**18. Monitoring and prevention of side effects**

**16.4. Purpura**

the most common affected sites [143].

**17.1. Behavioral effects**

**17.2. Psychic effects**

**17.3. Cognitive effects**

impairment with short-term exposure [149].

**17. Psychiatric and cognitive disturbances**

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

lethargy, mood lability, and even psychosis [144].

dent. The evening dose induces sleeplessness [145, 146].

When severe dermal atrophy and loss of intercellular substance occur by GCs, blood vessels lose their surrounding dermal matrix. The fragility of dermal vessels causes purpura. The dorsum of the hands, forearms, sides of the neck, face, and lower legs (sun exposed areas) are

Systemic GCs induce dose-dependent a wide range of psychiatric and cognitive disturbances, including memory impairment, agitation, anxiety, fear, hypomania, insomnia, irritability,

Increase in appetite resulting with weight gain is the most common behavioral side effect of long-term exposure to GCs. Weight gain does not correlate with the cumulative dose. Sleep disturbances are the second most common behavioral side effects of GCs and dose-depen-

Psychic side effects (PSE) of GCs are quantitatively/qualitatively distinct forms. Symptoms range from an initial slight increase in the overall sense of well-being (independent of improvement in their underlying disease activity) or low-grade mood changes, such as euphoria, grandiosity, emotional lability, depressed or elated mood, up to severe psychiatric disorders, and suicidality. The frequency ranges from 1.3 to 62% in adults. The predicted threshold dose for PSE is ≥20 mg/day of prednisone (or equivalent), but can be seen at very low dosages. PSE commonly develop within the first weeks of exposure, but may occur within few days or at any point during treatment, including withdrawal (especially after long-term and high dose exposures). A family history of depression, previous neuropsychiatric disorders, and alcoholism has also been reported as risk factors for the development of PSE. Women were more likely to develop depression, whereas men were more likely to develop mania. The risk of depression, mania, delirium, confusion, and disorientation increases, but suicidal behavior and panic disorder decreases with age. PSE often disappears shortly after dose reduction or discontinuation. Switching to alternative GCs may be helpful. Clinicians should ask about a

prior history of psychiatric disorder and refer patients to a psychiatrist [147–149].

Cognitive impairment is a common, dose-dependent side effect of GCs. Common symptoms are deficits in attention, concentration, memory retention, mental speed, and efficiency. Prolonged exposure to moderate/high doses of GCs may cause cumulative and long-lasting effects on specific brain areas. Low doses of GCs do not affect adult cognitive functions in both short- and long-term exposure. Older patients appear to be more sensitive to memory The same total dose of GCs among systemic treatments has different side effects. Splitdose regimens are more toxic than single daily-dose protocols. Both these protocols are more toxic than alternate-day treatment programs. In daily treatment regimens, SGCs with long biologic half-lives (e.g. dexamethasone) have a greater potential for side effects than analogs do with intermediate biologic half-lives (e.g. prednisone). High doses of systemic GCs can be administered for less than a week with partial safety, even though the same dose of drug administered for a more prolonged period will result in presumably, clinically significant side effects. The lowest dose of GCs should be used for the shortest period of time that is needed to achieve the treatment goals. Preexisting comorbid conditions (diabetes mellitus, hypertension, dyslipidemia, heart failure, cataract or glaucoma, peptic ulcer disease, use of nonsteroidal anti-inflammatory drugs, low bone density, or osteoporosis) may increase risk when GCs are required. To provide an optimal therapy, patient education is very important. Patients should be informed about the side effects of GCs. GCs generally stimulate the appetite, causes weight gain, elevated blood pressure, and glucose levels. Therefore, patients should be informed about the importance of diet when therapy is begun. The symptoms and signs of side effects related with GCs, should also be explained to the patients [32, 51–53]. For systemic therapy, the choice of specific GCs depends, partially, on clinical variables like underlying or accompanying diseases. Hydrocortisone is usually used for physiologic replacement and "stress" coverage in patients with HPA suppression. Hydrocortisone has a short biologic half-life and causes sodium and potassium retention. Thus, this agent is not commonly used for systemic immunosuppressive or antiinflammatory treatment. Fluorinated analogs, such as dexamethasone, have a long biologic half-life and little sodium-retaining potency. But long biologic half-life, may be associated with a greater potential for side effects. As a result, this group of SGCs is not commonly used in prolonged daily therapy regimens [54].
