How do thiazide diuretics cause hypokalaemia? How can this be avoided?
Inhibition of sodium-chloride symporter increases availability of sodium and chloride in urine. When the urine reaches the collecting duct, the increase in sodium and chloride availability activates Na+/K+-ATPase, which increases the absorption of sodium and excretion of potassium into the urine.
Long term administration of thiazide diuretics reduces total body blood volume. This activates the renin–angiotensin system, stimulates the secretion of aldosterone, thus activating Na+/K+-ATPase, increasing excretion of potassium in urine.
Use alongside an ACE inhibitor to avoid
Examples of potassium sparing diuretics, MOA, ADRs
Spironolactone (aldosterone antagonists), Amiloride (epithelial Na channel blockers)
Late DCT and CD
Spironolactone is a competitive aldosterone antagonist, reduces expression of ENaC channels in the collecting duct and late DCT which prevents reabsorption of water.
(Aldosterone normally adds sodium channels in the principal cells of the collecting duct and late distal tubule of the nephron)
Amiloride antagonise these channels directly
ADRs:
Hyperkalaemia, gynaecomastia
how does digoxin function as a diuretic?
Inhibits Na+/K+ ATPase in the tubules which means there is less of a sodium gradient for reabsorption
What are general ADRs of diuretics?
- Anaphylaxis and rash
- Hypovolaemia and hypotension, leading to AKI
- Electrolyte disturbance
- Metabolic abnormalities
Why should you not give ACE inhibitors with Spironolactone
Hyperkalaemia–> Arrhythmia
Why would you not give an amino glycoside and a loop diuretic? Examples
Both are ototoxic and nephrotoxic
Gentamicin and furosemide
Why would you not give digoxin with a thiazide or loop diuretic?
Hypokalaemia
Why would you not give beta blockers with thiazide diuretics?
Hyperglycaemia, hyperlipidaemia, hyperuricaemia
Why would you avoid steroids with thizide/loop diuretics?
Hypokalaemia
