MANNITOL
Chemistry - An osmotic diuretic, mannitol occurs as an odorless, sweet-tasting, white, crystallinepowder with a melting range of 165° - 168° and a pKa of 3.4. One gram is soluble in about 5.5 mlof water (at 25°) and it is very slightly soluble in alcohol. The commercially available injectableproducts have approximate pH's of 4.5 - 7.
Crystallization may occur at low temperatures in concentrations greater than 15% (see procedurefor resolubolization in Dosage Forms/Preparations section). Alternatively, heated storage chambers(35° - 50°C) have been suggested to assure that soluble product is available at all times.
Microwaving glass ampules/vials has been suggested, but explosions have been documented andthis procedure cannot be recommended. Supersaturated solutions of mannitol in PVC bags mayshow a white flocullant precipitate that will tend to reoccur even after heating.
Drugs reported to be compatible with mannitol include: amikacin sulfate, bretylium tosylate, cefamandole naftate, cefoxitin sodium, cimetidine HCl, dopamine HCl, gentamicin sulfate, metoclopramide HCl, netilmicin sulfate, tobramycin sulfate, and verapamil HCl.
Mannitol should not be added to whole blood products to be used for transfusion. Sodium orpotassium chloride can cause mannitol to precipitate out of solution when mannitol concentrationsare 20% or greater. Mannitol may be incompatible with strongly acidic or alkaline solutions.
Mannitol is reportedly stable when mixed with cisplatin for a short period of time, but advancedpremixing of the drugs should be avoided because of a complex that may form between the twodrugs.
Mannitol may have a nephro-protective effect by preventing the concentration of nephrotoxinsfrom accumulating in the tubular fluid. Additional y, it may increase renal blood flow andglomerular filtration by causing renal arteriole dilatation, decreased vascular resistance and decreased blood viscosity.
Mannitol does not appreciably enter the eye or the CNS, but can decrease intraocular and CSFpressure through its osmotic effects. Rebound increases in CSF pressures may occur after the drugis discontinued.
Uses, Indications - Mannitol is used to promote diuresis in acute oliguric renal failure, reduce intraocular and intracerebral pressures, enhance urinary excretion of some toxins (e.g., aspirin, somebarbiturates, bromides, ethylene glycol) and, in conjunction with other diuretics to rapidly reduceedema or ascites when appropriate (see Contraindications-/Precautions below). In humans, it is alsoused as an irrigating solution during transurethral prostatic resections.
Only 7-10% of mannitol is metabolized, the remainder is excreted unchanged in the urine. Theelimination half-life of mannitol is approximately 100 minutes in adult humans. Half-lives in cattleand sheep are reported to be between 40-60 minutes.
Contraindications/Precautions - Mannitol is contraindicated in patients with anuria secondary torenal disease, severe dehydration, intracranial bleeding (unless during craniotomy), severepulmonary congestion or pulmonary edema.
Mannitol therapy should be stopped if progressive heart failure, pulmonary congestion, progressive renal failure or damage (including increasing oliguria and azotemia) develop after mannitoltherapy is instituted.
Do not administer more than a test dose of mannitol until determining whether the patient hassome renal function and urine output. Adequate fluid replacement must be administered to dehydrated animals before mannitol therapy is begun. Do not give mannitol with whole blood products, unless at least 20 mEq/l of sodium chloride is added to the solution or pseudo-agglutination mayresult.
Other adverse effects that may be encountered include GI (nausea, vomiting), cardiovascular(pulmonary edema, CHF, tachycardia), and CNS effects (dizziness, headache, etc.).
Overdosage - Inadvertent overdosage can cause excessive excretion of sodium, potassium andchloride. If urine output is inadequate, water intoxication or pulmonary edema may occur. Treat byhalting mannitol administration and monitoring and correcting electrolyte and fluid imbalances.
Hemodialysis is effective in clearing mannitol.
Drug/Laboratory Interactions - Mannitol can interfere with blood inorganic phosphorus concentrations and blood ethylene glycol determinations.
Storage, Stability, Compatibility
Mannitol solutions are stable but are recommended to bestored at room temperature; avoid freezing.Crystallization may occur at low temperatures in concentrations greater than 15% (see procedurefor resolubolization in Dosage Forms/Preparations section). Alternatively, heated storage chambers(35° - 50°C) have been suggested to assure that soluble product is available at all times.
