Pharmacology of Diuretics + eGFR measurment Flashcards
What do all diuretics do? How does the body “antagonize” diuretics? What is the most important characteristic of a diuretic?
All diuretics inhibit the reabsorption of sodium. The nephron is designed to counteract attempts to increase Na in the lumen. “Where” the diuretic works in the most important characteristic
How do diuretics get into the lumen of the tubule? What do they compete with?
Most are secreted in the proximal tubule by oraganic anion transporters. They compete with uric acid and NSAIDs
What are the five classes of diuretics?
Carbonic anhydrase inhibitors Loop Thiazides Potassium-sparing Osmotic
What is acetazolamide?
A carbonic anhydrase inhibitor
What is the MOA of carbonic anhydrase inhibitors?
Act in the proximal tubule
What are the indications for carbonic anhydrase inhibitors?
What are the side-effects of CA inhibitors?
- glaucoma (reduces the production of aqueous humour)
- altitude sickness
- limited use in diuresis
Side effects
- metabolic acidosis
- renal stones (from alkaline urine)
- hypokalemia (Na is exchanged for K at distal sites)
How do loop diuretics work? Why are they so powerful? What does “high ceiling” mean?
MOA
- Inhibit reabsorption of Na, K and Cl by blocking NKCC in the TAL
They are powerful because they act at the last major site of sodium reabsorption and they have a high ceiling, which means that you can increase the dose a lot before the response plateaus.
What is furosemide?
A loop diuretic
What are the side effects of loop diuretics (x5)? Contraindicated in (x1)?
- loss of calcium and magnesium (blocking NKCC abolishes the electrical gradient needed to move these ions paracellularly)
- hypokalemia (loss of NKCC potassium, and exchange of potassium for sodium at a distal site)
- metabolic alkalosis (exchange of Na for H+ at a more distal site)
- hyperurecemia (–>gout)
- ototoxicity (NKCC also found in ear, depends on peak dose)
Contraindicated/Use caution with aminoglycoside antibiotics (they also cause ototoxicity)
What are the indications for loop diuretics? What are the contraindications?
- edema
- hypertension (not first line due to BID dosing)
- hypercalcemia
Contraindicated in: hypovolemia, severe electrolyte abnormalities
What is the MOA of thiazide diuretics?
They act at the distal tubule and inhibit NCC (Na Cl symporter)
What are indications for thiazide diuretics?
- hypertension
- edema (diuresis + reduced TPR…separate mechanisms)
- nephrogenic diabetes insipidus
What are side effects of thiazide diuretics?
- hypokalemia (downstream exchange of Na+ for K+, downstream exchange for H+)
- metabolic alkalosis (downstream exchange for H+)
- hypercalcemia (a good effect for some people…)
- hyperurecemia
- hyperlipidemia
- hyperglycemia
What is the MOA of potassium-sparing diuretics? What are prototypes?
Potassium sparing diuretics work in the late distal tubule/early collecting duct
Spironolactone is an aldosterone antagonist. It prevents the aldosterone receptor from going to the nucleus, and transcribing more ENaC. Without this channel, less Na is passively absorbed, and there is no need for K+ to leave in exchange.
Amiloride and triamterene are ENaC blockers.
What are the indications for potassium-sparing diuretics?
Hypertension (in fixed-dose combination)
CHF
Primary hyperaldosteronism
What is the relationship between serum creatinine and GFR? What implications does this have?
This means that for a person with normal GFR, a doubling of their SCr results in a 50% decrease in GFR, but for a person with impaired kidney function, a doubling of SCr doesn’t result in a huge absolute drop in GFR.
