Hyperosmotic agents are used to control acute episodes of severely elevated IOP. Common hyperosmotic agents include oral glycerol and intravenous mannitol.
When given systemically, hyperosmotic agents increase blood osmolality, creating an osmotic gradient between the blood and the vitreous humor that draws water from the vitreous cavity and reduces IOP. Because of the increased gradient, the higher the dose administered and the more rapid the administration, the greater the subsequent IOP reduction will be. A substance distributed only in extracellular water (eg, mannitol) is more effective than a drug distributed in total body water (eg, urea). The osmotic agent enters the eye more rapidly when the blood–aqueous barrier is disrupted than when it is intact, reducing the effectiveness of the drug and its duration of action.
Hyperosmotic agents are rarely administered for longer than a few hours because their effects are transient (a result of the rapid reequilibration of the osmotic gradient). They become less effective over time, and a rebound elevation in IOP may occur if the agent penetrates the eye and reverses the osmotic gradient.
Adverse effects of these drugs include headache, confusion, backache, acute congestive heart failure, and myocardial infarction. The rapid increase in extracellular volume and cardiac preload caused by hyperosmotic agents may precipitate or aggravate congestive heart failure. Intravenous administration is more likely to cause this problem than oral administration. In addition, subdural and subarachnoid hemorrhages have been reported after treatment with hyperosmotic agents. Glycerol can precipitate hyperglycemia or even ketoacidosis in patients with diabetes mellitus, because it is metabolized into glucose and ketone bodies. Hyperosmotic agents are contraindicated in patients with renal failure.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.