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hours.7,36,37 Glycerol is absorbed rapidly, is distributed in extracellular water, and has poor ocular penetration (table 8.4). These properties enhance the osmotic effect of the drug.

Approximately 80% of glycerol metabolism occurs in the liver, while 10% to 20% occurs in the kidney.38 Because the majority of glycerol is metabolized by the liver, it has a greater margin of safety compared with mannitol in patients with decreased renal function. Glycerol is filtered and almost completely reabsorbed by the renal tubules until high serum levels are achieved; when serum carrying capacity is exceeded, glycerol appears in the urine and osmotic diuresis occurs. Both the metabolism and the reabsorption of glycerol attenuate the osmotic diuresis after ingestion of this drug. About 10% to 30% of glycerol is combined with free fatty acids to form triglyceride, while the majority is converted to glucose. Glycerol produces 4.34 cal/g when oxidized to carbon dioxide and water.38 Diabetic patients, therefore, may develop hyperglycemia and ketosis if treated with glycerol.

In addition to hyperglycemia, patients frequently experience nausea and vomiting following ingestion of glycerol. This is a problem in the therapy of acute glaucoma and an even greater disadvantage for perioperative use.

8.8.2 Other Oral Osmotic Drugs

Isosorbide. is not commercially available at this time. After oral administration, isosorbide and glycerol are similar in their onset of action, time to maximal effect, and duration of effect.8,39,40 Although isosorbide is rapidly absorbed, it is distributed in total body water and penetrates the eye slowly. These properties may lessen the osmotic effect of the drug, especially in inflamed eyes. From 1 to 3 hours after oral administration of isosorbide, anterior chamber aqueous levels averaged 55% of plasma levels.8

More than 95% of the administered dose of isosorbide is excreted unchanged in the urine. Isosorbide produces no caloric load after ingestion because it is not metabolized, which is a major advantage when compared with glycerol for use in diabetic patients. Isosorbide is less likely than glycerol to produce nausea and

Table 8.4 Osmotic Drugs

Ocular

Drug Solution Metabolism Distribution

Penetration Advantages

Disadvantages

Oral Administration Glycerol3 Stable Yes

Extracellular

Poor

Isosorbide Stable

Total body water

Good

Intravenous Administration Mannitol Stable No

Extracellular Very poor

Less diuresis Penetrates eye poorly

Well-tolerated No caloric value Rapid absorption

Useful in nauseated patients Penetrates eye poorly

Nausea and vomiting Caloric load (especially adverse in diabetic patients) Penetrates eye slowly Diarrhea

Larger volume Intravenous administration aPrepared as a 50% (vol/vol) solution. bNot commercially available.

vomiting but more likely to produce diarrhea.21'32'40 The oral osmotic agent isosorbide should not be confused with the angina drug isosorbide dinitrate (Isordil).41 Ethyl alcohol has an oral dose for lowering IOP of 0.8 to 1.5g/kg, which is approximately 2 to 3mL/kg of body weight of a 40% to 50% solution (80 to 100 proof).12'21 Lower doses may not have a significant effect on IOP.42 Ethyl alcohol is rapidly absorbed; however, distribution in total body water and rapid penetration of the eye limit the degree and duration of the osmotic gradient. Alcohol also induces a hypotonic diuresis by inhibiting production of antidiuretic hormone, which tends to prolong and increase the osmotic gradient.

Ethyl alcohol is metabolized and, like glycerol, causes increased caloric load after ingestion' which may be particularly problematic for diabetic patients. The hypotonic diuresis may cause dehydration. Central nervous system side effects, nausea, and vomiting are well-known side effects that limit the short- and long-term use of the drug.

Although rarely used therapeutically, ethyl alcohol is readily available and can be used in an emergency situation when no other osmotic drug is available. Also, clinicians may be misled by IOP measurements that are temporarily lowered by alcohol. Peczon and Grant reminded us that ''the examiner would do well to be alert for the smell of alcohol on the patient's breath, since it is not uncommon for patients to seek courage from alcohol in preparation for examination.''12

Other oral osmotic drugs, including glycine, lactate, propylene glycol, and calcium chloride, have not been used widely for lowering IOP, usually because of adverse side effects.23

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