**13. Ocular side effects**

### **13.1. Glaucoma**

GCs induce morphological and functional changes in the trabecular meshwork (TM). These mechanisms are considered to be the leading cause of increased intraocular pressure during treatment with GCs. Systemic GCs are associated with a high incidence of glaucoma. All doses of GCs increase the risk for glaucoma. Nevertheless, doses of hydrocortisone 40 mg per day (prednisone 10 mg equivalent) were associated with an almost twofold increased risk. In patients over 40 years of age and with certain systemic diseases (e.g. diabetes mellitus, high myopia, connective tissue disease particularly rheumatoid arthritis), as well as relatives of patients with primary open-angle glaucoma (POAG), the risk for glaucoma induced by GCs increases. Glaucoma may lead to increased intraocular pressure, optic disc cupping, severe optic nerve damage, but considered a *silent* disease. *Because* there are no evident *symptoms*

until visual loss. Discontinuation of GCs leads to reversal of intraocular hypertension within a few weeks, but the optic nerve damage is often permanent [122, 123].

### **13.2. Cataracts**

**12. Gastrointestinal side effects**

108 Pharmacokinetics and Adverse Effects of Drugs - Mechanisms and Risks Factors

testinal bleeding (UGB), and pancreatitis.

and to delay the healing of ulcers [118–120].

a wide variety of diseases [121].

**13. Ocular side effects**

**13.1. Glaucoma**

**12.1. PU**

**12.2. UGB**

**12.3. Pancreatitis**

Side effects of GCs on the gastrointestinal system include peptic ulcers (PU), upper gastroin-

There is conflicting evidence related with the risk of PU for patients treated with glucocorticoid monotherapy. In a case-control study, there was no increased risk of PU at any dose or duration of glucocorticoid monotherapy. But in the same study, the combination of GCs with nonsteroidal anti-inflammatory drugs (NSAID), there was a significantly increased risk of peptic ulcer. Treatment with GCs may cause gastric irritation, more than PU [116, 117].

The incidence of UGB is low in patients treated with GCs alone and without a prior history of bleeding, but notably higher in patients receiving concomitantly anticoagulants and NSAIDs, and those with a history of bleeding. In the presence of different underlying diseases, such as rheumatoid arthritis, treatment with GCs may represent a more important risk factor for gastrointestinal complications than NSAIDs. In animal studies, GCs have been shown to increase gastric acid secretion, to reduce gastric mucus, to cause gastrin and parietal cell hyperplasia,

Although the exact mechanism is unknown, incidence of GCs induced pancreatitis is well established in the medical literature. One case-control study showed that the risk of acute pancreatitis was increased among current users of oral GCs compared with nonusers. This risk was highest 4–14 days after drug dispensation and the risk gradually decreased thereafter. Pancreatitis, commonly reported in chronic exposure to GCs, especially in large doses for

GCs induce morphological and functional changes in the trabecular meshwork (TM). These mechanisms are considered to be the leading cause of increased intraocular pressure during treatment with GCs. Systemic GCs are associated with a high incidence of glaucoma. All doses of GCs increase the risk for glaucoma. Nevertheless, doses of hydrocortisone 40 mg per day (prednisone 10 mg equivalent) were associated with an almost twofold increased risk. In patients over 40 years of age and with certain systemic diseases (e.g. diabetes mellitus, high myopia, connective tissue disease particularly rheumatoid arthritis), as well as relatives of patients with primary open-angle glaucoma (POAG), the risk for glaucoma induced by GCs increases. Glaucoma may lead to increased intraocular pressure, optic disc cupping, severe optic nerve damage, but considered a *silent* disease. *Because* there are no evident *symptoms*

Posterior subcapsular cataracts (PSC) induced by GCs appears bilaterally and is distinguishable from the more common types of cataract. Increased glucose levels, caused by an increased gluconeogenesis rate; inhibition of Na<sup>+</sup> /K+ -ATPase; increased cation permeability; inhibition of glucose-6-phosphate-dehydrogenase; inhibition of RNA synthesis; loss of ATP; and covalent binding of steroids to lens proteins are the possible mechanisms. These changes are specific for PSC induced by GCs. The risk appears to be both duration and dose-dependent. PSC is more likely to occur at higher doses of GCs. But as with other side effects, lower doses (<5 mg prednisone per day) have been linked to PSC [123, 124].
