Mannitol 1015846 220353921 2008-06-19T13:17:33Z 86.159.238.177 {{Drugbox| |IUPAC_name = (2R,3R,4R,5R)-Hexane-1,2,3,4,5,6-hexol | image=Mannitol structure.png | CAS_number=69-65-8 | CAS_number=87-78-5 | ATC_prefix=A06 | ATC_suffix=AD16 | ATC_supplemental={{ATC|B05|BC01}} {{ATC|B05|CX04}} | PubChem=453 | DrugBank=APRD01083 | C=6 | H=14 | O=6 | molecular_weight = 182.172 | bioavailability= ~7% | metabolism = [[Liver|Hepatic]], negligible. | elimination_half-life=100 minutes | excretion = [[Kidney|Renal]]: 90% | pregnancy_category = C: ([[United States|USA]]) | legal_status = ? | routes_of_administration= [[Intravenous]]<br>[[Mouth|Oral]] }} '''Mannitol''' or '''hexan-1,2,3,4,5,6-hexol''' (C<sub>6</sub>H<sub>8</sub>(OH)<sub>6</sub>) is a [[polyol]] that is used as an [[osmosis|osmotic]] [[diuretic]] agent and a weak [[kidney|renal]] [[vasodilator]]. It is a [[sorbitol]] [[stereoisomer]]. It was originally isolated from the secretions of the [[Flowering Ash]], called [[Manna]] after their resemblance to the Biblical food, and may also be referred to as '''Mannite''' and '''Manna Sugar'''.<ref>Cooley's Cyclopaedia of Practical Receipts, 6th ed. (1880)</ref> ==Chemical properties== Chemically, mannitol is a [[sugar alcohol]], or a [[polyol]]; it is similar to [[xylitol]] or [[sorbitol]]. However, mannitol has a tendency to lose a [[hydrogen]] [[ion]] in aqueous solutions, which causes the solution to become [[acid]]ic. For this, it is not uncommon to add a substance to adjust its [[pH]], such as [[sodium bicarbonate]]. ==Uses== Mannitol is used clinically to reduce acutely raised [[intracranial pressure]], until more definitive treatment can be given, e.g. after [[head trauma]] (although significant controversy exists over this use), and to treat patients with [[oliguric renal failure]]. It is administered [[intravenous]]ly, and is filtered by the [[glomerulus]] of the [[kidney]], but is incapable of being resorbed from the [[renal tubule]], resulting in decreased water and [[Sodium|Na]]<sup>+</sup> reabsorption via its [[osmosis|osmotic]] effect. Consequently, mannitol increases water and Na<sup>+</sup> excretion, thereby decreasing extracellular fluid volume. Mannitol can also be used to open the [[blood-brain barrier]] by temporarily shrinking the tightly coupled [[endothelial cell]]s that make up the barrier. This makes mannitol indispensable for delivering various drugs directly to the [[brain]] (e.g. in the treatment of [[Alzheimer's disease]]). Mannitol is also used as a [[sweetener]] for people with [[diabetes]]. Since mannitol has a negative [[heat of solution]], it is used as a sweetener in "breath-freshening" candies, the cooling effect adding to the fresh feel. In oral doses larger than 20g, mannitol acts as an osmotic [[laxative]], and is sometimes sold as a laxative for children. It is sometimes used as an [[adulterant]] or [[cutting agent]] for [[heroin]], [[methamphetamine]]s or other [[illicit drug]]s. In popular culture, when it is used in this manner, it is often referred to as ''baby laxative''. Many television shows and films depicting drug culture make references to ''baby laxative''. Mannitol can also be used to temporarily encapsulate a sharp object (such as a helix on a lead for an [[artificial pacemaker]]) while it is passing through the venous system. Because it dissolves readily in blood, the sharp point will become exposed by the time it reaches its destination. Mannitol may be administered in cases of severe [[Ciguatera]] poisoning. Severe [[ciguatoxin]], or "tropical fish poisoning" can produce