Systemic adverse effects

Acute Toxicity Studies. These studies should provide the following information the nature of any local or systemic adverse effects occurring as a consequence of a single exposure to the test material an indication of the exposure conditions producing the adverse effects, in particular, information on dose—response relationships, including minimum and no-effects exposure levels and data of use in the design of short-term repeated exposure studies. 

Direct airway administration of asthma medications through inhalation is the most efficient route and minimizes systemic adverse effects. 

Direct airway administration of asthma medications through inhalation is most efficient and minimizes systemic adverse effects. Poor inhaler technique can result in increased oropharyngeal deposition of the drug with decreased efficacy and increased adverse effects. Figure 11-1 provides... 

Systemic adverse effects are dose-dependent and are rare at low to medium doses however, high-dose inhaled corticosteroids have been associated with adrenal suppression, decreased bone mineral density, skin thinning, and easy bruising.3,29 Growth suppression in children may occur even with low-dose inhaled corticosteroids however, suppression appears to occur primarily in the first year of treatment and may be due to delayed growth with the potential of future catch-up growth.30... 

In patients taking NSAIDs, monitor for increases in blood pressure, weight gain, edema, skin rash, and central nervous system adverse effects such as headaches and drowsiness. 

Decongestants such as OTC pseudoephedrine are sympathomimetic agents that constrict capacitance vessels in the nasal turbinates.17 Decongestants effectively reduce nasal congestion and to some extent rhinorrhea associated with AR.8,12 The recommended dose of pseudoephedrine is 30 to 60 mg every 4 to 6 hours for a maximum daily dose of 240 mg.15 Systemic adverse effects such as irritability, dizziness, headache, tremor, tachycardia, and insomnia can occur. Additionally, use is associated with increased blood pressure and intraocular pressure and urinary obstruction.8,12... 

Local and systemic adverse effects are associated with AIT. Patients may experience pain or subcutaneous nodules at the injection site. In patients who suffer systemic symptoms soon after the injection, the AIT plan should be assessed and may need to be advanced more gradually. Systemic reactions, including anaphylaxis, are most likely to occur during the titration phase. Patients with asthma are at higher risk for systemic and fatal reactions. Patients should be monitored for... 

Systemic adverse effects associated with vaginal azoles are less frequent than with oral products. Local discomfort such as burning may occur with the first application. Fifteen percent of patients experience gastrointestinal side effects with orally administered antifungal agents.13 Oral ketoconazole is associated with hepatic toxicity at a rate of 1 in 15,000.14... 

Use of diethylpropion for a period longer than 3 months is associated with an increased risk for development of pulmonary hypertension. When used as directed, reported common central nervous system adverse effects included overstimulation, restlessness, dizziness, insomnia, euphoria, dysphoria, tremor, headache, jitteriness, anxiety, nervousness, depression, drowsiness, malaise, mydriasis, and blurred vision. In addition, diethylpropion can decrease seizure threshold, subsequently increasing a patient s risk for an epileptic event. Other organ systems also can adversely be affected, resulting in tachycardia, elevated blood pressure, palpitations, dry mouth, abdominal discomfort, constipation,... 

Keyset LA, Karl M, Nafziger AN, Bertino JS Jr. (2000) Comparison of central nervous system adverse effects of amantadine and rimantadine used as sequential prophylaxis of influenza a in elderly nursing home patients. Arch Intern Med 160 1485-1488... 

Immunocyanin is a stable modification of keyhole limpet hemocyanin, a non-heme, oxygencarrying copper protein found in arthropods and mollusca. It is an aspecific activator of both cellular and humoral reactions. Immunocyanin is used for the local treatment of bladder cancer. Its systemic adverse effects are usually limited to some mild fever. 

The systemic adverse effects of corticosteroids make them inappropriate as maintenance treatments and the first line treatments are the aminosalicylates. The original drug sulfasalazine is a chemical combination of sulfapyridine and 5 aminosalicylic acid. Following the discovery that the active... 

Lipworth BJ. Systemic adverse effects of inhaled corticosteroid therapy. A systematic review and meta-analysis. Arch Intern Med 1999 159 941-55. 

