When administering eye drops, even when completely correctly applied, several routes of absorption are possible and excess amounts can sometimes cause an unwanted systemic bioavailability of the drops when not completely absorbed into the eye. Furthermore, the concentration of active ingredients in such medicinal preparations is usually very high, so that despite the correct application of the recommended dose, considerable amounts may be absorbed in an unwanted manner through various routes. Children are subject to a much higher risk of systemic side effects because ocular dosing is not weight adjusted and physiological development (eg, liver status) differs from that of adults. There is a lack of information about pediatric dosing in the current literature. This review summarizes the most important clinically relevant systemic side effects that may occur during ophthalmic eye treatments. In this review, we discuss general pharmacokinetic considerations as well as the advantages, disadvantages, and consequences of administering drugs from some important drug groups to the eye.

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This report employed the SQUIRE publication guidelines for reporting healthcare quality improvement research. [Ogrinc G, Davies L, Goodman D, et al. SQUIRE 2.0 (Standards for QUality Improvement Reporting Excellence): revised publication guidelines from a detailed consensus process.

There is increasing evidence of sex differences in the action of anti-inflammatory drugs, with women being at significantly higher risk of adverse effects. Nevertheless, clinicians’ awareness of the implications of these sex differences on dosing and adverse event monitoring in routine practice is still in need of improvement. We reviewed the literature evaluating sex differences in terms of pharmacokinetics and pharmacodynamics of anti-inflammatory drugs. The anti-thrombotic activity of selective and non-selective COX-inhibitors tends to be stronger in men than women. Side effect profiles differ with regards to gastro-intestinal, renal and hepatic complications. Glucocorticosteroids were found to be more effective in men; women were more sensitive to corticosteroids when their oestradiol levels were high, a finding important for women taking hormonal contraception. TNF-alpha inhibitors have a longer half-life in men, leading to stronger immunosuppression and this a higher incidence of infections as side effects. Although research on sex differences in the effectiveness and safety of drugs is increasing, findings are often anecdotal and controversial. There is no systematic sex-differentiated reporting from clinical trials, and women are often under-represented. As personalized medicine is gaining in importance, sex, and gender aspects need to become integral parts of future research and policy making.

We present the case of a 51-year-old male patient who received adjuvant chemotherapy consisting of oxaliplatin, bolus and continuous 5-fluorouracil (5-FU) and leucovorin after anterior resection because of locally advanced rectal cancer. Preoperative chemotherapy with capecitabine (an oral 5-FU prodrug) had been well tolerated. Two days after initiation of the first course of chemotherapy, the patient reported typical chest pain. The ECG showed ST elevations and prominent T waves in almost all leads. Due to suspicion of a high-risk acute coronary syndrome, an urgent cardiac catheterization was performed. It showed a generally reduced coronary flow with multiple significant stenoses (including the ostia of the left and right coronary artery), as well as a highly reduced left ventricular function with diffuse hypokinesia. Due to the meanwhile completely stable situation of the patient after medical acute coronary syndrome treatment, no ad hoc intervention was performed to allow further discussion of the optimal management. Thereafter, the patient remained clinically asymptomatic, without any rise in cardiac necrosis parameters; only NT-pro-BNP was significantly elevated. A control cardiac catheterization 2 days later revealed a restored normal coronary artery flow with only coronary calcifications without significant stenoses, as well as a normal left ventricular ejection fraction. Cardiovascular symptoms occurred on the second day of continuous 5-FU treatment. As cardiotoxic effects seem to appear more frequently under continuous application of 5-FU, compared to the earlier established 5-FU bolus regimens, treating medical oncologists should pay special attention to occurring cardiac symptoms and immediately interrupt 5-FU chemotherapy and start a cardiologic work-up.