Lecture 57 and 58 - Diuretics

Question 1

Diuretic that works at the PCT

Answer 1

Acetozalamide

Question 2

Mechanism of Acetazolamide

Answer 2

apical carbonic anhydrase inhibition: inhibition of bicarbonate reclamation

therefore also blocking Na reabsorption via the Na/H counter transporter

Question 3

What limits the effectiveness of Acetazolamide; explain how

Answer 3

Glomerular Tubular Balance –
with decreased effective volume, increase filtration fraction, which increases efferent arteriole oncotic pressure, increasing reabsorption, decreasing diuresis

Question 4

What other transporters imporatnt for the efficacy of diuretics are located in the PCT?

Answer 4

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)

Question 5

what drug inhibits OATs and OCTs

Answer 5

Probenecid

Question 6

Indications for Acetazolamide

side effects

Answer 6

Poor Diuretic, 
Glaucoma
Epilepsy 
Altitude sickness
Metabolic alkalosis  
Periodic Paralysis 

side effects:
Drowsiness, Dizziness, HA, Fatigue
Metabolic Acidosis
Paresthesias,

Question 7

What class of diuretics work at the loop of henle; which part of the loop?

name the members of this class

Answer 7

Loop Diuretics

Thick Ascending Limb

Furosemide
Bumetanide
Torsemide

Question 8

Mechanism of action of loop diuretics:

Answer 8

Inhibition of the Na/K/2Cl Co transporter –

Therefore decreases Na Reabsorption (directly via the transporter) and (indirectly via paracellular transport)

Question 9

What is the specific gravity of diuresis with loop diuretics? what is the reason for this?

Answer 9

1.010 = Isosthenuria

Loss of ability to dilute (co transporter), but also loss of ability to concentrate (lose of medullary concentration gradient)

Question 10

Indications for Loop Diuretics

Answer 10

EDEMA – (HF, pulm edema, nephrotic syndrome )
HTN
Hypercalcemia (bc its prevents Ca paracellular absorption)

Question 11

side effect s of loop diuretics

Answer 11

Excessive Volume depletion
HypoKalemia
Hypocalcemia 
Hypomagnesemia 
Ototoxicity 
Hypokalemia 

(OH DANG – Ototoxicity, HypoKalemia/Calcemia, Dehydration, Allerigy, Nephritis, Gout)

Question 12

which loop diurteic has no risk of sulfa allergies

Answer 12

Ethaacrynic Acid

Question 13

What Limits the effectiveness of loop diruetics?

Answer 13

JGA – uses Cl as surrogate marker for volume

Body becomes Cl deplete with loop diuretics. Senses volume depletion. Activates RAS

Question 14

What diuretic class works at the DCT

name 2

Answer 14

Thiazide Diuretics

HCTZ
Metolazone

Question 15

mechanism of Thiazide diuretics:

Answer 15

Blocks Na/Cl Co transporter

Question 16

what will the urine concentration be for thiazide diuretics?

Answer 16

Isotonic or Hypertonic

Inhibits ability to dilute the urine, but not concentrate it

Question 17

Indications of Thiazides:

Answer 17

HTN - -first line (diuresis + vasodilatory effects)

Edema

Nephrogenic Diabetes Insipidus (Paradoxical anti-diruesis)

Hypercalciuria (increases Ca reabsorption) – good for people with kidney stones

Question 18

Side effects of thiazides

Answer 18

Hyponatremia (Contraindicated)

Hypokalemia

hyperlipidemia

hypercalcemia

Hyperuricemia

Question 19

2 classes of drugs that work at the CCD: name 2 members of each class

Answer 19

Enac Blocking K sparing drugs: amiloride, Triamterene

Aldosterone Blocking K sparing drugs: Spironolactone, Eplerenone

Question 20

How do these “spare” K?

Answer 20

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)

Question 21

Indications of ENAC blockres:

side effects?

Answer 21

Cirrhosis/Ascites –
(Maxide = HCTZ + Triamterene)

side effects: Hyperkalemia, Hypotension

Question 22

Indications of Mineralocorticoid blockers:

Side effects

Answer 22

Cirrhosis, CHF, hypoeraldosteronism

Side effects:
HyperK
Hypotension
Anti-androgen: Gynocomastia, ED

Question 23

Drugs that work at the Medullary Collectng Ducts – n
name class
name 3

Answer 23

Vaptans (Aquaretics)

Conivaptan (IV)
Tolvaptan(Oral)
Satavaptan

Question 24

Mechanism of Vaptans

Answer 24

V2 Receptor blockers (block ADH action)

prevent aquaporin insertion
Cannot concentrate the urine

Question 25

effect of vaptans?

why is there is no clinical indicaitns

Answer 25

Will make you pee more

but no mortality benefit; therefore no clinical indicatins

Question 26

what is the most powerful class of diuretic? (what is the prototypical drug of this class)

how are these drugs administered

Answer 26

Osmotic diuretics

(Mannitol)

IV only

Question 27

mechanism of osmotic diuretics:

Answer 27

Freely filtered and non reabsorbable; therefore draw water into the tubule lumen

Large volume diuresis

Question 28

Indications of osmotic duretics

Answer 28

Decreased Intracranial pressure

Free radiacl scavengers (therefore prevent peroxidation in conditions such as rhabdomyolysis)

Induced forced diuresis

Question 29

Side effects of osmotic diuretics

Answer 29

Initial ECFV expansion (the drug stays in the intravascular fluid)

Can exacerbate CHF

Question 30

What drug class can cause ototoxicity?

symptoms ?

Answer 30

loop diuretics

Vertigo, hearing loss