Diuretics

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Volume Regulation Pharmacology

luonut Nnedimma Ozoani

Volume Regulation Pharmacology

luonut Nnedimma Ozoani

Volume Regulation Pharmacology

luonut Nnedimma Ozoani

Loop Diuretics

luonut Courtney Rockwood

Diuretics

Natriuretic

drugs which alter renal hemodynamics

caffeine

dopamine

MOA: DA and beta 1 receptor agonist

effects:

carbonic anhydrase inhib

site 1

acetazolamide

MOA: inhibits both isoforms of carbonic anhydrase, thus inhibiting HCO3 reabsorbtion which also decreases Na reabsorbtion

indications:

metabolic acidosis

b/c it lowers plasma HCO3

K-sparing

site 4

competition with aldosterone

seldom used alone

contraindicated in pt with renal insufficiency

if pt. hypertensive or post-MI

epleronone

MOA: same as spironolactone, except...

specific for the mineralocorticoid receptor (does not bind androgen or progesterone receptors)

spironolactone

MOA: aldosterone receptor competitive antagonist

inhibs ability of aldosterone to increase the Na/K exchange

NOT specific for the mineralocorticoid receptor (also binds glucocorticoid receptors)

effects:

SLOW onset and offset

contraindications

pts w/ impaired renal function

pts w/ diabetes

anti-androgenic effects/hypoandrogenism

menstrual irregularities

impotence

gynecomastia

elevated aldosterone level (in those w/ HF)

hyperkalemia

disruption of electrical gradients

ENaC

triamterene

oral

some hepatic metabolism

shorter t1/2

amiloride

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

oral

unmetabolized (excreted uncharged by the kidney!)

direct inhibition of Na transport

thiazides

site 3

MOA: inhibits NCC (Na/Cl contransporter) -- inhibs NaCl reabsorbtion at DCT

unlike site 2 diuretics, DO NOT LEAD TO COUNTERCURRENT WASHOUT

contraindicated 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, H

decreased urinary excretion of: Ca, urate, Lo

if pt has high cholesterol or diabetes...

metolazone & indapamide

don't cause hyperglycemia

don't alter lipids

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

better AE profile

drug interactions

hypokalemia increases digitalis toxicity!!!

glucocorticoids

Li

site 2 diuretics

K-sparing diuretics

may prevent K loss - a useful interaction

AE

hypersensitivity reactions

increased serum lipoproteins, TG, LDL

chlorthalidolone

cholorthizide & hydrocholrothiazide

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

(loop) high-ceiling diuretics

site 2

torsemide

longer t1/2 permits qd dosing

2x bioavailability as furosemide

if diabetic pt...

ethacrynic acid and bumetanide have lower incidence of hyperglycemia

ethacrynic acid

no sulfonamide group!

bumetanide

potency differs from furosemide

drug of choice

furosemide

MOA: inhibits NKCC2 (by plugging up the Cl site) and also causes 'counter-current' washout

worsens gout

GI disturbances

hypertriglyceridemia

hyperglycemia

hyperaldosteronism

ototoxicity

hypokalemia

Osmotic

MOA: trap water in filtrate and osmotically prevent water reabsorbtion + cause diuresis by countercurrent washout

basically, they increase GFR by redistributing water from some place in the periphery to the kidney so that it can be eliminated

Contraindications:

Dehydration

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

Heart failure

osmotic diuretics will increase the circulating [pre]load

Natriuretic diuretics are ok to use though b/c they don't increase preload - they alter renal dynamics at the nephron instead of throughout vasculature

Peripheral edema

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

Anuria

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

AE:

n/v

HA

cerebral edema

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

Uses:

prophylaxis for acute renal failure

as long as there is SOME urine production though

pre-surgery, can reduce intracranial and intraocular pressure

must have at least SOME urine production

Isosorbide

greatest effect on the eye

used mostly prior to ocular surgery

Glycerol

Mannitol