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A short presentation on the common types of osmotic diuretic drugs
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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)