OSMOTIC DIURETICS

Osmotic 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 nephron

OD mol. :◦ block the reabsorption of solutes from the nephron

(especially Na)Or◦ are 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 action◦Osmosis; H20conc. bet. interstitium vs.

tubular fluid

Proximal tubule◦Osmosis; same as DLH

Collecting duct◦oppose ADH

Nephron 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+

◦Cl–◦HCO3

–

◦H2PO4 –

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)◦Headache◦Nausea◦Vomiting

Hypernatremia (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 disease

◦patients who are unresponsive to test doses of the drugs

EXAMPLES 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 electrolytes

Filtration (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. parenterally

Following IV injection, mannitol distributes freely to extracellular water.

Onset: 30 to 60 minutesDuration: 6 to 8 hours. Excretion: Mostly intact in urine

Therapeutic UsesProphylaxis of Renal Failure

◦X shut down of kidney; osmosis

Reduction of Intracranial Pressure

Reduction of Intraocular PressureAcute angle-closure glaucoma

◦STATOpen angle Glaucoma

◦Perioperative period

Therapeutic UsesTo treat drug intoxication

Adverse EffectsThrombophlebitisConvulsionsEdema (CHF, Pulmonary)HeadacheNauseaVomitingFluid and electrolyte imbalance

CONTRAINDICATIONSMannitol

◦Drug allergy◦Severe renal disease◦Pulmonary Edema◦Patients with active intracranial

bleeding (free mannitol mols.in ECF; CE)

Drug InteractionsNone

Preparations, 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 ICP

CONTRAINDICATIONSUrea

◦ may cause thrombosis or pain if extravasation occurs

◦ patients with impaired liver function

risk of blood ammonia levels

◦patients with active intracranial bleeding

CONTRAINDICATIONS

Glycerin ◦Hyperglycemia (metabolised)