Pharm Diuretics

Front 1

mannitol class?

Back 1

osmotic diuretic

Front 2

acetazolamide class?

Back 2

carbonic anhydrase inhibitor

Front 3

thiazide diuretic prototype?

Back 3

hydrochlorothiazide

Front 4

loop diuretic prototype?

Back 4

furosemide

Front 5

potassium sparing Na ch blker prototype?

Back 5

amiloride

Front 6

potassium sparing aldosterone antagonist prototype?

Back 6

spironolactone

Front 7

under nl physiological conditions what happens at the glomerulus?

Back 7

formation of protein-free ultrafiltrate

Front 8

what normally occurs at the proximal tubule?

Back 8

isotonic reabsoption of about 60% of filtered Na and water
partly determined by eff art BF which influences backload
partly det by CA activity for Na uptake in response to HCO3-

also has memb transporters for drug secretions (org acids, bases, ligands of mdr gene prod)

Front 9

what happens normally in the loop of henle?

Back 9

concentrate filtrate in desc limb

form free water in ascend limb due to active Na+ reabs (~25% of filtrate) by NaK2Cl symporter

Front 10

What normally happens in the distal convoluted tubule?

Back 10

reabsorption of ~10% of filtered Na by NaCl symporter (w/o water reabsorption)

Front 11

what normally happens in the collecting duct?

Back 11

reabsorb all but ~1% of remaining Na+ through channels activated by aldosterone

Na+ uptake drives K+ and H+ secretion

water permeability regulated by ADH through V2 receptor

Front 12

what's an osmotic diuretic?

Back 12

e.g. mannitol

compounds filtered but not reabsorbed

given in sufficient quantity to increase osm of tubular fluid

Front 13

where do osmotic diuretics act in the nephron?

Back 13

Mannitol:
throughout but espec in descending limb

Front 14

mechanism of osmotic diuretic?

Back 14

mannitol--acts mostly in desc limb:
Net effect=increase urine vol, proportional incr Na and Cl

increases osm press in filtrate and tubular urine to increase water retention in lumen

increased effect w/ incr renal BF

increase filtrate vol decreases Na conc that reduces extent of absorption

Front 15

what's the therapeutic use of an osmotic diuretic?

Back 15

1. maintain or restore urine vol and prevent acute tubular necrosis
2. reduce intracranial or intraocular pressure

Front 16

what are the side effects of osmotic diuretics?

Back 16

mannitol:
causes acute increase in ECF vol which leads to xs fluid loss, pulmonary edema, HA, nausea, vomit

Front 17

acetazolamide site of action?

Back 17

carbonic anhydrase inhibitor: works mainly on PCT

inhibits cytosolic and membrane bound CA (many cells of PT and CD)

Front 18

what does CA do in the Proximal tubule?

Back 18

mediates reabsorption of bicarb

blocked by acetazolamide which then inhibits HCO3- absorption from tubular fluid and increased alkalinity of urine

Front 19

do carbonic anhydrase inhibitors make urine alkaline or acidic?

Back 19

acetazolamide:
alkaline urine

block H+ production in PT resulting in decreased HCO3- absorption

Front 20

what effect does acetazolamide have on Na and K?

Back 20

carbonic anhydrase inhibitors:
causes diuresis w/ increased HCO3-, and increased Na+ and K+ excretion

Front 21

mechanism of carbonic anhydrase inhibitors?

Back 21

acetazolamide:
by CA inhibition, block H+ production in PT which means less HCO3- absorption form tubular fluid (alkaline urine)

distally, H+ and K+ normally exchange for Na+. CA inh increase K+ excretion by less H+ available

Front 22

what's the net result of acetazolamide?

Back 22

carbonic anhydrase inhibitor:

diuresis
increased HCO3-, K+, Na+ excretion

Front 23

what do repeated doses of acetazolamide cause?

Back 23

metabolic acidosis w/ decreased plasma HCO3- (increased excretion of HCO3-, Na, K+)

eventually, filtered HCO3- decreases and the drug loses efficacy

Front 24

what's the therapeutic use for a carbonic anhydrase inhibitor?

Back 24

acetazolamide:
no longer used as diuretic

lowers intraocular pressure for ocular HTN or open-angle glaucoma (new topical agent)

metabolic alkalosis (excrete HCO3-)

mountain sickness

Front 25

what's the difference among thiazide drugs?

Back 25

potency as diuretics, duration of action, extent of CA inhibition

Front 26

how do thiazide-type diuretics work?

Back 26

hydrochlorothiazide:

inhibit Na and Cl- reabsorption in cortical diluting site of DCT
bind NaCl symporter in apical memb.

some inhibit CA to increase HCO3- excretion

Front 27

whats the effect of acidosis or alkalosis on thiazide type diuretics?

Back 27

hydrochlorothiazide:
not affected
even though some inhibit CA, the main action isn't dependent on this effect

Front 28

what effect does hyrochlorothiazide have on urine solute concentrations?

Back 28

increase K+ (incr. Na to distal nephron enhances K+ exchange)

K+ loss depends on aldosterone (stimulates Na+ reabsorption)
and somewhat on CA inhibition (decrease H+ to xchange w/ Na)

Front 29

how are thiazide type diuretics given?