stroke-like symptoms. Mannitol is a non-permeating molecule; i.e., it cannot cross biological membranes. Mannitol is commonly used in the circuit prime of a [[heart lung machine]] during [[cardiopulmonary bypass]] (CPB). The presence of mannitol preserves renal function during the times of low blood flow and pressure, while the patient is on bypass. The solution prevents the swelling of [[endothelial cell]]s in the kidney, which may have otherwise reduced blood flow to this area and resulted in cell damage. Mannitol is also being developed by Australian pharmaceutical company Pharmaxis as a treatment for cystic fibrosis and bronchiectasis and as a diagnostic test for airway hyperresponsiveness. The mannitol is orally inhaled as a dry powder through what is known as an osmohaler and osmotically draws water into the lungs to thin the thick, sticky mucus characteristic of cystic fibrosis. This is intended to make it easier for the sufferer to cough the mucus up during physiotherapy. The critical component of the mannitol being the particle size distribution (PSD). The company has marketing approval for its diagnostic in Australia and Europe and is currently applying for approval from the FDA. Chemical Abstract Registry Numbers for Mannitol are *123897-58-5 *69-65-8 *75398-80-0 *85085-15-0 ==Controversy== The three studies<ref>Cruz J, Minoja G, Okuchi K. Improving clinical outcomes from acute subdural hematomas with the emergency preoperative administration of high doses of mannitol: a randomized trial. Neurosurgery. 2001 Oct;49(4):864-71. PMID 11564247</ref><ref>Cruz J, Minoja G, Okuchi K. Major clinical and physiological benefits of early high doses of mannitol for intraparenchymal temporal lobe hemorrhages with abnormal pupillary widening: a randomized trial. Neurosurgery. 2002 Sep;51(3):628-37; discussion 637-8. PMID 12188940</ref><ref>Cruz J, Minoja G, Okuchi K, Facco E. Successful use of the new high-dose mannitol treatment in patients with Glasgow Coma Scale scores of 3 and bilateral abnormal pupillary widening: a randomized trial. J Neurosurg. 2004 Mar;100(3):376-83. PMID 15035271</ref> which initially found that high-dose mannitol was effective in cases of severe head injury have been the subject of a recent investigation.<ref>Roberts I, Smith R, Evans S. [http://www.bmj.com/cgi/content/full/334/7590/392 Doubts over head injury studies.] BMJ. 2007 Feb 24;334(7590):392-4. PMID 17322250</ref> Although several authors are listed, it is unclear whether the authors had knowledge of how the patients were recruited. Further, the Federal University of São Paulo, which he gave as his affiliation, has never employed him. Currently, therefore, the [[Cochrane Collaboration|Cochrane review]] recommending high-dose mannitol<ref>Wakai A, Roberts I, Schierhout G. Mannitol for acute traumatic brain injury. Cochrane Database Syst Rev. 2005 Oct 19;(4):CD001049. PMID 16235278</ref> has been withdrawn pending re-evaluation, as there is some evidence that mannitol may worsen cerebral edema.<ref>Kaufmann AM, Cardoso ER. Aggravation of vasogenic cerebral edema by multiple-dose mannitol. J Neurosurg. 1992 Oct;77(4):584-9. PMID 1527619</ref> == See also == * [[Sorbitol]] * [[Xylitol]] ==References== <References/> ==External links== * {{RXlist|osmitrol}} * {{GPnotebook|1724907529}} [[Category:Sugar alcohols]] [[Category:Sweeteners]] [[Category:Polyols]] [[de:Mannit]] [[es:Manitol]] [[fr:Mannitol]] [[gl:Manitol]] [[it:Mannitolo]] [[hu:Mannit]] [[nl:Mannitol]] [[ja:マンニトール]] [[pl:Mannitol]] [[pt:Manitol]] [[ru:Маннит]] [[sv:Mannitol]] [[zh:甘露醇]]