L11 and L12 - Diuretics Flashcards
What are the 2 major indications for diuretics?
Treatment of volume overloaded states - water pils
Treatment of HTN
What are the different classes of drugs and where do they act on the nephron?
Carbonic Anhydrase Inhibitors = PCT
Loop Diuretics= Thick Ascending Loop of Henle
Thiazide Diuretics = DCT
K+ Sparing diuretics = Cortical collecting duct
Auqareitcs = Medullary Collecting Duct
Osmotic Diuretics = Everywhere!
What are the drugs that act in the Proximal Convoluted tubule? Name them, What is their action? Limitiations to action?
1) Acetazolamide = CA inhibitor that prevents dissociation of H2CO3 leading to bicarbonaturia and metabolic acidosis –> decrease NaHCO3 reclammation
Limitation: Glomerulotubular balance (ineffective diuretic)
2) Probenacid = Uricosuric drug that inhibits OATs and OTCs that normally allow substances bound to plasma proteins to get into tubular fluid
*THerefore - blocks the effects of diuretics bc cant get to lumen!!!
What is Acetazolamide? What is it used for? Side Effects? What are other similar drugs’ names?
Acetazolamide = used for Glaucoma, Altitude sickness, Metabolic Alkalosis and Periodic Paralysis
- tends not to cause significant natriuresis
Side Effect: Drowsiness, HA, Dizziness, fatigue, and Metabolic Acidosis
Others: Dorzolamide, Zonisamide
What is Probenacid used for? Side Effects?
Probenacid blocks OATs and OCTs in the PCT and used in the treatment of Gout to prevent Uric acid reabsorption.
*BLOCKS THE EFFECTS OF DIURETICS!
What are Osmotic Diuretics? What is their mechanism of action/how do they work?
Osmotic Diuretics are freely filtered and non-reabsorbable and so high osmotic concentration in tubules leads to drag of water and solutes from plasma space into tubules
- Induce convective movement of water and inhibits Na and water reabsorption downstream
**Agents = IV Mannitol!!! **
LARGE VOLUME DIURESIS - primarily WATER!
What are osmotic diuretics used for? What are the side effects?
Indications:
- reduce ICP in CNS
- Free radical scavenger after crush injury
- Induce forced diuresis to protect kidney from pigments like Myoglobin after Rhabdomyolysis
Side Effects: initial ECFV expansion (intravascular volume) which is bad in CHF
What is an endogenous pathological state causing osmotic diuresis?
Hyperglycemia!!!
DM and no insulin induce osmotic diuresis that can result in significant dehydration (hypernatremia) and polydypsia and polyuria
Dehydration bc no access to electrolyte free water and profoundly dehydrated
What drugs do you use to treat Hypercalcemia? What drugs do you use to treat Kidney stones? Why?
Hypercalcemia = Loops!
- Decrease paracellular transport of Ca and so loose Ca and Mg in urine
Hypercalcuria (Kidney stones) = thiazide!
-Increase Ca reabsorption and so less in urine
Name the Loop Diuretics. How and Where do they work?
Furosemide, Bumetanide, Torsemide, and Ethacrynic Acid
Inhibit Na-K-2Cl Co-transporter in the Thick Ascending lump of LOH
Decrease Na reabsorption directly and indirectly – lowers transtubular potential for paracellular transport
- Lose medullary concentration gradient
- Large volume isothenuric diuresis (sp gravity 1.010)
Ceiling Diuretic – threshold concentration needed to reach site of action but above therapeutic window no further effect
What are the indications for loop diuretics?
Edema – first line for CHF, Pulmonary edema, cirrhosis, Nephrotic syndrome
HTN – also has vasodilatory effects
Hypercalcemia – blocks paracellular transport of calcium and therefore overwhelms distal nephron and lose some in urine
Forced Diuresis
What are the side effects of loop diuretics?
Pee like a racehorse – Lasix = Lasts for 6 hours!
FIRST-AID: OH-DANG = Ototoxicity, Hypokalemia, Dehydration, Allergy, Nephritis (interstitial) and gout
Excess volume depletion and circulatory collapse!
Azotemia and Hyperuricemia
Hypokalemia – cardiac arrhythmias
Hypocalcemia and Hypomagnesemia
Ototoxicity – similar transporter in ear
Which Loop diuretics can cause bad allergy and why? Which ones can be oral?
Furosemide – variable oral availability, Sulfonamide = allergy!!!, Also Weak CA inhibitor and Vascular effects
Torsemide and Bumetanide – high oral bioavailability and have Sulfa moiety = allergy!!
Torsemide – Sulfonylura so lowers serum glucose
**Ethacrynic Acid = NO SULFA!!!!!! **
What drug class / drugs act on the Distal Convoluted tubule? How do they work?
THIAZIDES! And Metolazone!
Inhibit NaCl Symporter to decrease ability to form dilute urine but not concentrated urine (if ADH still works) causing moderate volume diuresis
*Therefore, Contraindicated in Hyponatremia!!
Also have vasodilatory effects
Also Increase Ca reabsorption – used to help w/ Kidney Stones
How do Thiazides increase Ca reabsorption?
Normally, Ca enters DCT cell through apical CA channel and re-enters blood through Na-Ca exchanger; but w/ Thiazides:
- Decrease intarcellular NA which means Basolateral Na-Ca exchanger works harder to keep Na in cell
- Pumps more Ca into blood making favorable gradient for CA reabsorption through Apical channel
Good to use at high doses for kidney stones!!! Hypercalcuria
