OSMOTIC DIURETICS

OSMOTIC DIURETICSOsmotic diuretics:is a type of diuretic that inhibits reabsorption of H20 and Na+.

Pharmacologically inert substances intravenously.

osmolarity of blood and renal filtrate. Properties of Osmotic Diuretics It is freely filtered at the glomerulus. It undergoes minimal reabsorption. It is not metabolized to a significant degree. It is pharmacologically inert (ie, it has no direct effects on the biochemistry or physiology of cells).

Osmotic diuretics:H20 retention: proximal tubule descending limb of loop of Henle (freely permeable to water)

Small enough molecules ultrafiltration barrier nephronOD mol. :block the reabsorption of solutes from the nephron (especially Na)Orare not easily absorbed from the nephron themselves; large enough not to pass through PT & DLLH (mannitol).

filtrate(solutes)filtrate : exert an osmotic effect that inhibits the reabsorption of water.

Sites of Action:Descending Loop of Henle:major site of actionOsmosis; H20conc. bet. interstitium vs. tubular fluid

Proximal tubuleOsmosis; same as DLH

Collecting ductoppose ADHNephron sites of action of diuretics

Therapeutic Uses:Acute or incipient renal failureAcute attacks of glaucomaReduce preoperative intraocular pressure (alter Starling forces; IaCV)Reduce pre-surgical or post-trauma intracranial pressure (cerebral edema) Prompt removal of renal toxins

EFFECTS ON URINARY EXCRETIONOsmotic diuretics increase the urinary excretion of nearly all electrolytes, including:Na+K+Ca2+Mg2+ClHCO3H2PO4

EFFECTS ON RENAL HEMODYNAMICS renal blood flow (RBF)

Little to no change in the glomerular filtration rate (GFR)

Toxicity/Adverse effects:DehydrationHyponatremia ( urine FR, contact bet. fluid & tub. cells, Na+ reabsorption)HeadacheNauseaVomitingHypernatremia (H20 diuresis > naturesis)TachycardiaAcidosis (prox. Tube. exc. of acids)Edema (all caps. Permeable; expt. brain)Fluid and Electrolyte Imbalance

CONTRAINDICATIONSGenerally, contraindicated in patients with:heart failure or pulmonary congestion frank pulmonary edema ( extracellular volume and hyponatremia; perm. caps.)patients who are anuric owing to renal diseasepatients who are unresponsive to test doses of the drugsExamples of Osmotic diuretics

MANNITOL (OSMITROL)Is a simple six-carbon sugar that possesses the four properties characteristic of an osmotic diuretic

Of the four, is the only one used for its diuretic actions

Mechanism of Diuretic ActionPromotes diuresis by creating an osmotic force within the lumen of the nephron.

concentration of mannitol in the filtrate, degree of diuresis; the more mannitol present, the greater the diuresis.No significant effect on the excretion of K+ and other electrolytesFiltration (of OD mols. in nephron)

Minimal Reabsorption

Remains w/n nephron

Osmotic force

X passive RA of H20

Urine Output

PharmacokineticsX diffuse across the GI epithelium and cannot be transported by the uptake systems that absorb dietary sugars. parenterallyFollowing IV injection, mannitol distributes freely to extracellular water.Onset: 30 to 60 minutesDuration: 6 to 8 hours. Excretion: Mostly intact in urineTherapeutic UsesProphylaxis of Renal FailureX shut down of kidney; osmosis

Reduction of Intracranial Pressure

Reduction of Intraocular PressureAcute angle-closure glaucomaSTATOpen angle GlaucomaPerioperative period

Therapeutic UsesTo treat drug intoxicationAdverse EffectsThrombophlebitisConvulsionsEdema (CHF, Pulmonary)HeadacheNauseaVomitingFluid and electrolyte imbalanceCONTRAINDICATIONSMannitolDrug allergySevere renal diseasePulmonary EdemaPatients with active intracranial bleeding (free mannitol mols.in ECF; CE)

Drug InteractionsNonePreparations, Dosage, and AdministrationAdministered by IV infusionTest dose of mannitol (12.5 g intravenously)Solutions for IV use: 5%-25%.Dosing depends on objective of therapy (prevention of renal failure, lowering of ICP, lowering of IOP)The usual adult dosage for preventing renal failure: 50 -100 gm /24 hours.The infusion rate should be set to elicit a urine flow of at least 30 to 50 mL/hr.

Low temperature: may crystallize (>15%).Observed for crystals prior to use.Preparations that contain crystals should be warmed (to redissolve the mannitol) and then cooled to body temperature for administration.A filter needle: vialIn-line filter: prevent crystals from entering the circulation.Urea, Glycerin, and IsosorbideThese agents are freely filtered at the glomerulus and undergo limited reabsorption which promotes osmotic diuresis.Are not used for osmotic diuresis.They are used only to reduce IOP and ICPCONTRAINDICATIONSUrea may cause thrombosis or pain if extravasation occurs patients with impaired liver function risk of blood ammonia levelspatients with active intracranial bleeding

CONTRAINDICATIONSGlycerin Hyperglycemia (metabolised)