Diuretics Flashcards
Mannitol
- MAO: exert osmotic force (inc oncotic pressure in the plasma) to pull water out of tubule and into plasma
- So only diuretic that does not enter tubular lumen
- Uses: reduce cerebral edema or intraocular pressures (pull water from cells into blood)
- Contraindication: CHF or pulmonary edema b/c rapid expansion of IV space can lead to worse or new edema (“flash” pulmonary edema)
Carbonic Anhydrase Inhibitors (MAO and uses)
- Acetazolamide
- MAO: inhibit carbonic anhydrase in proximal tubule
- Inhibits carbonic anhydrase in brush border and tubular cytoplasm; this bicarbonate in tubular lumen normally provides source of H+ which is used in the Na/H exchanger so this exchanger is inhibited –> less Na+ reabsorption
- Uses: reverse alkalemia (prevent bicarb reabsorption), epilepsy (to create metabolic acidosis), glaucoma (reduce aqueous humor), etc
Side Effects/Contraindication of Carbonic Anhydrase Inhibitors
- Side Effects: too much metabolic acidosis, alkaline kidney stones, hypokalemia, hypersensitivity rxn (sulfonamide)
- Contraindications: do not use if liver cirrhosis b/c it works on distal tubule too where it inc ammonia in blood
Loop Diuretics (MAO and uses)
- Furosemide, bumetanide, torsemide, ethacrynic acid
- MAO: inhibit Na-K-2Cl in TAL
- Blocks Na+ reabsorption directly
- By dec K and Cl entry… it eliminates the gradient that these 2 ions create that normally drives paracellular cations into tubule (Ca, Mg, Na) … so these are not reabsorbed
- Uses: edema from all volume overload states, treat hyperkalemia and hypercalcemia, treat hypervolemic hyponatremia (less of a medullary gradient - less water reabsorption/more water excretion @ collecting duct), HTN
Side Effects of Loop Diuretics
POTENT so can cause volume depletion, hypokalemia, hypocalcemia, hypomagnesium (can lead to cardiac arrhythmia), sulfa allergies (except ethacrynic acid), ototoxicity (same transporter in inner ear), hyperuricemia (less vol = more reabsorption), hyperglycemia, hyperlipidemia
Thiazide Diuretics (MAO and Uses)
- Hydrochlorothiazide, chlorthalidone, chlorothiazide, metolazone
- MAO: Inhibit Na-Cl symporter in distal tubule
- Directly prevents Na+ reabsorption
- Uses: HTN (also direct vasodilators), hypocalcemia/osteoporosis, prevent Ca-based kidney stones (less Ca in urine), nephrogenic DI (seems counterproductive BUT only mild dec volume which stimulates inc water/Na reabsorption in early proximal tubule so by the time you get to CD where the ADH is unresponsive there is not a lot of water left keep in urine)
Side Effects of Thiazide Diuretics
volume depletion, hypotension, hyponatremia (unlike loop they do not dec medullary gradient), hypokalemia, metabolic alkalosis, hypomagnesium, hypercalcemia, hyperuricemia, hyperlipidemia, hyperglycemia
Na+ Channel Blockers (MAO and uses)
(potassium-sparing)
- Triamterene & Amiloride
- MAO: block ENaC in principal cells of CD
- Directly prevents Na+ reabsorption
- Also gets rid of ROMK driving force which normally returns K+ to tubular lumen (urine) = K+ spared (more in blood)
- Uses: combo w/ loop or thiazide (can normalize K+ values or enhance effect), treat Liddle’s Syndrome (mutation of enhanced ENaC)
Side Effects of Na+ Channel Blockers
hyperkalemia (esp if on other drugs that cause hyperkalemia), triamterene specifically can cause glucose intolerance and photosensitivity
MR Antagonists (MAO and uses)
(potassium-sparing)
- Spironolactone & Eplerenone
- MAO: mineralocorticoid receptor antagonist (aldosterone is mineralocorticoid that binds MR) in principal cells of CD
- Act in principal cells themselves NOT tubular lumen
- Aldosterone-MR binding –> more ENaC so this is prevented
- Uses: primary hyperaldosteronism and secondary aldosteronism (CHF, liver cirrhosis, nephrotic syndrome)
Side Effects of MR Antagonists
Hyperkalemia, metabolic acidosis, spironolactone specifically binds progesterone/androgen receptors –> menstrual irreg, peptic ulcers, hirsuitism, erectile dysfunction
Relative Effectiveness of Diff Diuretics
Loop > thiazide > proximal/K-sparing
-Later distal tubules cannot compensate from dec Na reabsorption from loops
Diuretic Resistance and 4 Ways to Overcome
- Diuretic resistance - when same dose no longer reduces edema; likely due to compensation of more distal parts of nephron (hypertrophy or express more transporters over time)
- 1- Use higher dose
- 2- Combine multiple diuretics
- 3- Use more frequent doses or continuous infusion
- 4- dec Na+ in diet
Ceiling Dose (how is this affected by disease states?)
Amount needed to get adequate drug into tubular lumen (but do not want to exceed - no additional benefit w/ more side effects)
- Getting to this ceiling dose (max effect) may require more or less actual actual distributions of med
- Generally, as disease progresses you need higher dose to get same max effect/ceiling dose (likely b/c disease impairs delivery to tubular lumen)
- In CHF this is due to dec CO/ dec RBF
- In AKI/CKD this is due to lack of luminal secretion
