Therapeutic agents mannitol

The 2,3-dihydro-1,4-benzodioxin ring system has aroused increasing interest, owing to its presence in a large number of structures of important therapeutic agents, the activity of which is considerably influenced by the chirality of the heterocyclic unit. Most of the syntheses of optically pure 2-substituted-2,3-dihydro-1,4-benzodioxins start from 2-hydroxymethyl-2,3-dihydro-1,4-benzodioxin in chiral form this latter compound can be obtained from D-mannitol <76CC92l>, by direct con-... 

From Equation 28 it may be observed that the rate of drug release from an osmotically controlled system is directly proportional to the osmotic pressure within the tablet. As a result the osmotic pressure is an important design consideration for these systems. Osmotic pressure is a colligative property and is therefore dependent on the number of ions and molecules in solution. If the solubility of the drug is low, the inherent osmotic pressure within the tablet will be low and therefore the rate of drug release will be low. Under these conditions the inclusion of excipients, e.g., mannitol, sodium chloride, potassium chloride or hydrophilic polymers, is required within the tablet core. Upon dissolution within the tablet the osmotic pressure will increase thereby enhancing the rate of release of the therapeutic agent (a.47, a. 167). 

Conventional treatment of raised ICP in this condition consists of artificial ventilation, osmotherapy, and barbiturate administration. The value and duration of these measures has come under scrutiny. Prolonged hyperventilation has been discouraged, as the potential decrease in cerebral arterial blood flow resulting from additional hypocarbia might exacerbate tissue ischemia (34). Early use of agents such as glycerol or mannitol, at least in theory, may actually hasten tissue shifts and therefore lead to an aggravation of brain edema (35). Barbiturate therapy has to date failed to prove to be of therapeutic benefit in the treatment of postischemic brain edema (36). 

Therapeutically, mannitol administered parenterally is used as an osmotic diuretic, as a diagnostic agent for kidney function, as an adjunct in the treatment of acute renal failure, and as an agent to reduce intracranial pressure, treat cerebral edema, and reduce intraocular pressure. Given orally, mannitol is not absorbed significantly from the GI tract, but in large doses it can cause osmotic diarrhea see Section 14. 

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