Lecture 57 and 58 - Diuretics Flashcards
Diuretic that works at the PCT
Acetozalamide
Mechanism of Acetazolamide
apical carbonic anhydrase inhibition: inhibition of bicarbonate reclamation
therefore also blocking Na reabsorption via the Na/H counter transporter
What limits the effectiveness of Acetazolamide; explain how
Glomerular Tubular Balance –
with decreased effective volume, increase filtration fraction, which increases efferent arteriole oncotic pressure, increasing reabsorption, decreasing diuresis
What other transporters imporatnt for the efficacy of diuretics are located in the PCT?
Organic Cation Transporters -
Organic Anion Transporters -
(route of entry for diuretics, which are otherwise protien bound in the plasma and cannot get through the glomerular filter; Diuretics only work through the lumenal side)
what drug inhibits OATs and OCTs
Probenecid
Indications for Acetazolamide
side effects
Poor Diuretic, Glaucoma Epilepsy Altitude sickness Metabolic alkalosis Periodic Paralysis
side effects:
Drowsiness, Dizziness, HA, Fatigue
Metabolic Acidosis
Paresthesias,
What class of diuretics work at the loop of henle; which part of the loop?
name the members of this class
Loop Diuretics
Thick Ascending Limb
Furosemide
Bumetanide
Torsemide
Mechanism of action of loop diuretics:
Inhibition of the Na/K/2Cl Co transporter –
Therefore decreases Na Reabsorption (directly via the transporter) and (indirectly via paracellular transport)
What is the specific gravity of diuresis with loop diuretics? what is the reason for this?
1.010 = Isosthenuria
Loss of ability to dilute (co transporter), but also loss of ability to concentrate (lose of medullary concentration gradient)
Indications for Loop Diuretics
EDEMA – (HF, pulm edema, nephrotic syndrome )
HTN
Hypercalcemia (bc its prevents Ca paracellular absorption)
side effect s of loop diuretics
Excessive Volume depletion HypoKalemia Hypocalcemia Hypomagnesemia Ototoxicity Hypokalemia
(OH DANG – Ototoxicity, HypoKalemia/Calcemia, Dehydration, Allerigy, Nephritis, Gout)
which loop diurteic has no risk of sulfa allergies
Ethaacrynic Acid
What Limits the effectiveness of loop diruetics?
JGA – uses Cl as surrogate marker for volume
Body becomes Cl deplete with loop diuretics. Senses volume depletion. Activates RAS
What diuretic class works at the DCT
name 2
Thiazide Diuretics
HCTZ
Metolazone
mechanism of Thiazide diuretics:
Blocks Na/Cl Co transporter
what will the urine concentration be for thiazide diuretics?
Isotonic or Hypertonic
Inhibits ability to dilute the urine, but not concentrate it
Indications of Thiazides:
HTN - -first line (diuresis + vasodilatory effects)
Edema
Nephrogenic Diabetes Insipidus (Paradoxical anti-diruesis)
Hypercalciuria (increases Ca reabsorption) – good for people with kidney stones
Side effects of thiazides
Hyponatremia (Contraindicated)
Hypokalemia
hyperlipidemia
hypercalcemia
Hyperuricemia
2 classes of drugs that work at the CCD: name 2 members of each class
Enac Blocking K sparing drugs: amiloride, Triamterene
Aldosterone Blocking K sparing drugs: Spironolactone, Eplerenone
How do these “spare” K?
Enac Blockers:
block enac of the pricniple cell, therefore no Na resorbtion, no K excretion
Mineralocorticoid Receptor Blockers: Prevents action of aldosterone (prevents upreg of Na/K, Enac, and ROMK)
Indications of ENAC blockres:
side effects?
Cirrhosis/Ascites –
(Maxide = HCTZ + Triamterene)
side effects: Hyperkalemia, Hypotension
Indications of Mineralocorticoid blockers:
Side effects
Cirrhosis, CHF, hypoeraldosteronism
Side effects:
HyperK
Hypotension
Anti-androgen: Gynocomastia, ED
Drugs that work at the Medullary Collectng Ducts – n
name class
name 3
Vaptans (Aquaretics)
Conivaptan (IV)
Tolvaptan(Oral)
Satavaptan
Mechanism of Vaptans
V2 Receptor blockers (block ADH action)
prevent aquaporin insertion
Cannot concentrate the urine
effect of vaptans?
why is there is no clinical indicaitns
Will make you pee more
but no mortality benefit; therefore no clinical indicatins
what is the most powerful class of diuretic? (what is the prototypical drug of this class)
how are these drugs administered
Osmotic diuretics
(Mannitol)
IV only
mechanism of osmotic diuretics:
Freely filtered and non reabsorbable; therefore draw water into the tubule lumen
Large volume diuresis
Indications of osmotic duretics
Decreased Intracranial pressure
Free radiacl scavengers (therefore prevent peroxidation in conditions such as rhabdomyolysis)
Induced forced diuresis
Side effects of osmotic diuretics
Initial ECFV expansion (the drug stays in the intravascular fluid)
Can exacerbate CHF
What drug class can cause ototoxicity?
symptoms ?
loop diuretics
Vertigo, hearing loss