Microwaving glass ampules/vials has been suggested, but explosions have been documented andthis procedure cannot be recommended. Supersaturated solutions of mannitol in PVC bags mayshow a white flocullant precipitate that will tend to reoccur even after heating.
Drugs reported to be compatible with mannitol include: amikacin sulfate, bretylium tosylate, cefamandole naftate, cefoxitin sodium, cimetidine HCl, dopamine HCl, gentamicin sulfate, metoclopramide HCl, netilmicin sulfate, tobramycin sulfate, and verapamil HCl.
Mannitol should not be added to whole blood products to be used for transfusion. Sodium orpotassium chloride can cause mannitol to precipitate out of solution when mannitol concentrationsare 20% or greater. Mannitol may be incompatible with strongly acidic or alkaline solutions.
Mannitol is reportedly stable when mixed with cisplatin for a short period of time, but advancedpremixing of the drugs should be avoided because of a complex that may form between the twodrugs.
Pharmacology - MANNITOL
After intravenous administration, mannitol is freely filtered at the glomerulus andpoorly reabsorbed in the tubule. The increased osmotic pressure prevents water from beingreabsorbed at the tubule. To be effective, there must be sufficient renal blood flow and filtration formannitol to reach the tubules. Although water is proportionately excreted at a higher rate, sodium, other electrolytes, uric acid and urea excretions are also enhanced.Mannitol may have a nephro-protective effect by preventing the concentration of nephrotoxinsfrom accumulating in the tubular fluid. Additional y, it may increase renal blood flow andglomerular filtration by causing renal arteriole dilatation, decreased vascular resistance and decreased blood viscosity.
Mannitol does not appreciably enter the eye or the CNS, but can decrease intraocular and CSFpressure through its osmotic effects. Rebound increases in CSF pressures may occur after the drugis discontinued.
Uses, Indications - Mannitol is used to promote diuresis in acute oliguric renal failure, reduce intraocular and intracerebral pressures, enhance urinary excretion of some toxins (e.g., aspirin, somebarbiturates, bromides, ethylene glycol) and, in conjunction with other diuretics to rapidly reduceedema or ascites when appropriate (see Contraindications-/Precautions below). In humans, it is alsoused as an irrigating solution during transurethral prostatic resections.
Pharmacokinetics - MANNITOL
Although long believed to be unabsorbed from the GI, up to 17% of an oraldose is excreted unchanged in the urine after oral dosing in humans. After intravenous dosing, mannitol is distributed to the extracellular compartment and does not penetrate the eye. Unless thepatient has received very high doses, is acidotic, or there is loss of integrity of the blood-brainbarrier, it does not cross into the CNS.Only 7-10% of mannitol is metabolized, the remainder is excreted unchanged in the urine. Theelimination half-life of mannitol is approximately 100 minutes in adult humans. Half-lives in cattleand sheep are reported to be between 40-60 minutes.
Contraindications/Precautions - Mannitol is contraindicated in patients with anuria secondary torenal disease, severe dehydration, intracranial bleeding (unless during craniotomy), severepulmonary congestion or pulmonary edema.
Mannitol therapy should be stopped if progressive heart failure, pulmonary congestion, progressive renal failure or damage (including increasing oliguria and azotemia) develop after mannitoltherapy is instituted.
Do not administer more than a test dose of mannitol until determining whether the patient hassome renal function and urine output. Adequate fluid replacement must be administered to dehydrated animals before mannitol therapy is begun. Do not give mannitol with whole blood products, unless at least 20 mEq/l of sodium chloride is added to the solution or pseudo-agglutination mayresult.
Adverse Effects, Warnings
Fluid and electrolyte imbalances are the most severe adverse effectsgenerally encountered during mannitol therapy. Adequate monitoring and support are imperative.Other adverse effects that may be encountered include GI (nausea, vomiting), cardiovascular(pulmonary edema, CHF, tachycardia), and CNS effects (dizziness, headache, etc.).
Overdosage - Inadvertent overdosage can cause excessive excretion of sodium, potassium andchloride. If urine output is inadequate, water intoxication or pulmonary edema may occur. Treat byhalting mannitol administration and monitoring and correcting electrolyte and fluid imbalances.
Hemodialysis is effective in clearing mannitol.
Drug Interactions
Mannitol can increase the renal elimination of lithium.Drug/Laboratory Interactions - Mannitol can interfere with blood inorganic phosphorus concentrations and blood ethylene glycol determinations.