Aerosol treatment is the most effective way to avoid the systemic adverse effects of corticosteroid therapy. The introduction of corticosteroids such as beclomethasone, budesonide, ciclesonide, flunisolide, fluticasone, mometasone, and triamcinolone... 

Imiquimod is an immune response modifier shown to be effective in the topical treatment of external genital and perianal warts (ie, condyloma acuminatum see Chapter 61). The 5% cream is applied three times weekly and washed off 6-10 hours after each application. Recurrences appear to be less common than after ablative therapies. Imiquimod is also effective against actinic keratoses, and possibly, molluscum contagiosum. Local skin reactions are the most common side effect these tend to resolve within weeks after therapy. However, pigmentary skin changes may persist. Systemic adverse effects such as fatigue and influenza-like syndrome have occasionally been reported. 

Because it is not absorbed, sucralfate is virtually devoid of systemic adverse effects. Constipation occurs in 2% of patients due to the aluminum salt. Because a small amount of aluminum is absorbed, it should not be used for prolonged periods in patients with renal insufficiency. 

Benzocaine is an ester local anesthetic with a moderate onset of action and short duration. It is minimally absorbed and therfore relatively free from systemic adverse effects (toxic range of total dose 200 to 300 mg Tetzlaff, 2000). 

Tolerance to glucocorticoids in this, as in some other respects, varies from individual to individual some patients tolerate 30 mg of prednisone for a long time without developing Cushing s syndrome, while others develop symptoms at 7.5 mg the doses recommended today to avoid Cushing s syndrome in most patients are usually equivalent to hydrocortisone 20 mg. Cushing s syndrome and other systemic adverse effects can occur not only from oral and injected glucocorticoids, but also from topical and intranasal treatment (115) and intrapul-monary or epidural administration (SEDA-19, 376 SEDA-20, 370 116,117). 

Local and systemic adverse effects of ophthalmic glucocorticoids occur in children more often, more severely, and more rapidly than in adults, for unknown reasons. It could be that children have relatively immature chamber angles, giving rise to a rapidly increasing intraocular pressure (432). 

Topical administration to the nose The safety of nasal glucocorticoids in the treatment of allergic rhinitis has been reviewed (434,435). The local application of glucocorticoids for seasonal or perennial rhinitis often results in systemic adverse effects. The use of nasal sprays containing a glucocorticoid that has specific topical activity (such as beclomethasone dipropionate or flunisolide) seems to reduce the systemic adverse effects, but they can nevertheless occur, even to the extent of suppression of basal adrenal function in children (436). Local adverse effects include Candida infection, nasal stinging, epistaxis, throat irritation (437), and, exceptionally, anosmia (438). 

The effects of intrathecal administration, both wanted and unwanted, are still much debated (448). The question as to whether oral glucocorticoid therapy should be preferred to intrathecal injections is raised by the harmful effects that have sometimes occurred after the latter, although some of these may have been caused by irritative substances in the injection fluid (SEDA-6, 331). The same local glucocorticoid concentrations can probably be attained with fewer problems with oral administration. Epidural injection of glucocorticoids seems to be safer than intrathecal injection, but injection of high doses can cause the same systemic adverse effects as seen with oral treatment. Facial flushing and erythema after lumbar... 

Systemic adverse effects of topical administration Cushing s syndrome... 

Peak AS, Sutton BM. Systemic adverse effects associated with topically applied latanoprost. Ann Pharmacother 1998 32(4) 504—5. 

In a prospective non-comparative 6-month study of 34 women with mild to moderate endometriosis this approach gave marked relief of symptoms, and two-thirds of the women elected to continue treatment after the trial was completed (52). The staging of the disease was favorably affected. Administration of low doses in this manner seems to provide a means of avoiding significant systemic adverse effects while maintaining efficacy, but longer-term experience is required. 

Nervous system adverse effects are rare, constituting 0.5% of all adverse effects (2). Gemfibrozil-induced headache has been reported (3) and occurred in one patient... 

---