Back 29

almost always orally

Front 30

what are the major therapeutic uses for thiazide type diuretics?

Back 30

hydrochlorothiazide:
1. Hypertension
2. Edema (hepatic/CV/Renal origin)
3. Nephrogenic Diabetes insipidus
4. Ca nephrolithiasis

Front 31

how are thiazides useful for hypertension?

Back 31

Na depletion and decreased ECF volume

vasodilation and decrease TPR--direct sm effect

hypotensive agent alone or in combo

Front 32

what kinds of edema can hydrochlorothiazide be used for?

Back 32

edema of hepatic, cardiovascular or renal origin

Front 33

how are thiazides useful for nephrogenic diabetes insipidus?

Back 33

decrease(!) urinary excretion in pts w/ xs urine flow due to lack of ADH response

initial vol contraction may enhance PT fluid reabsorption and then decrease water distally to sites insensitive to ADH

Front 34

why are thiazides useful for calcium nephrolithiasis?

Back 34

hydrochlorothiazide:

increase Ca reabsorp in DCT

blked Na reabs enhances basolat Na-Ca exchanger--->increase Ca reab from lumen

reduced delivery of Ca to distal sites helps resolve tubular Ca stones

Front 35

side effects of hydrochlorothiazide?

Back 35

thiazide S/E's:
1. hypokalemia
2. hyperglycemia (aggrevate DM)
3. uric acid retention (ppt gout)
4. elevate plasma lipids
5. hypersensitivity rxns (rash, x-react w/ sulfonamides)

Front 36

how do loop diuretics work overall?

Back 36

Furosemide:
Primary effect=inhibition of Na+ and Cl- absorp in TAL.
Act on NaK2Cl symporter in luminal membrane
Also inhibit Na+ absorption in PT and to lesser extent distal sites.
Na and fluid volume excretion may increase from nl 1% of GFR to 25%
Impair ability to form dilute or concentrated urine; (urine osmolality approaches that of plasma. ("high ceiling" diuretics b/c max effect greatly exceeds other classes of diuretics.
Incr renin release by blking Cl flux into macula densa.

Front 37

Where do loop diuretics work?

Back 37

thick ascending loop of henle
act on NaK2Cl symporters
also inhib Na absorption proximally and a little distally

Front 38

why are loop diuretics called "high ceiling"?

Back 38

because max diuretic effect greatly exceeds that of other classes of diuretics

Front 39

what effect do loop diuretics have on the RAS?

Back 39

furosemide:
increase renin by blocking Cl influx into macula densa

Front 40

how much do loop diuretics incr Na and fluid excretion?

Is this concentrated or dilute urine?

Back 40

incr from nl 1% of GFR to 25%


impaired ability to form dilute or concentrated urine (osmolality approaches that of plasma)

Front 41

PK of furosemide/loop diuretics?

Back 41

po
highly bound to plasma proteins (can displace other drugs)

organic ions cleared by PT SECRETION (inhibitors of transporters like probenecid decr access to site of action and potency)

Front 42

use of loop diuretics?

Back 42

furosemide:
1. acute pulmonary edema (given i.v. as in HF)
2. edema (hepatic/CV/renal rigin)--espec if refractory to other classes w/ lesser max efficacy

Front 43

S/E's of loop diuretics?

Back 43

furosemide:
1. hypokalema, hypochloremia, dehydration, xs Mg and Ca loss (impaired reabsorption of cations in ascend limb)
2. uric acid retention
3. ototoxicity rare(trans or permanent deafness)
4. teratogen

Front 44

potassium sparing diuretics and site of action?

Back 44

amiloride: Na+ ch blker

spironolactone (aldo antag)

Front 45

where in the kidney do K+ sparing diuretics work?

Back 45

Spironolactone, amiloride:
at sitess of aldo activity: late DT and CDs
inhib reuptake of NA delivered to distal nephron (weak diuretics)
major effect: decr K+ excretion by reducing xchange w/ Na+ reabsorption

Front 46

mech of Na+ ch blkers?

Back 46

amiloride: K+ sparing diuretic
binds luminal loop of heterotrimeric protein ENaC w/ 6 apical memb spanning regions, blks Na entry.
decr K+ and H+ secretion

Front 47

use of Na ch blkers?

Back 47

amiloride:
in combo w/other diuretics to minimize K+ loss

Front 48

S/E's of Na channel blockers?

Back 48

amiloride:
hyperkalemia (do NOT give w/ spironolactone, K+ supplements, or ACEI's, etc)

Front 49

mech of aldosterone antagonist?

Back 49

spironolactone: K+ sparing diuretic
structural analog of aldo w/ no activity (comp. inhib)
prevents aldo mediated incr in Na+ reabsorption (ENaC)

(no effect in adrenalectomized pt or nl subject w/ low aldo)

Front 50

use of aldo antagonists?

Back 50

spironolactone:
decr K+ loss in conditions like hyperaldosteronism (secondary to cirrhotic edema, nephrosis, CHF)
decr hosp time and mortality in severe HF on other tx's

Front 51

S/E's of aldo antagonists?

Back 51

spironolactone:
hyperkalemia (contraindicated in renal failure due to xs risk)
hormonal effects (impotence and gynecomastia)