Diuretics

Osmotic

r

MOA: trap water in filtrate and osmotically prevent water reabsorbtion + cause diuresis by countercurrent washoutbasically, they increase GFR by redistributing water from some place in the periphery to the kidney so that it can be eliminated

Mannitol

Glycerol

Isosorbide

greatest effect on the eye

used mostly prior to ocular surgery

must have at least SOME urine production

Uses:

pre-surgery, can reduce intracranial and intraocular pressure

prophylaxis for acute renal failure

r

as long as there is SOME urine production though

AE:

cerebral edema

r

eventually the osmotic diuretics will diffuse from the plasma compartment out into the CSF -- the excess CSF volume can cause cerebral edema

HA

n/v

Contraindications:

Anuria

r

need at least SOME urine flow to get the osmotic diuretic out of your system

Peripheral edema

r

increasing the vascular volume with an osmotic diuretic will make the peripheral edema worse -- backs up into lungs and can lead to pulmonary edema!

Heart failure

r

osmotic diuretics will increase the circulating [pre]loadNatriuretic diuretics are ok to use though b/c they don't increase preload - they alter renal dynamics at the nephron instead of throughout vasculature

Dehydration

r

need some water in your body for an osmotic diuretic to redistribute it! osmotic diuretics would make dehydration worse

Natriuretic

(loop) high-ceiling diuretics

r

site 2

drug of choice

furosemide

r

MOA: inhibits NKCC2 (by plugging up the Cl site) and also causes 'counter-current' washoutIncreases urinary excretion of: Na, K, H, Cl, Mg, CaDecreases urinary excretion of: Urate, LiAlso a vasodilaor (will decr, L ventricular filling pressure and pulm. congestions)

AE:

hypokalemia

ototoxicity

hyperaldosteronism

hyperglycemia

hypertriglyceridemia

GI disturbances

worsens gout

if diabetic pt...

r

ethacrynic acid and bumetanide have lower incidence of hyperglycemia

bumetanide

potency differs from furosemide

ethacrynic acid

no sulfonamide group!

torsemide

2x bioavailability as furosemide

longer t1/2 permits qd dosing

direct inhibition of Na transport

thiazides

r

site 3MOA: inhibits NCC (Na/Cl contransporter) -- inhibs NaCl reabsorbtion at DCTunlike site 2 diuretics, DO NOT LEAD TO COUNTERCURRENT WASHOUTcontraindicated in pts with renal insufficiency!indications- essential HT- CHF (w/ NORMAL renal fxn)- mild edema- hypocalcemia & hypercalciuria)- diabetes insipidus (lack of ADNH)increased urinary excretion of: Na, K, Hdecreased urinary excretion of: Ca, urate, Lo

cholorthizide & hydrocholrothiazide

ineffective when GFR < 30ml/min (low renal fxn)

chlorthalidolone

AE

hyperglycemia

increased serum lipoproteins, TG, LDL

hypersensitivity reactions

drug interactions

K-sparing diuretics

r

may prevent K loss - a useful interaction

site 2 diuretics

Li

glucocorticoids

hypokalemia increases digitalis toxicity!!!

if pt has high cholesterol or diabetes...

metolazone & indapamide

better AE profile

exception to thiazide rule!: effective in renal failure when combined with a loop diuretic

don't alter lipids

don't cause hyperglycemia

K-sparing

r

site 4

disruption of electrical gradients

r

ENaC

amiloride

r

MOA: removes the drive to transport K across the cell (for excretion) -- by inhibiting Na influx thru ENaC, so less Na for the NaK ATPaseoral

unmetabolized (excreted uncharged by the kidney!)

triamterene

r

oral

shorter t1/2

some hepatic metabolism

competition with aldosterone

r

seldom used alonecontraindicated in pt with renal insufficiency

spironolactone

r

MOA: aldosterone receptor competitive antagonistinhibs ability of aldosterone to increase the Na/K exchangeNOT specific for the mineralocorticoid receptor (also binds glucocorticoid receptors)effects:slight diuresis, slight incr Na excretiongreater effect is to inhibit K lossSLOW onset and offset

AE:

hyperkalemia

elevated aldosterone level (in those w/ HF)

anti-androgenic effects/hypoandrogenism

gynecomastia

impotence

menstrual irregularities

contraindications

pts w/ diabetes

pts w/ impaired renal function

if pt. hypertensive or post-MI

epleronone

r

MOA: same as spironolactone, except...specific for the mineralocorticoid receptor (does not bind androgen or progesterone receptors)

AE:

hyperkalemia

carbonic anhydrase inhib

r

site 1

acetazolamide

r

MOA: inhibits both isoforms of carbonic anhydrase, thus inhibiting HCO3 reabsorbtion which also decreases Na reabsorbtionindications:NOT useful as diuretics!glaucoma (decreases movement of Na and water in aq humor)second line drug for epilepsyacute mountain sickness (d/t pulm or cranial edema)dissolusion of uric acid stones (b/c of alkanization of urine)

AE:

metabolic acidosis

r

b/c it lowers plasma HCO3

hypokalemia

drugs which alter renal hemodynamics

r

do NOT alter transporters

dopamine

r

MOA: DA and beta 1 receptor agonistfrequently combined with dobutamine (beta 1 agonist) in treating post-MI pts w/ poor renal blood floweffects:renal vasodilatorincreases GFRincreases renin production

caffeine